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Page numbers in italic refer to figures/tablesGreek letters are spelled out (e.g., alpha)
AAG (alpha-acid glycoprotein) 578
ABC drug transporters 92–95;see also efflux drugtransporters; P-glycoprotein
B1 transporters 92–93,94, 99
C transporters 92, 93–94G2 transporters 92, 94–95
ABC (awakening breathingcontrolled) trial 1046–1048
absence seizures 596
absolute drug potency 14
absorption; see also specificagents by name
pediatric pharmacology1129–1130, 1132
pharmacogeriatrics 1139systemic 580–581
acamprosate 1107
acceleromyography 1032–1034
ACCP guidelines 775
accumulation factors/index 66
ACE (angiotensin-convertingenzyme) inhibitors 731,735–736, 1096
acetaminophen see paracetamol
acetazolamide 790, 792
acetylcholine 330, 333–334chemical structure 612preclinical pharmacology 667synaptic transmission 200
acetylcholine receptors 374–375;see also muscarinicacetylcholine receptors;nicotinic acetylcholinereceptors
channel block 611desensitization block 611increased expression 622–624neuromuscular blockingdrugs 613, 624–625
non-competitive block609–611
perioperative medication 995postsynaptic transmission 609presynaptic transmission 608volatile anesthetics 371
acetylcholinesterase 79, 611–612,633–634, 635–636
acetylcholinesterase inhibition266–267, 634;see also neuromuscularblockade reversal
drug interactions 636–637paralysis reversal 1035pharmacokinetics 637side effects 637
acetylcysteine 997
acetylsalicylic acid 1099–1100;see also aspirin
acid-sensing ion channels 236
acquired cholinesterasedeficiency 617–618
acquired immunity 349–353
acronyms, non-ionotropic/non-Gprotein-coupled receptors 53
ACS see acute coronarysyndromes
ACTH see adrenocorticotropichormone
actin filaments 199, 278
action potentials 248, 259abnormal impulse activity257–258
active ion pumps 253amplitude 257, 258balance of currents , 250–251capacitance, cell 253,254–255, 258
cardiac action potential294, 295
cardiac cycle 316channel gating 251–253
channel selectivity 249–250, 251epicardial/endocardial 296factors affecting conductionvelocity 258–259
inactivation 252, 257–258membrane reaction time254–255
nerve impulse 253, 254neuromuscular function262–263, 265
Ohm’s Law 248–249propagation 256subthreshold responses255–256, 257
thresholds 256–257transmembrane currents/ionchannels 249
transmembrane proteins 253variable conductances 251
acupressure, for postoperativenausea and vomiting 1030
acute coronary syndromes 1091,1101–1102;see also myocardial ischemia
antiplatelet therapy,perioperative 1099–1100
definition/diagnosis1091–1092
pharmacologic/interventionalmanagement 1092,1093, 1094
acute kidney injury 783–784;see also kidney function
classification stages 785pharmacotherapy 794, 795risk factors 784
acute lung injury 814;see also lung function
acute myocardial infarction 886
acute respiratory distresssyndrome 814
adamantanes 980–982
adaptive immunity 349–353
addiction 486, 536; see also drug/alcohol users
definition 1106heroin 542opioid agonist-antagonists 540
additive interactions 147–148,1011–1012
adenomatous polyp preventionon vioxx (APPROVe)Trial 556
adenosine 294, 692, 694,700–701, 795
adenosine triphosphate (ATP)36, 625
adenylate cyclase 502
ADME (absorption, distribution,metabolism, elimination)85, 133
ADMET (absorption,distribution, metabolism,elimination, toxicity) 85
administration see drugadministration routes
adrenal insufficiency 816–817,1017–1018
adrenaline see epinephrine
adrenergic neurons 330
adrenoceptor antagonists 676,684–685; see also alpha-adrenoceptor agonists;beta-blockers
adverse drug reactions698, 700
antiarrhythmic agents693, 699–700
atenolol 682–683bisoprolol 683cardiovascular patients989, 999
carvedilol 680, 684celiprolol 683clinical pharmacology 681–682
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adrenoceptor antagonists (cont.)esmolol 683future study directions684
labetalol 684mechanisms of drug action676–677, 678
metoprolol 683–684nebivolol 681, 684preclinical pharmacology680–681
propranolol 682receptor signaling 677–680sotalol 682
adrenocorticotropic hormone815, 818–819
feedback inhibition 819stimulation test 820, 826
adverse drug reactions 15, 1117;see also allergic reactions;drug interactions;neurotoxicity
aminoglycosides 972–973anesthetic myopathysyndrome 137–139, 138
anti-neoplastics 988aprotonin 936argatroban 922aspirin 927autonomic nervous system 411azoles 978, 979calcium channel blockers 988carbepenems 969, 970cephalosporins 968–969circulatory effects, inhaledanesthetics 409–411
dantrolene 988dipyridamole 928direct thrombin inhibitors 924drug choice 1028–1029echinocandins 978, 980epsilon-aminocaproic acid/tranexamic acid 935
fluoroquinolones 976–977glycoprotein receptorinhibitors 930
gut motility/secretioninhibitors 848, 849, 850, 851
heparin 917–918histamine receptor antagonists843–844
inhaled anesthetics 407–409lincosamides 975–976lipopeptides 970, 971local anesthetics 582–583macrolides 973monobactams 969nitroimidazoles 978opioids 1061oxazolidinones 974–975penicillins 966, 967pharmacogenetics 132, 133polyenes 978, 980
polymyxins 971–972propofol 426–427, 450proton pump inhibitors 845sodium channel blockers,intermediate binding kinetics694, 695
sodium channel blockers, rapidbinding kinetics 695, 696
sodium channel blockers,slow binding kinetics696, 697
streptogramins 974, 975tetracyclines/glycylcyclines973, 974
thienopyridines 929thrombolytic agents 932trimethoprim/sulfamethoxazole976, 977–978
vancomycin 970, 971warfarin 925–926
AEDs see antiepileptics
aging, definition 1139;see also pharmacogeriatrics
agitation 533, 1041
agonists 6, 15; see also specificagents by name
allosteric receptor activationmodels 12
catalytic receptor model 9drug action targets,neurotransmitters 206
efficacy 7indirect 8multiple agonist sites 7–8, 8
AICD (automatic implantablecardiac defibrillator) 1096
AKI see acute kidney injury
AKIN (Acute Kidney InjuryNetwork) criteria784, 785
albumin 578, 807–808, 1131
albuterol 658
alcohol users 486, 998, 1001,1107–1109; see also drug/alcohol users
aldosterone 786
aldosterone antagonists 1096
alfentanilbioavailability 93bolus dosing 510–513closed-loop drugadministration 115–116
dose equivalence calculation67–68
open-loop TCI 112properties 538speed of onset 1007–1010transdermal administration124–125
ALI (acute lung injury) 814;see also lung function
A-Line AEP 180
alkaloids, opium 493–494
allergic reactions 1117, 1124;see also anaphylacticreactions
definitions/conceptualisations1117
antibacterial therapy 965antibiotics 1118antihistamines 1121aprotinin 1120blood products 1119drug additives/preservatives1119
FDA reporting mechanisms1121–1124
heparin 1119intravenous anesthetics458–460
latex 1120local anesthetics 582management strategies1120–1121
neuromuscular blockingagents 1119–1120
patient evaluation 1121polypeptides 1120protamine 1120treatment plan 1122–1123
allopregnalone 368
allosteric agonists 12
allosteric drug binding sites 4
allosteric enhancers 11
allosteric receptor activationmodels 11–12, 15, 12
alosetron 850
alpha-acid glycoprotein 578alpha-adrenoceptors 651–652,653, 654, 680
alpha-adrenoceptoragonists 478, 488, 648, 653,654–657, 658–659;see also specific agents byname
amnestic effects 482, 484anesthetic-sparing effects 483,486–487
anti-inflammatory effects484–485
cardioprotection 485cardiovascular patients –perioperative medication989, 999
cerebral circulation 481, 485clinical pharmacology 482,567, 656, 661–662
critical care applications 487critical care sedation 484
dosage/administration486–487, 567, 735–736
endocrine effects 481–482gastrointestinal effects 486hemodynamic effects 480–481hemodynamic stability 485mechanisms of drug action478–479, 567–568
neuroprotection 481pharmacodynamics 482–483pharmacokinetics 482preclinical pharmacology479–480, 567
renal effects 482renoprotection 485respiratory effects 486shivering 485vasodilators 730–731
alpha-adrenoceptor antagonists989, 999; see alsoadrenoceptor antagonists
alpha-glucosinade inhibitors879, 880
alpha-glutathione-S-transferase(GST) 80, 402
alpha-methylopa 656, 657
alphaxalone 368
alteplase 932;see also thrombolytic agents
althesin 456–457
alveolar-arterial gradient 393
alvimopan 543
Alzheimer’s disease 222, 995, 1157
ambulatory analgesia 1070
American Academy ofNeurology 590
American College of Critical CareMedicine guidelines 627
amino acids 890, 893–900,894–897
aminoglycosides 971, 972–973
aminopenicillins 966, 967
amiodarone 692, 693, 697–698, 702
amnesia 217–218, 220, 361, 478,488; see also alpha-adrenoceptor agonists;memory; sedatives
alpha-adrenoceptor agonists482, 484
anesthetic action mechanisms378
benzodiazepines 467chloral hydrate 487inhaled anesthetics 400–401muscarinic antagonists487–488
sedation 1041
Index
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AMPA receptors 37, 367–368, 375
amphetamine 660–661, 1112
amphoceterin B 977, 978, 979–980
amplification, signal 12–13, 17
amplification response,sympathetic nervoussystem 330
amplitude, action potentials257, 258
amputation, phantom limb pain1069–1070
analgesia 361; see also novelanalgesics; pain;postoperative analgesia;regional analgesia; and seespecific agents by name
action mechanisms 378,496–498
closed-loop drugadministration 117
efficiency, Oxford LeagueTable 555
maintenance of/emergencefrom anesthesia 1031
obstetrics 952–953open-loop TCI 110perioperative medication997–998, 1000
analytical validity,pharmacogenetics 133–134
anaphylactic reactions1117–1118, 1124;see also allergic reactions
agents causing 1118clinical manifestations 1118definitions/conceptualisations1117–1118
management strategies1120–1121
neuromuscular blocking drugs613, 614
patient evaluation 1121therapy 1121treatment plan 1122–1123
Andersen syndrome 307
anesthetic action mechanisms359, 374, 377–378
barbiturates 367–368brainstem/hypothalamus/thalamus 376
cerebral cortex 377defining anesthesia 361deviations from Meyer–Overton rule 359–360
drug action targets 361etomidate 362–364, 366hypothalamic–pituitary–adrenal axis 819–820
ketamine 374–375
Meyer–Overton correlation/unitary theory 359, 360, 361,378
neuroanatomy 375neurosteroids 368–369nitrous oxide 375propofol 367proteins as targets 360–361, 378spinal cord 374, 375–376structure–activity relationships362
volatile anesthetics 369–374xenon 375
anesthetic degradation 413
anesthetic myopathy syndrome137–139, 138
angina 742–743
angiogenesis 280, 283
angiotensin-converting enzyme(ACE) inhibitors 731,735–736, 1096
angiotensin II 284–285
angiotensin receptor blockers(ARBs) 732, 735–736, 1096
angiotensinogen 786
animal studiesacute kidney injury 795hemorrhagic shock 1016plasma volume expansioncalculation 801–802
relevance to humans1156–1157
anisoylated plasminogenactivator complex (APSAC)931–932
anorexia 890
ANP (atrial natriuretic peptide)786, 795
ANS see autonomic nervoussystem
antagonists 8–10, 15;see also specific agents byname
buprenorphine/nalbuphine 540catalytic receptor model 9drug action targets,neurotransmitters 206
drug interactions 147–148
anteretrovirals 979, 980
anterograde amnesia 467
antiarrhythmics see arrhythmia
antibacterialsallergic reactions 965aminoglycosides 971, 972–973carbepenems 969, 970cell membrane active agents964, 971–972
cell wall active agents 964,966–971
cephalosporins 966–969DNA synthesis targeting drugs964, 976–978
fluoroquinolones 964, 975,976–977
glycopeptides 964,970–971
lincosamides 964, 974, 975–976lipopeptides 964, 970, 971macrolides 964, 972, 973major antibacterial targets964
monobactams 969nitroimidazoles 964, 978oxazolidinones 964,974–975
penicillins 964, 966, 967,1118
polymyxins 964, 971–972predictors of antimicrobialeffect 963
ribosomal protein synthesisinhibitors 964, 972–976
streptogramins 964, 974,975
tetracyclines/glycylcyclines964, 972, 973–974
trimethoprim/sulfamethoxazole975, 976, 977–978
antibiotics; see also antibacterials;antifungals; antimicrobials
allergic reactions 1118prophylaxis issues 982
anticholinergics/anticholinesterases 672–673;see also parasympatholyticdrugs
antiemetics 860antipsychotics 601, 604asthma treatments 754–755motion sickness 856neostigmine pyrostigmineedrophonium 1146
paralysis reversal 1035pharmacogeriatrics 1146
anticoagulants 915, 919;see also platelet functionagents
non-ST-elevation myocardialinfarction/unstable anginamanagement 1095
perioperative medication992, 1000
ST elevation myocardialinfarction management1094–1095
anticonvulsants 564benzodiazepines 467clinical pharmacology565–566
dosage/administration 566mechanisms of drug action564, 565
obstetrics 954perioperative medication 994,1000
preclinical pharmacology564–565
antidepressants 206, 993, 1000;see also MAO inhibitors;tricyclics; SSRIs
antiemetics 855, 868–869;see also postoperative nauseaand vomiting
anesthesia 865–866benzamides 860–861corticosteroids 860, 865definitions 855management strategies 865neurokinin type 1 receptorantagonists 860, 864–865
neuroleptics 860, 861–862pharmacology 859–860premedication 865risk-adapted prophylaxis867–868
serotonin type 3 receptorantagonists 860, 862–864
antiepileptics (AEDs) 589–592,591–592, 605
adverse drug reactions 447,590, 592–595, 598
carbamazepine 593, 594,595, 596
clonazepam 593, 596disease interactions 589–590drug interactions 594ethosuxamide 593, 594,595, 596
felbamate 591–592, 593, 598fosphenytoin 598–599gabapentin 591–592, 593, 594,595, 598
lamotrigine 591–592, 593, 594,595, 597
levetiracetam 591–592, 593,594, 595–598
oxcarbazepine 591–592, 593,594, 595, 597
pharmacokinetics 589, 592,593, 595–598
phenobarbital 593, 594,595, 596
phenytoin 592–595pregabalin 594, 598primidone 594, 595, 596tiagabine 591–592, 593, 594,595, 597
topiramate 591–592, 593, 594,595, 597
valproate 593, 594, 595, 596zonisamide 591–592, 593, 594,595, 597
Index
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antifolates 964
antifungalsazoles 977, 978–979cell membrane active agents978–980
cell wall active agents 980echinocandins 977, 978, 980mechanism of drug action 978polyenes 977, 978, 979–980
antigens 349, 350, 830–831
antiherpes agents 980, 981
antihistamines 860, 1121, 1122
anti-inflammatories,perioperative medication997–998, 1000
anti-inflammatory agents forasthma
leukotriene antagonists/5-lipoxygenase inhibitors758–760
nedocromil sodium/sodiumcromoglycate 757–758
omalizumab 760–761
anti-influenza agents 980–982
antilipemic agents 990, 999
antimicrobials 963, 966, 983–984;see also antibacterials;antifungals; antivirals
allergic reactions 965anesthesia, surgicalprophylaxis 982
antibiotic prophylaxis issues 982major antimicrobial targets 963perioperative medication995, 1000
predictors of antimicrobialeffect 963–965
antimuscarinics 849–850
antineoplastics 988, 995, 996, 1000
antioxidants 794–795,901–902, 907
antiparkinsonian agents 994, 1000
antiplatelet agentssee anticoagulants; plateletfunction agents
antipseudomonal penicillins966, 967
antipsychotics 599, 605–606;see also lithium
adverse drug reactions600–601, 602, 603, 604, 605
chlorpromazine 599, 600,601, 604
delirium prevention/management 1052
disease interactions 604drug interactions 601–604
haloperidol 599, 600, 601,604–605
mechanisms of drug action599–600
perioperative medication994, 1000
pharmacokinetics 600, 601,604–605
quetiapine 600, 602, 605
antipsychotics, atypical 599, 605adverse drug reactions 600–601drug interactions 603–604
anti-rejection drugssee immunosuppressants
antistaphylococcal penicillins966, 967
antitussive effects, opioids 499
antiviralsanteretrovirals 979, 980anti-herpes virus agents 980, 981anti-influenza agents 980–982,981
anxiety, postoperative nauseaand vomiting 858
anxiolytics 1041benzodiazepines 467, 468metabotropic glutamatereceptor agonists 242
midazolam 453propofol 448–449
Aplysia (sea slug), memory/learning 210, 226
apneic threshold 407;see also respiratorydepression
apoptosis 48, 53, 1152, 1157
APPROVe (adenomatous polypprevention on vioxx) trial 556
aprepitant 860, 865
aprotonin 935–936adverse drug reactions 936allergic reactions 1120clinical pharmacology935–936
mechanism of drug action 935monitoring 936
APSAC (anisoylatedplasminogen activatorcomplex) 931–932
ARBs (angiotensin receptorblockers) 732, 735–736, 1096
ARDS (acute respiratory distresssyndrome) 814
area under the curve (AUC) 963
arecholine 668
argatroban 915, 921–922
adverse drug reactions 922clinical pharmacology 922dosage/administration 922mechanism of drug action 922new/emerging concepts 922preclinical pharmacology 922
arginine, nutritionalpharmacology 900, 901
arginine vasopressin (AVP)285, 786, 788–790, 957,1029, 1121
aripiprazole 599, 600, 601
aromatic ring 577–578, 585
arrhythmias/antiarrhythmicagents 296–297, 298, 299,689, 701–703; see also cardiacrhythm
administration 701alcohol users 1108amiodarone 692, 693,697–698, 702
beta-blockers 693, 699–700calcium channel blockers693–694, 700, 742, 745–746
cardiac rhythm 296cardiovascular patients,perioperative medication989–990, 999
disopyramide 691–693,695, 702
dofetilide 692, 693, 699, 702dosage 701–702flecainide 692, 693, 696, 702ibutilide 692, 693, 698–699, 702inhaled anestheticspharmacology 409–410
ion channels 689, 690–691, 690lidocaine 692, 693, 695, 702mechanisms of drug action 689mexiletine 692, 693,695–696, 702
moricizine 692, 693, 697, 702multiple channel blockers 693other antiarrythmic agents 694potassium channel blockers 693preclinical pharmacology691–692
procainamide 691–693, 694, 702propafenone 692, 693,696–697, 702
quinidine 691–693,694–695, 702
sodium channel blockers691–693
sotalol 692, 693, 698, 702STEMI/UA/NSTEMIadjunctive therapies 1096
tocainide 692, 693, 696, 702
arthritis 501
ascending pathways, paintransmission 229–230
ascending reticular activatingsystem 180–182
ASICs (acid sensing ionchannels) 236
aspiration pneumonitis 848
aspirin 548, 926–928adverse drug reactions 927analgesia, postoperative 1063clinical pharmacology926–927
dosage/administration 927mechanism of drug action 926monitoring 927new/emerging concepts 927–928Oxford League Table of NNT555
pharmacokinetic parameters553–550
sensitivity 557surgery 927
associativity 202
asthma treatments 751, 761–762administration 753, 754, 755,757, 758, 759–760, 760–761
anticholinergic agents 754–755beta adrenoceptor agonists751–753
clinical pharmacology752–753, 754, 755, 756–757,758, 759, 760
corticosteroids 756–757, 825induction of anesthesia 1017leukotriene antagonists/5-lipoxygenase inhibitors758–760
mechanisms of drug action751–752, 754–755, 756,757–758, 759, 760
methylxanthines 753–754nedocromil sodium/sodiumcromoglycate 757–758
new/emerging therapies 761non-steroidal anti-inflammatory drugs 557
omalizumab 760–761preclinical pharmacology752, 753–754, 755, 756,758, 759, 760
volatile anesthetics 755–756
atenolol 682–683, 700, 702
ATP (adenosine triphosphate)36, 625
ATP-binding cassette (ABC)transporters see ABC drugtransporters
atracurium blockade reversal 635
atrial natriuretic peptide (ANP)786, 795
atropine 668–669, 692
Index
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adverse drug reactions ofoverdose 672
clinical pharmacology669–672
gut motility/secretioninhibitors 851–852
heart rate 671paralysis reversal 1036psychedelics/party drugs1112–1113
AUC (area under the curve) 963
autobiographical memory 212
autoimmune diseases 353–354, 501
automatic implantable cardiacdefibrillator (AICD) 1096
automaticity 296–297, 298, 299;see also arrhythmias/antiarrhythmic agents;cardiac rhythm
autonomic nervous system(ANS) 330, 341–342
anesthetic action mechanisms361, 378
biochemical/molecularmechanisms 337–338
blood pressure control/vascular tone 1077–1078,1079, 1080
cell physiology 335–336cholinergic physiology336–337
failure/dysfunction 338–339functional assessment 338, 339inhaled anestheticspharmacology 411
neuromuscular blockingdrugs 613
organ physiology 333–335pharmacological modulation340–341
second messengers 338succinylcholine 618, 619sympathetic hyperactivity339–340
systems physiology 330–333
autoregulation of blood flow 319,320, 406
AVP (arginine vasopressin)285, 786, 788–790, 957,1029, 1121
awakening see emergence fromanesthesia
awakening breathing controlled(ABC) trial 1046–1048
awareness 177; see also sleep/consciousness
and anesthetic-inducedunconsciousness 179
brain/cell physiology 177
clinical context 179–180cognitive context 177–179during general anesthesia179–180, 400–401
axillary blocks 1067
axonsfunctional anatomy 574–575size 258–259
azathioprine 835
AZD3043 458
azimilide 692, 693
azoles 977, 978–979
B cells 352
bacterial infectionsee antibacterial therapy
bactericidal effects 963
bacteriostatic effects 963
balanced anesthesia 147, 513
ball-and-chain model 300
barbiturates, anesthetic 420;see also methohexital;thiamylal; thiopental
adverse drug reactions 447allergic reactions 459anesthetic action mechanisms374, 367–368
cerebral ischemia andanesthetic neuroprotection1152–1153
drug/alcohol users 1111immunosuppression 838postoperative nausea andvomiting 859
structure–activityrelationships 362
baroreflex 334–335, 649–651
basal autonomic tone 648
Bayesian optimization 115
BBB see blood–brain barrier
BChE (butyryl-cholinesterase)deficiency 134–135
BCRP (breast cancer resistanceprotein) 92, 94–95
BDNF (brain-derivedneurotrophic factor)1154
beach-chair position 1035
belladonna 1112–1113
benzamides 860–861
benzodiazepines 466, 475;see also specific agentsby name
adverse drug reactions 473anticonvulsant activity 467
anxiolytic effects 467, 468for awake fiberoptic intubation1053
calcium channel blockers-druginteractions 747
clinical pharmacology 468–469CNS7056X 458delirium prevention/management 1051
dosage/administration 473–475drug actions on memory 215,216, 217, 467
drug/alcohol users 1111glucocorticoids secretion 819hypnotic activity 468induction of anesthesia 1008mechanisms of drug action466–467
myorelaxant activity 468perioperative medication 994,1000
pharmodynamic differences470, 471–473
pharmokinetic differences469–471, 469, 470
preclinical pharmacology467–468
sedation 467, 1043, 1047
benzothiazepines 742, 743
benztropine 673
beraprost 774
BET (bolus, elimination,transfer) 104
beta-adrenoceptors 651–652,657–658, 677–680
figures 23, 653, 654, 678,679
beta-adrenoceptor agonists 648,657–658, 658–659
clinical pharmacology 737,752–753
dosage/administration735–736, 753
history/background 751mechanisms of drug action751–752
perioperative medication 997preclinical pharmacology 752preterm labor 954vasodilators 731
beta-blockers (beta-adrenoceptorantagonists);see also adrenoceptorantagonists
cardiovascular patients-perioperative medication987–988, 999
myocardial ischemia1097–1099
STEMI/UA/NSTEMIadjunctive therapies 1096
beta-lactams 964carbepenems 969, 970cephalosporins 966–969monobactams 969penicillins 966, 967
bethanechol 667–668
binding cooperativity 5;see also protein binding;receptor binding
bioavailability 63; see also specificagents by name
biologics 833
biotransformation, drug 72, 85;see also clearance; enzymes
basic drug metabolismconcepts 74
consequences of anestheticmetabolism 72–73
disease states 84–85drug interactions 82–83, 84geriatrics 82neurotransmitters 206pediatrics 81, 82pharmacogenetics 83–84pregnancy 81role of brain 81role of intestine 80role of kidney 80–81role of lung 81variation between patients82–85
bisoprolol 683
Bispectral Index (BIS) 114,179, 180
central nervous systemmonitoring 1046
depth of anesthesia 1032, 1033obstetrics 951
bleeding, calcium channelblockers 746
Bliss independence 149
blood–brain barrier 93, 95, 96drug transporters 95modulation for clinicalpurposes 93, 99
pediatric pharmacology 1131
blood–cerebrospinal fluidbarrier 97
blood gas solubility coeffcient386, 387, 388
blood hemoglobin concentration801
blood pressure 114, 1078–1079,1080; see also hemodynamics;hypertension; hypotension;vascular tone
blood products, allergic reactions1119
Index
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Cambridge University Press978-0-521-89666-5 - Anesthetic Pharmacology, Second EditionEdited by Alex S. Evers, Mervyn Maze and Evan D. KharaschIndexMore information
blood–retinal barrier (BRB) 96–97
blood volume status 791–793
body composition,pharmacogeriatrics1139–1140, 1147
body temperaturesee thermoregulation
BOLD (blood oxygenation level)response 211
bolus dosing of opioids 510–513
bone healthimmunosuppressants/anti-rejection drugs 838
non-steroidal anti-inflammatory drugs 557–558
bottom-up costing 168–169
bottom-up pathways of sleep/consciousness 177, 188
bowel sounds 890, 907
bowel surgery 399
brachial plexus blocks 1066–1067
bradychardia see cardiovasculareffects
brainbiotransformation, drug 81derived neurotrophic factor(BDNF) 1154
injury, crystalloid fluids 805
brainstem, anesthetic actionmechanisms 376
brainweb 210, 219
BRB (blood–retinal barrier) 96–97
breakpoint 963
breakthrough cancer pain 123,126, 509
breast cancer, and antipsychoticdrugs 604
breast cancer resistance protein(BCRP) 92, 94–95
breast milk transfer 950–951
breast surgery, chronic pain 1069breathing systems;see also respiratorydepression
inhaled anestheticspharmokinetics 392–393
spontaneous ventilationmaintenance 1018–1019
bronchial smooth musclerelaxants 614
bronchoconstriction 408, 409
bronchodilation 755–756;see also asthma treatments
Brugada syndrome 296, 298,301, 302
bubbles, inhaled anestheticspharmokinetics 393
buccal fentanyl 126
bupivacaine 566, 578, 584–585clinical pharmacology566–567
dosage/administration 567mechanisms of drug action566
preclinical pharmacology 566
buprenorphine 537antagonist effects 540;see also opioid agonist-antagonists
maintenance therapy540–542
burn injuries 624, 901, 907
butorphanol 537; see also opioidagonist-antagonists
butyrophenones 599;see also antipsychotic drugs
adverse drug reactions600–601
drug interactions 603postoperative nausea andvomiting 861–862
butyryl cholinesterase (BChE)deficiency 134–135
C channels see calcium ionchannels
C-reactive protein (CRP) 347
CABG (coronary artery bipassgraft) 1094
cachexin see tumor necrosisfactor
CACI (computer-assistedcontinuous infusion) 104
calcium ionsheart failure-positive inotropicdrugs for 707, 708
local anesthetics 239–240neuromuscular function263–264
regulation of neurosecretion197, 237, 743–745
role in long-term potentiation204
second messengers 24–26, 25vascular smooth muscle 278,278, 279
calcium ion channels 31–32,564–565, 747
calcium regulation 743–745dysfunction/disease states 304regulation 303–304structure and function 303
calcium ion channel blockers741, 744, 748–749, 988;see also ziconotide
adverse drug reactions 700,745–746
angina 742–743antiarrhythmic agents693–694, 700
arrhythmias 742calcium regulation 743–745cardiovascular effects 742, 999dantrolene 748drug interactions 746–747drug metabolism 745hemodynamic action 741for hypertension 741–742mechanisms of drug action743–745
perioperative cardioprotection743, 743
pharmacogenetics 747pharmacokinetics 746–745preterm labor 954–955pulmonary vasodilators770–771
regression of left ventricularhypertrophy 742
renal effects 747renal failure 743STEMI/UA/NSTEMIadjunctive therapies 1096
vasodilators 733–734,735–736, 737, 741
calcium sensitizers 734, 735–736
calcium/calmodulin/calcineurin-induced nuclear factor 832
CAM-ICU (ConfusionAssessment Method for theICU) 1049
cAMP 20, 24, 325, 625
CAN (central autonomicnetwork) 648
Canadian Critical Care Nutritionguidelines 903
cancer 53calcium channel blockers 746cytotoxic resistance 91–92, 93;see also efflux drugtransporters
immunology 354–355opioids in prevention ofmetastases 501
pain control 123, 124;see also pain transmission/transduction
subcutaneous administration124
cannabinoids 569, 1110–1111
can’t intubate can’t ventilatescenarios 620–621, 620–621
capacitance, cell 253, 254, 258
capases 786
capillary membrane 800
CAPRIE study 929
carbachol 667–668
carbamazepine 593, 594, 595, 596
carbepenems 969, 970
carbohydrates 892, 894–897
carbon monoxide 17, 405
carbonic anhydrase inhibitors 790
carboxylesterases 78–79
cardiac cell physiology 322–323
cardiac cycle 316–317
cardiac rhythm 293, 310;see also arrhythmias/antiarrhythmic agents
calcium ion channels 303–304cardiac action potential 294, 295cardiac inward rectifiers 307cell-to-cell coupling/gapjunctions 297–298
conduction pathways 293–294delayed rectifier Kþ currents304–306
disease states 302–303, 304,305, 306–307
drug action targets 308–310ion channels-generalstructure/function 299–301
ion channels-special features297, 300–301
layer-specificelectrophysiology/arrhythmias 296
neural control 293pacemaker current 307–308reentrant arrhythmias294–295
sodium ion channels 301–303transient outward currentITO 304
ultra-rapid delayed rectifier306–307
cardiac surgery/cardiologyepsilon-aminocaproic acid/tranexamic acid 934
infusion fluids 806sedation 1055
cardioplegia 1100–1101
cardiovascular depression 473
cardiovascular effects;see also heart function
acetylcholinesterase inhibition637
alpha-adrenoceptor agonists485, 487
crystalloid fluids 805
Index
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dexmedetomidine 1044drug interactions 1012, 1013immunosuppressants/anti-rejection drugs 836
inhaled anestheticspharmacology 412
induction of anesthesia1012–1014
local anesthetics 584non-steroidal anti-inflammatory drugs 555–556
opioid agonist-antagonists 540opioid clinical pharmacology534–535
opioids 499pharmacogeriatrics 1140propofol 449thiopental 1007
cardiovascular patients,perioperative medication987, 988, 991, 999–1000
alpha-adrenoceptorantagonists 989, 999
antidysrhythmics 989–990, 999antilipemic agents 990, 999beta-adrenoceptor antagonists987–988, 999
calcium channel blockers988, 999
diuretics 990, 1000nitrates 989, 999pulmonary vasodilators989, 999
renin angiotensin systemantagonists 988–989, 999
caregiver controlled analgesia(CCA) 1062–1063
carotid body relaxants 613–614
carvedilol 680, 684
caspases 52–53
CAT (computed axialtomography) scanning1054–1055
catabolism 890, 897, 900, 907
catalytic receptors 3–4, 9
catecholaminesanaphylaxis therapy 1122–1123clinical pharmacology 737dobutamine 713dopamine 712dopexamine 712–713dosage 719ephedrine 714epinephrine 710–711isoproterenol 713–714norepinephrine 711–712preclinical pharmacology709–710
receptor pharmacology729–730
catechol-O-methyltransferase(COMT) 336
CATIA (computer-assisted totalintravenous anesthesia) 104
cauda equina syndrome (CES) 582
CBF see cerebral blood flow
CCA (caregiver controlledanalgesia) 1062–1063
CCIP (computer-controlledinfusion pump) 104
CDAD (Clostridium difficile-associated diarrhea) 843
celecoxib long-term arthritissafety study (CLASS) 557
celiprolol 683
cell mediated immunity 349;see also T cells
cell membranes see membranes
cell signaling 17, 18, 18
cell surface receptors 18
cell-to-cell coupling 297–298
cell wall active agents 964,966–971, 980
central autonomic network(CAN) 648
central nervous systemantipsychotic drugs 603, 604drug barriers 93, 95, 96local anesthetics 583–584perioperative medication 993,995, 1000
propofol 449sedation 1045–1046
central sensitization 235
cephalosporins 966–969
cerebral blood flow (CBF)alpha-adrenoceptor agonists481, 485
inhaled anestheticspharmacology 406
response to hyper/hypocarbia407
cerebral cortex 377
cerebral injury 405–407, 413
cerebral ischemia 1158–1159anesthetic neuroprotection 1151excitotoxicity 1154influence of specificanesthetics 1152–1154
mechanism of drug action1152, 1154–1155
neurogenesis effects 1154–1155pathophysiology 1151–1152reconciliation of opposing effectsof anesthetics 1157–1158
cerebral metabolic rate (CMR)405–406
cerebral protection, inhaledanesthetics pharmacology 412
cerebral state index 1032
Cerebral State monitor 180
cerebrospinal fluid (CSF) 407
certain safety factor 15
CES (cauda equina syndrome) 582
chemical partition 90–91
chemical synapses 192–193, 194;see also synaptictransmission
chemotherapy drugs, perioperativemedication 995, 996, 1000
chest wall rigidity 534
children see pediatricpharmacology
chiralitylocal anesthetics 579–580, 585non-steroidal anti-inflammatory drugs 551
chloral hydrate 487, 488
chloroprocaine 578, 582
chlorpromazine 599, 600, 601, 604
choline esters 667–668
cholinergic neurons 330, 336–337
cholinesterases 78–79acquired cholinesterasedeficiency 617–618
inhibitors, perioperativemedication 995, 1000
neuromuscular blockingdrugs 617–618
cholinomimetic alkaloids 668
choroid plexus 97
chronic congestive heartfailure 337
chronic kidney disease (CKD)783, 784, 794; see also kidneyfunction
chronic medication users,anesthesia forsee perioperative medication
chronic obstructive pulmonarydisease (COPD) 452
chronic painaddiction to opioides 1107analgesia, postoperative1069–1070
opioid clinical pharmacology536
cigarette smoking see smoking
cimetidine 843–844
CIN (contrast-inducednephropathy) 794–795
circadian rhythm 815
circle systems, inhaledanesthetics 393
cirrhosis, liver 428
CLASS (celecoxib long-termarthritis safety study) 557
classificationdrug receptors 2–4, 18peripheral nerves 575
clearance 57–58, 74, 82, 83;see also biotransformation;enzymes
basic concepts 73–74pediatric pharmacology1131–1132
clinical pharmacology,information technology 160
clonazepam 593, 596
clonidine 567, 656analgesia, postoperative 1064clinical pharmacology 567dosage/administration 567mechanisms of drug action567–568
preclinical pharmacology 567preemptive analgesia 1068
clopidogrel 1099–1100
closed-loop control systems 1078
closed-loop drug administration103–104, 112, 116–118;see also target controlledinfusion
control algorithm 115, 116future study directions 116hypnotics 115–116opioids 116, 117pharmokinetic closed-loop113–114
pharmokinetic-dynamicclosed-loop 103, 114–115
prototype examples 115, 117set-point 115
Clostridium difficile-associateddiarrhea (CDAD) 843
clozapine 599, 600, 601
CMR (cerebral metabolic rate)405–406
CNG (cyclic nucleotide gated)ion channels 40–41
CNS see central nervous system
CNS7056X 458
coagulation 282–283, 912–915,1108; see also platelet function
Index
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cocaine 335, 340, 1111
Cockcroft–Gault equation 1140
codeineCYP2D6 84lactation 526Oxford League Table ofNNT 555
pharmacogenetics 519
cognitive outcomesanesthetic neurotoxicity1155–1156
post-operative dysfunction140, 212, 221–222, 1157
sedation complications 1042
coincidence detector 203
coinduction 1011
colchicine 997
collectins 347–348
colloid fluids 800, 805, 807–809blood volume status 793comparison with crystalloids809
monitoring 1034
colonoscopy, sedation 1055
COMMIT trial 929, 1097
compartment models 62, 63pharmacokinetics 58–61special 57thiopental 422
competitive inhibition 15, 9, 10,10, 609
complement system 346–347
compound A 403–404
computed axial tomography(CAT) scanning 1054–1055
computer-assisted continuousinfusion (CACI) 104
computer-assisted totalintravenous anesthesia(CATIA) 104
computer-controlled infusionpump (CCIP) 104
computer modeling,pharmacoeconomics 172, 173
COMT (catechol-O-methyltransferase) 336
concentration-dependentactivity 963
concentration–response curves14, 15, 158
conditioning 212–213, 216;see also memory
conductance, restingmembrane 258
conflicts of interest,pharmacoeconomics 174
Confusion Assessment Methodfor the ICU (CAM-ICU) 1049
congestive heart failure 1072
conjugation reactions 74
conscious memory 212, 216–219
consciousness, neural basis 177,188; see also sleep/consciousness
consolidation of memory/learning 217–218, 220
constipation 535
context-sensitive half-time 65intravenous infusion ofopioids 514, 515
open-loop TCI 109propofol 429, 431
continuous dose–responsecurves 14
contractile tissuemyocardial performance 324vascular smooth muscle 278,324–325
contrast-induced nephropathy(CIN) 794–795
control algorithm, closed-loopdrug administration115, 116
conversion to morphineequivalents, opioids1061–1062
convulsions 449, 533;see also antiepileptic drugs
cooperativity 202
COPD (chronic obstructivepulmonary disease) 452
coronary artery bypass graft(CABG) 1094
coronary artery disease (CAD)1097, 1099
coronary circulation 319, 326–327autoregulation of blood flow319, 320
blood pressure control/vascular tone 1084
metabolic control 319–320neurogenic control 320regulation of myocardialperfusion 319
coronary steal 410, 742
corticosteroidssee glucocorticoids
corticotropin-releasing hormone(CRH) 818–819
CORTICUS study 820
cortisol 815, 816, 819–820;see also glucocorticoids
costs/costing 168, 1029;see also pharmacoeconomics
costimulation 833–834
cotransmissions 194–195
coughing reflex 499, 534, 1027
covalent bonds 2
COX see cyclooxygenase
CP-122 864–865
craving, drugs/alcohol 1106
CRH (corticotropin-releasinghormone) 818–819
creatine 1140
critical care applicationsalpha-2 adrenoceptoragonists 487
delirium diagnosis 1049delirium prevention/management 1049–1052, 1053
induction of anesthesia1017–1018
nutritional pharmacology901–903
paradigms to improveoutcomes from sedation1046–1049
pharmacology of availabledrugs 1042–1044
sedation 484, 1041–1042,1044–1046
critical illness, effects onhypothalamic-pituitary-adrenal axis 820
CRP (C-reactive protein) 347
crystalloid fluids 800blood volume status 793comparison with colloids 809monitoring 1034solutions with electrolytes803–805
CSF (cerebrospinal fluid) 407
C-type inactivation 300
cumulation 66
cumulation ratio (CR) 66
curare 608, 633
Cushing reflex 649
Cushing’s syndrome 824
cyclic nucleotide gated (CNG)ion channels 40–41
cyclooxygenase (COX) 548expression in response totissue damage 550
expression/action 550inhibition by NSAIDs 550–552neuronal plasticity 550role in pain 548, 549
cyclooxygenase inhibitors 554,559, 955, 1063;see also aspirin; non-steroidalanti-inflammatory drugs
absorption 554cardiovascular effects 555–556CLASS 557clinical context 559distribution 554drug interactions 558gastrointestinal effects556–521
metabolism/excretion 554–555Oxford League Table of NNT555
pharmacodynamics 555–556pharmacokinetic parameters553–550
renal effects 557
cyclosporin A 93
cyclosporine 834–835, 1101, 1134
CYP see cytochrome
cys-loop drug-gated ion channel(LGICs) 3
cys-loop ion channel 35, 41,52
cystatin C 786
cystolic threonine kinases 51–52
cystolic tyrosine kinases 50–51
cytochrome (CYP) 74–78, 73,76, P450
alcohol 1107calcium channel blockers 745CYP1A2 78CYP2A6 78CYP2B 77CYP2C 78CYP2D 76–77, 77, 78, 1134CYP2E1 78, 1107CYP3A 75–76, 76, 81, 83, 84,519–520
pediatric pharmacology 1129ensure join all theseto cyp refs
pediatrics 81, 82pharmacogeriatrics 1140
cytokine receptors 50
cytokines 52, 352–353
cytoplasmic enzymes 50, 53
cytoskeleton, role in synaptictransmission 199
cytotoxic resistance 91–92, 93;see also efflux drugtransporters
Index
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dabigatran 915, 922–923
DAD (delayed afterdepolarization) 296, 297
damping, signal 13
danaparoid 915, 920–921clinical pharmacology 920dosage/administration 920–921mechanism of drug action 920new/emerging concepts 921
danger associated molecularpattern (DAMP) 349
dantrolene 625, 748, 988
darifenacin 673
DCCT (diabetes control andcomplications trial) 879
deadly nightshade 668–669
decision-making 166–167;see also pharmacoeconomics
declarative memory 212
decrement time, open-loopTCI 109
deep dorsal horn 235
definitions; see also terminologyaction potentials 248–249acute coronary syndromes1091–1092
addiction 1106aging 1139allergy 1117anaphylactic reactions1117–1118
anesthesia 361anti-emetics 855drug receptors 1drug targets 1drugs 1infants 1128memory/learning 212myocardial ischemia 1091neonates 1128open-loop TCI 105pain 227sedation/hypnosis 478xenobiotics 90
degradation, anesthetic 413
delayed after depolarization(DAD) 296, 297
delayed hypersensitivity(DTH) 354
delayed rectifier Kþ currentsdisease states 305, 306–307rapid 305slow 305–306ultra-rapid 306–307
delirium 221, 484diagnosis 1051–1049
prevention/management1049–1052, 1053
sedation 1041sedation complications 1042
delirium tremens 1108–1109
dendrites 226
dendritic spines 220
dense-cored vesicles 192
dependence, drug 1106, 1107;see also addiction
depolarizing blocking drugs 270
depressant drugs; see also moodeffects
alcohol 1107–1109benzodiazepines/barbiturates1111
cannabinoids 1110–1111opioids 1109–1110
depth of anesthesia monitors1032, 1033
descending modulatorypathways 230–231
desensitization see receptordesensitization
desflurane 397autonomic nervous systemeffects 411
glucocorticoids secretion 819inhaled anestheticspharmacology 397, 399
physicochemical properties 398sympathetic nervous system651
desmopressin 932–933clinical pharmacology 932–933dosage/administration 933mechanism of drug action 932new/emerging concepts 933
development, brain;see also pediatricpharmacology
anesthetic neurotoxicitysee neurotoxicity
pharmacodynamics 1133–1134pharmacogenetics 1134, 1135pharmacokinetics 1128, 1132
dexamethasone 860, 865
dexmedetomidine 185–187, 481,567, 656–657
analgesia, postoperative 1064for awake fiberoptic intubation1054
clinical pharmacology 567delirium prevention/management 1049, 1051
dosage/administration 567mechanisms of drug action567–568
preclinical pharmacology 567preemptive analgesia 1068sedation 1044, 1048–1049sleep/consciousness 218
dextrans 808
DHP see dihydropyridine
diabetes 53, 886–887;see also insulin
acute myocardial infarction 886autonomic nervous systemdysfunction 338–339
diet controlled 881emergency management 882hyperglycemic hyperosmolarstate 884–885
hypoglycemia 885–886immunosuppressants/anti-rejection drugs 836
ketoacidosis (DKA) 882–884metabolic control 881oral agents 880, 881–882perioperative management880–882, 992–993, 1000
perioperative risk factors 881postoperative nausea andvomiting 858
STEMI/UA/NSTEMIadjunctive therapies 1096
type 1 diabetes mellitus 879type 2 diabetes mellitus879–880
diabetes control andcomplications trial(DCCT) 879
diagnosis, delirium 1051–1049
diarrhea 906
diastolic ventricular function321–322
diazepamclinical pharmacology 469dosage/administration 473, 475drug actions on memory 215hypnotic activity 468immunosuppression 838myorelaxant activity 468pharmodynamics 472–473pharmokinetics 470–471, 470sedation/amnesia/anticonvulsant activity 467
diclofenac 548, 553–550, 555
dicyclomine hydrochloride 849
diet-controlled diabetes 881;see also nutritionalpharmacology
Digitalis glycosides 707–709, 719
digoxin 692, 694
dihydropyridine (DHP)733–734, 737, 741, 742, 743
dihydropyridine (DHP)-sensitivesubunit 743–744
diltiazem 692, 693–694, 700, 702
dipeptidyl peptidase-4 (DPP4)inhibitors 880
diphenoxylate hydrochloride851–852
dipravan see propofol
diprifusor 105
dipyridamole 928adverse drug reactions 928clinical pharmacology 928dosage/administration 928mechanism of drug action 928
direct costs 168–169
direct thrombin inhibitors(DTIs) 923–924
adverse drug reactions 924clinical pharmacology923–924
dosage/administration 924mechanism of drug action 923new/emerging concepts 924non ST elevation myocardialinfarction/unstable anginamanagement 1095
ST elevation myocardialinfarction management 1095
discounting costs 169
disease statesbiotransformation, drug 84–85cardiac rhythm 302–303
disopyramide 691–693, 695, 702
display systems, druginteractions 160–161
dissociation constants 4, 15
distribution
distribution phase of drugdelivery 59, 387–389;see also specific agents byname
mathematics of 389–390pediatric pharmacology1130–1131, 1132
disulfram 998, 1001, 1107
diureticscarbonic anhydraseinhibitors 790
cardiovascular patients990, 1000
dosage/administration 792loop diuretics 790–791osmotic diuretics 790pharmacotherapy 794potassium-sparing 791renal dopamine 786, 791thiazide diuretics 791
Index
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divergence, open-loop TCI 111
DKA (ketoacidosis) 882–884
DNA synthesis targeting drugs964, 976–978
dobutamine 659, 713, 719,1122–1123
dofetilide 692, 693, 699, 702
dolasetron 860, 864
dopamine 337, 659anaphylaxis therapy 1122–1123antipsychotic therapy 599–600dosage 719drug/alcohol users 1106postoperative nausea andvomiting 856
renal 786, 791, 794use in heart failure 712
dopaminergic receptor agonists658–659, 731, 735–736
dopexamine 712–713, 719
dorsal horn see spinal dorsal horn
dosage dependence, drugresponse analysis inindividuals 14
dose equivalence 66–68
dose–response relationships 57additive interactions 150linear/nonlinear 148target controlled infusion 103
double-reciprocal plot 5
downregulation 22
DPP4 (dipeptidyl peptidase-4)inhibitors 880
dreams 451
dronabinol 569
droperidol 860postoperative nausea andvomiting 861–862, 1030
safety considerations 861–862
drug abuse 531, 532, 540;see also addiction; drug/alcohol users
drug accumulation 66
drug addicts see addiction;drug/alcohol users
drug additives/preservatives,allergic reactions 1119
drug administration routes 123,124, 126, 129
drug dosage relativeto route 127
enteral routes 127, 898–899,903–904, 905–906
epidural 127–129, 523–524
extra vascular 436fentanyl 126, 1011induction of anesthesia 1011inhalation 125intrathecal 127–129, 523intramuscular administration123
methadone 127neuraxial routes 124, 127–129parenteral routes 904, 905rectal routes 127safety considerations 129subcutaneous administration124
sublingual administration 125transdermal administration124–125
transmucosal routes 125–127
drug/alcohol users 1106–1107,1113–1114
alcohol 1107–1109amphetamine 1112benzodiazepines/barbiturates1111
cannabinoids 1110–1111cocaine 1111drug abuse 531, 532, 540inhalants 1113opioids 1109–1110perioperative medication 998,1001
psychedelics/party drugs1112–1113
drug binding 4–6, 5, 6–13, 15
drug delivery modifications1046–1048
drug effects 6, 13–15
drug input, pharmacokinetics62–63
drug interactions 147, 151,161–162, 845
additive/synergistic/antagonistic interactions147–148, 153–154,1011–1012
aminoglycosides 972–973antiepileptic drugs 589–590antipsychotic drugs 601–604azoles 978, 979biotransformation, drug82–83, 84
calcium channel blockers746–747
carbepenems 969, 970cephalosporins 968–969dantrolene/calcium channelblockers 988
drug transporters 99echinocandins 978, 980fluoroquinolones 976–977gut motility/secretioninhibitors 851
histamine receptor antagonists844
induction of anesthesia1011–1012, 1013
interaction models 150–152isobologram 148–149ketamine 436lincosamides 974, 975–976lipopeptides 970, 971macrolides 973monobactams 969neuromuscular blockingdrugs 625
new/emerging concepts 158–160nitroimidazoles 978non-steroidal anti-inflammatory drugs 558
opioids/propofol 154–158,159, 519–520
oxazolidinones 974–975penicillins 966, 967pharmacogenetics 133polyenes 978, 980polymyxins 971–972propofol 432, 448proton pump inhibitors 845real-time visualization 160–161response surface methodology149–150, 151, 158–161
streptogramins 974, 975tetracyclines/glycylcyclines 974thiopental 424–425trimethoprim/sulfamethoxazole976, 977–978
vancomycin 970, 971volatile anesthetics/opioids152–154
drug metabolismsee biotransformation;clearance; enzymes
drug receptors see receptors
drug registration, role ofpharmacoeconomics 167–168
drug targets 1, 15; see also specificagents by name
pain transmission/transduction–generalanesthetics 232, 237–239
pain transmission/transduction–localanesthetics 239, 241
sleep/consciousness 185sleep/consciousness–class 1agents 185, 186, 187
sleep/consciousness–class 2agents 185
sleep/consciousness–class 3agents 185
drug tolerance see tolerance
drug transporters 90, 99–100;see also efflux drugtransporters
ABC gene family 92–95blood–brain barrier 93, 95, 96blood–cerebrospinal fluidbarrier 97
blood–retinal barrier 96–97cellular boundaries 91drug interactions 99experimental methods 98–99future study directions 99gastrointestinal tract 97,fig 7.6.
kidney 97–98lipid bilayers 90, 91liver 97localized pharmacokineticspaces 91
modulation for clinicalpurposes 93, 99
placenta 98SLC21 transporters 95–96small molecule partition90–91
specially protected anatomicspaces 96
xenobiotic transporters 92
drugs, definition 1
DTH (delayed hypersensitivity)354
DTIs see direct thrombininhibitors
d-tubocurarine 270
dual transmission,neurotransmitters 194–195
Duchenne muscular dystrophy303
EACA see epsilon-aminocaproicacid/tranexamic acid
eating behavior, andpostoperative nausea andvomiting 858;see also nutritionalpharmacology
ECC (excitation contractioncoupling) 323–324
ECG (electrocardiograms) 316
Echinaceae 999
echinocandins 977, 978, 980
eclampsia 953–954
ECM (extracellular matrix)277–278
Ecstasy 660, 1112–1113
ECV (extracellular fluid volume)800
ED50 15
edrophonium 1035
EEG see electroencephalography
Index
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effect compartment concept63–64
effect-site model 14, 64fentanyl/alfentanil 67–68open-loop TCI 106–107,107–109
propofol 429–432
efficacy, drug 6, 14, 15, 7
efflux drug transporters 91–92ABC gene family 92–95breast cancer resistanceprotein 92, 94–95
multi-drug resistant proteins92, 93–94
P-glycoprotein 92–93, 94
eicosanoids 734, 735–736, 737
electrical synapses 192;see also synaptictransmission
electrocardiograms (ECG) 316
electrochemical gradients 253
electroencephalography (EEG)central nervous systemmonitoring 1045–1046
class 1 agents 185, 186closed-loop drugadministration 114
depth of anesthesia 1032dose equivalence calculation67–68
inhaled anestheticspharmacology 405–406
memory/learning 210–211sleep/consciousness 179–180,181, 185, 187
elimination phase of drugdelivery 59
half-life 59–60inhaled anestheticspharmokinetics 389
local anesthetics 582neuromuscular blocking drugs616, 617, 618
organs/enzymes 73thiopental 422
ELISA diagnosis 918
Emax (maximal effect) models 6,15, 155
emergence from/maintenance ofanesthesia 1027, 1036
adverse drug reactions1028–1029
blood pressure control 1029cost of drugs 1029drug choice 1027–1029fluid pharmacokineticsmonitoring 1033–1035
ketamine 451malignant hyperthermia 1028
medicinal supplements toprimary anesthetic 1029–1031
monitors 1032–1034neuromuscular functionmonitoring 1032–1034
nitrous oxide 1031pain control 1031paralysis 1030–1031paralysis reversal 1035–1036patient stability 1027posterior scoliosis correction/wake-up test 1036
postoperative nausea andvomiting 1028, 1029–1030
postoperative pain 1028salivation 1028speed/quality of emergence/wakening 1027–1028
temperature 1031temperature monitors 1032ventilation 1035
en passant synapses 192
enantiomeric pairs 360, 361
encainide 692, 693
end-stage renal disease (ESRD)783; see also kidney function
endocrine effects, alpha-2adrenoceptor agonists481–482
endocytic drug receptors 4
endocytosis pathways 198, 206
endogenous opioid system230, 494
endoscopy sedation 1055
endothelin 282
endothelin agonists/antagonists774
clinical pharmacology 737dosage/administration735–736
vasodilators 732
endothelium, vascular 280,727–728, 729
endothelium-dependentrelaxation 280–281
endothelium-derivedhyperpolarizing factor281–282
endothelium-derived relaxingfactor see nitric oxide
endplate see neuromuscularjunction
endplate potential 196
end-stage organ failure743, 830; see alsoimmunosuppressants/anti-rejection drugs
energy expenditure 891–892,891–892
and ventricular function1080–1081, 1081–1082
enfluranemetabolism 392
enoximone 715
enteral routes of drugadministration 127, 898–899,903–904, 905–906
enteric nervous system 330, 333;see also autonomic nervoussystem
entropy monitors 180, 1032
environmental enrichment, andneurogenesis 1154
enzymes;see also biotransformation;clearance
cystolic tyrosine kinases 50–51cytochrome 73, 74–78, 76,77, 81
cytoplasmic 50, 53drug receptors 2, 4esterases 78–79glucuronosyltransferase 79–80glutathione-S-transferase 80intrinsic guanylate cyclaseactivity 50
intrinsic serine/threoninekinase activity 49–50
linked cell surface receptors 18receptor protein tyrosinephosphatases 48–49
tyrosine kinase-associatedreceptors 47–48, 49
ephedrine 651, 655, 660blood pressure control 1029dosage 719use in heart failure 714
epidural anestheticcomplications 1066obstetrics 951–952postoperative 1064–1065preemptive analgesia1068–1069
routes of drug administration127–129, 523–524
vasopressor treatment 957
epilepsy see antiepileptic drugs
epinephrine 330, 333, 651, 658–659
additives 580, 586anaphylaxis therapy 1121,1122–1123
dosage 719reversal syndrome 601use in heart failure 710–711
episodic memory 211, 212drug actions on 215, 216–219and procedural memory 216
serial parallel independenttaxonomy of memory215, 216
epsilon-aminocaproic acid/tranexamic acid 933–935
adverse drug reactions 935cardiac surgery 934clinical pharmacology 934dosage/administration 935mechanism of drug action933–934
new/emerging concepts 935orthopedic surgery 934
equianalgesic conversions1061–1062
equilibrium binding affinity 4
equilibrium dissociationconstants 4, 15
equipotency/potency ratios 67
equipotent infusion rates 68;see also pharmacokinetics
ergot alkaloids 661, 955–956
ERPs (event related potentials)210–211, 217–219
esmolol 79, 683, 699, 702
esomeprazole 846
ESRD (end-stage renal disease)783; see also kidney function
ester hydrolysis 617–618
esterases 78–79
estrogens 996
ethosuxamide 593, 594, 595, 596
etidocaine 578, 584–585
etomidate 436, 438, 452–453, 460allergic reactions 459anesthetic action mechanisms362–364, 366, 374, 378
cerebral ischemia andanesthetic neuroprotection1153
cortisol secretion 819critical care applications/adrenal insufficiency1017–1018
decrement time 431disposition parameters 445distribution/metabolism/excretion 436–437
dosage/administration 437hemorrhagic shock 1016induction of anesthesia 1008,1013
new formulations 457pharmacogeriatrics 1145physicochemical properties 436postoperative nausea andvomiting 859
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etomidate (cont.)side effects 445structure–activityrelationships 362
structure/stereochemistry436, 445
sympathetic nervoussystem 651
trauma/hemodynamicallyunstable patients 1016
EuroQol (ED-5D) 170
event-related potentials (ERPs)210–211, 217–219
evolution, and pharmacogenetics134
excitation contraction coupling(ECC) 323–324
excitotoxicity 40, 1154
exercise, and neurogenesis1154
exocytosis 264, 335
experimental design
full factorial 150
pharmacoeconomics 172
experimental methods, drugtransporters 98–99
explicit memory 212
extracellular fluid volume(ECV) 800
extracellular matrix (ECM)277–278
extracellular signaling 18
extrapyramidal effects 600–601,603, 673
eye injury 1016–1017
eyelash reflex 1010
facilitated PCI 1093–1094
factor Xa inhibitors 1095;see also fondparinux
fainting 1078
false transmitters 660
families, receptor 2, 15
famotidine 845
fats see lipids
FDA (Food and DrugAdministration)
drug use in pregnancycategories 949
reporting mechanisms, allergicreactions 1121–1124
felbamate 591–592, 593, 598
femoral nerve blocks 1067
fentanyl
analogs, cardiovascular effects1013–1014; see alsoalfentanyl; buccal fentanyl;remifentanil; sufentanil
bioavailability 93bolus dosing of opioids510–513
dose equivalence calculation67–68
drug interactions 152–154,563
epidural 523–524hemorrhagic shock 1016induction of anesthesia 1008open-loop TCI 112oral transmucosaladministration 521
pharmacogeriatrics 1140–1141properties 538routes of drug administration126, 1011
sedation 1043subcutaneous administration521–522
transdermal administration124–125
fetal metabolism 950, 1109;see also obstetrics
fiberoptic intubation, sedationfor 1052–1054
fibrin clots 913; see also plateletfunction
fibrinogen therapy 1093
Fink effect 389
first-pass metabolism 73–74
fish oil 905, 907
5-aldosterone antagonists 1096
5-HT receptors see serotonin/5-HT receptors
5-lipoxygenase inhibitors758–760
flecainide 692, 693, 696, 702
fluconazole 519, 978, 979
fluid pharmacokinetics 802–803,802, 1033–1035
flumazenil 473
flunitrazepam 215
fluoride-induced nephrotoxicity401–402, 413
fluoroquinolones 964, 975,976–977
fluoxetine 519
focal ischemia 1151, 1154;see also cerebral ischemia
fondaparinux 915, 1094–1095clinical pharmacology 921dosage/administration 921mechanism of drug action 921
Food and Drug Administrationsee FDA
food, and postoperative nauseaand vomiting 858;see also nutritionalpharmacology
forgetting 217–218, 220;see also amnesia; memory
fornix 218
forward genetics 362
fosphenytoin 598–599
fospropofol 433, 455–456
Fourier theorem 179
Frank-Starling mechanism 1077
front-end kinetics 62, 423–424
full agonists 6, 11, 15
full factorial experimental design150
functionalization reactions 74
fungal infection agentssee antifungals
fuzzy logic 115
GABA (gamma-aminobutyricacid)
anesthetic action mechanisms365
anesthetic neurotoxicity1155–1156
barbiturates, anesthetic 367benzodiazepines 466–467, 475chloral hydrate 487etomidate 362–364, 366neuroprotection/neurotoxicity1151
neurosteroids 368–369pediatric pharmacology 1133propofol 367receptors 12, 200–201, 467sleep/consciousness 186, 187,218
sleep/wakefulness switch377
structure–activity relationships362
volatile anesthetics 369–370
gabapentin 564, 591–592, 593,594, 595, 598
analgesia, postoperative 1068clinical pharmacology565–566
dosage/administration 566mechanisms of drug action564, 565
preclinical pharmacology564–565
preemptive analgesia 1068
ganglionic blockers 733,735–736, 737
gap junctions 297–298
garlic 992, 999
gastric acid secretion 345, 843;see also gut motility/secretioninhibitors
gastrointestinal effects 535alpha-adrenoceptor agonists486, 487
non-steroidal anti-inflammatory drugs556–521
nutritional pharmacology905–906
opioids 499, 500proton pump inhibitors versushistamine receptorantagonists 847
gastrointestinal tract 97;see also gut; ulcers
gastroparesis 858
GCs see glucocorticoids
gelatin 809
gender differencesopioid effects 533postoperative nausea andvomiting 857
preconditioning effects 1154
general anesthesiaand Alzheimer’s disease 222awareness during 179–180drug actions on memory 215obstetrics 951, 952pain transmission/transduction 232, 237–239
and sleep 177, 188unconscious memory/learningduring 215–216
genetic engineering,thrombolytic agents 931
genetic pharmacodynamics135–136
genetic pharmacokinetics 134
genomic drug susceptibilityprofiling 142;see also pharmacogenetics
genotype–phenotypescorrelations 133
genotypes 133
Gepts model 428
geriatrics see pharmacogeriatrics
ginger 992, 999
Index
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Gingko biloba 992, 999
Ginseng 999
GLN (glutamine) 900, 904–905,907
global ischemia 1151
glomerular filtration rate (GFR)783, 787–788
glossary of terms, myocardialischemia 1091;see also definitions
GLP-1 (glycogen-like peptide )analogs 879–880
glucocorticoid receptors (GRs)814–815
glucocorticoids 814, 826anaphylaxis therapy 1123anti-emetics 860, 865asthma treatments 756–757cellular activity 814–815clinical pharmacology820–824, 821–823
mechanism of drug action 815metabolism/excretion 824organ specific/physiologicalresponses 816–818
perioperative management824–826, 997, 1000
preparation/potency 820–824,821–823
production/circulation/inactivation 815–816
side effects 817, 824
glucoseinfusion fluids 806–807intracellular fluid flux 803loading 807nutrition 892
glucose homeostasis 874, 875fasted state 874–876glucose intolerance/insulinresistance 876
metabolic responses tosurgery/trauma 876–877
metabolic syndrome 876postprandial state 874
glucuronosyltransferase (UGT)79–80
glutamate receptor family 36–40,41, 37, 232; see alsoN-methyl-D-aspartate(NMDA) receptors
AMPA receptors 37karinate receptors 37–39receptor localization 40synaptic transmission 200volatile anesthetics 371–373,373–374
glutamine (GLN) 900,904–905, 907
glutathione-S-transferase (GST)80, 402
glycine 200–201, 803receptors 39, 369–371
glycogen 874–876
glycogen-like peptide 1 (GLP-1)analogs 879–880
glycopeptides 964, 970–971
glycoprotein receptor inhibitors930–931
adverse drug reactions 930clinical pharmacology 930dosage/administration 931mechanism of drug action 930monitoring 930surgery/anesthesia 930–931
glycopyrrolate 672, 1036
glycylcyclines 964, 972, 973–974
goal-directed fluid therapy 805
goal-directed sedation 1046
gonadotropins 956–957
gout preparations 997
G-protein-coupled receptors(GPCRs) 2–3, 17, 18, 19,26, 286
autonomic nervous system 340heart contractility control 325local anesthetics 240–241, 576properties of signal transductionpathways 17–19, 20
receptor desensitization 22–24,23, 23
second messengers 24–26, 25signal damping 13signal transduction 17, 18, 18signaling pathway 19, 18slow synaptic transmission 201structure and function 19–22,20, 21
graded dose–response studies 15
graded drug effects 6
graded log drug concentrationresponse 14
granisetron 860, 864
growth factors 49
GST (glutathione-S-transferase)80, 402
GTP(guanine nucleotide) bindingproteins 19; see alsoG protein-coupled receptors
guanabenz 656, 657
guanfacine 656, 657
guanylate cyclase activity 50
guarded receptor hypothesis 576
guidelinesAmerican College of CriticalCare Medicine 627
ACCP 775Canadian Critical CareNutrition 903
delirium prevention/management 1052, 1053
Society of Critical CareMedicine 1041
gutbiotransformation, drug 80failure 901;see also gastrointestinaleffects; ulcers
integrity 903–904;see also glutamine
opioid metabolism 520
gut motility/secretion inhibitors842, 851, 852–853;see also proton pumpinhibitors
5-HT agonists 850adverse drug reactions 843–844,845, 848, 849, 850, 851
anti-muscarinic agents849–850
drug interactions 844, 845, 851gastric acid secretion 843histamine receptor antagonists843–845, 847–848
motility 842new/emerging concepts 852normal gut 842opioids 850–852practical approach to patients843
prebiotics/probiotics 852secretions/fluid turnover842–843
somatostatin and analogues848–849
hemorrhage, gastrointestinal 847
half-maximal effectconcentration 6, 15
half-time/half-life 59–60
hallucinations, and ketamine 451
halogenated anesthetics 362
haloperidol 599, 600, 601,604–605, 1051–1052
halothane 397, 399, 1155metabolism 392myocardial contractility/arrhythmias 409–410
physicochemical properties 398
Harlequin syndrome 1067
head trauma, infusion fluids 806
health policy 166;see also pharmacoeconomics
health-related quality of life 170
Health Utility Index (HUI2) 170
heart failure 325–326, 1072;see also myocardial ischemia;positive inotropic drugs
heart function 316, 317–319,326–327; see alsocardiovascular effects;coronary circulation
blood pressure control/vascular tone 1080, 1081
cardiac cycle 316–317cardiac pump function 317–319cell physiology 322–323contractile tissue 324contractility control 324–325diastolic ventricular function321–322
drug action targets 326and energetics 1080–1081,1081–1082
excitation contractioncoupling 323–324
heart failure 325–326
heart rate 671, 1084myocardial metabolism325–326
organ physiology 320–322pace-maker tissue 323–324
heat shock proteins (HSPs) 900
Helicobacter eradicationregimes 847
hematologic agents,perioperative medication992; see also platelet function
hemodynamics;see also hypertension;hypotension; vascular tone
alpha-adrenoceptor agonists480–481, 485
blood pressure control 114,1078–1079, 1080
calcium channel blockers 741impedance 1082–1083,1083–1084
induction of anesthesia1015–1016
inhaled anestheticspharmacology 409, 410
STEMI/UA/NSTEMIadjunctive therapies 1097
hemorrhagic shock, animalstudies 1016
hemostasis physiology 912–915fig 57.4.; see also plateletfunction
heparin 915, 915adverse drug reactions 917–918allergic reactions 1119
Index
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heparin (cont.)clinical pharmacology 917dosage/administration918–919
mechanism of drug action 915new/emerging concepts 919NSTEMI/unstable anginamanagement 1095
perioperative medication 992preclinical pharmacology915–917
STEMI management 1094
heparin-inducedthrombocytopenia (HIT) 918
hepatic function see liverfunction
hepatitisalcohol users 1108immune-mediated 398, 399,402–403
metabolism 392
herbal medicine 992, 998–999,1001
HERG blockade 305, 309–310
hernia, chronic pain 1069
heroin addiction 542;see also addiction; drug/alcohol users; opioidagonists/antagonists
herpes 980, 981
HES (hydroxyethyl starch) 793,808–809
high-dose opioid anesthesia 513
Hill analysis, multiple agonistsites 8
Hill coefficient 8
Hill equation 8
hippocampus 218anesthetic neurotoxicity 1155memory/learning 213–214, 219synaptic plasticity 203
hirudin related compoundssee direct thrombininhibitors
histamine receptor antagonists843–845
adverse drug reactions843–844
cimetidine 843–844drug interactions 844famotidine 845nizatidine 844–845neuromuscular blocking drugs613, 614
opioid clinical pharmacology535
ranitidine 844
succinylcholine 620versus proton pump inhibitors847–848
HIV (human immunodeficiencyvirus) 979, 980, 983
immunology 355–356opioids 501
HLA (human leucocyte antigens)349, 350, 356
Hofmann elimination 618
homeostasis 53, 1139
hormonal effectsopioid clinical pharmacology535
perioperative medication996–997, 1000
hormone response elements(HREs) 53
Horner’s syndrome 1067
HPA see hypothalamic-pituitary-adrenal axis
HPV (hypoxic pulmonaryvasoconstriction) 409,768–769
HSPs (heat shock proteins) 900
HU12 (Health Utility Index) 170
human leucocyte antigens (HLA)349, 350, 356
human plasma infusion fluidssee infusion fluids
humoral immunity 349
HX0507 456
hybrid physiologic models 61
hydralazine 771, 954
hydraulic model ofpharmacokinetics 58–59
hydrocodone 538
hydrogen bonds 2
hydrogen fluoride toxicity404–405
hydromorphone 516oral administration 521properties 538sedation 1043
hydrophobic interactions 2
hydroxyethyl starch (HES) 793,808–809
hyoscine butylbromide 673, 849
hyperalgesia 503, 1110
hyperglycemia 600–601,884–885, 906
hyper/hypocapnia 407
hyperkalemia 886
hyperlipidemia 836–837
hypersensitivity 353–354
hypertension 486;see also hemodynamics;pulmonary hypertension;vascular tone
alcohol users 1108
antihypertensive 954calcium channel blockers741–742
immunosuppressants/anti-rejection drugs 836
maintenance of/emergencefrom anesthesia 1029
obstetrics 954
hypertonic electrolyte solutions805–806
hypnosis, definition 478
hypnotics; see also sedationallergic reactions 458–460benzodiazepines 468closed-loop drugadministration 115–116, 117
open-loop TCI 110pharmacogeriatrics1142–1145, 1144, 1146,
hypocretin 187–188
hypoglycemia 885–886, 906
hypotension;see also hemodynamics;vascular tone
maintenance of/emergencefrom anesthesia 1029
vasopressor treatment 957
hypotensive anesthesia 486
hypothalamic-pituitary-adrenalaxis (HPA) 818
anesthetic action mechanisms376–377, 819–820
control of secretion818–819
critical illness effects 820feedback inhibition 819
hypothalamus 218
hypothermia 1031, 1032
hypovolemic shock 805
hypoxemia 770
hypoxia 389
hypoxic pulmonaryvasoconstriction (HPV) 409,768–769
hysteresis 424
ibuprofen 548, 553–550, 555
ibutilide 692, 693, 698–699, 702
ICDSC (Intensive Care DeliriumScreening Checklist)1051–1049
Ice 660
iceberg phenomenon 609, 610
ICF (intracellular fluid flux) 803
ICV (intracellular fluid volume)800, 803
ICP (intra-cerebral pressure) 407
idiopathic ventricular fibrillation(IVF) syndromes 296, 298,301, 302
IFV (interstitial fluid volume) 800
IL-18 786
ileal brake 842
ileus 535, 543, 890, 901
iloprost 773
IM (intramuscularadministration) 123, 522
imidazolines see alpha-adrenoceptor agonists
immobility 361anesthetic action mechanisms378
general anesthesia 232,237–239
neuromuscular blockingdrugs 624
immunoglobulin isotopes 346
immunology 345–346, 356–357acquired/adaptive immunity349–353
alpha-adrenoceptor agonists487
anatomical barriers to diseasepathogens 345, 346
B cells 352cancer 354–355cytokines 352–353
hepatitis 398, 399, 402–403HIV 355–356hypersensitivity 353–354inflammatory response 346,347–349
innate immunity 345–349physiological barriers todisease pathogens 345–347
T cells/cell mediated immunity350–352
transplantation 356
immunoreceptors 50–51, 340
immunosuppressants 830, 831,838–839; see also T-cells
adverse drug reactions 835anesthetic agents 838anesthetic implications 836–838
Index
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azathioprine 835conduct of anesthesia 838cyclosporine 834–835diazepam/thiobarbiturates 838drug interactions 834–835glucocorticoids 817–818mechanism of drug action830–833
mycophenolate mofetil 834,835–836
opioids 501, 838perioperative medication995–996, 1000
preclinical pharmacology833–834
protocols 836, 837rapamycin 834, 835tacrolimus 835
impedance 317hemodynamics 1082–1083,1083–1084
matching to vasculature 1083
implicit memory 212–213
inactivationaction potentials 252ball- and-chain model 300cardiac rhythm 300–301slowly inactivating channels257–258
inamrinone 715–716, 719
incremental cost-effectivenessratio 168
indirect antagonists 10
indirect costs 169
indocyanine green dye 801
indoleamines 1112–1113
induction agents 1007
induction of anesthesia 1007,1020–1021
asthma patients 1017cardiovascular effects1012–1014
critical care applications/adrenal insufficiency1017–1018
drug choice 1007–1008drug interactions 1011–1012,1013
etomidate 1017–1018history 1007inhaled anesthetics 1010–1011intercranial pressure/compliance 1019
intubation withoutneuromuscular blockingagents 1011
laryngeal mask airwayinsertion 1018
myoclonus/rigidity 1014–1015
open eye injury 1016–1017opioids as sole agents 1010pain on injection 1014psychotomimetic effects 1015rapid sequence induction 1016remifentanil infusion 1020,1021
routes of drug administration1011
speed of onset 1007–1010spontaneous ventilationmaintenance 1018–1019
target-controlled infusion1019–1020
trauma/hemodynamicallyunstable patients 1015–1016
induction immunosuppression836, 837
infants; see also pediatricsdefinition 1128developmentalpharmacodynamics 1134
infection; see also antibacterials;antifungals; antimicrobials
acetylcholine receptors 624biotransformation, drug 85
control 838
postoperative 449
surgical site infections 982
infertility 53
inflammationacetylcholine receptors 624biotransformation, drug 85hypersensitivity 353–354
inflammatory response 347–349malignant 814;see also glucocorticoids
metabolic syndrome 876and neuronal death 1151–1152vascular endothelium 282–283
influenza 980–982, 981
information technology (IT) 160
infraclavicular blocks 1067
infusion fluids 800, 809, 810adverse drug reactions804–805, 806, 807, 808, 809
clinical use 804, 806, 807, 808,809
colloid fluids 807–809crystalloid fluids 803–805,809
fluid pharmacokinetics802–803, 802
glucose solutions 806–807hypertonic electrolytesolutions 805–806
intracellular fluid flux 803optimizing 805outcome studies 805
physiology of fluid distribution800, 801
plasma volume expansioncalculation 800–802
uncontrolled hemorrhage809–810
inhalants, drug/alcohol users 1113
inhaled anesthetics 369–374
administration 523anesthetic action mechanisms374, 378
asthma treatments 755–756cerebral ischemia andanesthetic neuroprotection1153
drug interactions 152–154hemodynamics 1079induction of anesthesia1010–1011
maintenance of/emergencefrom anesthesia 1027–1029
perioperative medication 997,1000
pharmacology see belowpharmacogeriatrics1146–1147, 1148
pharmokinetics see belowpostoperative nausea andvomiting 858–859
routes of drug administration125
inhaled anestheticspharmacology 397, 413
adverse autonomic nervoussystem effects 411
adverse circulatory effects409–411
adverse drug reactions 413adverse pulmonary effects407–409
background information onspecific drugs 398–400
beneficial effects 400–401cardio-protection 412cerebral injury 405–407, 413cerebral protection 412delivery systems 400, 401fluoride-inducednephrotoxicity 401–402, 413
hepatic injury 402–403, 413hepatic protection 412hydrogen fluoride toxicity404–405
malignant hyperthermia 401, 413minimum alveolarconcentration 397–398
minimizing injuriouseffects 405
organ protection 411–412physicochemical properties 398renal injury 403–404renal protection 412
inhaled anestheticspharmokinetics 385, 386, 394
age/pregnancy effects 393–394alveolar-arterial gradient 393breathing systems 392–393concentration/second gaseffects 385–388
diffusion into gas spaces 393distribution 387–389elimination 389lipid delivery 394mammillary model 390–391mathematics of distribution389–390
metabolism 391–392physiologically basedpharmacokinetic models 391
terminology 385–386, 387, 388uptake 386–387uptake measurement 390
inhaled nitric oxide (INO)771–773
inhibition, competitive/non-competitive 15, 16,15, 609
inhibitory postsynaptic potential(IPSP) 200–201
injectionpain on 449, 1014
speed, neuromuscular blockingdrugs 615
innate immunity 345–349
inositol triphosphate 24–26, 25
inotropes 1086–1087insulin 874, 886–887;see also diabetes
acute myocardial infarction 886acute severe illness 886administration 877–878analogs 878–879biosynthesis/release 877degradation 877delivery to tissues 877diabetic regimes 879, 881, 882glargine/detemir 879glucose homeostasis 874–877hyperkalemia 886isophane protamine 878perioperative medication 993pharmokinetics 878–879physiological effects 874resistance 876, 884, 892signal 877soluble/regular 878STEMI/UA/NSTEMIadjunctive therapies 1096
use as drug 877zinc/protamine suspensions 878
intangible costs 169
integration of drug effects 3, 13
Index
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integrins 51
Intensive Care DeliriumScreening Checklist (ICDSC)1051–1049
interaction models 147,150–152; see also druginteractions
intercranial compliance 1019
intercranial pressure 1019
interferons 346, 352–353
interleukin-2 receptor genetranscription 834
interleukin-2 receptor signaling832–833, 834
internalization 22
interscalene blocks 1067
interstitial fluid volume(IFV) 800
intestine see gutbiotransformation, drug 80opioid metabolism 520
intracathecal analgesia 1065
intracellular drug receptors 4,17, 18
intracellular fluid flux (ICF) 803
intracellular fluid volume (ICV)800, 803
intracerebral pressure (ICP) 407
intramuscular administration(IM) 123, 522
intrathecal routes of drugadministration 127–129, 523
intravenous anesthetics 444, 460allergic reactions 458–460new formulations 456–458opioid clinical practice/physiological principles513–517
pharmacokinetics 420, 437–438;see also barbiturates;etomidate; ketamine;midazolam; propofol
intrinsic efficacy 7, 15intrinsic guanylate cyclaseactivity 50
intrinsic serine/threoninekinase activity 49–50
intubationnon-depolarizingneuromuscular blockingdrugs 620–621
without neuromuscularblocking agents 1011
inverse agonism 11, 15
ion channels 28, 41;see also calcium; ligand-gated; potassium; sodium;transient receptor potential;two-pore potassium
ion channels; voltage-gated ionchannels
anesthetic action mechanisms378
antiarrhythmic agents 689,690–691, 690
cardiac rhythm 297, 299–301cerebral ischemiapathophysiology 1151–1152
drug action targets 308–310gating 251–253genetics 297membrane electrophysiology28
neuromuscular blocking drugs611
pain transmission/transduction 239–241
structure/function 299–301transmembrane currents 249transmembrane proteins 253
ion gradients 253
ion pumps 4, 253
ionic bonds 2
ionotropic receptors 34, 41, 35,200; see also positiveinotropic drugs for heartfailure
5-HT receptors 36, 35AMPA receptors 37cys-loop ion channel 35, 41five families of 34–35glutamate receptor family 37,41, 37
glycine receptors 36karinate receptors 37–39N-methyl-D-aspartatereceptors 39–40, 38
P2X receptor family 36, 41receptor localization 40
iontophoretic transdermalsystem (ITS) 1141
ipratropium 673
IPSP (inhibitory postsynapticpotential) 200–201
irreversibleantagonists 9–10, 15drug effects 6
ischemia 486; see also cerebralischemia
focal 1151, 1154inhaled anesthetics 401, 413
isobolograms 148–149
isoconcentration nomogram 514
isoflurane 397and Alzheimer’s disease 222drug interactions 152–154glucocorticoids secretion 820inhaled anestheticspharmacology 397, 398
metabolism 392neurogenesis 1155physicochemical properties 398
isophane protamine (NPH)insulin 878
isoproterenol 653, 657anaphylaxis therapy 1122–1123dosage 719use in heart failure 713–714
ISPOCD I trial 221
IT (information technology) 160
itraconazole 519
ITS (iontophoretic transdermalsystem) 1141
IVA-SIM 104
IVF (idiopathic ventricularfibrillation) syndromes 296,298, 301, 302
James, William 188
jimsonweed 668–669
JM1232 457–458
K channels see potassium ionchannels; two-porepotassium ion channels
kainate receptors (KAR) 37–39
Kalman filters 115
kava kava 999
ketamine 435, 438, 450–452,460, 563
administration routes, extravascular 436
allergic reactions 459and alpha-adrenoceptoragonists 486
analgesia, postoperative1063–1064
anesthetic action mechanisms374–375, 374
biotransformation, drug 434cerebral ischemia andanesthetic neuroprotection1153–1154
clinical pharmacology 563–564concentration/effectrelationship 435–436
disposition parameters 445distribution/metabolism/excretion 433–434, 435
dosage/administration 436, 564drug interactions 436indications 451
induction of anesthesia1008, 1019
mechanisms of drug action563, 564
nasal transmucosaladministration 126–127
patient-controlled analgesia1062
physicochemical properties 433preclinical pharmacology 563preemptive analgesia 1068psychotomimetic effects 1015side effects 445speed of onset 1007–1010structure/stereochemistry433, 445
transfer to effect site 435
ketoacidosis, diabetic (DKA)882–884
ketoacids 874–876kidney function 783, 795;see also acute kidney injury
alpha-adrenoceptor agonists482, 487
analgesia, postoperative 1072antioxidants 794–795
aspirin 927atrial natriuretic peptide 795biotransformation, drug80–81, 85
calcium channel blockers 743,747
chronic disease 783, 784, 794clearance 802crystalloid fluids 805diuretics 790–791, 792, 794dopamine 794drug transporters 97–98
end-stage disease 783experimentalpharmacotherapy 795
fluoride-inducednephrotoxicity 401–402
glomerular filtration rate 783,787–788
immunosuppressants/anti-rejection drugs 836
inhaled anestheticspharmacology 403–404, 412
injury 783monitoring 785–786non-steroidal anti-inflammatory drugs 557
neuromuscular blockadereversal 637
neuromuscular blocking drugs616, 617, 622, 623
nutritional pharmacology 907opioid effects 533pediatric pharmacology1132, 1133
perfusion 793
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perioperative morbidity784–785
pharmacogeriatrics 1140,1148
pharmacokinetics 430,524–525
pharmacotherapy 793–794propofol 430, 449protection during anesthesia412, 485, 791–793
salt/water homeostasis 786sugammadex 643urine formation 786–790volume status 791–793
KIM-1 786
kinetic–dynamic model 158
Kir genes 307
kiss-and-run 198–199, 264
knockin animals 362, 467
knockout animals 362
labetalol 684, 954
lactated Ringer’s (LR) solution793, 803–804;see also crystalloid fluids
lactation 525–526
Lambert–Eaton myasthenicsyndrome 625
lamina, spinal dorsal horn 234–235
lamotrigine 591–592, 593, 594,595, 597
Langmuir isotherms 4
lansoprazole 846
laryngeal mask airway (LMA)insertion 1018
latex, allergic reactions 1120
layer-specific electrophysiology296
LD50 15
learning 220, 373;see also memory
leflunomide (LFM) 834
lethality (LD50) 15
leucocytes 349
leukotriene antagonists 758–760,997, 1000
levetiracetam 591–592, 593, 594,595–598
levobupivacaine 566clinical pharmacology 566–567dosage/administration 567mechanisms of drug action566
preclinical pharmacology 566
levosimendan 717–718, 719, 734
LGICs (cys-loop drug-gated ionchannels) 3
lidocaine 693antiarrhythmic agents 692,695, 702
cerebral ischemia/anestheticneuroprotection 1153
physico-chemical properties 578systemic effects 583toxicity 582–583
ligand-gated ion channels 18, 415-HT receptors 36, 35AMPA receptors 37autonomic nervous system 340cys-loop ion channel 35, 41five families of ionotropicreceptors 34–35, 35
glutamate receptor family36–40, 41
glycine receptors 36ionotropic glutamate receptors37, 37
ionotropic/metabotropicreceptors 34
kainate receptors 37–39N-methyl-D-aspartatereceptors 39–40, 38
P2X receptor family 36, 41receptor localization 40transient receptor potential ionchannels 40–41
ligands, opioid receptor 497
lincosamides 964, 974, 975–976
Lineweaver–Burke plot 5
lipid/s 893–899
bilayers 90, 91
drug delivery 394
emulsion 584–585
lowering drugs 1096nutritional pharmacology894–897
solubility 388, 577–578, 585
Lipinski’s rule of fives 97
lipopeptides 964, 970, 971
lipopolysaccharide (LPS) 348
lithium 603, 994, 1000
liver functionalcohol users 1108analgesia, postoperative 1072biotransformation, drug 84–85cirrhosis 428drug transporters 97immunosuppressants/anti-rejection drugs 837–838
inhaled anestheticspharmacology 402–403, 412
injury 402–403, 413neuromuscular blocking drugs618, 622, 623
non-steroidal anti-inflammatory drugs 558
nutritional pharmacology 905opioid effects 533organ failure 905, 1072pediatric pharmacology 1129,1132–1133
pharmacogeriatrics 1140,1148
propafol 427, 430, 449protection 412pharmacokinetics 427, 430, 524
LMA (laryngeal mask airway)insertion 1018
LMWH (low molecular weightheparin) 1095
local anesthetics 574, 586alkanization 580, 586allergic reactions 582cardiovascular effects 584central nervous system effects583–584
classification of peripheralnerves 575
distribution 581–582elimination 582epinephrine additives580, 586
functional anatomy of axons574–575
G protein-coupledreceptors 576
ion channels 239–241ionization 578–580lipid solubility 577–578, 585mechanisms of drug action575–576
methenoglobinemia 583molecular targets 239, 241new/emerging concepts584–585
obstetrics 951–952opioid additives 580, 586pharmacokinetic parameters582
pharmacokinetics 580physico-chemical properties577, 578
protein binding 578, 585systemic absorption 580–581systemic effects 583tissue toxicity 582–583
Loewe additivity druginteractions model 148
logistic equation 8
long QT syndrome (LQTS) 10,139–140, 296, 298, 301, 302
delayed rectifier Kþ currents305, 306
long-acting insulin analogs 879
long-term potentiation (LTP) 202maintenance 204–205memory/learning 210, 218, 220NMDA receptor dependent202–204
non NMDA-dependent 205and second messengers 204
long-term synaptic depression(LTD) 205–206
loop of Henle 786–790, 790–791
loop diuretics 790–791, 792
loperamide 93, 850–851
lorazepamclinical pharmacology 469dosage/administration 473,474–475
pharmodynamics 471–472pharmokinetics 469–470, 470sedation 1043, 1047
lower motor neuron lesions623–624
low-molecular-weight heparin(LMWH) 1095
LPS (lipopolysaccharide) 348LQTS see long QT syndrome
LSD (lysergic acid) 1112–1113
LTD (long-term synapticdepression) 205–206
LTP see long-termpotentiation
luciferase 360–361
lumbar paravertebralblocks 1067
lung function 81;see also pulmonaryhypertension; pulmonaryvasodilators
acetylcholinesteraseinhibition 637
acute lung injury 814, 1119adverse drug effects 407–409elimination 389, 427inhaled anestheticspharmacology 407–409
non-steroidal anti-inflammatorydrugs 557
pharmacogeriatrics 1140propofol 427, 449routes of drug administration125
lupus erythematosus 596
lymphocytes 349–350
lysergic acid (LSD) 1112–1113
M6G (morphine-6-glucuronide)1139; see also morphine
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ma huang 651, 999
MAC see minimum alveolarconcentration
macrolides 964, 972, 973
magnesium 694, 733, 737
magnesium sulphatepre-eclampsia 953–954preterm labor 955STEMI/UA/NSTEMIadjunctive therapies 1096
magnetic resonance imaging(MRI) 1054–1055
maintenance of anesthesiasee emergence from/maintenance of anesthesia
maintenanceimmunosuppression 836, 837
major histocompatibilitycomplex (MHC) 349, 350,830–831
malignant hyperpyrexia 451, 453
malignant hyperthermia (MH)137–139, 138, 401, 413
dantrolene 748drug choice 1028xenon 399
malnutrition see nutritionalpharmacology
mammillary models 59etomidate 436–437inhaled anestheticspharmokinetics 390–391
methohexital 425propofol 427–429thiopental 422
mannitol 790, 792
MAOIs (monoamine oxidaseinhibitors) 340, 660, 993,1000
Mapleson’s water analogy 388,389
marijuana 1110–1111
marinol (dronabinol) 569
Mark II Health Utility Index(HU12) 170
Marsh model 111, 428, 429–432
mast cells 614
maternal pharmacokinetics949–951; see also obstetrics
mathematical modelsinhaled anestheticspharmokinetics 389–390
open-loop TCI 105–106pharmacodynamic model 57pharmacokinetic model 57
maximal effect (Emax) models 6,15, 155
maximizing efficiency of targetsedation and reducingneurological dysfunction(MENDS) study 484, 488
MBC (minimum bactericidalconcentration) 963
MDIs (metered dose inhalers) 523
MDMA (methylenedioxy/methamphetamine)1112–1113
MDR (multidrug resistancetransporter) genes 92
mean effect time (MET) 65–66, 429
mean residence time (MRT) 58
mechanotransduction ionchannels 236–237
medical decision-making 166–167;see also pharmacoeconomics
medullary vasomotor center 652,648–649
MedWatch program 1121–1124
meglinitides 879, 880
melatonin 458
membrane, cell 254, 800
active agents 964, 971–972, 978–980
capacitance 253, 254, 258
drug transporters 91
electrophysiology 28
potential 28
properties 253, 254
reaction time 254–255
transmembrane currents 249
transmembrane proteins 2, 253
transmembrane pumps 4
transmembrane receptors 51–53
memory 210–211, 222;see also amnesia
conscious 212, 216–219consolidation/forgetting217–218, 220
definitions 212–213delirium 221drug actions 215, 216–219drug targets 218–221during anesthesia 215–216neuro-mechanistic processes213–214
NMDA receptors 373perception/working memory212, 226
perioperative period 211–212
postoperative cognitivedysfunction 221–222
procedural memory/conditioning 212–213, 216
serial parallel independenttaxonomy 215, 216
unconscious 212–213, 215–216
MENDS (maximizing efficiencyof target sedation andreducing neurologicaldysfunction) study 484, 488
meperidine 538, 1141
mephentermine 653, 655–656
MEPP (miniature endplatepotential) 196
mesenchymal stem cells (MSC)356
mesolimbic dopamine system1106
MET (mean effect time)65–66, 429
metabolic responses to surgery/trauma 876–877; see alsosurgical stress response
metabolic syndrome 876
metabolism, drugsee biotransformation;clearance; enzymes
metabotropic glutamate receptor(mGlu5) agonists 242
metabotropic receptors 34, 41, 35
metamphetamine 660–661
metaraminol 653, 655–656
metered dose inhalers (MDIs) 523
metformin 879, 880, 993
methadone 126, 127, 516, 521, 538
methenoglobinemia 583
methohexital 425, 426, 438,446–447
adverse drug reactions 447allergic reactions 459decrement time 431disposition parameters 445dosage/administration 425–426pharmacokinetic modeling 425physicochemical properties 425side effects 445speed of onset 1007–1010structure/stereochemistry425, 445
methoxamine 653, 655
methoxyflurane 392
methylenedioxy-methamphetamine(MDMA) 1112–1113
methylphenidate 660–661
methylxanthines 753–754
metoprolol 683–684, 700, 702
mexiletine 692, 693, 695–696,702
Meyer–Overton correlation359, 360
mGlu5 (metabotropic glutamatereceptor) agonists 242
MH see malignant hyperthermia
MHC (major histocompatibilitycomplex) 349, 350, 830–831
MI (myocardial infarction) 886,1091–1092
MIC (minimum inhibitoryconcentration) 963–965
microemulsions 454
microtubules 199
midazolam 453, 460allergic reactions 459, 460clinical pharmacology 468CYP3A 84dosage/administration 473–474pharmacogeriatrics 1144–1145pharmodynamics 471pharmokinetics 469, 469sedation 1043structure/stereochemistry 445
midodrine 655
milrinone 715, 716, 719
minerals, nutritionalpharmacology 894–897,901–902, 904
miniature endplate potential(MEPP) 196
minimum alveolar concentration(MAC) 152–153, 397–398
obstetrics 951, 952pharmacogeriatrics 1147
minimum bactericidalconcentration (MBC) 963
minimum inhibitoryconcentration (MIC)963–965
mivacurium 623
MLCP (myosin light chainphosphatase) 726
MMF (mycophenolate mofetil)834, 835–836
MOC-etomidate 457
model predicted control 115
modeling, pharmacokinetic1135–1136
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MODS (multiple organdysfunction syndrome) 814
modulated receptorhypothesis 576
modulation, pain 227, 230–231,236; see also paintransmission/transduction
molecular biology 1, 2
molecular targets see drug targets
moment analysis 58
monitoringmaintenance of/emergencefrom anesthesia 1032–1034
sedation 1044–1046
monoamine oxidase (MAOs)inhibitors 340, 660, 993,1000
monobactams 969
mood effects 340;see also depressant drugs
calcium channel blockers 742opioid agonist-antagonists539–540
propofol 448–449sedation complications 1042
moricizine 692, 693, 697, 702
morphine; see also opioidsbolus dosing 510–513drug interactions 563history 531intramuscular administration522
oral administration 520oral transmucosaladministration 521
Oxford League Tableof NNT 555
pharmacogeriatrics 1141properties 538sedation 1042subcutaneous administration521–522
transdermal administration522–523
mortality rates reduction,nutritional pharmacology890, 900, 907
motility, gut 842; see also gutmotility/secretion inhibitors
motion sickness 856, 858
motor functionsee neuromuscular function
motor neuron lesions 623–624
MRI (magnetic resonanceimaging) 1054–1055
MRPs (multi-drug resistantproteins) 92, 93–94
MRSA infection 982
MRT (mean residence time) 58
MSC (mesenchymal stem cells)356
mu partial agonists 537
mucociliary function, lung408–409
mucous membranes, barriers todisease pathogens 345
multicompartment models 390
multidrug resistance transporter(MDR) genes 92
multidrug resistant proteins(MRPs) 92, 93–94
multimodal analgesia,postoperative 1067–1068
multiple organ dysfunctionsyndrome (MODS) 814
MUMPS (multi-unit, multi-pathsystem) model 152
muscarine 668
muscarinic acetylcholinereceptors 666;see also parasympatholyticdrugs
acetylcholinesterase inhibition637
neuromuscular blockingdrugs 614
perioperative medication 995succinylcholine 618, 619
muscarinic antagonists 487–488,1036
muscle; see also neuromuscularfunction; vascular smoothmuscle
body composition in elderlypatients 1139–1140
contraction physiology 724–726distribution phase of drugdelivery 388
nicotinic acetylcholinereceptors 267–268, 269–270,270–271
muscle relaxants;see also vasodilators
benzodiazepines 468calcium channel blockers 747chemical structure 612closed-loop drugadministration 116, 117
immunosuppressants/anti-rejection drugs 838
perioperative medication 994
mutually exclusive binding 8
myasthenia gravis 624–625, 995
mycophenolate mofetil (MMF)834, 835–836
myelin sheath 574–575
myelination 256
myocardial contractility409–410
myocardial infarction 886,1091–1092; see alsonon-ST-elevation myocardialinfarction; ST-elevation
myocardial infarction
myocardial ischemia 1091,1101–1102
acute coronary syndromes1091
acute coronary syndromesdefinition/diagnosis1091–1092
acute coronary syndromespharmacologic/interventional management1092, 1093, 1094
antiplatelet therapy,perioperative 1099–1100
beta-blocker therapy,perioperative 1097–1099
cardioplegia 1100–1101glossary of terms 1091inhaled anestheticspharmacology 411
non-ST-elevation myocardialinfarction/unstable anginamanagement 1094, 1095
ST elevation myocardialinfarction management1092–1095
statin therapy, perioperative1098, 1099
STEMI/UA/NSTEMIadjunctive therapies1096–1097
thoracic sympathectomy 1100
myocardial performancesee cardiovascular effects;coronary circulation; heartfunction
myocardial perfusion 319
myoclonus 1014–1015
myofilament calcium sensitizersclinical pharmacology 717dosage 719levosimendan 717–718pimobendan 717preclinical pharmacology716–717
thyroid hormone 717–718
myogenic contraction 279–280
myogenic tone 726
myosin 278
myosin light chain phosphatase(MLCP) 726
Naþ channels see sodium ionchannels
N-acetylcysteine (NAC) 794–795
nalbuphine 537, 540
nalmefene 543
nalorphine 537
naloxone 542
naltrexone 542, 1107
NANC (nonadrenergicnoncholinergic) mechanisms284, 333
naproxen 548cardiovascular effects 556OxfordLeagueTable ofNNT 555pharmacokinetic parameters553–550
narcotics, terminology 531
Narcotrend 180
nasal transmucosal routes ofdrug administration 126–127
natural penicillins 966, 967
nausea see anti-emetics;postoperative nausea andvomiting
NDBs see non-depolarizingneuromuscular blocking drugs
nebivolol 681, 684
necrosis 1151–1152
nedocromil sodium 757–758
neonatesdefinition 1128metabolism 950
of drug addicts 1110
pediatric pharmacology 1128
neostigmine 633, 637, 1035;see also neuromuscularblockade reversal
Nernst equation 28, 249–250, 251
nerve growth factor (NGF)242, 571
nerve impulse 253, 254
nerve terminals 192
nervous system agonists 487
neural control of cardiacrhythm 293
neuraminidase inhibitors980–982, 981
neuraxial routes of drugadministration 124, 127–129
Index
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neuroanatomy 375
neurogenesis 1154–1155
neurogenic control 320
neurokinin type 1, 860 receptorantagonists 864–865
neuroleptic malignant syndrome(NMS) 994
neuroleptics 860, 861–862
neuromechanistic processes ofmemory/learning 213–214
neuromuscular blockade reversal633, 643–644, 1035–1036
according to anesthetic drugadministered 636
acetylcholinesterase drugs635–636
acetylcholinesterasesinhibitors 634
depth of blockade 635dosage/administration 636drug interactions 636–637monitoring 637–639neuromuscular junctionacetylcholinesterase 633–634
neuromuscular junctionplasticity 633
nonclassic drugs 639;see also sugammadex
pharmacokinetics 637residual effects 639side effects 637spontaneous clearance 636variation between patients 637,643
neuromuscular blocking agents(NMBAs) 608, 627–628;see also succinylcholine
acetylcholine receptors622–624, 624–625
acetylcholine receptor relaxanteffects 613
acetylcholinesterase enzyme611–612
administration 625–626adverse drug reactions 618allergic reactions 1119–1120bronchial smooth musclerelaxant effects 614
carotid body relaxant effects613–614
clinical pharmacology-non-depolarizing drugs 620–622
contraindications 619dosage/administration620–621
drug interactions 625duration of action 621elimination/metabolism 616,617–618
ester hydrolysis 617–618extended use 627
factors affectingpharmacokinetics 615–617
hepatic disease 622, 623histamine release 613, 614Hofmann elimination 618intrinsic activity 613intubation without 1011mechanisms of drug action609–611
neuromuscular function622, 624
neuromuscular transmission608–609
pharmacogeriatrics 1145–1146pharmacokinetics 615postsynaptic transmission 609preclinical pharmacology614–615
presynaptic transmission 608rapid sequence induction 626recovery index 621–622renal function 622, 623structure-activity relationships612, 613
variation between patients 626
neuromuscular function 114,261, 265
acetylcholinesterase inhibition266–267
action potentials 262–263,265
calcium voltage-gated ionchannels 263–264
depolarizing blocking drugs 270monitoring 637–639,1032–1034
muscle nicotinic acetylcholinereceptors 267–268
neuromuscular blocking drugs622, 624
neuromuscular junctionstructure/function 261, 262,263
neuromuscular transmission270–271
noncompetitive inhibitors269–270
nondepolarizing competitiveblocking drugs 270
presynaptic terminal,transmitter release 262–265
quantal transmitter release 264receptor activation 268–269receptor desensitization 269synaptic cleft 265–267vesicle cycling 264, 265vesicle fusion 263–264vesicle fusion proteins264–265, 266
neuromuscular junction (NMJ)acetylcholinesterases 633–634neuromuscular blockingdrugs 625
plasticity, synaptic 633structure/function 261, 262, 263succinylcholine 618, 619–620
neuromuscular transmission270–271, 608–609, 610
neuronal activity/signalling 29
neuronal death 1151–1152;see also neurotoxicity
neuronal plasticity 550
neuronal regulation 726, 727
neuropathic pain 231, 536
neuroprotection 1151,1158–1159; see also cerebralischemia; neurotoxicity
age effects 1157alpha-2 adrenoceptor agonists481
reconciliation of opposingeffects of anesthetics1157–1158
neuroradiology, sedation for1054–1055
neurosteroids 368–369, 374
neurotoxicity 1155–1156,1158–1159;see also neuroprotection
age effects 1157alcohol 1107mechanism of drug action1156, 1157
reconciliation of opposingeffects of anesthetics1157–1158
relevance of rodent models tohumans 1156–1157
neurotransmitters;see also synaptictransmission; specificneurotransmitters by name
agonist/antagonist drug actiontargets 206
biotransformation, drug actiontargets 206
calcium regulation 197chemical identity 193–194,194–195
classes of 194–195, 206drug transporters 90duration of action 199ganglionic blockers 733glutamate as 36mechanism of transmitterrelease 196
neurogenesis 1154
presynaptic release 262–265re-uptake drug actiontargets 206
stages of chemical transition193, 194
storage of neurotransmitters 196storage, drug action targets 206synthesis, drug actiontargets 206
volatile anesthetics 373–374
neutrophil gelatinase-associatedlipocalin (NGAL) 785–786
newborn babies see neonates
NFAT (nuclear factor of activatedT cells) 831–832, 834
NFkB 52–53
NHLBI International ConcensusReport on Diagnosis andTreatment of Asthma 825
nicotine see smoking
nicotinic acetylcholinereceptors 2–4
acetylcholinesteraseinhibition 637
barbiturates, anesthetic 368drug receptor categorization 2ketamine 374
muscle 267–268, 269–270,270–271
neuromuscular blockingdrugs 613
neuromuscular function267–268, 269–270, 270–271
nifedipene 954–955
nitratescardiovascular patients,perioperative medication989, 999
STEMI/UA/NSTEMIadjunctive therapies 1096
nitric oxide 280, 281anesthetic action mechanisms374, 375
blood pressure control/vascular tone 1087
cardiovascular actions410–411
diffusion into gas spaces 393heart contractility control 325inhaled 771–773maintenance of/emergencefrom anesthesia 1031
metabolism 392nitrovasodilators 728–729pharmacology 399–400physicochemical properties 398postoperative nausea andvomiting 858
preterm labor 955signal transduction 17sympathetic nervous system 651toxicity 140, 141vascular reactivity 281
nitroimidazoles 964, 978
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nitrovasodilators 728–729,737, 771
nizatidine 844–845
NMBAs see neuromuscularblocking agents
N-methyl-d-aspartate (NMDA)receptors 39–40, 38, 200
anesthetic action mechanisms373
anesthetic neurotoxicity1155–1156
drug addicts 1110ketamine 374–375, 563, 564long-term potentiation202–204
neuroprotection/neurotoxicity1151
nitrous oxide 375psychedelics/party drugs1112–1113
reconciliation of opposingeffects of anesthetics1157–1158
volatile anesthetics 371–373xenon 375
N-methylnaltrexone 543
NMJ see neuromuscular junction
NMS (neuroleptic malignantsyndrome) 994
nocioception/nocioceptive pain227–228, 231, 1061–1063;see also pain transmission/transduction
nomenclature/categorization,drug receptors 2–4, 18
nonadrenergic noncholinergic(NANC)mechanisms 284, 333
noncompetitive block 15, 9, 10,10, 609
muscle nicotinic acetylcholinereceptors 269–270
neuromuscular blocking drugs609–611
nondepolarizing neuromuscularblocking drugs (NDBs) 270
clinical pharmacology620–622
recovery index 621–622
nonenzymatic decay 618
nonimmobilizers 359
nonionotropic/non-G-protein-coupled receptors 47, 54
acronyms 53caspases and NFkB 52–53cystolic serine/threoninekinases 51–52
cystolic tyrosine kinases 50–51cytokine receptors 50
cytoplasmic enzymes 53immunoreceptors 50–51integrins 51intrinsic guanylate cyclaseactivity 50
intrinsic serine/threoninekinase activity 49–50
nuclear receptors 53–54plasma membrane receptorslinked to cytoplasmicenzymes 50
plasma membrane receptorswith intrinsic enzymeactivity 47
receptor tyrosine phosphatases48–49
tyrosine kinase-associatedreceptors 47–48, 49
non-operating-room anesthesia(NORA) 1054
non-rapid eye movement sleep(NREM) 182–183, 479
nonspecific binding 4
non-ST-elevation myocardialinfarction (NSTEMI) 1091,1101–1102
definition/diagnosis 1091–1092management strategies1094, 1095
pharmacologic/interventionalmanagement 1092, 1093,1094
nonsteroidal anti-inflammatorydrugs (NSAIDs) 548, 559;see also cyclooxygenase-2-specific inhibitors
absorption 551–552analgesia, postoperative 1063asthma 557bone healing 557–558cardiovascular effects 555–556chirality 551classification according tochemical structure 551
clinical context 559cyclooxygenase expression/action 550, 550
cyclooxygenase inhibition550–552
cyclooxygenase/prostaglandinsrole in pain 548, 549
distribution 552–553drug interactions 558gastrointestinal effects556–521, 847–848
hepatic effects 558metabolism/excretion 554neuronal plasticity 550Oxford League Tableof NNT 555
perioperative medication998, 1000
pharmacodynamics 555–556pharmacokinetics 551,553–550
platelet function 557preemptive analgesia 1068prostaglandins synthesis/action 548–550
renal effects 557
NORA (non-operating roomanesthesia) 1054
norepinephrine (NE) 284, 330,335–336, 659
anaphylaxis therapy 1122–1123dosage 719pharmacological modulation340–341
use in heart failure 711–712
norketamine 435
normal saline (NS) 793, 803, 804,805; see also crystalloid fluids
novel analgesics 563, 571–572alpha-adrenoceptor agonists567, 568
anticonvulsants 564–566calcium channel blockers568–569
cannabinoids 569ketamine 563–564peptide growth factor andreceptors 571
sodium channel blockers566–567
transient receptor potential ionchannels 570–571
NPH (isophane protamine)insulin 878
NREM (non-rapid eyemovement sleep)182–183, 479
NS (normal saline) 793, 803, 804,805; see also crystalloid fluids
NSAIDs see non-steroidalanti-inflammatory drugs
NSTEMI see non-ST-elevationmyocardial infarction
N-type inactivation 300
nuclear drug receptors 4
nuclear factor of activated T cells(NFAT) 831–832, 834
nuclear receptors, non-ionotropic/non-G protein-coupled53–54
nucleus tractus solitarius(NTS) 1078
nutritional pharmacology890–891, 907
administration routes 903–904arginine 900, 901
burn injury 901, 907carbohydrates 892, 894–897critical care applications901–903
designing nutritional supportregimes 894–897
energy expenditure 891–892,891–892
enteral routes 903–904, 905–906enteral routes formulary898–899
gastrointestinal complications905–906
glutamine 900glutamine (GLN) 904–905indications 901–903lipids 893–899, 894–897metabolic complications 906monitoring 904–905neurogenesis 1154
nutritional guidelines 903parenteral routes 904, 905proteins/amino acids 893–900,894–897
renal function 907supplements, alcohol users1107
surgical patients 901timing of feeding 904trace elements 901–902, 904
OATs (organic aniontransporters) 94, 95–96,97–98
OBD (opioid bowl dysfunction)535, 543
obesity; see also nutritionalpharmacology
neuromuscular blocking drugs615–616
postoperative nausea andvomiting 857
propofol pharmacokinetics428, 430
objective evaluation, andsubjective experience 177
obstetrics 81, 948, 949, 958–959see also neonates
absorption/uptake 949alcohol users 1109analgesia 952–953antiepileptic drugs 590antihypertensive therapy 954breast milk transfer 950–951distribution 949effects of pregnancy 393–394elimination 950ergot alkaloids 955–956fetal/neonatal metabolism 950general anesthesia 951, 952gonadotropins 956–957local anesthetics 951–952
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obstetrics (cont.)maternal pharmacokinetics949–951
metabolism 949–950neuromuscular blockingdrugs 616
ocytocics 955oxytocin 955pharmacodynamics 951–953pharmacogenetics 948pharmacokinetics 525, 949
placental transfer/metabolism98, 950
pre-eclampsia 953–954progesterone antagonists 956propofol 957–958prostaglandins 956remifentanil 958tocolytics 954–955vasopressor treatment ofhypotension from spinalanesthesia 957
OCT (organic cationtransporters) 94, 97–98
octreotide 848–849
ocytocics 955
offset of drug effect 66
Ohm’s Law 248–249, 285
OHSS (ovarian hyperstimulationsyndrome) 956–957
olanzapine 599, 600, 601, 602
omalizumab 760–761omega–3 fatty acids 905, 907
omeprazole 845–846
ondansetron 860, 863–864
one-volume kinetic model 802
onset of drug effect 65, 615
open eye injury 1016–1017
open-loop TCI 103–104, 110,116–118; see also targetcontrolled infusion
comparison with manualinfusion 107–109
context-sensitive half-time/decrement time 109
control strategy 106, 107effect-site targeting 106–109history/definitions 104–105mathematical model 105–106model selection 111–112performance evaluation 109–111plasma targeting 106, 107–109variation between patients 112,113, 114
opioids 493, 494, 503–504,1061–1063; see also drugadministration routes;
fentanyl; morphine;meperidine; propofol;remifentanyl
acute/chronic effects 532addiction 1107additives 580, 586agonists/antagonistssee belowanalgesia, postoperative1061–1063
analgesic action mechanisms496–498
antitussive effects 499for awake fiberoptic intubation1054
cardiovascular effects 499classes of 497clinical pharmacologysee below
clinical practice/physiologicalprinciples see below
closed-loop drugadministration 114–115,116, 117
conversion to morphineequivalents 1061–1062
drug interactions 152–154,154–158, 519–520, 533
drug interactions, figures 153,155, 156, 157, 158, 159
drug/alcohol users/addicts1109–1110
effects not mediated by opioidreceptors 532
endogenous 494gastrointestinal effects 499, 500genetic responsivity 136genetics 136–137, 494, 496gut motility/secretioninhibitors 850–852
hyperalgesia 503immunosuppression 501, 838induction of anesthesia 1010intercranial pressure/compliance 1019
metabolism 518natural/semisynthetic/synthetic 493–494
obstetrics 959open-loop TCI 110,111–112, 114
perioperative medication997–998, 1000
pharmacogeriatrics1140–1142, 1143
postoperative nausea andvomiting 859
protein binding 518pruritis 500–501receptor signaling 496receptor structure/ligandinteractions 495–496, 497
receptors 494–495, 496, 497, 498respiratory depression498–499
rotation, drug addicts 1110sedation 1042–1043, 1046–1047tolerance 23–24, 501–503,535–536, 563–564, 1070–1071opioid agonists/antagonistsalvimopan 543analgesia 537–539antagonist effects 540cardiovascular effects 540chronic administration 540–542general properties 537nalmefene 543naloxone 542naltrexone 542N-methylnaltrexone 543respiratory depression 540sedation/mood effects 539–540smooth muscle effects 540
opioid bowl dysfunction (OBD)535, 543
opioid clinical pharmacology496–498, 531, 532–533, 536,543–544
analgesia 532–533cardiovascular effects 534–535chronic effects 535–536chronic pain 536coughing reflex suppression534
histamine release 535hormonal effects 535nausea 534opioid agonists 531physical dependence 536pupil constriction 534respiratory depression533–534
sedation 533skeletal muscle rigidity 534smooth muscle spasm 535specific drugs 536–541, 538terminology 531
opioid clinical practice/physiological principles509, 526
apnea and rate of opioidadministration 518
bolus dosing of opioids510–513, 537
drug interactions 519–520epidural 523–524hepatic disease 524inhalational administration 523intramuscular administration522
intrathecal 523intravenous infusion 513–517,537
lactation 525–526opioid metabolism 518opioid protein binding 518oral administration 520, 520
oral transmucosaladministration 521
pharmacogenetics 518–519pharmacokinetic half-lives 516pharmacokinetic/pharmacodynamic data 511
plasma concentration profiles517, 540
pregnancy 525renal disease 524–525selection and use of opioids510, 511
subcutaneous administration521–522
transdermal administration522–523
opthalmic agents, perioperativemedication 998, 1000
opthalmic surgery 486
oral agents/administrationdiabetes 881–882hypoglycaemic agents 880opioids 520, 520platelet function 988
oral transmucosal administration(OTM) 521
oral transmucosal fentanyl citrate(OTFC) 125–126
orexin 187–188
organ protection
heart 743, 743
inhaled anesthetics 401, 411–412
kidney 412, 485, 791–793
liver 412
organic anion transporters(OAT) 94, 95–96, 97–98
organic cation transporters(OCT) 94, 97–98
orphan receptors 19
orthopedic surgery 934
orthosteric drug binding sites 4
OSCS (oversulfated chondroitinsulfate) 919
osmotic diuretics 790
OTFC (oral transmucosalfentanyl citrate) 125–126
OTM (oral transmucosaladministration) 521
outcome studies, sedation1046–1049
ovarian hyperstimulationsyndrome (OHSS) 956–957
oversulfated chondroitin sulfate(OSCS) 919
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oxazolidinones 964, 974–975
oxcarbazepine 591–592, 593, 594,595, 597
Oxford League Table of NNT 555
oxybutinin 673
oxycodone 521, 538, 555
oxygen consumptionsurgical stress response 1041ventricular function1081–1082
oxytocin 955
oxytocin-receptor agonists 955
P2X receptor family 36, 41
PABA (para-amino benzoicacid) 582
pacemaker current 307–308
pacemaker tissue 323–324
pain; see also analgesia; regionalanalgesia
cyclooxygenase/prostaglandinsrole 548, 549
on injection 449, 1014
pain transmission/transduction227, 241; see also perception;pain
abnormal impulse activity257–258
ascending pathways 229–230biochemical/molecularmechanisms 236–237, 243
descending modulatorypathways 230–231
molecular targets–generalanesthetics 232, 237–239, 243
molecular targets–localanesthetics 239, 241, 243
neuron heterogeneity 232–234new/emerging concepts 242,243
nocioceptor types 232organ physiology 231, 243plasticity, synaptic 235–236primary afferent nocioceptors227–228, 231–232, 233, 243
spinal cord 228–229spinal dorsal horn neurondiversity 234–235
spinal dorsal horn synapse234, 243
systems physiology 227, 242–243voltage-gated ion channels237, 239–241
PAMPs (pathogen-associatedmolecular pattern molecules)346
pancreas 874–877, 1108;see also glucose homeostasis
pancuronium 608, 612, 1030–1031
pantoprazole 846–847
para-amino benzoic acid(PABA) 582
paracetamol 552, 553–550, 555,1063
paradoxical reactions 1145
paralysisbutyryl-cholinesterasedeficiency 134–135
maintenance of/emergencefrom anesthesia 1030–1031
reversal see neuromuscularblockade reversal
parametric drug responseanalysis in individuals 13
parasympathetic nervous system284, 330, 331–333;see also autonomic nervoussystem
parasympatholytic drugs668–669, 673–674
adverse drug reactions ofoverdose 672
atropine 669–672clinical pharmacology 669glycopyrrolate 672mechanisms of drug action669
other anticholinergic agents672–673
scopolamine 672
parasympathomimetic drugs 666clinical pharmacology667–668
mechanisms of drug action666–667
preclinical pharmacology 667synthetic choline esters667–668
parecoxib 553–550;see also cyclooxygenase-2-specific inhibitors
parenteral nutrition 904, 905
Parkinson’s disease 603, 604
perioperative medication 994,1000
paroxetine 519
partial agonists 6, 9, 11, 15, 537
partial pressure 385–388
party drugs 1112–1113
PASMCs (pulmonary arterysmooth muscle cells) 768–769
pathogen-associated molecularpattern molecules(PAMPs) 346
patient compliance, dosingregimes 520
patient state index (PSI) 1032
patient-controlled analgesia(PCA) 515–517,1061–1063
patient-controlled epiduralanalgesia (PCEA) 1065
patient-controlled transdermalfentanyl (PCT-fentanyl)125, 522
pattern recognition receptors(PPRs) 346, 347
PBPKs (physiologically basedpharmacokinetic models)61–62, 391, 422–424, 432
PCI see percutaneous coronaryintervention
PCP (phencyclidine) 1112–1113
PDE inhibitorssee phosphodiesteraseinhibitors
peak effect, morphine 1141
pediatric pharmacology 1128,1136
absorption 1129–1130, 1132analgesia, postoperative1071–1072
biotransformation, drug 81, 82blood–brain barrier 1131definitions 1128developmentalpharmacodynamics1133–1134
developmentalpharmacogenetics 1134, 1135
developmentalpharmacokinetics 1128,1132
distribution 1130–1131, 1132drug metabolism 1131–1132extrahepatic elimination1133
hepatic elimination 1129,1132–1133
induction of anesthesia1010–1011
neonates 1128pharmacokinetic modeling1135–1136
protein binding 1131renal elimination 1133
PEEP (positive end-expiratorypressure) 1035
penicillins 964, 966, 967allergic reactions 1118
pentazocine 537
pentoxifylline 992
peptide growth factor/receptors571
perceptionmemory/learning 212
pain 140, 227; see also paintransmission/transduction
perceptual memory 215, 216
percutaneous coronaryintervention (PCI)
facilitated 1093–1094primary 1093reperfusion therapy 1093rescue 1093
perfusion, neuromuscularblocking drugs 615
perioperative cardioprotection743, 743
perioperative ischemiaevaluation study (POISE)1097–1099, 1101
perioperative medication 987,988, 999; see alsocardiovascular patients;perioperative medication
analgesics/anti-inflammatories997–998, 1000
anticoagulant medications992, 1000
anti-diabetic agents 992–993,1000
antiinfective agents 995, 1000anti-neoplastics 988, 995, 996,1000
antiplatelet agents 990–992, 996central/peripheral nervoussystem agents 993, 1000
glucocorticoids 824–826herbal preparations998–999, 1001
hormones/metabolics996–997, 1000
immunosuppressants995–996, 1000
opthalmic agents 998, 1000pentoxifylline 992respiratory agents 997, 1000tobacco/alcohol cessationagents 998, 1001
peripheral nervous system648–649, 993, 1000
persistent vegetative states178, 179
personalized medicine 83
PF0713 457
P-glycoprotein (P-gp) 92–93, 94,99; see also ABC drugtransporters
phagocytosis 345–346
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phantom limb pain 1069–1070
pharmacodynamics 1, 15drug receptors 1–4drug-receptor interactions4–6, 6–13, 147
effects on organisms 13–15genetic 135–136models 57non-steroidal anti-inflammatory drugs 555–556
pharmacoeconomics 166, 174–175computer modeling 172, 173conflict of interest 174cost-benefit analysis 172cost-effectiveness/utilityanalysis 170, 171–172
cost-identification analysis 171costs 168direct costs 168–169discounting 169
drug costs 1029health policy 166health-related quality of life170
incremental cost-effectivenessratio 168
indirect costs 169intangible costs 169medical decision-making166–167
quality of life 169quality of postoperativerecovery 170
quality-adjusted life years 171,170–171, 171–172
results interpretation 173–174,174
role in drug registration 167–168skewness in cost data 169, 169willingness to pay 172
pharmacogenetics 83–84, 132, 142analytical validity 133–134anesthetic action mechanisms362–363
autonomic nervous system340–341
basic concepts 132–133biotransformation, drug 83–84butyryl-cholinesterasedeficiency 134–135
calcium channel blockers 747cardiac rhythm 297, 310clinical utility 134clinical valididy 134drug susceptibility profiling 142genetic pharmacodynamics135–136
genetic pharmacokinetics 134genotype-phenotypescorrelations 133
genotypes 133longQT syndrome 10, 139–140
malignant hyperthermia 136,137–139
new/emerging concepts 141,140–141
obstetrics 948opioids 136–137, 494, 496,518–519, 533
pediatric pharmacology 1134,1135
phenotypes 133voltage-gated ion channels 41
Pharmacogenetics KnowledgeBase 141
Pharmacogenetics ResearchNetwork 140
pharmacogeriatrics 1139, 1147absorption 1139anticholinesterases 1146autonomic nervous systemdysfunction 338
biotransformation, drug 82body composition 1139–1140,1147
cardiopulmonary function1140
clinical pharmacology-general1140
hepatic function 1140, 1148inhaled anestheticspharmokinetics 393–394
minimum alveolarconcentration 398
neurogenesis 1154neuromuscular blocking drugs616, 1145–1146
neuroprotection/neurotoxicity1157
opioids 533, 1140–1142,1143
postoperative nausea andvomiting 856–857
propofol pharmacokinetics428, 430
renal function 1140, 1148sedative hypnotics 1142–1145,1144, 1146
volatile anesthetics 1146–1147,1148
pharmacokinetics 69, 57;see also specific agents byname
basic parameters 57–58compartment models 58–61dose equivalence 66–68drug accumulation 66drug input 62–63drug interactions 147effect compartment concept63–64
genetic 134local anesthetics 580–582modeling 57
pediatric pharmacology1135–1136
physiologically based models61–62
predictors of offset 65–66predictors of onset 64–65special compartment models 57variation between patients68–69
pharmacologic potencysee potency
pharmaconutritionsee nutritional pharmacology
pharmokinetic closed-loop drugadministration 113–114
pharmokinetic-dynamic closed-loop drug administration103, 114–115
phase II block, neuromuscularblocking drugs 611
phase III metabolism 91;see also ion channels; lipidbilayers
phencyclidine (PCP) 1112–1113
phenobarbital 593, 594, 595, 596
phenobenzamine 656, 661
phenothiazine-thioxanthenes599, 600–601, 601–603
phenotypes 133
phentolamine 662
phenylalkylamines 742, 743
phenylephrine 654–655, 1029
phenylpropanolamine 661
phenytoin 592–595, 692, 693
phosphodiesterase (PDE)inhibitors 732
anaphylaxis therapy 1123blood pressure control/vascular tone 1087
clinical pharmacology 714–715dosage/administration 719,735–736
enoximone 715inamrinone 715–716milrinone 715, 716preclinical pharmacology 714pulmonary vasodilators 774
physical dependence 536
physicochemical interactions 147
physiologically basedpharmacokinetic models(PBPK) 61–62, 391,422–424, 432
PID (proportional-integral-differential) controller 115
pilocarpine 668
pimobendan 717
pipenzepine 673
piperazinyl quinazoles 662
pituitary-adrenal failure 825
PKC (protein kinase C) 26, 279,286–287
placental transfer/metabolism 98,950; see also obstetrics
plasma cholinesterases 79, 617–618plasma infusion fluidssee infusion fluids
plasma membrane receptorslinked to cytoplasmicenzymes 50
cystolic tyrosine kinases 50–51cytokine receptors 50immunoreceptors 50–51integrins 51
plasma membrane receptors withintrinsic enzyme activity 47
intrinsic guanylate cyclaseactivity 50
intrinsic serine/threoninekinase activity 49–50
receptor protein tyrosinephosphatases 48–49
tyrosine kinase-associatedreceptors 47–48, 49
plasmamembrane transporters 90
plasma protein binding 615
plasma targeting, open-loop TCI106, 107–109
plasma volume (PV) 800–802
plasticity, synaptic 24, 202, 203,220, 550
neuromuscular junction 633N-methyl-D-aspartatereceptors 373
spinal dorsal horn synapse235–236
platelet function agents 919,936–937; see alsoanticoagulants; heparin
aprotonin 935–936argatroban 921–922aspirin 926–928calcium channel blockers 746dabigatran 922–923danaparoid 920–921desmopressin 932–933dipyridamole 928epsilon-aminocaproic acid/tranexamic acid 933–935
fondaparinux 921glycoprotein receptorinhibitors 930–931
hemostasis physiology 912–915
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hirudin related compounds923–924
non-steroidal anti-inflammatory drugs 557
non ST elevation myocardialinfarction/unstable anginamanagement 1095
oral agents 988perioperative medication990–992, 996, 1099–1100
prostacyclin 928protamine 919–920rivaroxiban 921ST elevation myocardialinfarction management1095
thienopyridines 928–930thrombolytic agents931–932
warfarin 924–926
pleiotropy 19
PMNs (polymorphonuclearleukocytes) 576
POCD (post-operative cognitivedysfunction) 140, 212,221–222, 1157
POI (postoperative ileus) 535,543, 890, 901
POISE (perioperative ischemiaevaluation study) 1097–1099,1101
political decision-making, healthpolicy 166; see alsopharmacoeconomics
polydrug abuse 1106;see also drug/alcohol users
polyenes 977, 978, 979–980
polymorphism, pediatricpharmacology 1134, 1135;see also pharmacogenetics
polymorphonuclear leukocytes(PMNs) 576
polymyxins 964, 971–972
polypeptides, allergicreactions 1120
PONV see postoperative nauseaand vomiting
popliteal nerve block 1067
population-based drug responses14–15, 14
population efficacy 15
population pharmacokinetics68–69
porphyria 447
positive end-expiratory pressure(PEEP) 1035
positive inotropic drugs for heartfailure 706–707, 719–720;see also catecholamines
administration 718–719Digitalis glycosides 707–709,719
dosage 719mechanisms of drug action707, 708
myofilament calciumsensitizers 716–718, 719
phosphodiesterase inhibitors714–715, 716, 719
posterior scoliosis correction1036
postganglionic sympatheticnerves 649
postherpetic neuralgia (PHN)564, 565–566
postoperative analgesia 1061,1072–1073
ambulatory analgesia 1070caregiver controlled analgesia1062–1063
chronic pain 1069–1070clonidine 1064, 1068dexmedetomidine 1064, 1068drug choice 1028epidural 1064–1065, 1066,1068–1069
heart failure 1072immunosuppressants/anti-rejection drugs 838
inpatients/special populations1070–1072
intracathecal analgesia 1065ketamine 1063–1064, 1068liver failure 1072multimodal 1067–1068non-steroidal anti-inflammatory drugs 1063,1068
opioids 1061–1062,1061–1063, 1070–1071
patient-controlled analgesia1061–1063
pediatrics 1071–1072preemptive analgesia 1068–1069renal insufficiency 1072systemic 1061–1064
postoperative cognitivedysfunction (POCD) 140,212, 221–222, 1157
postoperative ileus (POI) 535,543, 890, 901
postoperative nausea andvomiting (PONV) 855,868–869; see also antiemetics
anesthesia 865–866anesthesia-related risk factors858–859
drug choice 1028incidence 855maintenance of/emergencefrom anesthesia 1029–1030
patient risk factors 856–858physiology 855–856, 857risk-adapted prophylaxis867–868
scoring system 866–867definition 855ketamine 451opioids 499, 500, 516, 534post-operative 452–453
postsynaptic dorsal columnpathway 230
postsynaptic membrane 193
postsynaptic potential 200–201
postsynaptic response, nicotinicacetylcholine receptors267–268
postsynaptic transmission,neuromuscular blockingdrugs 609
post-traumatic stress disorder484, 1041, 1042
potassium ion channels 32–34,49; see also two-porepotassium ion channels
local anesthetics 239neuroprotection/neurotoxicity1151
volatile anesthetics 371, 372
potassium ion channelactivators 537
clinical pharmacology 737dosage/administration 735–736vasodilators 732–733
potassium ion channel blockersadverse drug reactions 699antiarrhythmic agents 693
potassium-sparing diuretics 791
potency 15drug effects 6equipotency ratios 67neuromuscular blockingdrugs 615
potential energy 1081
POVOC scoring, postoperativenausea and vomiting 867
PPRs (pattern recognitionreceptors) 346, 347
prazozin 662
prebiotics 852
preconditioning effects, andgender 1154
prediction errors, open-loopTCI 109
pre-eclampsia 953–954
preemptive analgesia 1068–1069
pregabalin 594, 598
pregabalin 564clinical pharmacology 565–566dosage/administration 566mechanisms of drug action564, 565
preclinical pharmacology564–565
preemptive analgesia 1068pregnancy
pregnancy see obstetrics
prehospital resuscitation 806
premedicationanti-emetics 865immunosuppressants/anti-rejection drugs 838
pressure–volume analysis
energetics 1080–1081impedence matching tovasculature 1083
ventricular function 1080–1081
pressure–volume loops 318
presynaptic inhibition 201
presynaptic transmission262–265, 608
presystemic metabolism 73–74
preterm labor 954–955
primary afferent nocioceptors227–228, 231–232, 233
primary PCI 1093
primidone 594, 595, 596
priming 212–213, 620, 621
proarrhythmia 745–746
probiotics 852
procainamide 691–693, 694, 702
procedural memory 212–213, 216
progesterone antagonists 956
propafenone 692, 693, 696–697,702
propantheline 673, 849–850
propofol 426–427, 438, 447–448,460
administration 108, 432–433adverse drug reactions 449–450allergic reactions 459–460analogs 433, 454–456anesthetic action mechanisms374, 367, 378
for awake fiberopticintubation 1054
Bayesian optimization115, 116
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propofol (cont.)cerebral ischemia andanesthetic neuroprotection1153
closed-loop drugadministration 115–116
compartmental analysis427–429, 430
context-sensitive half-time429, 431
decrement time 431disposition parameters 445distribution/metabolism/excretion 427
drug dosage parameters 113drug interactions 154–158,159, 432, 448
formulations 432–433glucocorticoids secretion 819hemorrhagic shock 1016induction of anesthesia 1008infusion syndrome 140, 450laryngeal mask airwayinsertion 1018
maintenance of/emergencefrom anesthesia 1027–1029
model selection 111new formulations 453–454nonhypnotic effects 448–449obstetrics 957–958open-loop TCI 114pharmacogeriatrics1142–1144, 1144
physicochemical properties 427physiologically basedpharmacokinetic models 432
postoperative nausea andvomiting 859, 1028
sedation 448–449, 1043–1044,1048–1049, 1054
side effects 445speed of onset 1007–1010structure-activity relationships362
structure/stereochemistry 427,445
sympathetic nervous system651
transfer to effect site 429–432
proportional-integral-differential(PID) controller 115
propranolol 682, 692, 700, 702
prostacyclin 773–774, 928
prostaglandinsobstetrics 956
role in pain 548, 549
synthesis/action 548–550
prostanoids 281
protamine 919–920allergic reactions 1120clinical pharmacology 919–920
dosage/administration 920mechanism of drug action 919new/emerging concepts 920
suspensions 878
protein binding; see also receptorbinding
local anesthetics 578, 585neuromuscular blocking drugs615
obstetrics 949opioids 518pediatric pharmacology 1131thiopental 421
protein kinase C (PKC) 26, 279,286–287
proteins 893–900
as drug targets 360–361, 378nutritional pharmacology894–897
structure, drug receptors 1–2vesicle fusion 264–265, 266
proton pump inhibitorsadverse drug reactions 845drug interactions 845esomeprazole 846versus histamine receptorantagonists 847–848
lansoprazole 846omeprazole 845–846pantoprazole 846–847rabeprazole 847
pruritis 448–449, 500–501, 535
pseudoephedrine 661
pseudo-irreversible drugeffects 6
PSI (patient state index) 1032
psychedelics/party drugs1112–1113
psychiatric disorders 1106
psychotomimetic effects 1015
pulmonary artery smooth musclecells (PASMCs) 768–769
pulmonary function see lungfunction
pulmonary hypertension 409,767–768, 776
approaches 775classification 768evaluation 769hypoxic pulmonaryvasoconstriction 768–769
new/emerging therapies775–776
therapy 769–770
pulmonary vasodilators 770, 776;see also vasodilators
adverse drug reactions 770
calcium channel blockers770–771
cardiovascular patients,perioperative medication989, 999
combination therapies 774–775endothelin antagonists 774nitric oxide inhalation 771–773nitrovasodilators 771phosphodiesterase inhibitors774
prostacyclin 773–774
pumps, ionic 4, 253
pupil constriction, opioids 534
purinergic agonists 735–736
PV (plasma volume) 800–802
qualia 177
quality of life 169, 170
quality of postoperativerecovery 170
quality-adjusted life years(QALYs) 170–171, 171–172,171
quantal responses/quantaldose–response curves 14
quantal transmitter release 264
quetiapine 600, 601, 602, 605
quinidine 519, 691–693,694–695, 702
RA (rheumatoid arthritis) 998
rabeprazole 847
radioactive tracers 801
radiology, sedation for 1054–1055
RAGE (receptor for advancedglycation end products) 349
Ramsay Sedation Scale (RS)1044, 1045
ranitidine 844
rapamycin 834, 835
rapid acting insulin analogs878–879
rapid delayed rectifier current 305
rapid eye movement sleep (REM)178, 183–184
rapid sequence induction620–621, 626, 1016
RAS see renin angiotensin systemantagonists
RASS (Richmond Agitation-Sedation Scale) 1045, 1049,1050
rate of rise of alveolarconcentration 385
ray experimental design 150
Raynaud’s disease 282
real-time visualization160–161
rebound effects, statin therapywithdrawal 1099
rebound hypoglycemia 807
receptor/s 1–4, 15, 10
activation, neuromuscularfunction 268–269
for advanced glycation endproducts 349
binding 4–13, 15definition 1desensitization 2, 22–24, 23,269, 337
downregulation 22families 2, 15guanylyl cyclases 18internalization 22neuromuscular blocking drugs611
nomenclature/categorization2–4, 18
opioids 494–495physico-chemical forces 2
protein structure 1–2
protein tyrosine phosphatases 18,48–49, 286
selectivity 6
serine/threonine kinases 18signaling 496, 831–832,832–833
structure/ligand interactions495–496
superfamilies 2, 15, 18, 10TNF 52–53
tyrosine kinases 18, 47–48, 49,50–51, 242
recirculatory models 61, 424
recovery curves 65
recovery index, neuromuscularblocking drugs 615, 621–622
rectal routes of drugadministration 127
rectification 690
red man syndrome 971, 982
REE (resting energy expenditure)891–892, 891–892
reentrant arrhythmias 294–295
refractory periods 252
regional analgesiaambulatory 1070clinical outcomes 1065–1066complications 1066–1067
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postoperative 1064–1067,1071–1072
techniques 1064–1065
registration, drug 167–168
regression of left ventricularhypertrophy 742
rejection, transplants 830, 831;see also immunosuppressants
relative decrement times 65
REM (rapid eye movement sleep)178, 183–184
remifentanil 63for awake fiberoptic intubation1054
bolus dosing 510–513drug interactions 158, 159enzymes of drugmetabolism 79induction of anesthesia 1020,1021
maintenance of/emergencefrom anesthesia 1031
obstetrics 958open-loop TCI 112pharmacogeriatrics 1141–1142,1143
pharmacokinetics 69properties 538sedation 1043, 1046–1047speed of onset 1007–1010
renal function see kidneyfunction
renal threshold 807
renin angiotensin system (RAS)antagonists 732, 999
dosage/administration735–736
pharmacology 731–733, 737,988–989
reperfusion therapy 1093
rescue PCI 1093
resistance, cytotoxic 91–92, 93;see also efflux drugtransporters
respiratory agents, perioperativemedication 997, 1000
respiratory depression;see also breathing systems
alpha-adrenoceptor agonists486
analgesia, postoperative 1069benzodiazepines 473drug interactions 1012, 1013maintenance of/emergencefrom anesthesia 1035
opioid agonist-antagonists 540opioids 498–499, 509, 512,518, 533–534
pharmacogeriatrics 1140
and rate of opioidadministration 518
threshold 407
response surface methodology(RSM) 149–150, 151
agonists 151navigating the responsesurface 159
new/emerging concepts158–160
opioids 153, 155propofol 155, 156, 157real-time visualization 160–161remifentanyl 156, 157volatile anesthetics 153
resting energy expenditure (REE)891–892, 891–892
resting potential 249–250, 251
retching, definition 855;see also anti-emetics;postoperative nausea andvomiting
reteplase 932;see also thrombolytic agents
reticular activating system 377
retrograde messengers 205
revatropate 673
reverse genetics 362–363
reverse use-dependent block 690
reversible drug effects 6, 1155
rheumatoid arthritis (RA) 998
Rho-activated protein kinases279, 286–287
ribosomal protein synthesisinhibitors 964, 972–976
Richmond Agitation-SedationScale (RASS) 1045, 1049, 1050
RIFLE criteria, acute kidneyinjury (AKI) 784
rigidity 534, 1014–1015
Riker Sedation-Agitation Scale(SAS) 1044, 1045
Ringer’s (LR) solution 793,803–804; see also crystalloidfluids
risk factors, postoperative nauseaand vomiting 856–858,858–859
risperidone 599, 600, 601, 602
ritodrine 658
rivaroxiban 915, 921
RKTs (receptor tyrosinekinases) 18, 47–48, 49,50–51, 242
rofecoxib see cyclooxygenaseinhibitors
ropivacaine 566clinical pharmacology 566–567dosage/administration 567mechanisms of drug action 566preclinical pharmacology 566
routes of drug administrationsee drug administration routes
R-PTP (receptor protein tyrosinephosphatases) 48–49, 286
RS (Ramsay Sedation Scale)1044, 1045
RSM see response surfacemethodology
ryanodine receptor (RYR1)137–139
SAAM II software system 510
safety considerationsalternate routes of drugadministration 129
calcium channel blockers741–742
droperidol 861–862, 1030neuromuscular transmission609, 610
opioids 526sugammadex 643
saline, normal (NS) 793, 803,804, 805; see also crystalloidfluids
salivation 1028
salt/water homeostasis 786
SAS (Riker Sedation-AgitationScale) 1044, 1045
saturated disc model 270–271
scales, sedation 1044–1045
SCCM (Society of Critical CareMedicine) guidelines 1041,1052, 1053
Schild analysis 8
Schnider population PK model428, 429–432
Schüttler model 428
sciatic nerve block 1067
scopolamine 487–488, 672;see also parasympatholyticdrugs
adverse drug reactions ofoverdose 672
anti-emetics 860mechanisms of drug action 669psychedelics/party drugs1112–1113
second gas effects 387, 388
second messengers 19, 24–26,651; see also cAMP
autonomic nervous system 338calcium ions/inositoltriphosphate 24–26
and long-term potentiation 204slow synaptic transmission 201
secretions, gut 842–843;see also gut motility/secretioninhibitors
sedation 361, 1041, 1056;see also delirium; hypnotics;and see specific agents by name
amnistics 478, 487–488;see also alpha-adrenoceptoragonists
anesthetic action mechanisms378
for awake fiberoptic intubation1052–1054
benzodiazepines 467, 1043,1047, 1053
cardiology 1055central nervous systemmonitoring 1045–1046
complications 1041–1042definition 478dexmedetomidine 1044,1048–1049, 1051, 1054
drug choice 1046–1049endoscopy 1055goal-directed/protocolized1046
modifying delivery pattern1046–1048
monitoring 1044–1046opioid agonist-antagonists539–540
opioids 533, 1042–1043,1046–1047, 1054
outside operating room1054–1055
paradigms to improveoutcomes 1046–1049
pharmacogeriatrics1142–1145, 1146
pharmacology of availabledrugs 1042–1044
propofol 448–449, 1043–1044,1048–1049, 1054
radiology procedures1054–1055
scales 1044–1045
SEDline 180
seizures 449, 533, 583;see also antiepileptic drugs
selective serotonin reuptakeinhibitors (SSRIs) 519, 993,1000
selectivity 6, 15
selenium 901–902
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self-medication 1106;see also drug/alcohol users
semantic memory 212, 215,216
senescencesee pharmacogeriatrics
serial parallel independent (SPI)taxonomy of memory 215,216
serine 49–50
serotonin/5-HT receptors 36, 52
agonists 850, 1112–1113
antagonists 860, 862–864and postoperative nausea andvomiting 856
set-point, closed-loop drugadministration 115
seven-transmembrane receptorssee G-protein-coupledreceptors
severe illness, insulin therapy 886
sevoflurane 397glucocorticoids secretion 820induction of anesthesia1010–1011
inhaled anestheticspharmacology 397, 398–399
metabolism 392neurogenesis 1155physicochemical properties398
sex differences see genderdifferences
SF-36 (36-Item Short Form) 170
shivering 485
short bowel syndrome 848
short-term memory 226
Sicilian Gambit 691, 692
signaling
amplification 12–13, 17
cell signaling 17, 18, 18
damping 13G protein-coupled receptors19, 18
interleukin-2 receptor 832–833properties 17–19transduction 17, 18, 18
T cell receptor 831–832, 832–833
silent synapses 205
single nucleotide polymorphisms(SNPs) 340–341;see also pharmacogenetics
SIRS (systemic inflammatoryresponse syndrome) 814
skeletal muscle rigidity 534,1014–1015
skin, barriers to diseasepathogens 345
SLC (solute carrier) proteins 90
SLC (solute carrier) transporters95–96
sleep/consciousness 177, 177, 188alpha-adrenoceptor agonists482–483, 484, 488
anesthetic action mechanisms376–377
awareness in clinical context179–180
awareness in cognitive context177–179
brain/cell physiology 177class 1 agents 185, 186, 187class 2 agents 185class 3 agents 185and general anesthesia 177, 188memory/learning 218molecular targets 185new/emerging anesthetics185–188
non-rapid eye movement sleep182–183
rapid eye movement sleep183–184
switching between sleep/wakestates 184–185, 376–377
wakefulness 180–182
slow delayed rectifier current305–306
slow synaptic transmission 201
small hydrophyllic drugs 6
small molecule partition 90–91
smoking 330coughing reflex 1027postoperative nausea andvomiting 857
tobacco cessation agents 998,1001
smooth muscle effects;see also vascular smoothmuscle; vasodilators
opioid agonist-antagonists 540neuromuscular blocking drugs614
spasm 535
SMX (sulfamethoxazole) 975,976, 977–978
SNAP II 180
SNARE complex 196–197, 265
SNPs (single nucleotidepolymorphisms) 340–341;see also pharmacogenetics
Society of Critical Care Medicine(SCCM) guidelines 1041,1052, 1053
sodium bicarbonate 1123
sodium ions 803
sodium ion channels 31, 237,243, 309
cardiac rhythm 301–303dysfunction/disease states302–303
factors affecting conductionvelocity 258
local anesthetics 239, 575–576,585
regulation 302structure and function 301–302sodium ion channel blockers;see also bupivacaine;levobupivacaine; ropivacaine
with intermediate bindingkinetics 691–693, 694, 695
with rapid binding kinetics 693,695, 696
with slow binding kinetics 693,696, 697
sodium cromoglycate 757–758
solifenacin 673
solubility coeffcient, blood-gas386, 387, 388
solute carrier proteins 90
solute carrier transporters 95–96
somatic nociception 231
somatostatin 848–849
sotalol 682, 692, 693, 698, 702
spare receptors 12, 15, 13
specificity 6, 15, 17, 202
speed of injection,neuromuscular blockingdrugs 615
SPI (serial parallel independent)taxonomy ofmemory 215, 216
spinal anesthesia 957;see also epidural
anesthetic action mechanisms374, 375–376
pain transmission/transduction 228–229
spinal dorsal horn 234neuron diversity 234–235plasticity 235–236synapse 234
spinobulbar projections 230
spinohypothalamic tract 230
spinothalamic tract 229, 230
SSIs (surgical site infections) 982;see also antibacterials;antifungals; antimicrobials;infection
SSRIs (selective serotoninreuptake inhibitors) 519,993, 1000
ST elevation myocardial infarction(STEMI) 1091, 1101–1102;see alsomyocardial ischemia
definition/diagnosis 1091–1092management strategies1092–1095
pharmacologic/interventionalmanagement 1092, 1093,1094
St John’s Wort 999
Stanpump 104
starch 808–809
Starling equation 800
statinsperioperative medication 990,999, 1098, 1099
vasodilators 736
steal, coronary 410
Stellenbosch 104
Stelpump 104
stem cell therapy 736, 795
stereoselectivity 6
steroid anesthetics 362, 456–457;see also glucocorticoids
steroid receptor superfamily 18
Stevens-Johnson syndrome595, 596
stimulantsamphetamine 1112cocaine 1111inhalants 1113psychedelics/party drugs1112–1113
stoichiometry 5–6
streptogramins 964, 974, 975
streptokinase 932;see also thrombolytic agents
stressautonomic nervous system 330corticotropin-releasinghormone 819
glucocorticoids 816induction of anesthesia1015–1016
metabolic responses to 876–877opioids 499
surgical stress response 339–340,825, 826, 990, 1041
Index
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ulcers, proton pump inhibitorsversus histamine receptorantagonists 848
stroke see cerebral ischemia
structure-activity relationshipsanesthetic action mechanisms362
neuromuscular blocking drugs612, 613
subcutaneous administration124, 521–522
subjective experience, andobjective evaluation 177
subliminal memory 212–213, 226
sublingual administration 125
subthreshold responses255–256, 257
succinylcholine 608adverse drug reactions 618chemical structure 612clinical pharmacology618–620
contraindications 619elimination/metabolism 616non-competitive block 609–611pharmacogeriatrics 1146phase II block 611rapid sequence induction 626
sufentanil 538
sugammadex 643–644chemistry 640paralysis reversal 1036pharmacodynamics 641–643pharmacokinetics/metabolism640–641
postoperative nausea andvomiting 859
safety considerations 643variation between patients 643
suicide 601
sulfamethoxazole (SMX) 975,976, 977–978
sulfiting agents, allergicreactions 1119
superactivation 502superfamilies 2, 15, 18, 10
supraclavicular blocks 1067
supra molecular activationclusters 830
surgeryaspirin 927glycoprotein receptorinhibitors 930–931
metabolic/stress responses to339–340, 825, 826, 876–877,990, 1041
nutritional pharmacology 901
type, and postoperative nauseaand vomiting 858
thienopyridines 929
surgical site infections (SSIs) 982;see also antibacterials;antifungals; antimicrobials;infection
surmountability 8, 15
sympathetic hyperactivity 339–340
sympathetic microneurography651
sympathetic nervous system283–284, 330, 648, 662;see also autonomic nervoussystem
amplification response 330anesthetics 651baroreflex 649–651, 650basal autonomic tone 648medullary vasomotor center648–649
postganglionic sympatheticnerves 649
systems physiology 330–331,332
sympatholytic drugs 661, 663clinical pharmacology 661–662mechanisms of drug action 661
sympathomimetic drugs 651,662–663
alpha-adrenoceptor agonists654–657
background/history 651beta-adrenoceptor agonists657–658
clinical pharmacology 654indirect-acting 659–661mechanisms of drug action651–652, 653, 654
mixed receptor agonists658–659
synapse specificity 202
synaptic boutons 192
synaptic cleft 192, 265–267
synaptic plasticity see plasticity;synaptic
synaptic transmission 39–40,192, 206–207;see also neurotransmitters;vesicles; synaptic
chemical identity ofneurotransmitters 193–194,194–195
chemical synapses structurefunction 192–193
control of vesicle secretion196–197
cytoskeleton role 199drug action targets 206
dual transmission 194–195electrical synapses structure/function 192
endocytosis pathways 198fast transmission in CNS 200GABAA receptors 200–201glutamate receptors 200kiss-and-run 198–199long-term depression 205–206long-term potentiation 204–205mechanism of transmitterrelease 196
neurotransmitter duration ofaction 199
NMDA receptor dependentlong-term potentiation202–204
non-NMDA-dependentlong-term potentiation 205
presynaptic inhibition 201retrograde messengers 205second messengers 201, 204silent synapses 205slow synaptic transmission 201stages of chemical transition193, 194
storage of neurotransmitters 196
synergistic drug interactions147–148, 153–154,1011–1012
synthetic choline esters 667–668
systemic absorption 580–581
systemic inflammatory responsesyndrome (SIRS) 814
T cells 349, 350–352, 830;see also immunosuppressants
antigen presentation/cellsurface events 830–831
calcium/calmodulin/calcineurin-induced nuclearfactor 832
clonal proliferation 834immunosuppressants/anti-rejection drugs 833
interleukin-2 receptor signaling/cell cycle regulation832–833, 834
receptor signalling 831–832,832–833
tachyplasis 13, 15
tacrolimus 835
tardive dyskinesia 600, 603
TARGET (therapeutic arthritisresearch and gastrointestinalevent trial) 557
target controlled infusion (TCI)103–104, 116–118;see also closed-loop drugadministration; open-loop TCI
dose–response relationship 103induction of anesthesia1019–1020
targets see drug targets
T-cell antigen receptor complex(TCR) 830, 833
TCI see open-loop TCI; targetcontrolled infusion
TCR (T-cell antigen receptorcomplex) 830, 833
TD4756 458
TD50 15
TEA (thoracic epiduralanesthesia) 1100
telenzepine 673
temiverine 673
temperature, bodysee thermoregulation
tenecteplase 932;see also thrombolytic agents
terbutaline 658
terminal plexus 649
terminology; see also definitions
drug receptors 2–4, 18inhaled anestheticspharmokinetics 385–386,387, 388
myocardial ischemia 1091opioids 531
test doses, allergic reactions 1121
tetracyclines 964, 972, 973–974,973–974
tetrodotoxin (TTX) 566–567
TFPI (tissue factor pathwayinhibitor) 282
TGAs (thermally generatedaerosols) 523
thalamus, anesthetic actionmechanisms 377
theophylline 753–754, 997, 1000
therapeutic arthritis research andgastrointestinal event trial(TARGET) 557
therapeutic end points 15
therapeutic index 15
thermally generated aerosols(TGAs) 523
thermoregulationmaintenance of/emergencefrom anesthesia 1031
temperature monitors 1032neuromuscular blocking drugs616–617
Index
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thermoTRP ion channels 236
thiamylal 445, 446, 459
thiazide diuretics 791, 792
thiazolinediones (TZD) 879, 880,993
thienopyridinesadverse drug reactions 929clinical pharmacology 929dosage/administration 929mechanism of drug action 929new/emerging concepts929–930
platelet function 928–930surgery/anesthesia 929
thiopental 68, 420, 438, 444–446,460
allergic reactions 459compartment models 422decrement time 431disposition parameters 445distribution 421–422dosage/administration 425, 426drug interactions 424–425early mixing 422elimination 422history 1007induction of anesthesia1008
pharmacogeriatrics 1144physicochemical properties420–421
physiologically basedpharmacokinetic models61–62, 391, 422–424, 432
protein binding 421side effects 445speed of onset 1007–1010structure/stereochemistry 420,421, 445
sympathetic nervous system651
transfer to effect site 424, 424
36-Item Short Form (SF-36) 170
thoracic epidural anesthesia(TEA) 1100
thoracic paravertebral blocks1067
thoracic sympathectomy 1100
threonine kinases 49–50, 51–52
thresholds, action potentials256–257
thrombolysis in myocardialinfarction (TIMI) 1094
thrombolytic agents 931–932adverse drug reactions 932clinical pharmacology931–932
dosage/administration 932evaluation 931
genetic engineering 931mechanism of drug action 931
thrombomodulin (TM) 282
thrombophlebitis 452
thrombosis, role of vascularendothelium 282–283
thrombus formation 912–915;see also platelet function
THRX-918661 458
thyroid hormone 717–718,996–997, 1000
TIAC (titration of intravenousagents by computer) 104
tiagabine 591–592, 593, 594, 595,597
tidal volumes 1035
tight glucose control 906
time to peak effect 432
time-dependent activity 963
TIMI (thrombolysis inmyocardial infarction) 1094
tiotropium 673
tissue binding, pediatricpharmacology 1131
tissue factor pathway inhibitor(TFPI) 282
tissue plasminogen activator(tPA) 931–932
titration of intravenous agents bycomputer (TIAC) 104
TIVATrainer 104
TLRs (toll-like receptor ligands)347, 348
TM (thrombomodulin) 282
TMN (tuberomammillarynucleus) 376–377
TMP (trimethoprim) 975, 976,977–978
TNF see tumor necrosis factor
TNS (transient neurologicalsyndrome) 583
tobacco cessation agents 998,1001; see also smoking
tocainide 692, 693, 696, 702
tocolytics 954–955
tolazoline 662
tolerance 13, 15addicts, to opioids 1109–1110alpha-adrenoceptor agonists480
ketamine reversal of opioid 563
opioids 23–24, 501–503,535–536, 563–564, 1070–1071
toll-like receptor ligands (TLRs)347, 348
tolterodine 673
top-down costing 168–169
top-down pathways, sleep/consciousness 177, 188
topiramate 591–592, 593, 594,595, 597
total body water 800
total duration of action,neuromuscular blockingdrugs 615
toxicity 15; see also adverse drugreactions; allergic reactions;neurotoxicity
tPA (tissue plasminogenactivator) 931–932
trace elements 894–897, 901–902,904
tramadol 538, 555, 1063
tranexamic acid see epsilon-aminocaproic acid/tranexamic acid
transactivation 53
transdermal administration124–125, 522–523
transdermal therapeutic systemof fentanyl (TTS-fentanyl)522
transduction, pain see paintransmission/transduction
transfer to effect siteketamine 435propofol 429–432thiopental 424, 424
transfusion-associated acute lunginjury (TRALI) 1119
transgenic animals 362–363
transient neurological syndrome(TNS) 583
transient outward current 304
transient receptor potential(TRP) ion channels 4, 40–41,570
thermoTRP 236TRPA1 571TRPV1 570, 571TRPV4 570–571
transitional compounds 359
transmembrane currents 249
transmembrane proteins 2, 253
transmembrane pumps 4
transmembrane receptors51–52, 52–53
transmission, pain see paintransmission/transduction
transmitter-gated ion channels 4
transmucosal routes of drugadministration 125–127,126–127
transplantation 356, 830, 831;see also immuno-suppressants
transrepression 53
TREK-1 see two-pore potassiumion channels
TRP ion channels see transientreceptor potential ionchannels
trauma see stress
treprostinil 773–774
tricyclic antidepressants 335, 340,993, 1000
triggered automaticity 296–297,298, 299
triggering receptor expressed onmyeoloid cells (TREM-1) 348
trimethoprim (TMP) 975, 976,977–978
tropisetron 860, 864
tropomyosin 1092
troponin 1092
TRPA1 571
TRPV1 channels 241
TRPV1 receptor agonists/antagonists 570, 571
TRPV4 channels 570–571
truncal rigidity 534
TTS-fentanyl 522
tuberculosis 501
tuberomammillary nucleus(TMN) 376–377
tumor necrosis factor (TNF) 890
inhibitors 998, 1000
receptors 52–53
two-pore potassium ion channels(TREK-1)
anesthetic action mechanisms372
nitrous oxide 375volatile anesthetics 371xenon 375
tyrosine 335, 651
Index
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tyrosine hydroxylase 335
tyrosine kinase-associatedreceptors 18, 47–48, 49,50–51, 242
TZD (thiazolinediones) 879, 880,993
UA see unstable angina
UGT (glucuronosyltransferase)79–80
ulcers, gastric 486non-steroidal anti-inflammatorydrugs 556–521, 847–848
proton pump inhibitors versushistamine receptorantagonists 848
ultra-rapid delayed rectifier306–307
unconscious memory 212–213,215–216; see also sleep/consciousness
unfractioned heparin (UFH) 1095
unitary theory of anesthesia 359,360, 361, 378
United States Renal Data System(USRDS) 784
unstable angina (UA) 1091,1092, 1101–1102;see also myocardial ischemia
definition/diagnosis1091–1092
management strategies 1094,1095
pharmacologic/interventionalmanagement 1092, 1093,1094
upper motor neuron lesions623–624
uptake measurement, inhaledanesthetics 390
uptake rate, terminology 385
urethane 177
urine formation 786–790
urine output calculation 801
urine retention 535
use-dependent block 690
uterine contraction 955
valdecoxib 553–550;see also cyclooxygenase-2-specific inhibitors
validity, analytical 133–134
valproate 593, 594, 595, 596
vamicamide 673
Van der Waals interactions 2
vancomycin 970–971, 982
vanillylmandeic acid (VMA) 336
vaporizers 400
variable conductances , 251–253
variation between patients;see also gender differences
biotransformation, drug 85clearance 82, 83disease states 84–85drug biotransformation 82–85drug interactions 82–83, 84
drug response analysis inindividuals 13–14, 14
drug response analysis inpopulations 14–15, 14
neuromuscular blocking drugs626
obstetrics 949open-loop TCI 112, 113, 114opioid effects 532–533pain perception 140pharmacogenetics 83–84pharmacokinetics 68–69
vascular reactivity 277, 288angiogenesis 280, 283angiotensin II 284–285arginine vasopressin 285coagulation/inflammation282–283
control of 285–286drug action targets 286–287endothelin 282endothelium-dependentrelaxation 280–281
endothelium-derivedhyperpolarizing factor281–282
endothelium-derived relaxingfactor 280, 281
extracellular matrix 277–278nitric oxide 281nonadrenergic noncholinergicmechanisms 284
parasympathetic nervoussystem 284
prostanoids 281sympathetic nervous system283–284
vascular endothelium 280,727–728, 729
vascular smooth muscle (VSM)278, 288, 726;see also vasodilators
calcium voltage-gated ionchannels 278, 278, 279
contractile proteins 278contraction mechanisms 278,278
control of contractile site 726endothelium role 727–728, 729
molecular mediators/pharmomechanical coupling725, 726–727, 728
myogenic contraction 279–280neuronal regulation of vasculartone and electromechanicalcoupling 726, 727
physiology of musclecontraction 724–726
vascular surgery, infusionfluids 806
vascular system 317, 1079–1080;see also cardiovasculareffects; heart function
vascular tone 1077–1078,1088;see also hemodynamics;hypertension; hypotension
autonomic nervous system1077–1078, 1079, 1080
coronary perfusion 1084energetics 1080–1081,1081–1082
heart rate 1084hemodynamic problems andimpedence 1083–1084
hemodynamics 1078–1079,1080
impedence/optimalhemodynamics 1082–1083
inotropes 1086inotropes-risks 1086–1087nitric oxide 1087oxygen consumption1081–1082
pharmacology of availabledrugs 1083, 1084–1085
pressure-volume analysis 1083
vasoactive agents 991;see also vasodilators
ventricular function1080–1081, 1081–1082
vasodilators 348, 724, 736–737,1085–1086;see also pulmonaryvasodilators
alpha-adrenergic agonists/antagonists 730–731,735–736
angiotensin convertingenzyme inhibitors 731,735–736
angiotensin receptor blockers732, 735–736
beta-adrenergic agonists 731,735–736, 737
blood pressure control/vascular tone 1085–1086
calcium channel blockers733–734, 735–736, 737
calcium sensitizer 734,735–736
catecholamine receptorpharmacology 729–730, 737
clinical pharmacology 737control of contractile site 726dopamine agonists 731,735–736
dosage/administration735–736
eicosanoids 734, 735–736, 737endothelin receptor agonists732, 735–736, 737
endothelium role 727–728, 729ganglionic blockers 733,735–736, 737
hemodynamics 1078magnesium 733, 737mechanism of drug action724, 725
molecular mediators/pharmomechanical coupling725, 726–727, 728
myogenic tone 726neuronal regulation of vasculartone/electromechanicalcoupling 726, 727
new/emerging concepts734–736
nitrovasodilators 728–729, 737phosphodiesterase inhibitors732, 735–736
physiology of musclecontraction 724–726
potassium channel activators732–733, 735–736, 737
renin inhibitors 732, 735–736renin-angiotensin pathwaypharmacology 731–733, 737
vasopressin see argininevasopressin
Vaughan Williams drugclassification 691
vecuronium 612
ventilation mode 410–411
ventilatory depressionsee respiratory depression
ventricular functionsee cardiovascular effects;coronary circulation; heartfunction
ventrolateral preoptic nucleus(VLPO) 376–377
verapamil 692, 693–694, 700, 702
vesicles, synaptic 192;see also synaptic transmission
control of vesicle secretion196–197
cycling 197–198, 206, 264, 265drug action targets 206fusion 263–264, 264–265, 266heterogeneity 199
Index
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Cambridge University Press978-0-521-89666-5 - Anesthetic Pharmacology, Second EditionEdited by Alex S. Evers, Mervyn Maze and Evan D. KharaschIndexMore information
vesicles, synaptic (cont.)neuromuscular function263–264, 265
storage of neurotransmitters 196
vessel-poor group 388
vessel-rich group 388
vigabatrin 591–592
VIGOR (vaux gastrointestinaloutcomes research) 557
viral infection, and cancer 354;see also antivirals
visceral nociception 231, 232
vitamins 904alcohol users 1108nutritional pharmacology894–897, 901–902
VLPO (ventrolateral preopticnucleus) 376–377
VMA (vanillylmandeic acid) 336
volatile anesthetics see inhaledanesthetics
voltage-gated ion channels 4, 41,301; see also calcium ionchannels; potassium ionchannels; sodium ionchannels
effect on neuronal activity/signalling 29
local anesthetics 239–241pain transmission/transduction 237
structure and function 29–31types of 29
voltage-sensitive gating299, 301
volume kinetics 802–803, 802
volume of distribution 57, 615
volume status, kidney function791–793
vomiting; see also anti-emetics;postoperative nausea andvomiting
definition 855physiology 855–856, 857
voriconazole 978, 979
VSM see vascular smooth muscle
wakefulness 177, 179, 180–182;see also sleep/consciousness
wakening see emergence fromanesthesia
wake-up test 1036
warfarin 915, 924–926adverse drug reactions925–926
clinical pharmacology 925dosage/administration 926mechanism of drug action924–925
new/emerging concepts 926pediatric pharmacology 1134
waterbody composition in elderlypatients 1139–1140
nutritional pharmacology894–897
total body water 800
water tank analogy 388, 389
websitesdelirium 1049nutritional pharmacology 907
willingness to pay 172
withdrawal from drugs/alcohol1106, 1108–1109
wobble, open-loop TCI 111
Wolff–Parkinson–White (WPW)syndrome 703, 746
working memory 212, 226
xenobiotic transporters 92
xenobiotics 90, 97, 833
xenon 1156anesthetic action mechanisms374, 375
cerebral ischemia and anestheticneuroprotection 1154
diffusion into gas spaces 393inhaled anestheticspharmacology 399
metabolism 392
zero-phase coherence 219
ziconotide 568clinical pharmacology568–569
dosage/administration 569drug interactions 746–747mechanisms of drug action568–569
preclinical pharmacology 568
zinc fingers 53
zinc suspensions 878
ziprasidone 599, 600, 602
Zollinger–Ellison syndrome 847
zonisamide 591–592, 593, 594,595, 597
Index
1194
www.cambridge.org© in this web service Cambridge University Press
Cambridge University Press978-0-521-89666-5 - Anesthetic Pharmacology, Second EditionEdited by Alex S. Evers, Mervyn Maze and Evan D. KharaschIndexMore information
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