Pharmacology

Local Anesthetics

Local Anesthetics• Amides vs. Esters• Pharmacodynamics and Pharmacokinetics• Calculating LAs• Injections

Amides

• Metabolized in the liver

Esters

• Metabolized by pseudocholinesterase in plasma

Amides

• Lidocaine• Bupivicaine• Mepivicaine• Articaine• Prilocaine

Esters

• Procaine• Cocaine• Tetracaine• Benzocaine• More toxic, more

allergic (methylparaben)

Amides• Lidocaine (Xylocaine) safest in children• Bupivicaine (Marcaine) not safe in children• Mepivicaine (Carbocaine, Polocaine) causes least vasodilation• Articaine (Septocaine) has one ester chain• Prilocaine (Citanest) methemglobinemia

Esters• Procaine• Cocaine vasoconstrictor• Tetracaine• Benzocaine

Pharmacodynamics

• Sodium channel blocker• Only non-ionized (free base) form can

penetrate neuron membrane• Critical length

Pharmacokinetics• ↑ blood flow shorter duration of action• ↑ lipid solubility/hydrophobicity more potent

longer duration of action• ↑ protein binding longer duration of action• ↓ pKa faster onset of action

– Mepivicaine: 7.6– Lidocaine, prilocaine, articaine: 7.8– Bupivicaine: 8.1

Calculating Local Anesthetic

• 1mL of liquid at sea level weighs 1g• Carpule/cartridge of anesthetic contains

1.8mL• So entirety of liquid in carpule weighs how

much?• 1.8g or 1800mg• But this isn’t very relevant clinically…

Calculating Local Anesthetic

• For 100% solution, 1.8g or 1800mg• For 1% LA,

• For 2% lidocaine, 36mg per carpule• For 4% articaine, 72mg per carpule

18mg

Practice Question

• A carpule of 2% lidocaine solution with 1:100,000 epinephrine would contain how much epinephrine in mg?

• For .001% epinephrine, 0.018mg

Vasoconstrictor

1. Prolong numbness2. Reduce toxicity3. Promote hemostasis

Toxicity

• Max epinephrine for ASA I patient= 0.2mg• Max epinephrine for cardiac patient= 0.04mg• Max lidocaine without vasoconstrictor= 4.4mg/kg• Max lidocaine with vasoconstrictor= 7mg/kg

Local Anesthetics

Delivering Local Anesthetic

• “Slow” injection is 1 carpule per minute

Needle Dimensions

• Length– Short= 20mm– Long= 32mm

• Diameter– 30-gauge= 0.3mm– 27-gauge= 0.4mm– 25-gauge= 0.5mm

Inferior Alveolar Nerve Block

• Highest failure rate• Halstead= classic• Gow-Gates= open mouth• Akinosi= closed mouth

3/4 carpule

Buccal Nerve Block

• Done in tandem with IAN block

1/4 carpule

Mental Nerve Block

• Locate rubbery bundle with finger

• Mental foramen by apices of premolars

1/3 carpule

Incisive Nerve Block

• Same as mental nerve block except hold pressure for 2 minutes after injection to force anesthetic into mental foramen

1/3 carpule

Posterior Superior Alveolar Block

• Maxillary molars• 16mm depth (half the

length of long needle)• High hematoma risk

1/2 carpule

Infraorbital Block

• Maxillary anteriors + premolars

• Also called true ASA block• Infraorbital foramen

1/2 carpule

Greater Palatine Nerve Block

• Posterior hard palate• Greater palatine foramen

1/4 carpule

Nasopalatine Block

• Hard palate from canine to canine

• Most painful

1/4 carpule

Local Infiltration

• Enter in vestibule• Aim for root apex• Works well in anterior

because facial cortical plate is thin

1/2 carpule

Antibiotics

Sulfonamides

• Bacteriostatic• Folate synthesis inhibitor (competes with

PABA)• Sulfadiazine, Sulfamethoxazole

Fluoroquinolones

• Bactericidal• DNA synthesis inhibitor• Ciprofloxacin, Levofloxacin

Penicillins• Bactericidal• Cell wall synthesis inhibitor, β-lactam• Cross-allergenic with cephalosporins because they are chemically related

• Penicillin G IV, more sensitive to acid degradation• Penicillin V oral• Amoxicillin broad spectrum• Augmentin amoxicillin + clavulanic acid (β-lactamase-resistant)• Methicillin β-lactamase-resistant• Dicloxacillin “• Ampicillin best/broadest gram-negative spectrum• Carbenicillin used specifically against pseudomonas

Cephalosporins

• Bactericidal• Cell wall synthesis inhibitor, β-lactam• 1st Gen= Cephalexin (Keflex)• 2nd Gen= Cefuroxime• 3rd Gen= Ceftriaxone• 4th Gen= Cefepime• 5th Gen= Ceftaroline

Monobactams

• Bactericidal• Cell wall synthesis inhibitor, β-lactam• Aztreonam

Carbapenems

• Bactericidal• Cell wall synthesis inhibitor, β-lactam• Imipenem

Tetracyclines

• Bacteriostatic• Protein synthesis inhibitor (30S ribosomal

subunit)• Tetracycline, Doxycycline, Minocycline• Broadest antimicrobial spectrum

Macrolides

• Bacteriostatic• Protein synthesis inhibitor (50S ribosomal

subunit)• Erythromycin, Clarithromycin, Azithromycin

Mac likes to throw mice

Lincosamides

• Bacteriostatic• Protein synthesis inhibitor (50S ribosomal

subunit)• Clindamycin, Lincomycin

Link also hides mice

When is Antibiotic Prophylaxis Required?

• Cardiovascular conditions– Prosthetic heart valve– History of endocarditis– Heart transplant with valvulopathy/valve dysfunction– Congenital heart problems

• Compromised immunity– Organ transplant– Neutropenia– Cancer therapy

Rx for Infective Endocarditis Prophylaxis

• First choice Amoxicillin 2g 1 hr before tx• Children, first choice Amoxicillin 50mg/kg 1 hr before tx• PCN allergy Clindamycin 600mg 1 hr before tx• Children, PCN allergy Clindamycin 20mg/kg 1 hr before tx• Non-oral (IV or IM) Ampicillin 2g 30 min before tx• Children, non-oral Ampicillin 50mg/kg 30 min before tx

Rx for Prosthetic Joint Prophylaxis

• First choice Keflex 2g 1 hr before tx

When is Antibiotic Prophylaxis NOT Required?

• Cardiovascular conditions– Cardiac pacemaker– Rheumatic fever without valvular dysfunction– Mitral valve prolapse without valvular

regurgitation

Side Effects• What causes GI upset and pseudomonas colitis? Clindamycin

• What is most likely to cause superinfection? Broad spectrum antibiotics

• What is associated with aplastic anemia? Chloramphenicol

• What is associated with liver damage? Tetracycline

• What is associated with allergic cholestatic hepatitis? Erythromycin estolate

Drug Interactions

• Cidal and static drugs cancel each other out• Penicillin & probenecid• Tetracycline & antacids/dairy• Broad spectrum antibiotics & anticoagulants• Antibiotics & oral contraceptives• Macrolides & seldane/digoxin

Drug Concentration

• Clindamycin à bone• Tetracycline à gingival crevicular fluid

Antivirals & Antifungals

• Acyclovir, Valcyclovir à herpes• Fluconazole, Ketoconazole à candidiasis– Clotrimazole (Mycelex) is in troche form

Analgesics

NSAIDs• Aspirin (ASA) COX 1 and 2 blocker (irreversible) GI• Ibuprofen (Motrin, Advil) COX 1 and 2 blocker (reversible) kidney• Naproxen (Aleve) COX 1 and 2 blocker (reversible)• Ketorolac (Acular) COX 1 and 2 blocker (reversible) IV, IM, or oral• Indomethacin COX 1 and 2 blocker (reversible) blood dyscrasias• Phenylbutazone (“Bute”) COX 1 and 2 blocker (reversible) for animals• Diflunisal (Dolobid) COX 1 and 2 blocker (reversible) longer half-life• Celecoxib (Celebrex) COX 2 blocker• Meloxicam (Mobic) COX 2 blocker arthritis

Acetaminophen• Acetaminophen inhibits pain in CNS liver• Drug of choice in feverish child, whereas aspirin can cause Reye’s Syndrome

Maximum Dose

• Ibuprofen 3.2g/day• Acetaminophen 4g/day

Therapeutic Effects of Aspirin

• Analgesic à inhibit COX 1 and 2 (PG synthesis)• Anti-inflammatory à same• Antipyretic à inhibit PG synthesis in

temperature regulation center of hypothalamus

• Bleeding time à inhibit TXA2 synthesisthereby inhibiting platelet aggregation

Toxic Effects of Aspirin

• Occult bleeding from GI tract• Tinnitus• Nausea and vomiting• Metabolic acidosis• Decreased tubular resorption of uric acid• Salicylism• Delirium• Hyperventilation

Corticosteroids

• Prednisone• Hydrocortisone• Triamcinolone• Dexamethasone

Therapeutic Effects of Steroids

• Analgesic à inhibit phospholipase A2 (AA synthesis)

• Anti-inflammatory à same

Side Effects of Steroids

• Gastric ulcers• Immunosuppression• Acute adrenal insufficiency• Osteoporosis• Hyperglycemia• Redistribution of body fat

Narcotics/Opioids• mu-opioid receptor agonists (in CNS)• Morphine• Hydrocodone• Oxycodone• Oxycontin controlled release• Codeine suppresses cough reflex, cough syrup• Tramadol (Ultram) similar to codeine• Heroin• Fentanyl• Sufentanil• Carfentanil• Meperidine (Demerol) lethal if combined with an MAOI

Combination Narcotics

• Vicodin Hydrocodone + APAP• Percocet Oxycodone + APAP• Tylenol 1 300mg APAP + 8mg Codeine• Tylenol 2 300mg APAP + 15mg Codeine• Tylenol 3 300mg APAP + 30mg Codeine• Tylenol 4 300mg APAP + 60mg Codeine

Therapeutic & Side Effects of Morphine

• Miosis• Out of it• Respiratory depression• Pneumonia• Hypotension• Infrequency• Nausea and vomiting• Euphoria and dysphoria

Overdose and Addiction

• Naloxone inverse agonist, emergency• Naltrexone antagonist, treat addiction• Methadone treat addiction• Pentazocine mixed agonist-antagonist• Nalbuphine mixed agonist-antagonist• Buprenorphine mixed agonist-antagonist

Nitrous Oxide

• Horace Wells was first to use for own extraction by his assistant

• Sensation before onset à tingling• Side effect à nausea• Long term exposure à peripheral neuropathy• MAC 105%• Diffusion hypoxia

General Principles

• Pharmacokinetics– pH– First Pass Effect– Volume of Distribution– Phase I vs. Phase II Metabolism– First-order vs. Zero-order Kinetics– Drug-drug interactions

• Pharmacodynamics – Type I vs. Type II Dose Response Curves

Pharmacokinetics

0. Administration1. Absorption2. Distribution3. Metabolism4. Clearance/Elimination

What the body does to the drug

(0) Administration

• Oral= ingestion through mouth• Sublingual= dissolved under the tongue• Subcutaneous= injected under the skin• IM= intramuscular, injected into muscle• IV= intravenous, injected into vein• Inhalation= breathed in• Topical= applied to skin or mucous membrane

How is a drug delivered?

(1) Absorption

• Drugs must cross epithelial and/or endothelial cell layers to enter the body

How does a drug get into the body?

Local drugs

Systemic drugs

Passive diffusionFacilitated diffusionActive transport

Bioavailability

pH Considerations

• Acid/base properties of drug and pH of the environment can affect the charge state of a drug and hence alter its absorption– For weak acids, we want pH < pKa– For weak bases, we want pH > pKa

Acid Drug Base Drug

Acidic Environment

Non-ionized Ionized

Basic Environment

Ionized Non-ionized

(2) Distribution

• Most drugs must reach the blood in order to be distributed effectively

How does a drug get to the target site?

• Oral drugs undergo the first pass effect

First Pass Effect

Hepatic portal system

Volume of Distribution (Vd)

• Describes distribution of drug across the three body water compartments– Plasma (4%)– Interstitial (16%)– Intracellular (40%)

• Women, obese, and older people generally have less body water than the “average man”– Adipose has lowest water content– Brain and muscle have highest water content

• Binding to serum proteins lowers Vd and “traps” drugs in the blood as hydrophilic molecules

75 kg

(3) Metabolism

• Phase I– Functionalization (oxidation, reduction, hydrolysis)– Cytochrome P450

• Phase II– Conjugation (glucouronide, glutathione, glycine)– UDP-glucouronosyltransferase

How is a drug molecule chemically altered by the body?

Drug Metabolite Inactive(possibly inactive)

Phase I Phase II

Acetaminophen

Reduction GlutathionationPhase I Phase II

(4) Clearance/EliminationHow is a drug molecule eliminated from the body?

Urine

Drug

Feces

Phase I Phase II

Elimination Kinetics

• First-order kinetics– Constant fraction of drug is eliminated per unit

time (%/hour)– More common

• Zero-order kinetics– Constant amount of drug is eliminated per unit

time (mg/hour)– Less common– Higher risk of drug accumulation

Drug-Drug Interactions

• One drug affects the pharmacokinetics of another drug, most commonly metabolism– Induction à drug #1 induces liver cytochrome

enzymes resulting in increased metabolism and reduced effect of drug #2

– Inhibition à drug #1 competes for metabolism or directly inhibits liver cytochrome enzymes resulting in decreased metabolism and increased toxicity of drug #2

Drug-Drug InteractionsDental Drug Interacting Drug Effect

Diazepam Clarithromycin Increased sedation because of reduced metabolism of benzodiazepine

Tetracyclines Oral antacids (TUMS)

Reduced absorption of tetracyclines

Aspirin Anticoagulants Increased bleeding tendency

Aspirin Probenecid Decreased effect of probenecid

Aspirin Methotrexate Increased methotrexate toxicity

Acetaminophen Alcohol Increased risk of liver toxicity in chronic alcoholics

Local anesthetics Acetylcholinesterase inhibitors

Reduced effectiveness of acetylcholinesterase inhibitor

PrescribedDose

AdministeredDose

Active Dose

Intensity of effect

Medical errorsPatient compliance

AbsorptionDistributionMetabolismClearance

Pharmacokinetics

Drug-receptor interaction Pharmacodynamics

General Principles

• Pharmacokinetics– pH– First Pass Effect– Volume of Distribution– Phase I vs. Phase II Metabolism– First-order vs. Zero-order Kinetics– Drug-drug interactions

• Pharmacodynamics – Type I vs. Type II Dose Response Curves

Pharmacodynamics

• Almost all drug targets are proteins– Receptors– Ion channels– Enzymes– Carriers

• How a drug interacts with its target to produce therapeutic (and toxic) effects– Agonist– Antagonist– Inverse agonist

What the drug does to the body

Agonist

• Mimics the effects of an endogenous agonist molecule– Full agonist= can produce 100% of its desired effect– Partial agonist= cannot produce 100% of its desired

effect

Antagonist• Inhibits normal function of endogenous agonist– Competitive antagonist= competes with agonist for the

same binding site on the receptor– Non-competitive antagonist= binds to a different non-

overlapping binding site, but still prevents the binding of agonist

Inverse Agonist

• Inhibits the basal activity of a receptor in the absence of the normal agonist

• Binds to a special kind of receptor that is active at rest in order to inhibit its basal activity

Type I Dose Response Curve

• X-axis indicates dose of drug• Y-axis indicates response/efficacy of drug• Can be either hyperbolic or sigmoid/log form

Type I Dose Response Curve

• Intrinsic activity= maximal effect (Emax) of a drug– Full agonist has intrinsic

activity of 1– Partial agonist is between

0 and 1– Antagonist has intrinsic

activity of 0

Type I Dose Response Curve

• Efficacy= effect of a drug as a function of binding• Affinity= attractiveness of a drug to its receptor– The lower the dissociation constant (Kd) the higher

the affinity

• Potency= power of a drug at a specific concentration– Usually measured by the effective concentration of

drug (EC50) leading to half its maximal effect (50% response)

Type I Dose Response Curve

• Competitive antagonist shifts agonist curve RIGHT• Noncompetitive antagonist shifts agonist curve DOWN

Type II Dose Response Curve• X-axis still indicates dose of drug• Y-axis indicates number of subjects responding to

a drug, rather than the efficacy of a drug

Type II Dose Response Curve• ED50= effective dose where 50% of population responded effectively

(treated)• TD50= toxic dose where 50% of population experienced toxic side effects• LD50= lethal dose where 50% of population responded lethally (died)

TI= LD50/ED50In animal studies

TI= TD50/ED50In human studies

Therapeutic window

Dose Response Curves

• Type I: dose vs. efficacy of drug• Type II: dose vs. response of patient

Additive

• Combining drugs combines their individual degrees of effect

Antagonistic• Combining drugs causes a lesser effect than either one alone

– Chemical antagonism= drug binds directly to another drug to put it out of commission

– Receptor antagonism= competition between two drugs for a single receptor– Pharmacokinetic antagonism= one drug affects the PK of another via pH, etc.– Physiologic antagonism= two drugs producing opposing effects on the same

tissue via distinct receptors

Synergistic

• Combining drugs leads to more than the sum of the two independently

ANS Pharmacology

• Autonomic Nervous System– Sympathetic Nervous System– Parasympathetic Nervous System

• Receptors in the ANS• Cholinergic Drugs (PSNS)• Adrenergic Drugs (SNS)

ANS Physiology• In general, PSNS and SNS

nerves control the same organs, but have opposing effects on them!– SNS is fight or flight– PSNS is rest and digest, feed

and breed• All nerve pathways originate

from the CNS (brain + spinal cord)– 12 cranial– 0 cervical– 12 thoracic– 5 lumbar– 5 sacral

PSNS SNS

Fight or Flight• Pupil dilation

• Dry mouth

• Increased heart rate

• Airway relaxation

• Slowed digestion

• Bladder relaxation

Rest and Digest, Feed and Breed • Pupil constriction

• Stimulated salivation

• Decreased heart rate

• Airway constriction

• Stimulated digestion

• Bladder constriction

Receptors in the ANS

• Ionotropic= ion channel• Metabotropic= G-protein coupled receptor

Receptors in the ANS• Cholinergic= binds acetylcholine– Nicotinic (nAChR)= also binds nicotine; ionotropic– Muscarinic (mAChR)= also binds muscarine; metabotropic

• Adrenergic= binds Epi/NE; metabotropic

SNS

PSNS

M

A

A

N

N

N

Receptors in the ANS

SNS

PSNS

• Cholinergic= binds acetylcholine– Nicotinic (nAChR)= also binds nicotine; ionotropic– Muscarinic (mAChR)= also binds muscarine; metabotropic

• Adrenergic= binds Epi/NE; metabotropic

SNS vs. PSNS• By the distinct effects they have on the same organs

– PSNS à promote “rest and digest” and “feed and breed”– SNS à promote “fight or flight”

• By the region of the spinal cord from which they arise– PSNS à craniosacral– SNS à thoracolumbar

• By the lengths of their pre- and postganglionic neurons– PSNS à long pre-ganglionic, short post-ganglionic near target organ– SNS à short pre-ganglionic to sympathetic trunk, long post-ganglionic

• By the neurotransmitters they use– PSNS à ACh everywhere– SNS à ACh to the ganglion, NE from nerves and Epi/NE from adrenal gland

• By the neurotransmitter receptors that they use– PSNS à muscarinic metabotropic receptors on target organs– SNS à adrenergic metabotropic receptors on target organs

Synthesis of Acetylcholine

• Acetyl CoA + choline = acetylcholine– Catalyzed by choline acetyltransferase– Reversed by acetylcholinesterase

NMACh

Muscarinic Receptors

M2M1 M3 M4 M5

CNS Heart CNS CNSSmoothmuscle

Muscarinic Receptors

• Bradycardia= ↓ heart rate (chronotropy) and ↓ electrical conduction (dromotropy)

• SLUDS= salivation, lachrymation, urination, defecation, sweating

• BAM= bronchoconstriction, abdominal cramps, miosis

M2

M3

M Agonists

• Non-selective for muscarinic receptors so will affect all of them (M1-5) if systemic

• Therefore should not be used systemically with:– Peptic ulcers—gastric acid– Asthma/COPD—bronchoconstriction– CHF—decreased cardiac output

M

M AgonistsDirect-acting activates M receptor, congener (mimic) of ACh

Pilocarpine stimulates saliva or eye drops to constrict pupils

Methacholine methacholine acetylcholine

Indirect-acting non-competitively inhibits acetylcholinesterase (anticholinesterase)

Neostigmine reversibly inhibits cholinesterase, but can also directly affect NMJ

Physostigmine “

Edrophonium “

Organophosphate insecticides

irreversibly inhibits cholinesterase, poisoning can be treated with Pralidoxime

Nerve gases “

M

M Antagonists/AntimuscarinicsCompetitive inhibitors block M receptor, compete with ACh

Atropine reduces saliva or emergency drug to treat bradycardia (can also cause tachycardia)

Scopolamine “

Propantheline “

M

N Antagonists/Ganglionic BlockersNon-depolarizing blocks N receptor at allosteric site

Mecamylamine used to be used as an antihypertensive

Hexamethonium “

Depolarizing binds to N receptor but cannot be removed

Nicotine addictive substance found in tobacco products

N

N Antagonists/Neuromuscular Blockers

Non-depolarizing blocks N receptor at active site

Tubocurarine arrow poison

Depolarizing binds to N receptor but cannot be removed

Succinylcholine prevent laryngospasm and as a skeletal muscle relaxant during surgery

N

N

Synthesis of Epinephrine and Norepinephrine

• Tyrosine à L-DOPA à dopamine à NE à Epi– Catecholamines= dopamine, NE, Epi– Monoamines= dopamine, NE, Epi, serotonin (5-

HT), histamine

AEpi

NE

Adrenergic Receptors

α1 α2 β1 β2

Heart Smoothmuscle

Smoothmuscle

Smoothmuscle

α-receptors

• Vasoconstriction, urinary retention, pupil dilation (mydriasis)

• Vasoconstriction*

α1

α2

β-receptors

• Tachycardia= ↑ heart rate and ↑ electrical conduction and ↑ strength of contraction (inotropy)

• Renin release from kidneys

• Bronchodilation, vasodilation*, stop peristalsis

β1

β2

Adrenergic Agonists

Isoproterenol activates all β receptors

Norepinephrine activates all α receptors and β1

Epinephrine activates all α and β receptors

Phenylphrine (Sudafed) activates α1 receptor, reduce swelling via peripheral vasoconstriction

Oxymetazoline (Afrin nasal spray) “

Dobutamine activates β1 receptor, kickstarts the heart

Albuterol activates β2 receptor, bronchodilator used as an emergency inhaler

A

Adrenergic AntagonistsCompetitive antagonists block adrenergic receptors, compete with NE

Prazosin blocks α1 receptor

Chlorpromazine (CPZ) blocks α1 receptor and D2 receptor

Metoprolol blocks β1 receptor (cardioselective)

Atenolol “

Propranolol blocks all β receptors, prolongs lidocaine duration

Carvedilol blocks all β receptors and α1

Phentolamine blocks all α receptors

Phenoxybenzamine “

A

Sympathomimetics

Amphetamine stimulates release of stored NE

Tyramine (wine, cheese, chocolate) “

Ephedrine “

Cocaine inhibits reuptake of NE and dopamine

Methylphenidate “ psychostimulant for ADHD

Tricyclic antidepressants inhibits reuptake of serotonin and NE

Monoamine oxidase inhibitors blocks enzymatic degradation of monoamines

ANE

Sympatholytics

Guanethidine inhibits release of NE

Reserpine depletes NE stores thus inhibiting release

Clonidine α2 agonist (CNS) which actually blocks SNS signal

Methyldopa α2 agonist (CNS) which actually blocks SNS signal

ANE

Epinephrine Reversal

• Vasoconstrictor effect of epinephrine is converted into a vasodilator effect in the presence of an α-blocker whereby the β2 vasodilator effect becomes the major vascular response

• Basically α-blocker cancels out epinephrine’s α activation effects and it only activates β receptors

Vasovagal Reflex

• NE can activate baroreceptors which stimulate vagal reflex to reduce heart rate, leading to an opposite response to what NE usually does

• Atropine blocks this reflex

Circulatory System

• Human circulatory system is a closed system

• Pump= cardiac output (CO)• Tubing= peripheral

resistance (PR)• Fluid= blood volume (SV)

Circulatory System• BP= CO x PR• CO= SV x HR• Systole= pressure in arteries

when heart contracts• Diastole= pressure in arteries

when heart relaxes• Preload= pressure in

ventricles before heart contracts

• Afterload= pressure in arteries against which the ventricles must pump

BP= SV x HR x PR

120/80

AntihypertensivesFor high blood pressure

Diuretics decrease renal reabsorption of sodium thus resulting in net fluid loss and reduction in blood pressure

Furosemide Loop or high-ceiling

Hydrochlorothiazide (HCTZ) Thiazide (hypokalemia)

Spironolactone K+ sparing (hyperkalemia)

AntihypertensivesFor high blood pressure

Vasodilators open K+ channels to cause vasodilation

Hydralazine

CCBs block calcium influx in order to cause vasodilation

Verapamil may induce gingival hyperplasia

Diltiazem “

Amlodipine “

Nifedipine “

AntihypertensivesACE Inhibitors blocks the enzyme that converts angiotensin I into angiotensin

II the latter of which is a potent vasoconstrictor

-prils

ARBs competitive antagonist at angiotensin II receptor again blocking a potent vasoconstrictor

-sartans

For high blood pressure

Renin

ACE

AntianginalsFor insufficient oxygen to cardiac muscle

Antianginals

Nitroglycerin vasodilation of smooth muscle in coronary arteries to ↑ O2 supply

Propranolol reduces oxygen demand by relaxing the heart

CCBs reduces oxygen demand by reducing peripheral resistance via vasodilation

Anti-CHF DrugsFor failure of heart to pump enough blood

Cardiac Glycosides block Na/K ATPase to increase calcium influx and promote positive inotropy in cardiac muscle cells only

Digoxin

Digitalis

ACE Inhibitors blocks the enzyme that converts angiotensin I into angiotensin II the latter of which is a potent vasoconstrictor

-prils

Anti-ArrhythmicsFor an irregular heartbeat

• Type 1 drugs= Na+ channel blockers for cardiac muscle only– 1A= lengthens refractory period to slow heartbeat– 1B= shortens refractory period to hasten

heartbeat

• Type 2 drugs= beta blockers• Type 3 drugs= K+ channel blockers• Type 4 drugs= Ca2+ channel blockers (CCBs)

Anti-ArrhythmicsFor an irregular heartbeat

Drug Name Type Arrhythmia

Quinidine Type 1A a-fib, supraventricular tachyarrhythmia

Procainamide “ “

Lidocaine Type 1B ventricular arrhythmia

Propranolol Type 2 paroxysmal tachycardia

Verapamil Type 4 a-fib, paroxysmal tachycardia, supraventricular tachyarrhythmia

Digitalis Cardiac glycoside

a-fib, paroxysmal tachycardia; digitalis-induced arrhythmia can be reversed with Phenytoin

Continuum of CNS Excitability

D S GABA

N M A

Antipsychotics

1st Generation D2 blocker

Haloperidol tardive dyskinesia

Phenothiazines tardive dyskinesia; specific examples are Chlorpromazine, Thioridazine, and Fluphenazine

2nd Generation D and 5HT blocker

Clozapine not as many side effects

For schizophrenia

D

S

AntidepressantsSSRI selective serotonin reuptake inhibitor

Fluoxetine anticholinergic side effects

Citalopram “

Trazodone “

SNRI/TCA serotonin and NE reuptake inhibitor, tricyclic antidepressants

Amitriptyline “

Imipramine “

MAOI monoamine oxidase inhibitors

Phenelzine “

Tranylcypromine “

Lithium is drug of choice for manic depression (bipolar disorder).

For depression

Anxiolytics/Sedatives

• Benzodiazepines• Barbiturates

For anxiety or sedation

Benzodiazepines• Increase GABA binding and chloride

ion influx to slow down the CNS• Ideal drug for oral sedation in the

dental setting• Propylene glycol can induce

thrombophlebitis in large veins

GABA

Benzodiazepine (BZD)

Diazepam 2-10mg Valium 1 hour before dental appointment

Triazolam Halcion

Chlordiazepoxide

Barbiturates

• Same mechanism as BZD• Barbs are contraindicated in patients with

intermittent porphyria because they will aggravate the disease

• Barb overdose causes respiratory depression

GABA

Barbiturate

Thiopental quick onset, short duration of action

• The more soluble the agent in blood, the more you need to reach critical tension in the brain

• Stage I: analgesia/feeling better• Stage II: delirium• Stage III: surgical anesthesia• Stage IV: medullary paralysis

General Anesthetics

General Anesthetic

Halothane hepatotoxicity

Parkinson’s Disease

• Substantia nigra to striatum is main pathway• Due to dopamine deficiency in brain• Dopamine cannot cross the BBB, but its precursor

levodopa (L-DOPA) can• Carbidopa blocks DOPA decarboxylase, allowing

L-DOPA to cross the BBB where it can be converted to dopamine once in the brain