Clinical Pharmacology and

HEMODYNAMICS DISORDERS

Sulanto Saleh-Danu R.,MD., SpFK.Dept. of Pharmacology & Therapy

Div.Clinical PharmacologyFac of Medicine, GMU.

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Objective.

After following this lecture to be able to - understand what’s the hemodynamic and hemodynamics

- understand hemodynamics emergency

- understand rational use of medicine (pharmacotherapy) in the situation of hemodynamics emergency

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HEMODYNAMICS.

Is the study of the relationship between PRESSURE, RESISTANCE and the FLOW of BLOOD in the cardiovasluar system.

( Aaronson, PI. & Ward J P T., 2000)

Is the study of the movement of the blood and the forces concerned there in.

( Doorland’s Illustrated Medical Dictionary, 27th ed., 1988).

Hemodynamic, pertaining to the movementsinvolved in the circulation of the blood.

( Doorland’s Illustrated Medical Dictionary, 27th ed.,1988)

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(copy from :Aaronson,PI., Ward,J.P.T., 1999)

CO = (MABP-CVP)/ TPR

CO = cardiac output,MABP = mean arterial blood pressure,TPR = total peripheral resistance,CVP = central venous pressure

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AO = aortaLg. arteries = large arteriesSm.arteries = small arteriesART = arteriolesCAP = capillariesVEN = venuleSV = venousSm veins = small veinsLg veins = large veins

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HEMODYNAMIC EMERGENCYHEMODYNAMIC EMERGENCY

PRESSURE : - hypertension - hypotension

RESISTANCY : - obtruction of vessel - peripheral vasoconstriction - massive bleeding

FLOW OF THE BLOOD : - blood viscocity - angina/O2 supply 6

HAEMODYNAMICS

PRESSURE

-Hypertension

-Hypotension

- Stroke / CVA - Vital organ damages.

- Shock

RESISTANCE -Vasoconstriction.

-Obstruction

FLOW OF BLOOD -Scleroting of areteries

-Increase of velocity

BLOOD PRESSURE7

ThrombusEmboli

Hematokrit

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HYPOTENSION HYPOTENSION

SHOCKSHOCK

BLOOD PRESSUREHYPOTENSION

SHOCK organs perfusion

ORGANS / TISSUESDAMAGES

EMERGENCYACTION

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BLOOD FLOWBLOOD FLOW

ORGANSORGANSPERFUSIONPERFUSION

REVERSEIBLEREVERSEIBLE

IRREVERSIBLEIRREVERSIBLE

CELLULAR / TISSUE / ORGAN CELLULAR / TISSUE / ORGAN INJURY / DAMAGESINJURY / DAMAGES

DEATHDEATH

CRITICAL PERIODE

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Classification of shock by mechanism and common causes.

Hypovolemic shock

Cardiogenic shock

Obstructive shock

Distributive shock

( Messina, L.M., et al., 2003 ) 11

HypovolemicHypovolemicshockshock

ReducedReducedpreloadpreload

CardiogenicCardiogenicshockshock

ReducedReducedSystolicSystolic

performanceperformance

ObstructiveObstructiveshockshock

Reduced Reduced Ability toAbility to

Fill ventricleFill ventricleIn diastoleIn diastole

DistributiveDistributiveshockshock

SevereSevereMyocardialMyocardialdepressiondepression

Severe Severe Decrease inDecrease in

SystemicSystemicVascularVascular

resistanceresistance

Decrease inDecrease inStroke volumeStroke volume

Decrease in CODecrease in CO HypotensionHypotension

Severe decrease inSevere decrease inTissue & organ blood flowTissue & organ blood flow

Multiple organ system Multiple organ system failurefailure

MaldistributionMaldistributionOf blood flowOf blood flowIn microcircul.In microcircul.

( Parrillo, JE., 1991 )

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Hypovolemic shock

1. Loss of blood (hemorrhagic shock) - External hemorrhagic : trauma, gastrointestinal bleeding, etc. - Internal hemorrhagic : hematoma, hemothorax, hemoperitoneum.

2. Loss of plasma : burns, exfoliative dermatitis.

3. Loss of fluid and electrolytes - External : vomiting, diarrhea, excessive sweating, hyperosmolar states (diabetic ketoacidosis, nonketotic coma) - Internal ( “third spacing”) : Pancreatitis, Ascites, Bowel obstruction.

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Cardiogenic shock

- Dysrhythmia : - Tachyarrhythmia - Bradyarrhythmia

- “Pump failure” : secondary to myocardial infarction or other cardiomyopathy.

- Acute valvular dysfunction (especially regurgitant lesions )

- Rupture of ventricular septum or free ventricular wall

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Obstructive shock

- Tension pneumothorax

- Pericardial diseases ( tamponade, constriction)

- Diseases of pulmonary vasculature (massive pulmonary emboli, pulmonary hypertension)

- Cardiac tumor ( atrial myxoma )

- Left atrial mural thrombus

- Obstructive valvular diseases (aortic or mitral stenosis)

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Distributive shock

- Septic shock

- Anaphylactic shock

- Neurogenic shock

- Vasodilator drugs- Vasodilator drugs

- Acute adrenal insufficiency

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TREATMENT and MANAGEMENT SHOCKTREATMENT and MANAGEMENT SHOCK

1.1. GENERAL MEASURE GENERAL MEASURE : “ ABC “ VENTILATION Oxygen supply Advanced Cardiogenic Life Support (ACLS) Folley Catheter urinary output Laboratory : blood count electrolyt glucose blood gas analyse coagulation parameter blood group bacterial cultur

2.2. CENTRAL VENOUS PRESSURE ( CVP ) orCENTRAL VENOUS PRESSURE ( CVP ) or PULMONARY CAPILLARY WEDGE PRESSURE (PCWP) PULMONARY CAPILLARY WEDGE PRESSURE (PCWP)

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3. VOLUME REPLACEMENT.3. VOLUME REPLACEMENT. I.V. LINE ( better use TRANFUSION SET ) HEMORRHAGIC SHOCK : HEMORRHAGIC SHOCK : BLOOD SUBSTITUTES / WHOLE BLOOD / PBRC (Packed Blood Red Cells) + isotonic solution preventing increase of Hmt. HYPOVOLEMIC SHOCK HYPOVOLEMIC SHOCK : Rapid bolus ISOTONIC CRISTALLOID 1 L CARDIOGENIC SHOCK :CARDIOGENIC SHOCK : ISOTONIC CRISTALLOID ( smaller volume ) SEPTIC SHOCK SEPTIC SHOCK : Large volume ISOTONIC CRISTALLOID.

SHOCK in TRAUMA CAPITIS SHOCK in TRAUMA CAPITIS HYPERTONIC SALINE (7.5%) plus DEXTRAN.

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4.4. MEDICATIONSMEDICATIONS 4.1. VASOACTIVE THERAPY 4.1. VASOACTIVE THERAPY : INOTROPIC agents VASOPRESSOR agents - AFTER ADEQUATE FLUID RESUSCITATION - DEPENDS ON CARDIAC OUTPUT AgentsAgents : - Dobutamine - Nor-adrenaline/Nor-epinephrine - Adrenaline/Epinephrine - Dopamine - Vasopressin ( antidiuretic hormon /ADH ) DISTRIBUTIVE/VASODILATOR SHOCK

4.2. CORTICOSTEROID 4.2. CORTICOSTEROID SEPTIC SHOCK 4.3. Activated Protein C 4.3. Activated Protein C as antithrombotic, profibrinolytic and Anti-inflamatory ( SEPTIC SHOCK) 4.4. ANTIBIOTIC4.4. ANTIBIOTIC DEFINITIVE THERAPY in SEPTIC SHOCK 4.5. SODIUM BICARBONATE 4.5. SODIUM BICARBONATE SEPTIC SHOCK with LACTIC ACIDOSIS

DRUGS USED IN DRUGS USED IN NON-CARDIOGENIC SHOCKNON-CARDIOGENIC SHOCK

- Cathecholamines and sympathomimetic amines:Cathecholamines and sympathomimetic amines: adrenaline (epinephrine); noradrenaline (norepinephrine);adrenaline (epinephrine); noradrenaline (norepinephrine); isoprenaline (isoproterenol); dopamine; dobutamine; etc.isoprenaline (isoproterenol); dopamine; dobutamine; etc.

- others :- others : glucagon; naloxone; corticosteroids; etc. glucagon; naloxone; corticosteroids; etc.

First of all : do not forget insert the iv line.First of all : do not forget insert the iv line.

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PRINCIPLES SHOCK MANAGEMENT :PRINCIPLES SHOCK MANAGEMENT :

1.1. ALLEVIATING THE PRECIPITATING CAUSE OF SHOCK;ALLEVIATING THE PRECIPITATING CAUSE OF SHOCK;

2.2. TREATING THE HAEMODYNAMIC AND TREATING THE HAEMODYNAMIC AND METABOLIC CONSEQUENCES;METABOLIC CONSEQUENCES;

3. MANAGING THE SECONDARY MEDICAL3. MANAGING THE SECONDARY MEDICAL COMPLICATIONS ( renal failure; pulmonary oedema etc.)COMPLICATIONS ( renal failure; pulmonary oedema etc.)

(Benowitz, N.L., et al., 1997)

see lecture: shock managementsee lecture: shock management..

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HYPERTENSIONHYPERTENSION

PREVENTPREVENT

VITAL ORGAN FAILUREVITAL ORGAN FAILURE

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BLOOD PRESSURE HYPERTENSION

Classification Systolic Diastolic (mmHg) (mmHg)

Normotension (normal) < 120 and/or < 80Prehypertension 120 – 139 and/or 80 – 89 Stage 1 Hypertension 140 – 159 and/or 90 – 99 Stage 2 Hypertension 160 – 179 and/or 100 – 109

Stage 3 ( severe) HT 180 - 209 and/or 110 – 119

Stage 4 (very severe) HT > 210 and/or > 120

( JNC V & VII, 2003)

emergency25

HYPERTENSION CONSEQUENCIESHYPERTENSION CONSEQUENCIES

ORGAN DAMAGES : ORGAN DAMAGES : - KIDNEYS - KIDNEYS eg. Renal Failure eg. Renal Failure - EYES ( RETINA) - EYES ( RETINA) eg. Retinopathia /Blindness eg. Retinopathia /Blindness - BRAIN - BRAIN eg. CVA ( Stroke )/ TIA eg. CVA ( Stroke )/ TIA - HEART - HEART eg. LVH,MI, Heart Failure eg. LVH,MI, Heart Failure

DEATHDEATH26

MANAGEMENT VERY SEVERE HYPERTENSION(HYPERTENSIVE EMERGENGY).

MUST BE BALANCE RISK AND EFFICACY URGENT REDUCTION BP : hypertensive encephalopathy;

acute hypertensive heart failure; dissecting aneurysma; etc.

SHOULD BE HOSPITALIZED INITIAL GOAL : REDUCE BP BY NO MORE THAN 25 % WITHIN

FIRST 2 HOURS; BP:160/100 mmHg within next 2-6 hours until at least 24 hours.

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PHARMACOTHERAPY.

PARENTERAL : 1. sodium nitroprusside 0.3 microgram /kg/minute iv for 10 minutes then increase/decrease 0.3 microgram/kg/minute every 5-10 minutes reach the maintain BP level.

ALTERNATIVELY,

2 diazoxide 30 mg iv, increase as necessary in 30 – 60 mg bolus dose at 5 to 10 minute interval, up to 300 mg;

3. hydralazine 5 to 10 mg slowly i.v.repeat at 20 minute interval;

4. clonidine 150 – 300 microgram im or slowly iv over 10 minutes

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LESS URGENT SITUATION:

PHARMACOTHERAPY ORALWhere oral therapy is appropriate, use :

- amlodipine 5 – 10 mg, or - felodipine sustained-release 2.5 – 10 mg, or - nifedipine (tablet) 10 – 20 mg or

- methyldopa 250 – 500 mg, or - prazosin 2 – 5 mg, or - captopril 6.25 mg – 50 mg (not sublinguallly).

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If MYOCARDIAL ISCHAEMIA is also present :If MYOCARDIAL ISCHAEMIA is also present :

- ß-blockerß-blocker ( with or without : ( with or without : Calcium channelCalcium channel blocker : amlodipine or felodipine SRblocker : amlodipine or felodipine SR ) )

TREATMENT SHOULD BE CONTINUEDTREATMENT SHOULD BE CONTINUED

BP BP TO SATISFACTORY LEVEL TO SATISFACTORY LEVEL

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PHARMACOTHERAPEUTIC MANAGEMENTOF HYPERTENSION.

CLASS. DIURETICS DIURETICS: - Thiazides, - Loop diuretics, - Potassium-sparring diuretics and aldosterone antagonist, - Osmotic diuretics, - Mercurial diuretics, - Carbonics anhydrase inhibitors, - Diuretics with potassium.

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-THIAZIDES & THIAZIDE-RELATED DIURETICS. DRUGS : Thiazide : Bendroflumathiazide Benzthiazide Chlorothiazide Hydrochlorothiazide (HCT) Hydroflumethiazide

Related : Chlortalidone Indapamide Xipamide Metolazone.

ADVERSE EFFECTS : - hypokalaemeia, - increased plasma insulin, glucose, cholesterol, hypersensitivity reaction, and impotence.

INDICATIONS : Old ages, Black race congestive heart failure, CONTRAINDICATION : dyslipidaemia.

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CLASS Beta-receptor Blockers.

Non-selective : propranolol (blocks ß-1&2) nadolol timolol pindolol (also partial ß-receptor agonist)

Selective : metoprolol ( blockß-1 ) atenolol acebutolol (also partial ß-receptor agonist) celiprolol (also partial ß-receptor agonist)

Also block : labetalol α – receptor bucindolol carvidelol

α – receptor : prazosin blockers terazosin doxazosin

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INDICATIONS : angina, after myocard infarction.INDICATIONS : angina, after myocard infarction. ((αα-receptor blockers : -receptor blockers : diabetes, dyslipidaemia, benign prostaticdiabetes, dyslipidaemia, benign prostatic hypertrophy).hypertrophy).

ADVERSE EVENTS : bronchospasm, fatigue, negative inotropy, CNS ADVERSE EVENTS : bronchospasm, fatigue, negative inotropy, CNS disturbance (nightmares), hypoglycaemia, disturbance (nightmares), hypoglycaemia, dyslipidaemia.dyslipidaemia. ((αα-receptor blockers : postural hypotension,-receptor blockers : postural hypotension, oedema. Less common –urinary incontinence,oedema. Less common –urinary incontinence, dizziness).dizziness).

CONTRAINDICATIONS : asthma bronchiale, diabetes, peripheralCONTRAINDICATIONS : asthma bronchiale, diabetes, peripheral vascular disease, dyslipidaemia. vascular disease, dyslipidaemia.

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CLASS Ca 2+ - CHANNEL BLOCKERS

nifedipine amlodipine nicardipine isradipine felodipine lacidipine

diltiazem

verapamil

ADV. EVENTS: headache flushing fatigue tachycardia, peripheral oedema bradycardia negative inotropy SA & AV node block with verapamil and diltiazem.

INDICATIONS : angina, renal-insufficiency, cerebrovascular diseases.

CONTRAIDICATIONS : Congestive heart failure, pregnancy, avoid combination with ß-blockers

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CLASS. ACE (angiotensine converting enzym) INHIBITOR.

captopril INDICATIONS : congestive heart failure, enalapril postmyocardial infarction, diabetes. lisinopril benazepril fosinopril ADVERSE EVENTS : postural hypotension ramipril (first dose), cough, ARF, fatigue, quinapril headache, dizziness, perindopril allergic reactions) trandolipril

CONTRAINDICATIONS : pregnancy, renovascular disease, aortic stenosis.

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CLASS. A-II RA (Angitensin-II receptor antagonist).

candesartan eprosartan irbesartan losartan olmesartan temilsartan valsartan

INDICATION ~ ACE Inhibitor

ADVERSE EVENTS : almost no cough, rare renal function, electrolytes (must be monitor 1 or 2 weeks after commencing treatment)

CONTRAINDICATION ~ ACEi.

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CORONARY ISCHAEMIC SYNDROME

SYNDROMES ATTRIBUTABLE TO MYOCARDIAL ISCHAEMIC SECONDARY TO CORONARY OBSTRUCTION.

( PLEASE : ( PLEASE : CARDIOVASCULAR EMERGENCY CARDIOVASCULAR EMERGENCY by dr. LUCIA KRIS DINARTI SpPD, SpJ. ). by dr. LUCIA KRIS DINARTI SpPD, SpJ. ).

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MANAGEMENT MANAGEMENT (PHARMACOTHERAPY) (PHARMACOTHERAPY) OF STABLE ANGINA) OF STABLE ANGINA)

-Relieve / prevent painRelieve / prevent pain-Slow progression of Slow progression of

atherosclerosisatherosclerosis-Improve prognosisImprove prognosis

ACUTE ATTACK :

-STOP ACTIVITIES-GLYCERYL TRINITRATE spray 400 microgram metered dose sublingually, repeat once after 5’ if pain persists (max of 2 meter dose); OR-GLYCERYL TRINITRATE tablt 300 to 600 microgram s.l. repeat every 3 to 5 minute (max.1800 µg); OR-ISOSORBIDE DINITRATE tablt 5 mg s.l., repeat every 5’ (max. 3 tablt)

WARNING.AVOID NITRATES if the patient has usedsildenafil (Viagra) in the previous 24 hours ORtadalafil (Cialis) in the previous 5 days

CONTINUING THERAPY:

-ASPIRIN 75 to 300 mg p.o. daily OR if intolerant:-CLOPIDOGREL 75 mg daily PLUS EITHER:-ATENOLOL 25 – 100 mg p.o.daily OR-METOPROLOL 25-100 mg p.o. daily 40

MANAGEMENT UNSTABLE ANGINAMANAGEMENT UNSTABLE ANGINA

This CONDITION : is a This CONDITION : is a MEDICAL EMERGENCYMEDICAL EMERGENCY

AGGRESIVEAGGRESIVEPHARMACOTHERAPYPHARMACOTHERAPY

REVASCULARIZATION :REVASCULARIZATION :PTCA or CABGPTCA or CABG

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DRUGS THERAPY FAILSDRUGS THERAPY FAILSand/orand/or

HIGH RISK MIHIGH RISK MI

REVASCULARIZATION: REVASCULARIZATION:

PTCA PTCA ( PercutaneusTransCoronary Angioplasty )( PercutaneusTransCoronary Angioplasty )CABGCABG (Coronary Artery Bypass Grafting) (Coronary Artery Bypass Grafting)

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BLOCK : BIOMEDICAL SCIENCES I; II and IIIBLOCK : BIOMEDICAL SCIENCES I; II and III

BLOCK : CIRCULATION and RESPIRATIONBLOCK : CIRCULATION and RESPIRATION

BLOCK : HEMOPOETIC and LYMPHOID DISORDERS;BLOCK : HEMOPOETIC and LYMPHOID DISORDERS; HEMOSTASIS; SHOCKHEMOSTASIS; SHOCK

BLOCK : NEPHROLOGY; UROLOGY and BODY FLUIDBLOCK : NEPHROLOGY; UROLOGY and BODY FLUID

BLOCK : Elective BLOCK : Elective GUIDE TO GOOD PRESCRIBING GUIDE TO GOOD PRESCRIBING

FOR YOUR SELF LEARNING : 0PEN & LEARN AGAIN THIS BLOCK !!!0PEN & LEARN AGAIN THIS BLOCK !!!

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