Clinical Pharmacology and

HEMODYNAMICS
DISORDERS
Sulanto Saleh-Danu R.,MD., SpFK.
Dept. of Pharmacology & Therapy
Div.Clinical Pharmacology
Fac of Medicine, GMU.
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Objective.

After following this lecture to be able to

- understand whats 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.
( Doorlands Illustrated Medical Dictionary, 27
th
ed., 1988).
Hemodynamic, pertaining to the movements
involved in the circulation of the blood.
( Doorlands Illustrated Medical Dictionary, 27
th
ed.,1988)
3
(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 = aorta
Lg. arteries = large arteries
Sm.arteries = small arteries
ART = arterioles
CAP = capillaries
VEN = venule
SV = venous
Sm veins = small veins
Lg veins = large veins
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HEMODYNAMIC EMERGENCY
PRESSURE : - hypertension
- hypotension
RESISTANCY : - obtruction of vessel
- peripheral vasoconstriction
- massive bleeding
FLOW OF THE BLOOD : - blood viscocity
- angina/O2 supply
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HAEMODYNAMICS
PRESSURE
-Hypertension

-Hypotension
- Stroke / CVA
- Vital organ
damages.

- Shock
RESISTANCE
-Vasoconstriction.

-Obstruction
FLOW OF BLOOD -Scleroting of areteries

-Increase of velocity
BLOOD PRESSURE
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Thrombus
Emboli
Hematokrit
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HYPOTENSION


SHOCK
BLOOD PRESSURE
HYPOTENSION
SHOCK
organs perfusion
ORGANS / TISSUES
DAMAGES
EMERGENCY
ACTION
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BLOOD FLOW
ORGANS
PERFUSION
REVERSEIBLE
IRREVERSIBLE
CELLULAR / TISSUE / ORGAN
INJURY / DAMAGES
DEATH
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 )
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Hypovolemic
shock
Reduced
preload
Cardiogenic
shock
Reduced
Systolic
performance
Obstructive
shock
Reduced
Ability to
Fill ventricle
In diastole
Distributive
shock
Severe
Myocardial
depression
Severe
Decrease in
Systemic
Vascular
resistance
Decrease in
Stroke volume
Decrease in CO
Hypotension
Severe decrease in
Tissue & organ blood flow
Multiple organ system
failure
Maldistribution
Of blood flow
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

- Acute adrenal insufficiency
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TREATMENT and MANAGEMENT SHOCK
1. 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. CENTRAL VENOUS PRESSURE ( CVP ) or
PULMONARY CAPILLARY WEDGE PRESSURE (PCWP)
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3. VOLUME REPLACEMENT.
I.V. LINE ( better use TRANFUSION SET )

HEMORRHAGIC SHOCK :
BLOOD SUBSTITUTES / WHOLE BLOOD /
PBRC (Packed Blood Red Cells)
+ isotonic solution preventing increase of Hmt.
HYPOVOLEMIC SHOCK :
Rapid bolus ISOTONIC CRISTALLOID 1 L
CARDIOGENIC SHOCK :
ISOTONIC CRISTALLOID ( smaller volume )
SEPTIC SHOCK :
Large volume ISOTONIC CRISTALLOID.

SHOCK in TRAUMA CAPITIS HYPERTONIC SALINE (7.5%)
plus DEXTRAN.
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4. MEDICATIONS
4.1. VASOACTIVE THERAPY : INOTROPIC agents
VASOPRESSOR agents
- AFTER ADEQUATE FLUID RESUSCITATION
- DEPENDS ON CARDIAC OUTPUT
Agents : - Dobutamine
- Nor-adrenaline/Nor-epinephrine
- Adrenaline/Epinephrine
- Dopamine
- Vasopressin ( antidiuretic hormon /ADH )
DISTRIBUTIVE/VASODILATOR SHOCK

4.2. CORTICOSTEROID SEPTIC SHOCK
4.3. Activated Protein C as antithrombotic, profibrinolytic
and Anti-inflamatory
( SEPTIC SHOCK)
4.4. ANTIBIOTIC DEFINITIVE THERAPY in SEPTIC SHOCK
4.5. SODIUM BICARBONATE SEPTIC SHOCK with
LACTIC ACIDOSIS
DRUGS USED IN NON-CARDIOGENIC SHOCK
- Cathecholamines and sympathomimetic amines:
adrenaline (epinephrine); noradrenaline (norepinephrine);
isoprenaline (isoproterenol); dopamine; dobutamine; etc.

- others :
glucagon; naloxone; corticosteroids; etc.
First of all : do not forget insert the iv line.
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PRINCIPLES SHOCK MANAGEMENT :


1. ALLEVIATING THE PRECIPITATING CAUSE OF SHOCK;

2. TREATING THE HAEMODYNAMIC AND
METABOLIC CONSEQUENCES;

3. MANAGING THE SECONDARY MEDICAL
COMPLICATIONS ( renal failure; pulmonary oedema etc.)
(Benowitz, N.L., et al., 1997)
see lecture: shock management.
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HYPERTENSION



PREVENT



VITAL ORGAN FAILURE
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BLOOD PRESSURE
HYPERTENSION
Classification Systolic Diastolic
(mmHg) (mmHg)

Normotension (normal) < 120 and/or < 80
Prehypertension 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)

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

- -blocker ( with or without : Calcium channel
blocker : amlodipine or felodipine SR )




TREATMENT SHOULD BE CONTINUED



BP TO SATISFACTORY LEVEL
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PHARMACOTHERAPEUTIC MANAGEMENT
OF HYPERTENSION.
CLASS. 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 -1&2) nadolol
timolol
pindolol (also partial -receptor agonist)

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

Also block : labetalol
receptor bucindolol
carvidelol

receptor : prazosin
blockers terazosin
doxazosin

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

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

CONTRAINDICATIONS : asthma bronchiale, diabetes, peripheral
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 -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 : CARDIOVASCULAR EMERGENCY
by dr. LUCIA KRIS DINARTI SpPD, SpJ. ).
Next slide
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MANAGEMENT (PHARMACOTHERAPY)
OF STABLE ANGINA)

-Relieve / prevent pain
-Slow progression of atherosclerosis
-Improve 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 g);
OR
-ISOSORBIDE DINITRATE tablt
5 mg s.l., repeat every 5 (max.
3 tablt)
WARNING.
AVOID NITRATES if the patient has used
sildenafil (Viagra) in the previous 24 hours OR
tadalafil (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
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MANAGEMENT UNSTABLE ANGINA
This CONDITION : is a MEDICAL EMERGENCY
AGGRESIVE
PHARMACOTHERAPY
REVASCULARIZATION :
PTCA or CABG
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DRUGS THERAPY FAILS
and/or
HIGH RISK MI
REVASCULARIZATION:

PTCA ( PercutaneusTransCoronary Angioplasty )
CABG (Coronary Artery Bypass Grafting)
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BLOCK : BIOMEDICAL SCIENCES I; II and III

BLOCK : CIRCULATION and RESPIRATION

BLOCK : HEMOPOETIC and LYMPHOID DISORDERS;
HEMOSTASIS; SHOCK

BLOCK : NEPHROLOGY; UROLOGY and BODY FLUID

BLOCK : Elective GUIDE TO GOOD PRESCRIBING
FOR YOUR SELF LEARNING :
0PEN & LEARN AGAIN THIS BLOCK !!!
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