GM.

AMAN
BAG. FARMAKOLOGI FK. UNUD
 INTRODUCTION
 BLOOD PRESSURE DETERMINED BY:
> Blood volume
> Symphatetic tone
> Vascular smooth muscle tone
> Angiotensin effect
STRATEGIES FOR TREATING HYPERTENSION

 REDUCTION OF BLOOD VOLUME

 REDUCTION OF SYMPHATETIC TONE

 REDUCTION OF VASCULAR SMOOTH MUSCLE

TONE

 REDUCTION OF ANGIOTENSIN EFFECT

REDUCTION OF BLOOD VOLUME
 Thiazide Diuretic :
> the most important for anti hypertensive drug
> especially for long term therapy
> for mild and moderate hypertension
 Furosemide Diuretic:
> used in severe hypertension
> malignant hypertension
REDUCTION IN SYMPHATETIC TONE

 Centrally acting sympathoplegic drugs

 Ganglion blocking agents
 Adrenergic neuron blocking drugs
(Postganglionic Symphatetic Nerve
Terminal Blocker)
 Adrenoceptor blocking drugs
 CENTRALLY ACTING SYMPATHOPLEGIC
DRUGS
 CLONIDINE
> selective α2 agonist
> can cause rebound hypertension if
administration stop suddenly
> can cause sedation
 CENTRALLY ACTING SYMPHATOPLEGIC
DRUG
 METHYLDOPA
> converted to α methyl dopamine and
α methylnorepinephrine
> selective α2 agonist
> can cause sedation
> compensatory response salt retention
 GANGLION BLOCKING AGENTS
(GABA)
 Hexamethonium & Trimetharphan
> block parasympathetic nerve, can cause
Atropine like effect
> block symphatetic nerve, can cause
orthostatic hypotension and sexual
dysfunction
 POSTGANGLIONIC SYMPHATETIC NERVE
TERMINAL BLOCKER
 RESERPINE
> inhibit reuptake (uptake 1 & uptake2)
> depletion of NE, Dopamine, Serotonin
(peripheral and central)
> toxic effect : depression
 POSTGANGLIONIC SYMPHATETIC NERVE
TERMINAL BLOCKERS
 GUANETHIDINE
> guanethidine uptake together with NE
and store in NE vesicle (NE + G)
> if stimulated nerve terminal release NE
& G together
> so that the effect of NE in postsynaptic
decrease: BP decrease (systolic and
diastolic)
ADRENOCEPTOR BLOCKER
 α BLOCKERS
> non selective (Phentolamine & Phenoxyben-
zamine) : block α1 and α2 receptor
> selective α1 blocker (Prazosin)

 β BLOCKERS
> Propranolol
> Bisoprolol
 Non selective a receptor blocker:
> Block a1 and a2 receptor
> Block a2 receptor can cause increase
NE release
> Stimulate β1 receptor, cause tachycardia
 Selective α1 receptor blocker:
> Selectively block α1 receptor
> Do not stimulate NE release
> No tachycardia
 β BLOCKERS

 NON CARDIOSELECTIVE (Propranolol)

 CARDIOSELECTIVE (Metoprolol, Bisoprolol)
 PARTIAL AGONIST with ISA (Pindolol, Acebutolol)
 BLOCK α AND β RECEPTOR (Labetalol)
β BLOCKERS
 PROPRANOLOL:
> Eficacious in hypertension and ischemia
heart disease
> Used in mild to moderate hypertension
> In severe hypertension, β blockers useful in
preventing tachycardia by direct action
of vasodilator (eg. Hydralazine)
 Mechanism of action:
> Reduce COP
> Decrease vascular resistance
> Reduce Angiotensin
 VASODILATORS
 ORAL VASODILATORS: hydralazine, Minoxidil
> used for long term
 PARENTERAL VASODILATORS : Nitroprusside,
Diazoxide.
> used to treat hypertensive emergencies
 CALCIUM CHANNEL BLOCKERS (CCB):
Amlodipine, Verapamil, Diltiazem
> used in both circumstances
ANGIOTENSIN ANTAGONIST
 ACE INHIBITOR : Captopril, Enalapril
> Angiotensin II & Aldosteron blood level reduce
> Bradykinin probably increase
> Minimal compensatory response
> Side effect : cough
 ANGIOTENSIN RECEPTOR BLOCKER (ARB):
Losartan, Valsartan
The six antihypertensive
recommended by WHO:
 Diuretics
 Beta Blockers
 ACE Is
 CCBs
 Alpha Blockers
 ARBs
Monotherapy
versus
Polypharmacy
Advantages of monotherapy
 Patients more convenient with
monotherapy
 Many patients do well on a single drug in
mild - moderate hypertension
 Simplicity / better compliance
 Less side effect
 If side effect do occur, the Physician know
the drug responsible
 Current recommendation for the
management of hypertension

Monotherapy at low dose

Titrated upward to higher dose

Achieved BP control Do not achieved BP control

Added another class

continued of AH agent
The problem of monotherapy
 Response rate with 1 class of AH is low
 Waste the time for titrated dosage upward or
switch drug in order to reach goal BP
 Many of the common adverse events are
dose dependent
 Compensatory response
 Increased rate of adverse event lead to
decrease patient compliance
Hypertension
Treatment

Decreased Blood Pressure

Increased sympathetic Renin increased

out flow (RAAS)
(peripheral resistance)
blocked by blocked by diuretics
beta blocker ACE I
Salt and water
tachycardia retention

Increased BP
 JNC VII
( Joint National Committee Report on Prevention Detection, Evaluation and Treatment of
High Blood Pressure )

Stage I Hypertension Stage II Hypertension

( 140 - 159 / 90 - 99 ) (>160/>100)

Polypharmacy
Monotherapy with
Polypharmacy 2 drug combination for most
thiazide ( most ), ACEI,
Combination between thiazide usually Thiazide and ACEI,
ARB, BB, CCB
and ather class ARB,BB,CCB

Not at goal BP

Optimize dosages
Add additional drugs
TERIMAKASIH