Anti Hipertensi

Curriculum Vitae
Nama : Prof. Dr. dr. Rozaimah Zain-Hamid, MS, SpFK

Fakultas Kedokteran, USU, Medan * Staf Pengajar Program S2 Biomedik & Program Administrasi Kebijakan Kesehatan; Program S3 Kedokteran, Sekolah Pascasarjana, USU, Medan * Wakil Ketua Komisi Nasional Etika Penelitian Kesehatan (KNEPK), Republik Indonesia
Pekerjaan : * Guru Besar Tetap Departemen Farmakologi dan Terapeutik,
Riwayat Pendidikan: * Dokter (dr), dari Fakultas Kedokteran, USU. Medan * Magister Sains (MS), Ilmu Kedokteran Dasar (Basic Medical Sciences), dari Fakultas Pascasarjana, Universitas Indonesia, Jakarta * Doktor (Ph.D), Farmakologi Klinik (Clinical Pharmacology), dari Institute of Post-graduated Studies, Universiti Sains Malaysia, Malaysia * Spesialis Farmakologi Klinik (Sp.FK), dari Dewan Penilai Kepakaran Persatuan Dokter Ahli Farmakologi Klinik Indonesia (PERDAFKI) Pusat, Jakarta.
ROZAIMAH ZAIN-HAMID
Department of Pharmacology and Therapeutics Faculty of Medicine Universitas Islam Sumatera Utara
Sustained arterial hypertension

Damages blood vessels in kidney, heart, brain etc
Renal failure, coronary disease and stroke

Zain-Hamid, R; Faculty of Medicine UISU.
Elevated blood pressure
Multifactorial: Genetic inheritance, psychological stress, environmental & dietary factors
Epidemiologic studies of hypertension
The risk of damages to kidney, heart, brain are directly related to extent of blood pressure elevation
Even mild hypertension (blood pressure 140/90 mm Hg) in young or middle-aged adults
The risk of eventual end organ damage


Other positive risk factors: Smoking, hyperlipidemia, diabetes, manifestations of end organ damage at the time of diagnosis, and family history of cardiovascular disease
The risk of eventual end organ damage

Effective pharmacologic lowering of blood pressure
Prevent damages of blood vessels
Morbidity and mortality rate

BP = CO x PVR
BP = Blood Pressure
CO = Cardiac Output
PVR = Peripheral Vascular Resistance
Sites of blood pressure control
1.RESISTANCE (arterioles) 2. CAPACITANCE (venules) 3. PUMP OUTPUT (heart) 4. VOLUME (kidneys)
Renal
Contribute to maintain blood pressure
Regulating the volume of intravascular fluid
Baroreflexes, mediated by sympathetic nerves + Humoral mechanism (renin-angiotensin-aldosterone system)
To coordinate function of 4 control sites
Maintain normal blood pressure

Regulation of normal blood pressure

A. Baroreflex :
Stretching of blood vessels ( blood pressure)

stimulation
Carotid Baroreceptor
inhibition
Release of central sympathomimetics

Regulation of normal blood pressure

B. Renal response in blood pressure regulation Renal perfusion pressure renal arteriole pressure
receptor stimulation
Redistribution of renal blood supply
renin production
angiotensin II production
Salt & water reabsorption
Direct peripheral vasoconstriction
aldosterone synthesis
Regulation of blood pressure in hypertensive
Baroreceptors & Renal blood volume-pressure control system
To be set at a higher level of blood pressure

ANTIHYPERTENSIVE AGENTS
1.Diuretics (alter sodium & water balance):
depleting body sodium & blood volume
2. Sympathoplegic agents :
peripheral vascular resistance inhibiting cardiac function venous pooling in capacitance vessels
ANTIHYPERTENSIVE AGENTS
3. Direct vasodilators:
relaxing vascular smooth muscle
4. Agents that block production action of angiotensin:

peripheral vascular resistance &
blood volume
or
Sites of action of the major classes of antihypertensive drugs

1.CNS / Vasomotor Center :
methyldopa, clonidine, guanabenz & guanfacine
2. Sympathetic nerve terminals :

guanethidine, guanadrel & reserpine
3. Symphatetic ganglia :
trimetaphan
4. - receptors of heart :
propranolol & other -blockers
Sites of action of the major classes of antihypertensive drugs

5. Blood vessels : 5.1. -receptors of vessels :
prazosin & other 1-blockers
5.2. Vascular smooth muscle :

hydralazine, minoxidil, nitroprussid, diazoksid, verapamil & other Ca++ channel blocker
Sites of action of the major classes of antihypertensive drugs 6. Renal :
6.1. Renal tubulus :

thiazides, etc
6.2. - receptor of juxtaglomerular cells that release renin :

propranolol & other -blockers
6.3. Angiotensin Converting Enzyme :

captopril & other ACE inhibitors
Antihypertensive agent: Drugs that alter sodium & water balance (Diuretics)
Diuretics
Therapeutic end point in treating hypertension
Daily natriuresis
Diuretics
To oppose the tendency toward sodium retention in a relatively sodium-depleted patient
Diuretics
Potassium loss is coupled to reabsorption of sodium
Restriction of dietary sodium intake potassium loss

Diuretics
blood volume & cardiac output
Peripheral vascular resistance may
After 6-8 weeks

Cardiac output return to normal
Peripheral vascular resistance may
Diuretics
Effective in blood pressure by 10-15 mm Hg in most patients
Diuretics alone
Adequate treatment for mild or moderate essential hypertension

Treatment for mild or moderate hypertension and normal renal & cardiac function
Thiazide diuretics Treatment for severe hypertension
Diuretics + sympathoplegic + vasodilator drugs

More powerful diuretics : acting on the loop of Henle

Severe hypertension, when multiple drugs with sodium - retaining properties are used
Renal insufficiency, when GFR < 30 or 40 mL/min.
Cardiac failure or cirrhosis, where sodium retention is marked

Potassium sparing diuretics
To avoid excessive potassium depletion, particularly in patients taking digitalis
To enhance the natriuretic effects of other diuretics
Thiazide diuretics
More natriuretic at higher doses ( >100 200 mg hydrochlorothiazide)
When used as a single agent, lower doses (25 50 mg) exerts as much antihypertensive effect do higher doses
Most common adverse effect of diuretics

Potassium depletion ( hypokalemia) Magnesium depletion Impair glucose tolerance
serum lipid & uric acid concentration
Antihypertensive agent: Drugs that alter sympathetic nervous system function
Antihypertensive drugs that alter sympathetic nervous system function

1. Centrally acting sympathoplegic
2. Inhibition transmission through autonomic ganglia 3. Reducing release of norepinephrine from sympathetic nerve endings 4. Block postsynaptic adrenoceptors
1. Centrally acting sympathoplegic
Cause sedation & mental depression, disturbances of sleep (nightmare)
2. Inhibition transmission through autonomic ganglia
Produce toxicity from inhibition of parasympathetic regulation, in addition to profound sympathetic blockade
3. Reducing release of norepinephrine from sympathetic nerve endings
Cause effect similar to those of surgical sympathectomy

(inhibition of ejaculation, hypotension that is increased by upright posture & after exercise)
4. Block postsynaptic adrenoceptors
Produce a more selective spectrum of effects depending on the class of receptor to which they bind
Used alone may be limited by retention of sodium & expansion of blood volume More effective when used concomitantly with a diuretics
Adrenoceptor antagonist
Antihypertensive drugs :
Block postsynaptic adrenoceptors (adrenoceptor antagonist)
- adrenoceptor-blocking agents
(propranolol, metoprolol, nadolol, carteolol, atenolol, pindolol, acebutolol, labetalol)
- adrenoceptor-blocking agents
(prazosin & other -blockers)
- blockers (propranolol)
Indication:
Mild to moderate hypertension
Severe hypertension
preventing the reflex tachycardia that often results from treatment with direct vasodilator
Mechanism of action:
Antagonizes 1and 2 - adrenoceptors First administration CO (bradycardia)
Continued treatment peripheral resistance

Inhibits the stimulation of renin production by cathecolamine (mediated by 1- receptors) Depression of the renin angiotensin aldosterone system
Pharmacokinetics :
Peroral first pass metabolism;
T : 3-6 hours
Withdrawal syndrome : nervousness, tachycardia, intensity of angina &BP
Side effects :
Predictable extension of - blocking action occur in patients with myocardial reserve, asthma, peripheral vascular insufficiency & diabetes Other side effects : diarrhea, constipation, nausea, vomiting, mental depression, nightmares, insomnia etc
Plasma triglycerides & HDL-cholesterol, which theoretically could contribute to atherogenesis
- blockers (metoprolol)
Equipotent to propranolol as a 1- blockers
More selective to 1- receptor than propranolol asthmatic patients, diabetes and other peripheral vascular disease Inhibiting stimulation 2 reseptor 50-100 fold less potent than propranolol
Cardios selectivity is not complete: eksaserbasi asma

- blockers (nadolol, carteolol, atenolol)
Nadolol & carteolol non selektif 1-blocker Atenolol & betaxolol selective - 1 blocker & longer T once a day dosages to obtain a satisfactory therapeutic effect should dosage 4-5/day Renal function nadolol, carteolol & atenolol
- blockers (labetalol)
BP systemic vascular resistance without significant alteration in HR or CO
Has -blocking action & - blocking action, ( : = 3 : 1)

For treatment hypertension with pheochromocytoma & hypertensive emergency
- blockers
(Prazosin, terazosin & doksazosin)
Pharmacokinetic
- First pass metabolism
(Prazosin, terazosin & doxazosin)

Mechanismof action
Blocking 1 in arterioles & venules BP arterioles & venules dilatation 1- receptors selectivity produce less reflex tachycardia Retention of salt & fluid occurs when these drugs are administered without diuretics
- blockers
(Prazosin, terazosin & doxazosin)

Pharmacokinetic : First pass metabolism (liver) Side effects :
- blockers
postural hypotension first dose should be small & administered at bedtime

Other side effects : dizziness, palpitation, & headache
ACE-inhibitors
(Angiotensin Converting Enzyme- Inhibitors)
ACE- Inhibitors
Captopril, enalapril, lisinopril

Benazepril, fosinopril, quinapril,
ramipril
(Long-acting members of ACE-inhibitors)
ACE- Inhibitors
(Captopril)
Mechanism of action :
Inhibitory action on renin - angiotensin system
Stimulation kalikrein - kinin system
ACE- Inhibitors
(Captopril)
Mechanism of action :
Improved intrarenal hemodynamics glomerular efferent arteriole resistance
intraglomerular capillary pressure

ACE- Inhibitors
(Captopril)
Pharmacokinetics :
Bioavailability : +70 % & decreased by 30 - 40 % (if drug take with the food) T : 3 hours
Blood levels correlate poorly with clinical response

ACE- Inhibitors
(Captopril) Side effects :
Severe hypotension
(hypovolemia diuretics, salt limited, dirrhea)
Other side effects :

Acute renal failure, hyperkalemia, cough
Contra indication :
pregnancy (malformation)
Conclusions :
Effective pharmacologic lowering BP has been shown to prevent damage to blood vessels & reduce morbidity and mortality
Antihypertensive agents give different mechanisme to regulate blood pressure Combination of antihypertensive agents is necessary to optimize hypertension therapy
Antihypertensive agent: Centrally acting sympathoplegic drugs
Methyldopa Clonidine
Antihypertensive agent: Centrally acting sympathoplegic drugs
Methyldopa & clonidine slightly different hemodynamic effects :

clonidine lowers heart rate & cardiac output more than does methyldopa
they may act primarily on different populations of neurons in vasomotor center of the brain stem
Methyldopa
Useful for mild to moderately severe hypertension
peripheral vascular resistance, with variable in heart rate & cardiac output Sometimes cause postural hypotension (orthostatic hypotension) One potential advantage of methyldopa is renal vascular resistance

Anti Hipertensi

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Anti Hipertensi

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Curriculum Vitae

Nama : Prof. Dr. dr. Rozaimah Zain-Hamid, MS, SpFK

Pekerjaan : * Guru Besar Tetap Departemen Farmakologi dan Terapeutik,

Sustained arterial hypertension

Renal failure, coronary disease and stroke

Elevated blood pressure

Multifactorial: Genetic inheritance, psychological stress, environmental & dietary factors

Zain-Hamid, R; Faculty of Medicine UISU.

Epidemiologic studies of hypertension

Zain-Hamid, R; Faculty of Medicine UISU.

Epidemiologic studies of hypertension

The risk of eventual end organ damage

Epidemiologic studies of hypertension

The risk of eventual end organ damage

Effective pharmacologic lowering of blood pressure

Prevent damages of blood vessels

Morbidity and mortality rate

Zain-Hamid, R; Faculty of Medicine UISU.

Sites of blood pressure control

1.RESISTANCE (arterioles) 2. CAPACITANCE (venules) 3. PUMP OUTPUT (heart) 4. VOLUME (kidneys)

Zain-Hamid, R; Faculty of Medicine UISU.

Contribute to maintain blood pressure

Regulating the volume of intravascular fluid

Zain-Hamid, R; Faculty of Medicine UISU.

Baroreflexes, mediated by sympathetic nerves + Humoral mechanism (renin-angiotensin-aldosterone system)

To coordinate function of 4 control sites

Maintain normal blood pressure

Regulation of normal blood pressure

Stretching of blood vessels ( blood pressure)

Release of central sympathomimetics

Regulation of normal blood pressure

Redistribution of renal blood supply

Salt & water reabsorption

Direct peripheral vasoconstriction

Zain-Hamid, R; Faculty of Medicine UISU.

Regulation of blood pressure in hypertensive

Baroreceptors & Renal blood volume-pressure control system

To be set at a higher level of blood pressure

4. Agents that block production action of angiotensin:

Zain-Hamid, R; Faculty of Medicine UISU.

Sites of action of the major classes of antihypertensive drugs

2. Sympathetic nerve terminals :

Sites of action of the major classes of antihypertensive drugs

prazosin & other 1-blockers

5.2. Vascular smooth muscle :

Zain-Hamid, R; Faculty of Medicine UISU.

Sites of action of the major classes of antihypertensive drugs 6. Renal :

6.1. Renal tubulus :

6.2. - receptor of juxtaglomerular cells that release renin :

6.3. Angiotensin Converting Enzyme :

Zain-Hamid, R; Faculty of Medicine UISU.

To oppose the tendency toward sodium retention in a relatively sodium-depleted patient

Zain-Hamid, R; Faculty of Medicine UISU.

Restriction of dietary sodium intake potassium loss

After 6-8 weeks

Adequate treatment for mild or moderate essential hypertension

Thiazide diuretics Treatment for severe hypertension

Diuretics + sympathoplegic + vasodilator drugs

More powerful diuretics : acting on the loop of Henle

Cardiac failure or cirrhosis, where sodium retention is marked

Potassium sparing diuretics

To avoid excessive potassium depletion, particularly in patients taking digitalis

To enhance the natriuretic effects of other diuretics