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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
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
BP = CO x PVR
BP = Blood Pressure
CO = Cardiac Output
PVR = Peripheral Vascular Resistance
Renal
Carotid Baroreceptor
inhibition
renin production
angiotensin II production
aldosterone synthesis
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
Zain-Hamid, R; Faculty of Medicine UISU.
ANTIHYPERTENSIVE AGENTS
3. Direct vasodilators:
relaxing vascular smooth muscle
or
3. Symphatetic ganglia :
trimetaphan
4. - receptors of heart :
propranolol & other -blockers
Zain-Hamid, R; Faculty of Medicine UISU.
Antihypertensive agent: Drugs that alter sodium & water balance (Diuretics)
Diuretics
Therapeutic end point in treating hypertension
Daily natriuresis
Zain-Hamid, R; Faculty of Medicine UISU.
Diuretics
Diuretics
Potassium loss is coupled to reabsorption of sodium
Diuretics
blood volume & cardiac output
Peripheral vascular resistance may
Diuretics
Effective in blood pressure by 10-15 mm Hg in most patients
Diuretics alone
Treatment for mild or moderate hypertension and normal renal & cardiac function
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
Zain-Hamid, R; Faculty of Medicine UISU.
Produce toxicity from inhibition of parasympathetic regulation, in addition to profound sympathetic blockade
Zain-Hamid, R; Faculty of Medicine UISU.
Produce a more selective spectrum of effects depending on the class of receptor to which they bind
Zain-Hamid, R; Faculty of Medicine UISU.
Used alone may be limited by retention of sodium & expansion of blood volume More effective when used concomitantly with a diuretics
Zain-Hamid, R; Faculty of Medicine UISU.
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)
Zain-Hamid, R; Faculty of Medicine UISU.
- blockers (propranolol)
Indication:
Mild to moderate hypertension
Severe hypertension
preventing the reflex tachycardia that often results from treatment with direct vasodilator
Zain-Hamid, R; Faculty of Medicine UISU.
- blockers (propranolol)
Mechanism of action:
Antagonizes 1and 2 - adrenoceptors First administration CO (bradycardia)
- blockers (propranolol)
Pharmacokinetics :
Peroral first pass metabolism;
T : 3-6 hours
- blockers (propranolol)
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
Zain-Hamid, R; Faculty of Medicine UISU.
- blockers (propranolol)
- 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
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
Zain-Hamid, R; Faculty of Medicine UISU.
- blockers (labetalol)
- blockers
(Prazosin, terazosin & doksazosin)
Pharmacokinetic
- First pass metabolism
- blockers
- blockers
ACE-inhibitors
(Angiotensin Converting Enzyme- Inhibitors)
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
ACE- Inhibitors
(Captopril)
Pharmacokinetics :
Bioavailability : +70 % & decreased by 30 - 40 % (if drug take with the food) T : 3 hours
ACE- Inhibitors
(Captopril) Side effects :
Severe hypotension
(hypovolemia diuretics, salt limited, dirrhea)
Contra indication :
pregnancy (malformation)
Zain-Hamid, R; Faculty of Medicine UISU.
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
Zain-Hamid, R; Faculty of Medicine UISU.
Methyldopa Clonidine
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
Zain-Hamid, R; Faculty of Medicine UISU.