Mata Kuliah Farmakologi I

Obat-Obat Anti Hipertensi & Obat KardiovaskularNikmatul Ikhrom Eka Jayani, S.Farm., M.FarmKlin., Apt.

PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG

PUSTAKAGoodman & Gilmans Manual of Pharmacology and Therapeutics, Basic & Clinical PharmacologyKatzung, Basic & Clinical Pharmacology 10th edLippincott, Illustrated Reviews Pharmacology 4th edNeal, At a Glance Farmakologi MedisLullman, Colour Atlas of Pharmacology dll

DefinisiHipertensi didefinisikan sebagai salah satu Systolic Blood Pressure (SBP) > 140 mm Hg atau Diastolic Blood Pressure (DBP) > 90 mm Hg.

Klasifikasi Tekanan Darah

Normal100

BP ClassificationSBP mHgDBP mmHg

Faktor Utama yang mempengaruhi Tekanan Darah

Pathophisiology of hypertension

Pathophisiology of hypertension

Pathogenesis of hypertension

Kontrol Tubuh terhadap Tekanan Darah

OBAT-OBAT HIPERTENSIA ACE-1 / ARB / 1-BLOCKER B BETA-BLOCKERC Ca-ANTAGONIS, centralling agentD DIURETICE Etc (lainnya) ex : reserpine

Mekanisme untuk Kontrol Tekanan Darah 1= vasodilators, 2= -blockers3=-blockers4= AT II blocker 5= Centrally sympatholytics6= ACE inhibitors 7= diuretics

Antihipertensi Renin Inhibitor, Angiotensin Converting Enzym Inhibitor (ACE i), Angiotensin Receptor Blocker (ARB)AliskirenCaptopril, Lisinopril, enalaprilValsartan, Candesartan, Telmisartan

levels, ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention. Antihipertensi ACE i (1)

Antihipertensi ACE i (2)

1 blockersThe availability of drugs that selectively block 1 adrenergic receptors without affecting 2 adrenergic receptors is : Prazosin, terazosin, and doxazosinPharmacological Effects. Initially reduce arteriolar resistance and increase venous capacitanceDuring long-term therapy vasodilation persists, but cardiac output, heart rate, and plasma renin activity return to normal. Renal blood flow is unchanged during therapy 1 adrenergic blockers cause a variable amount of postural hypotension, depending on the plasma volume. first-dose phenomenon, in which symptomatic orthostatic hypotension occurs within 90 minutes of the initial dose of the drug or after a dosage increase (50% of patients, especially in patients who are already receiving a diuretic or an a receptor antagonist.)

Centralling agent A. ClonidineThis 2-agonist diminishes central adrenergic outflow, is used primarily for the treatment of hypertension that has not responded adequately to treatment with two or more drugs. Clonidine does not decrease renal blood flow or glomerular filtration and, therefore, is useful in the treatment of hypertension complicated by renal disease.

B. MethyldopaThis 2-agonist is converted to methylnorepinephrine centrally to diminish the adrenergic outflow from the CNS.This leads to reduced total peripheral resistance and a decreased blood pressure. Cardiac output is not decreased, and blood flow to vital organs is not diminished. It has been used in hypertensive pregnant patients.

Antihipertensi Beta Blocker (1)

Antihipertensi Beta Blocker (2)

Calcium-channel blockersThe calcium-channel blockers are divided into three chemical classes, each with different pharmacokinetic :Diphenylalkylamines: Verapamil. Verapamil is the least selective of any calcium-channel blocker and has significant effects on both cardiac and vascular smooth muscle cellsBenzothiazepines: Diltiazem. Like verapamil, diltiazem affects both cardiac and vascular smooth muscle cells; however, it has a less pronounced negative inotropic effect on the heart compared to that of verapamil.Dihydropyridines:first-generation : Nifedipine second-generation : Amlodipine, Felodipine, Isradipine, Nicardipine, and Nisoldipine.All dihydropyridines have a much greater affinity for vascular calcium channels than for calcium channels in the heart. They are therefore particularly attractive in treating hypertension.

Antihipertensi DiuretikAcetazolamideMethazolamideThiazidFurosemideAsam EtakrinatBumetanidAmiloridTriamterenSpironolaktonManitol

reserpineReserpine binds tightly to adrenergic storage vesicles in central and peripheral adrenergic neurons and remains bound for prolonged periods of time. The interaction inhibits the vesicular catecholamine transporter that facilitates vesicular storage. Thus, nerve endings lose their capacity to concentrate and store norepinephrine and dopamine.Both with reserpine. cardiac output and peripheral vascular resistance are reduced during long-term therapy.Orthostatic hypotension

Obat-Obat Gagal Jantung

Obat InotropikPositive inotropic agents enhance cardiac muscle contractility and thus, increase cardiac outputinotropic action is the result of an increased cytoplasmic calcium concentration that enhances the contractility of cardiac muscle

A. DigitalisThe cardiac glycosides are often called digitalis or digitalis glycosides, because most of the drugs come from the digitalis (foxglove) plant.The cardiac glycosides influence the sodium and calcium ion flows in the cardiac muscle, thereby increasing contraction of the atrial and ventricular myocardium (positive inotropic action).The drugs have a low therapeutic index.The most widely used agent is digoxin

Digitalis toxicity is one of the most commonly encountered adverse drug reactions

Side effects often can be managed by discontinuing cardiac glycoside therapy, determining serum potassium levels (decreased K+ enhances potential for cardiotoxicity), and if indicated, giving potassium supplements.

Intoxication signscardiac arrhythmias, which under certain circumstances are life-threatening, e.g., sinus bradycardia, AV-block, ventricular extrasystoles, ventricular fibrillation (ECG); CNS disturbances altered color vision (xanthopsia), agitation, confusion, nightmares, hallucinationsgastrointestinal anorexia, nausea, vomiting, diarrhea; renal loss of electrolytes and water, which must be differentiated from mobilization of accumulated edema fluid that occurs with therapeutic dosage

B. -Adrenergic agonists-Adrenergic stimulation improves cardiac performance by causing positive inotropic effects and vasodilation.Dopamine and Dobutamine is the most commonly used

C. Phosphodiesterase inhibitorsAmrinone and milrinone are phosphodiesterase inhibitors

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********Tubuh mempunyai banyak mekanisme untuk mengontrol tekanan darah : tubuh dapat mengubah jumlah darah yang dipompa jantung, diameter arteri dan volume darah yang beredar di tubuh. Mekanisme kontrol melalui sympathetic autonomic norvous system dan oleh ginjal. Saraf simpatik merangsang kelenjar adrenal untuk merelease epinephrine dan norepinephrine. Hormon tersebut menstimulasi jantung berdenyut lebih cepat, selain itu juga mempengaruhi pembuluh darah. Saraf simpatik juga menstimulasi ginjal, sehingga terjadi penurunan ekskresi sodium (natrium) dan air yang akhirnya menyebabkan peningkatan volume darah.Kontrol darah oleh ginjal adalah apabila tekanan darah naik, maka ginjal akan meningkatkan ekskresi air dan garam. Sebaliknya ketika tekanan darah turun maka ginjal akan menurunkan ekskresi garam natrium dan air, ginjal mengeluarkan enzim renin yang akan mengubah angiotensin menjadi AT II yang menyebabkan vasokonstriksi arteriol, menstimulai saraf simpatik dan menyebabkan pelepasan hormon aldosterone dan antiduretik yang menyebabkan ginjal meretensi air dan natrium*****************Heart failure is accompanied by compensatory neurohormonal responses including activation of the sympathetic nervous and renin-angiotensin systems. Although these responses initially help to maintain cardiovascular function by increasing ventricular preload and systemic vascular tone, with time they contribute to the progression of myocardial failure. Increased ventricular afterload, due to systemic vasoconstriction and chamber dilation, causes a depression in systolic function. In addition, increased afterload and the direct effects of angiotensin and norepinephrine on the ventricular myocardium cause pathological remodeling characterized by progressive chamber dilation and loss of contractile function. The figure illustrates several mechanisms that appear to play important roles in the pathophysiology of heart failure, and the sites of action of pharmacological therapies that have been shown to be of clinical value. ********