Antihypertensive Drugs

Antihypertensive DrugsChapter 11LEI-ANN JESSICA R. CABULAY

HYPERTENSIONElevation of blood pressure from the normal range (varies with age)2 classifications:PRIMARY/ESSENTIAL HYPERTENSION- no definite cause, idiopathicSECONDARY HYPERTENSION- with underlying disease process

1. DIURETICSlower blood pressure by reduction of blood volumethiazides (eg, hydrochlorothiazide)- used in mild hypertension loop diuretics (eg, furosemide)- used in moderate and severe hypertension and in hypertensive emergencies.

Side Effects:Muscle weakness and crampsLoss of sodium and potassium saltsDizziness and nauseaKidney problemsHeart damageMinimal compensatory response

SYMPATHOLPLEGICSA. Baroreceptor-Sensitizing AgentsA few natural products, such as veratrum alkaloids, appear to increase sensitivity of baroreceptor sensory nerves and reduce SANS outflow while increasing vagal tone to the heart. These agents are toxic and no clinically available drugs act at this siteSYMPATHOLPLEGICSB. Central Nervous System-Active AgentsDecrease sympathetic outflow by activation of alpha 2 receptors in the CNSEg. Clonidine and methyldopaDecrease cardiac output, decrease vascular resistanceSide effects: rebound hypertension (if stopped abruptly) and sedation

SYMPATHOLPLEGICS

C. Ganglion-Blocking DrugsNicotinic blockers that act in the ganglia are very efficacious, but because their adverse effects are severe, they are now considered obsolete. Hexamethonium and trimethaphan are extremely powerful blood pressure-lowering drugs.SYMPATHOLPLEGICS

D. Postganglionic Sympathetic Nerve Terminal BlockersReserpine- deplete adrenergic nerve terminals of its norepinephrine storesGuanethedine, Guanadrel-deplete and block release of the stores of norepinephrineMAOIs- form false transmitter (octopamine) in sympathetic post ganglionic neuron terminalsOBSOLETESYMPATHOLPLEGICSE. Adrenoceptor BlockersAlpha blockers- reduce vascular resistance and decrease venous returnNon Selective alpha blockers- no value in chronic hypertension because of its SE of excessive tachycardiaAlpha 1 selective blockers- (prazosin, doxazosin, terazosin)Has SE of orthostatic hypotension (first few doses)Relax smooth muscle in the prostrate, which is useful in BPH

SYMPATHOLPLEGICSE. Adrenoceptor BlockersBeta blockers- propanolol, atenolol, carvedilol, metoprololInitially: reduce cardiac outputLater: decrease vascular resistance due to reduced angiotensin levels

VASODILATORSDrugs that dilate blood vessels by acting directly on smooth muscle cells through nonautonomic mechanisms, thereby decreasing blood pressure Vasodilators act by four major mechanisms:release of nitric oxideopening of potassium channels (which leads to hyperpolarization)blockade of calcium channels, and activation of D1 dopamine receptors

VASODILATORSA. Hydralazine and MinoxidilHydralazine-acts through the release of nitric oxide from endothelial cellsHydalazine induced lupus erythematosus-reversible, dosage must be < 200mg/dLMinoxidil- systemic administration is reserved for severe hypertensionMinoxidil minoxidil sulfate- potassium channel opener that hyperpolarizes and relaxes vascular smooth muscleSE: hirsutism- topical agent for baldnessVASODILATORSB. Calcium Channel-Blocking Agents- effective vasodilatorsNifedipine- prototype of dihydropyrimidine calcium channel blockerVerapamil- decreases cardiac outputDiltiazem- decreases cardiac outputVASODILATORSC. Nitroprusside, Diazoxide, and FenoldopamVasodilators used in hypertensive emergencyNitroprussideLight sensitive, short acting agent

VASODILATORSC. Nitroprusside, Diazoxide, and FenoldopamDiazoxide- thiazide derivative, (-) diuretic propertiesOpens potassium channels, thus, hyperpolarizing and relaxing smooth musclesDecreases insulin release and can be used to treat hypoglycemia caused by insulin producing tumorsFenoldopam-activate dopamine D1 receptor prompt marked arteriolar vasodilationUsed in hypertensive emergencies

ANGIOTENSIN ANTAGONISTSACE inhibitors (pril drugs)- inhibit enzyme angiotensin converting enzyme, kinases II, peptidyl dipeptidase leading to:Reduction of angiotensin II and aldosteroneIncrease in endogenous vasodilators of kinin family (bradykinin)Renal protective, useful in patients with diabetes & heart failureToxicities: cough, renal and fetal toxicitiesTERATOGENANGIOTENSIN ANTAGONISTSAngiotensin II Receptor Blockers (sartan drugs)Competitively inhibit angiotensin II at its AT 1 receptor siteLower incidence of coughFetal and renal toxicitiesTERATOGENRENIN INHIBITOR

RENIN INHIBITORAliskirenToxicities: headache, diarrheaTERATOGENCLINICAL USES OF ANTIHYPERTENSIVEDRUGSA. Stepped Care (Polypharmacy)overall toxicity can be reduced and compensatory responses minimized by the use of multiple drugs at lower dosages in patients with moderate or severe hypertensioneach additional agent is chosen from a different subgroup until adequate blood pressure control has been achieved.

CLINICAL USES OF ANTIHYPERTENSIVEDRUGSThe usual steps include:lifestyle measures diuretics (a thiazide)(3) sympathoplegics (a blocker)(4) ACE inhibitors, and(5) vasodilators. The vasodilator chosen first is usually a calcium channel blocker.The ability of drugs in steps 2 and 3 to control the compensatory responses induced by the others should be noted (eg, propranolol reduces the tachycardia induced by hydralazine)

CLINICAL USES OF ANTIHYPERTENSIVEDRUGSB. MonotherapyThis approach to treatment of mild and moderate hypertension has become more popular than stepped care because of its simplicity, better patient compliance, andwith modern drugsa relatively low incidence of toxicity.CLINICAL USES OF ANTIHYPERTENSIVEDRUGSC. Age and EthnicityBeta blockers- very effective to Whites and young patientsDiuretics- very effective to Blacks and elderly

CLINICAL USES OF ANTIHYPERTENSIVEDRUGSD. Hypertensive Emergency(formerly called malignant hypertension) accelerated form of severe hypertension associated with rising blood pressure and rapidly progressing damage to vessels and end organs. Management must be carried out on an urgent basis in the hospital. Powerful vasodilators (nitroprusside, fenoldopam, or diazoxide) are combined with diuretics (furosemide) and blockers to lower blood pressure to the 140160/90110 mm Hg range promptly (within a few hours). Further reduction is then pursued more slowly.