DRUGS USED IN HYPERTENSION Presented by Sara Khalid

DRUGS USED IN HYPERTENSION Presented by: Sara Khalid Memon – Group B 3 3 rd year, MBBS, LUMHS

HYPERTENSION: Hypertension can be defined as: A sustained rise in blood pressure. It is a condition in which the arteries have persistently high blood pressure, making harder for the heart to pump blood in the vessels. Basically it has 2 main components; the SYSTOLIC and the DIASTOLIC blood pressure.

Parameters on which blood pressure depends Cardiac output Total Peripheral Resistance SYSTOLIC BP DIASTOLIC BP > Stroke Volume And Heart Rate Preload: Preload can be defined as the initial stretching of the cardiac myocytes prior to contraction (EDV) Afterload: Afterload is the load against which the heart has to pump(TPR)

H Y P E R T E N S I O N

PHARMACOLOGICAL WAYS TO TREAT HYPERTENSION > Centrally acting sympatholytic drugs > Ganglionic Blockers > Sympathetic Nerve Ending Blockers > Adrenergic Receptor Blockers a) Alpha 1 blockers b) Beta blockers c) Mixed blockers > Direct Vasodilators > Calcium Channel Blockers > Angiotensin Converting Enzyme Inhibitors >Angiotensin Receptor Blockers >Renin Inhibitor > Diuretics

Centrally acting sympatholytic drugs: Clonidine: Advantage: Used in Hypertension when other drugs have not responded adequately. Disadvantage: Sedation, Depression, rebound hypertension on withdrawal Alpha-Methyl Dopa: Advantage: Used in Hypertension when other drugs have not responded adequately. Has less effects on FETUS so can be used in pregnancy. Disadvantage: Sedation, Depression, causes hematologic immunotoxicity (making coomb’s test +ve)

Sympathetic Nerve Ending Blockers: Guanethidine: Replaces norepinephrine in the vesicle and itself acts as false neurotransmitter. Disadvantage: Orthostatic Hypotension. Reserpine: Reserpine irreversibly blocks the Vesicular monoamine transporter. This normally transports free amine neurotransmitters from the cytoplasm of the presynaptic nerve terminal into storage vesicles. Disadvantage: Depression of CNS Metyrosine: Makes the Tyrosine hydroxylase enzyme dysfunctional. Disadvantage: Diarrhea, Trembling of hands and fingers

Adrenergic Receptor Blockers A) Alpha blockers: Selectives: Prazosine, terazosin Adverse Effect: Orthostatic Hypotension Non-Selectives: Phenoxybenzamine, Phentolamine Adverse Effect: Tachycardia, Palpitation B) Beta blockers : Selectives: Metoprolol, Atenolol Adverse Effect: Dizziness, Drowsiness, Fatigue, Diarrhea Non-Selectives: Propranolol Adverse Effect: Drowsiness, Sedation, Asthma

C) Mixed blockers: Acting on Alpha as well as on Beta receptors. Labetolol, Carvidolol, Bucindolol Adverse Effects: Drowsiness, Fatigue, Insomnia, Orthostatic Hypotension NOTE: Nebivolol is a newer beta blocker with some direct vasodilator action Relatively very less adverse effects and is highly cardioselective !!!

Vasodilators Hydralazine: Acts primarily on the arteries and arterioles. >Advantage: Accepted method for controlling blood pressure in pregnant hypertensives. >Disadvantage: Almost always causes reflex tachycardia. Minoxidil: Dilates resistance vessels >Advantage: Used in hypertension refractive to other drugs. Other use is causing hypertrichosis >Disadvantage: Fluid retention, Reflex Tachycardia

Calcium Channel Blockers Verapamil: Acts on both cardiac and smooth muscles(more action on heart) Advantage: Additional used in treatment of angina, supraventricular tachyarrythmias, migraine headache Disadvantage: Facial flushing, dizziness, constipation Diltiazem: Acts on both cardiac and smooth muscles equally. Advantage: Used for hypertension, Angina Disadvantage: Hypotension, bradycardia

Nifedipine: Acts more on arterial smooth muscles than on heart Advantage: Vasoselective Disadvantage: Lethargy, Bradycardia, Hypotension

Angiotensin Converting Enzyme Inhibitors Captopril, Enapril, Lisinopril, Prindropril, Ramipril Advantage: Effective in CCF and Diabetic Nephropathy too Angiotensin II Receptor Blockers Losartan, Cadesartan, Valsartan, Telmisartan Advantage: Do not increase the bradycardia level. Renin Inhibitors Aliskiren, Pepstatin Advantage: Acts directly on the required substrate.

Adverse Effects of ACE Inhibitors C A P T O P R I L Cough (dry Cough) Angioedema Proteinuria Taste changes Hypotension Contraindicated in Pregnancy Rashes Increased K+ Levels Low Ang II and Aldosterone levels

Diuretics Advantage: Effective in controlling blood pressure in long term. Controls BP in Supine as well as standing positions so postural hypotension doesn’t occur. > Loop Diuretics : Furosamide > Thiazides : Hydrochlorothiazide > Potassium Sparing Diuretics : Amiloride, Spironolactone Disadvantage: Of Thiazides include, hypokalemia, hyperuricemia; Of Loop Diuretics include, Ototoxicity; Of Potassium Sparing group include, Gastric upsets, Gynecomastia in males, Menstrual irregularities in females.

TREATMENT PLANS > Diuretics are very effective in Elderly patients, Blacks, Inexpensive and can be used for Prolonged maintenance. > Beta Blockers are wonderful if the patient also has supraventricular tachycardia and/ Angina and/ MI and/Migraine. > Beta blockers and ACE inhibitors are very effective in white and young hypertensives. > Vasodilating drugs cause salt and water retention and cardiostimulatory effects. > Hydralazine should be used with diuretics and beta blockers. > Alpha Blockers always cause postural hypotension.

New Antihypertensive Drugs >Monatepil, a dual alpha-receptor and calcium channel blocker, has potent antihypertensive effect, lowers serum cholesterol and also has antiatherosclerotic effect. >Dual ACE and endopeptidase inhibitor, such as alatriopril, has a "broad spectrum" antihypertensive effect and may be effective in majority of hypertensive patients. Many other are under clinical testing and not yet approved. . !

NON PHARMACOLOGICAL WAYS TO TREAT HYPERTENSION > Physical Exercise > Weight loss > Salt Restriction > Avoid Smoking > Reducing Alcohol Consumption > Relaxation techniques > K+ rich diets > Red meat should be avoided

Thank you ! =)