Hypertension Lecture PDF

HYPERTENSION REAGAN KABUKA (BPHARM, MPH) INTRODUCTION Hypertension is the most common cardiovascular disease It is defined as sustained high Blood Pressure >140/90mmHg BP CLASSIFICATION ETIOLOGY Essential Hypertension (90%): - No specific cause Family history En...

HYPERTENSION REAGAN KABUKA (BPHARM, MPH) INTRODUCTION Hypertension is the most common cardiovascular disease It is defined as sustained high Blood Pressure >140/90mmHg BP CLASSIFICATION ETIOLOGY Essential Hypertension (90%): - No specific cause Family history Environmental factors: 1- Stress 2- Obesity 3- High Sodium diet 4- Smoking 5- Alcohol 6- Physical exercise REGULATION OF BLOOD PRESSURE B.P is proportional to product of Cardiac output (C.O) and Peripheral vascular resistance (PVR) Physiologically, B.P is maintained by moment-to-moment regulation of C.O and PVR exerted at 4 anatomic sites: - Arterioles, Post-capillary venules, heart and kidney Regulation of B.P occurs through Baroreceptors and Sympathetic nervous system: - Carotid baroreceptors (stimulated by stretch of blood vessel wall by internal pressure) normally send inhibitory impulses to Vasomotor centre (VMC) in the medulla - A fall in B.P causes carotid baroreceptors to send fewer inhibitory impulses to VMC increasing sympathetic activity to the heart - increasing sympathetic activity to the heart (increased C.O) as well as arteriolar vasoconstriction (increased PVR) and vasoconstriction of the venules (increased venous return) CONT This baroreflex acts in response to: - Changes in posture - Decrease in PVR secondary to vasoconstrictors - Decreased intravascular volume due to low sodium diet, diuretics, blood loss and C.H.F. Renin-Angiotensin-Aldosterone System (RAAS): By controlling blood volume, kidney is responsible for long term B.P control This occurs through: 1- Decreased Renal perfusion pressure resulting in increased Renal salt and water reabsorption 2- Decreased pressure in renal arterioles leading to increased Renin. This results in formation of Angiotensin II leading to vasoconstriction, increased NE and secretion of Aldosterone which results in increased B.P. In hypertensive patients, Baroreceptors and RAAS are set at a higher level of B.P and antihypertensive drugs act by interfering with these mechanisms Classification of Antihypertensive Drugs 1. Diuretics 2. Drugs acting on the sympathetic system: A. Central acting: - Clonidine, Moxonidine, Methyldopa B. Beta-Adrenergic Blockers: - Propranolol, Atenolol C. Alpha-Adrenergic Blockers: - Prazocin, Doxazocin D. Adrenergic Neuronal Blockers: - Reserpine 3. Angiotensin-Converting Enzyme Inhibitors (ACEI’s) 4. Angiotensin II Receptor Blockers (ARB’s) 5. Calcium Channel Blockers (CCB’s) 6. Vasodilators: A. Arterial: -Hydralazine, Minoxidil, Fenoldopam, Diazoxide B. Mixed: - Sodium nitroprusside DIURETICS Diuretics decrease B.P by depleting body sodium stores and reducing blood volume Used as monotherapy in mild or moderate hypertension Combined with other classes in severe hypertension Thiazides are the most frequently used class of diuretics: - Effective at low doses (Hydrochlorothiazide 12.5mg daily) - Usually combined with K+ sparing diuretics - If another drug is required, ACEI’s and ARB’s are used (i.e. decrease K+ loss by Thiazides) Toxicity of Diuretics include hypokalemia, hypomagnesemia, increased serum lipid and impair glucose tolerance increasing the risk of ischemic heart disease, hyperuricemia and sexual impairment BETA-ADRENOCEPTOR BLOCKERS Beta-blockers provide effective therapy for all grades of hypertension. Used in combination with Vasodilators in cases of severe hypertension to prevent reflex tachycardia that occurs with these drugs Preparations and Dosage: 1- Propranolol: - Non-selective and lipophilic. 20mg Tabs twice daily; increased rapidly until optimal B.P control 2- Atenolol: - Selective and hydrophilic. 50-100mg Tabs once daily 3- Carvedilol: - Vasodilatory lipophilic Beta-blocker with additional Alpha-1 blocking effect; 3.125- 12.5mg once daily orally. 4- Labetalol: - Alpha-1 and Beta adrenergic receptor blocker used I.V in hypertensive emergency. ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI’s) Mechanism of action: - ACEI’s inhibit angiotensin-converting enzyme which is responsible for the formation of angiotensin II and breakdown of bradykinin. This results in: 1- Reduction of plasma angiotensin II causing arteriolar and venular vasodilatation. 2- Reduction of aldosterone leading to salt and water excretion with K+ retention. 3- Preservation of kinins which are vasodilators. 4- ACEI’s inhibit Angiotensin II formation in tissues (heart and blood vessels) preventing myocardial hypertrophy and remodeling following myocardial infarction. Examples are enalapril, captopril, lisinopril and ramipril ADVERSE EFFECTS OF ACEIs 1st dose hypotension (Start with small dose). Skin rash. Persistent dry cough (Raised bradykinin and increased PGs); may be relieved by NSAIDS. Temporary loss of taste. Proteinuria and Nephrotic syndrome in patients with renal disease. Neutropenia (Rare but Serious). Hyperkalemia occurs in patients with renal insufficiency, or those taking Betablockers and/or Potassium-sparing diuretics. Angioedema (Raised bradykinin and auto-antibodies). Fetopathic (Hypotension, Anuria and renal failure). Therefore ACEIs are contraindicated in pregnancy. Acute renal failure. Contraindicated in Bilateral renal artery stenosis. ANGIOTENSIN RECEPTOR BLOCKERS (ARB’s) They are competitive blockers of Angiotensin II receptor Type 1 (AT1). Orally active; Bioavailability