Hypertension Drugs PDF

Hypertension medications  Blood pressure regulation We have 2 mechanisms: Baroreceptor (quickly acts) Renin-angiotensin (in long term) Classification of diuretic drugs  Diuretics  Thiazides  Hydrochlorothiazide, Chlorthalidone, Metolazo...

Hypertension medications  Blood pressure regulation We have 2 mechanisms: Baroreceptor (quickly acts) Renin-angiotensin (in long term) Classification of diuretic drugs  Diuretics  Thiazides  Hydrochlorothiazide, Chlorthalidone, Metolazone  Mechanism of action: Inhibition of Na+ sodium reabsorption in the distal tubule  Thiazides in hypertension The first line of treatment (especially in postmenopausal women or women with osteoporosis) is just HTN Side effects: Hyponatremia Hypokalemia Hyperglycemia (resistance to insulin production) Hyperuricemia (drug competes with urea excretion) Hyperlipidemia (increased TG and LDL) Hypercalcemia  Loop diuretics Furosemide, Bumetanide, Torsemide, Etacrynic acid Mechanism of action: Inhibition of sodium reabsorption in the ascending part of the loop of Henle The third line of treatment Severe HTN (first choice) HTN + kidney failure (first choice) HTN + abdominal/pulmonary edema (first choice)  Loop diuretics  Side effects: Hypokalemia (hypokalemic metabolic alkalosis) Hyperuricemia (drug competes with urea excretion) Hypocalcemia Hypomagnesemia Ototoxicity Allergic reaction  Potassium sparing diuretics Aldosterone antagonist: Spironolactone Non-antagonists of aldosterone: Amiloride, Triamterene Mechanism of action: Reducing the reabsorption of sodium in the collecting ducts and reducing the release of potassium into the urine They do not have a diuretic effect and do not affect blood pressure. Prevention of potassium excretion in the use of loop diuretics and thiazides  Potassium sparing diuretics  Side effects:  Hyperkalemia  Spironolactone:  Gynecomastia  Women's menstrual disorders  Inflammation and kidney stones (Triamterene)  Inhibitors of the adrenergic system 1. Centrally acting adrenergic blocking drugs 2. Ganglion blocking drugs (Mecamylamine) 3. Adrenergic neuron blocking drugs (Reserpine) 4. Adrenergic receptor antagonists: alpha blocker or beta blocker  Central adrenergic blocking drugs Methyldopa decreases central (CNS) sympathetic outflow They stimulate central alpha2 receptors that control the vasomotor center of the medulla L-dopa analog participates in epinephrine center pathway. Alpha-methyl norepinephrine is produced. Usage: chronic hypertension during pregnancy  Methyldopa (side effect) Sedation Depression sleep disturbance Nightmare Orthostatic hypotension Increased prolactin secretion Bone marrow suppression Bradycardia Headache Tolerance  Preeclampsia & Eclampsia Preeclampsia is a multisystem disorder characterized by the combination of elevated BP (above 130/90 mm Hg) and proteinuria (300 mg or more in 24 hours) that develops after the 20th week of gestation. Rarely, women with preeclampsia develop seizures. If seizures do develop, the condition is then termed Eclampsia. Preeclampsia poses serious risks for the fetus and mother. Risks for the fetus include intrauterine growth restriction, premature birth, and even death.  Preeclampsia & Eclampsia Management of mild preeclampsia depends on the duration of gestation. If preeclampsia develops near term, and if fetal maturity is certain, induction of labor is advised. If mild preeclampsia develops earlier in gestation, experts suggest measures include bed rest, prolonged hospitalization, treatment with antihypertensive drugs, and prophylaxis with an anticonvulsant.  Preeclampsia & Eclampsia The definitive intervention for severe preeclampsia is delivery. If the fetus is not sufficiently mature, immediate delivery could threaten its life. If the patient elects to postpone delivery, then BP can be lowered with drugs. The drug of choice for lowering BP is labetalol (20 mg by IV bolus over 2 minutes); dosing may be repeated at 10-minute intervals up to a total of 300 mg.  Preeclampsia & Eclampsia Because severe preeclampsia can evolve into eclampsia, an antiseizure drug may be given for prophylaxis. Magnesium sulfate is the drug of choice. If eclampsia develops, magnesium sulfate is the preferred drug for seizure control. Initial dosing consists of a 4- to 6-gm IV loading dose followed by 5 gm IM injected into each buttock every 4 hours or continuous IV infusion of 1 to 2 gm/hr.  Central adrenergic blocking drugs Clonidine After intravenous injection, clonidine produces a brief rise in blood pressure followed by more prolonged hypotension. α adrenoceptors in arterioles After oral, clonidine reduces sympathetic and increases parasympathetic tone, resulting in blood pressure lowering and bradycardia.(BID is prescribed)  Clonidine Clonidine also binds to a nonadrenoceptor site, the imidazoline receptor, which may also mediate antihypertensive effects. Side effects: Dry mouth and sedation are common. Clonidine should not be given to patients who are at risk for mental depression and should be withdrawn if depression occurs during therapy. Concomitant treatment with tricyclic antidepressants may block the antihypertensive effect of clonidine.  Clonidine Withdrawal of clonidine after protracted use, particularly with high dosages (more than 1 mg/d), can result in life-threatening hypertensive crisis. Patients exhibit nervousness, tachycardia, headache, and sweating after omitting one or two doses of the drug. Adrenergic receptor antagonists - alpha blockers Prazosin and terazosin selective alpha-1 antagonists Laetalol Decreased peripheral vascular resistance (vasodilation) in arteries and veins Sodium and water retention They are the third line of HTN HTN+ benign prostate hyperplasia (first line)  Alpha blocker - side effects  Reflex tachycardia  Orthostatic hypotension  Nasal congestion - increased volume of nasal mucus  Miosis  Other side effects of alpha receptor blocking Adrenergic antagonists - beta blockers Beta-1 blockers: Atenolol, Metoprolol Non-selective beta-1 and-2: nadolol, propranolol, Timolol, pindolol Inhibition of beta1 receptor in the heart and reduction of cardiac output In the next step, brain beta inhibition kidney (renin inhibition) Second line of treatment HTN+ MI HTN + migraine HTN + Stable angina  Beta blockers - side effects Bradycardia AV Block CNS effects: sleep disorders, depression, nightmares Worsening of asthma Impaired lipid profile Covering symptoms of hypoglycemia  Angiotensin synthesis inhibitors Captopril, Enalapril, Lisinopril It inhibits the angiotensin converting enzyme (ACE) that hydrolyzes angiotensin I to angiotensin II Inhibition of the enzyme that destroys bradykinin (dilator) First line of treatment HTN+ MI HTN + HF HTN + Diabetes  ACE inhibitors - complications  Dry cough  Angioedema  Hyperkalemia  Blood pressure reduction caused by the first use  Acute kidney failure  Prohibited in pregnancy  angiotensin II Receptor Blockers (ARBs) Valsartan, Saralasin and losartan Angiotensin II receptor inhibition Side effects and use similar to captopril without dry cough In pregnancy, it increases the possibility of fetal malformations  Calcium channel blockers Dihydropyridine (nifedipine, amlodipine) Non Dihydropyridine (verapamil, diltiazem) Blocking the entry of calcium into the smooth muscles of the arteries (vasodilation) Decreased heart rate, decreased contractility First line of treatment HTN+ angina HTN + asthma HTN + supraventricular arrhythmia Hypertensive urgency  Calcium channel blockers - side effects Headache Hypotension Facial flushing Reflex tachycardia Drowsiness Ankle edema Dihydropyridine Bradycardia weakening of the heart Heart failure Non Dihydropyridine AV block Constipation (both)  Vasodilators Oral vasodilators include Hydralazine and Minoxidil, which are used for long-term outpatient treatment of high blood pressure. Injectable vasodilators include Nitroprusside and Fenoldopam, which are used to treat hypertensive emergencies. Calcium channel blockers, which are used in both. Nitrates, which are used primarily in ischemic heart disease and sometimes in hypertensive emergencies.  Vasodilators Hydralazine: release of NO Minoxidil : opening of ATP-dependent potassium channels The third line of treatment Common complications: Reflex tachycardia, palpitations and angina  Vasodilators - complications Minoxidil: hairiness (hirsutism) Fluid accumulation around the heart Hydralazine: Lupus-like syndrome (idiosyncrasy) in the first 6 months of treatment Positive Coombs test  Vasodilators Sodium Nitroprusside Effect on Artery and Vein Treatment of hypertension emergencies as well as severe heart failure Release of nitric oxide (activation of guanylyl cyclase) In the absence of heart failure, blood pressure decreases due to decreased vascular resistance, while cardiac output remains unchanged or decreases slightly  Sodium Nitroprusside  Sodium nitroprusside in aqueous solution is light sensitive and therefore must be prepared fresh before each use and covered with opaque foil.  Nitroprusside is a complex of iron, cyanide groups, and a nitroso part.  Sodium Nitroprusside  The most serious toxicity is related to cyanide accumulation.  Metabolic acidosis, arrhythmia, excessive hypotension, and death have resulted.  Treatment: Sodium thiosulfate and hydroxycobalamin  Thiocyanate toxicity manifests as weakness, disorientation, psychosis, muscle spasms, and seizures.  Vasodilators Fenoldopam Fenoldopam is a peripheral arteriolar dilator used for hypertensive emergencies and postoperative hypertension. It acts primarily as an agonist of dopamine D1 receptors resulting in dilation of peripheral arteries and natriuresis. Its half-life is 10 minutes. The drug is administered by continuous intravenous infusion. The major toxicities are reflex tachycardia, headache, and flushing. Fenoldopam also increases intraocular pressure and should be avoided in patients with glaucoma.  Vasodilators Diazoxide Diazoxide is an effective and relatively long-acting potassium channel opener that causes hyperpolarization in smooth muscle and pancreatic β cells. Because of its arteriolar dilating property, it was formerly used parenterally to treat hypertensive emergencies. A dose of 300 mg by rapid injection was recommended. Diazoxide inhibits insulin release from the pancreas Oral dosage for hypoglycemia is 3–8 mg/kg/day in 3 divided doses, with a maximum of 15 mg/kg/day.  Diazoxide The most significant toxicity from parenteral diazoxide has been excessive hypotension Occasionally, hyperglycemia complicates diazoxide use, particularly in persons with renal insufficiency. Diazoxide causes renal salt and water retention