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59 291 section 3, lecture 2 diuretics increase in na+ excretion
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59-291 Section 3, Lecture 2 Diuretics: -increase in Na+ excretion (naturesis) Thiazide and Related diuretics -decreased PVR due to decreases muscle contraction -an economical and effective treatment -protect against osteoporosis Loop diuretics -used in patients with poor kidney function where thiazide derivatives will not be effective 1 vasodilators α-antagonists β-antagonists Angiotensin II receptor antagonists β-antagonists βantagonists CNS-directed sympatholytics ACE inhibitors Angiotensin II receptor antagonists diuretics 2 Potassium-Sparing Diuretics -mild diuretic and antihypertensive effect -Minimize renal-K+ loss thus preventing hypokalemia -If the patient can’t tolerate these drugs then use thiazide and take KCl tablets Drug Classification Diuretics Thiazide and loop diuretics Blood cell deficiencies, hyperlipidemia, hyperuricemia, hypokalemia, and other electrolyte changes Aggravation of diabetes Increase serum levels of lithium. Hypotensive effect decreased by NSAIDs and augmented by ACE inhibitors Common Adverse Effects Common Drug Interactions Potassium-sparing diuretics Hyperkalemia Hyperkalemic effect increased by ACE inhibitors and potassium supplements 3 Sympatholytics Drug Classification α-Adrenergic receptor antagonists β-Adrenergic receptor antagonists Common Adverse Effects Dizziness, first-dose syncope, fluid retention, and orthostatic hypotension Bradycardia, bronchoconstriction, depression, fatigue, impaired glycogenolysis, and vivid dreams Common Drug Interactions Hypotensive effect increased by β-adrenergic receptor antagonists and diuretics Cardiac depression increased by diltiazem and verapamil. Hypotensive effect decreased by NSAIDs Hypotensive effect decreased by tricyclic antidepressants Sedative effect increased by CNS depressants Same as clonidine Same as clonidine Hypotensive effect increased by levodopa. Other interactions same as those of clonidine Adrenergic receptor antagonists Centrally acting drugs Clonidine Dry mouth, fatigue, rebound hypertension, and sedation Guanabenz Guanfacine Methyldopa Same as clonidine Same as clonidine but milder Autoimmune hemolytic anemia, hepatitis, and lupuslike syndrome. Other adverse effects same as those of clonidine 4 vasodilators α-antagonists β-antagonists Angiotensin II receptor antagonists β-antagonists βantagonists CNS-directed sympatholytics ACE inhibitors Angiotensin II receptor antagonists diuretics 5 Angiotensin Inhibitors Drug Oral Bioavailabili ty Absorption Reduced by Food Active Metabolite Duration of Action (Hours) Angiotensin-converting enzyme inhibitors Benazepril Captopril Enalapril Fosinopril Lisinopril Quinapril Ramipril Angiotensin receptor antagonists Losartan 33% 10% Carboxylic acid metabolite None None 24 37% 75% 60% 36% 25% 60% 55% No 30-40% No No No 25-30% No Benazeprilat None Enalaprilat* Fosinoprilat None Quinaprilat Ramiprilat 24 12-Jun 24 24 24 24 24 Valsartan Candesartan 25% 15% 40% No 24 24 6 Angiotensin inhibitors 1. ACE inhibitors 2. Angiotensin receptor inhibitors Renin secretion induced by: 1-Symp. Outflow 2-reduction in BP and wall tension in renal arterioles 3-reduced NaCl reabsorbtion AT1 AT1 G-proteins – IP3 7 ACE inhibitors Adverse effects • Increase fetal morbidity and mortality, especially during 2nd and 3th trimesters • Renal failure in patients with bilateral renal artery stenosis 8 Drug Classification Common Adverse Effects Common Drug Interactions Angiotensin inhibitors Angiotensin-converting enzyme (ACE) inhibitors Acute renal failure, angioedema, cough, hyperkalemia, loss of taste, neutropenia, and rash Increase serum levels of lithium. Hyperkalemic effect increased by potassiumsparing diuretics and potassium supplements. Hypotensive effect decreased by NSAIDs Serum levels of drug increased by cimetidine and decreased by phenobarbital Angiotensin receptor antagonists Hyperkalemia 9 Vasodilators • Organic nitrites and nitrates – Amyl nitrites; (nitrites), administered by inhalation – Nitroglycerin (glyceryl trinitrate); sublingual, oral or transdermal administration • Calcium channel blockers – Amlodipine, felodipine – Diltiazem, verapamil 10 Tolerance Aldehyde dehydrogenase releases NO from nitroglycerin, and this process is accompanied with formation of superoxide anion free radical (O2-) that in turn, deactivate aldehyde dehydrogenase -to avoid periodically interrupt the administration of the drugs Pills –sublingual Sustained release- patches, skin ointments, IV Adverse effects- headaches, hypotension, dizziness, reflex tachycardia, use β-blocker in combination 11 Ca2+- channel blockers (CCBs) Suppress cardiac activity and relax smooth muscles-in combination increase coronary blood flow Side effects: fatigue, headache, dizziness, flushing, peripheral edema Occasionally cause gingival hyperplasia 12 Selection of Antihypertensive Drugs for Patients with Specific Traits or Concurrent Diseases Patient Characteristic Most Preferred Drugs Diuretic, ACEI, CCB Diuretic, CCB Methyldopa, labetalol β-blocker, CCB β-blocker, ACEI, aldosterone antagonist Diuretic, ACEI, ARB, β-blocker Diuretic, ACEI, ARB ACEI, ARB Diuretic, ACEI, ARB, β-blocker, CCB CCB, ACEI α-blocker β-blocker, CCB Diuretic β-blocker Least Preferred Drugs Centrally acting α2 agonist β-blocker ACEI, ARB Hydralazine, minoxidil Age over 65 years African heritage Pregnant Angina pectoris Myocardial infarction Congestive heart failure Recurrent stroke prevention Chronic kidney disease Diabetes Asthma Benign prostatic hyperplasia Migraine headache Osteoporosis 13
