1. 1 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

2. 2 vasodilators  -antagonists  -antagonists Angiotensin II receptor antagonists CNS-directed sympatholytics ACE inhibitors diuretics

3. 3 Drug ClassificationCommon Adverse EffectsCommon Drug Interactions 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 Potassium-sparing diuretics HyperkalemiaHyperkalemic effect increased by ACE inhibitors and potassium supplements 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

4. 4 Adrenergic receptor antagonists α-Adrenergic receptor antagonists Dizziness, first-dose syncope, fluid retention, and orthostatic hypotension Hypotensive effect increased by β-adrenergic receptor antagonists and diuretics β-Adrenergic receptor antagonists Bradycardia, bronchoconstriction, depression, fatigue, impaired glycogenolysis, and vivid dreams Cardiac depression increased by diltiazem and verapamil. Hypotensive effect decreased by NSAIDs Centrally acting drugs ClonidineDry mouth, fatigue, rebound hypertension, and sedation Hypotensive effect decreased by tricyclic antidepressants Sedative effect increased by CNS depressants GuanabenzSame as clonidine GuanfacineSame as clonidine but milderSame as clonidine MethyldopaAutoimmune hemolytic anemia, hepatitis, and lupuslike syndrome. Other adverse effects same as those of clonidine Hypotensive effect increased by levodopa. Other interactions same as those of clonidine Drug ClassificationCommon Adverse Effects Common Drug Interactions Sympatholytics

5. 5 vasodilators  -antagonists  -antagonists Angiotensin II receptor antagonists CNS-directed sympatholytics ACE inhibitors diuretics

6. 6 DrugOral Bioavailabili ty Absorption Reduced by Food Active Metabolite Duration of Action (Hours) Angiotensin-converting enzyme inhibitors Benazepril37%NoBenazeprilat24 Captopril75%30-40%None12-Jun Enalapril60%NoEnalaprilat*24 Fosinopril36%NoFosinoprilat24 Lisinopril25%NoNone24 Quinapril60%25-30%Quinaprilat24 Ramipril55%NoRamiprilat24 Angiotensin receptor antagonists Losartan33%10%Carboxylic acid metabolite 24 Valsartan25%40%None24 Candesartan15%NoNone24 Angiotensin Inhibitors

7. 7 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 AT 1 G-proteins – IP3

8. 8 ACE inhibitors Adverse effects Increase fetal morbidity and mortality, especially during 2 nd and 3th trimesters Renal failure in patients with bilateral renal artery stenosis

9. 9 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 potassium- sparing diuretics and potassium supplements. Hypotensive effect decreased by NSAIDs Angiotensin receptor antagonists HyperkalemiaSerum levels of drug increased by cimetidine and decreased by phenobarbital Drug ClassificationCommon Adverse EffectsCommon Drug Interactions

10. 10 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

11. 11 Tolerance Aldehyde dehydrogenase releases NO from nitroglycerin, and this process is accompanied with formation of superoxide anion free radical (O 2 - ) 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  -blocker in combination

12. 12 Ca 2+ - 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

13. 13 Patient Characteristic Most Preferred Drugs Least Preferred Drugs Age over 65 years Diuretic, ACEI, CCBCentrally acting α 2 agonist African heritage Diuretic, CCBβ-blocker Pregnant Methyldopa, labetalol ACEI, ARB Angina pectoris β-blocker, CCBHydralazine, minoxidil Myocardial infarction β-blocker, ACEI, aldosterone antagonist Congestive heart failure Diuretic, ACEI, ARB, β-blocker Recurrent stroke prevention Diuretic, ACEI, ARB Chronic kidney disease ACEI, ARB Diabetes Diuretic, ACEI, ARB, β-blocker, CCB Asthma CCB, ACEIβ-blocker Benign prostatic hyperplasia α-blocker Migraine headache β-blocker, CCB Osteoporosis Diuretic Selection of Antihypertensive Drugs for Patients with Specific Traits or Concurrent Diseases