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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 osteoporosisLoop diuretics-used in patients with poor kidney function where thiazide derivatives will not be effective

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vasodilators

-antagonists

-antagonists

-antagonists

-antagonists

Angiotensin II receptor antagonists

Angiotensin II receptor antagonists

CNS-directed sympatholytics

ACE inhibitors

diuretics

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Drug Classification Common Adverse Effects Common 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

Hyperkalemia Hyperkalemic 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

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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

  Clonidine Dry mouth, fatigue, rebound hypertension, and sedation

Hypotensive effect decreased by tricyclic antidepressants Sedative effect increased by CNS depressants

  Guanabenz Same as clonidine Same as clonidine

  Guanfacine Same as clonidine but milder Same as clonidine

  Methyldopa Autoimmune 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 Classification Common Adverse EffectsCommon Drug Interactions

Sympatholytics

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vasodilators

-antagonists

-antagonists

-antagonists

-antagonists

Angiotensin II receptor antagonists

Angiotensin II receptor antagonists

CNS-directed sympatholytics

ACE inhibitors

diuretics

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Drug Oral Bioavailability

Absorption Reduced by Food

Active Metabolite

Duration of Action (Hours)

Angiotensin-converting enzyme inhibitors

Benazepril 37% No Benazeprilat 24

Captopril 75% 30-40% None 12-Jun

Enalapril 60% No Enalaprilat* 24

Fosinopril 36% No Fosinoprilat 24

Lisinopril 25% No None 24

Quinapril 60% 25-30% Quinaprilat 24

Ramipril 55% No Ramiprilat 24

Angiotensin receptor antagonists

Losartan 33% 10% Carboxylic acid metabolite

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Valsartan 25% 40% None 24

Candesartan 15% No None 24

Angiotensin Inhibitors

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Angiotensin inhibitors1. ACE inhibitors2. 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

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ACE inhibitors Adverse effects

• Increase fetal morbidity and mortality, especially during 2nd and 3th trimesters

• Renal failure in patients with bilateral renal artery stenosis

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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

Hyperkalemia Serum levels of drug increased by cimetidine and decreased by phenobarbital

Drug Classification Common Adverse Effects Common Drug Interactions

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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

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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 -blocker in combination

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Ca2+- channel blockers (CCBs)

Suppress cardiac activity and relax smooth muscles-in combination increase coronary blood flow

Side effects: fatigue, headache, dizziness, flushing, peripheral edemaOccasionally cause gingival hyperplasia

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Patient CharacteristicMost Preferred Drugs

Least Preferred Drugs

Age over 65 years Diuretic, ACEI, CCB

Centrally acting α2

agonist

African heritage Diuretic, CCB β-blocker

Pregnant Methyldopa, labetalol

ACEI, ARB

Angina pectoris β-blocker, CCB Hydralazine, 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, ACEI β-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