Download Chapter 16 Cholinesterase Inhibitors

Drugs Acting on the ReninAngiotensin-Aldosterone System
Drugs Acting on the ReninAngiotensin-Aldosterone System
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Physiology of the renin-angiotensinaldosterone system
Angiotensin-converting enzyme inhibitors
Angiotensin II receptor blockers
Aldosterone antagonists
Physiology of the ReninAngiotensin-Aldosterone System
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Type of angiotensin
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Angiotensin I
Angiotensin II
Angiotensin III
Actions of angiotensin II
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Vasoconstriction
Release of aldosterone
Alteration of cardiac and vascular structure
Physiology of the ReninAngiotensin-Aldosterone System
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Actions of aldosterone
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Regulation of blood volume and blood pressure
Pathologic cardiovascular effects
Fig. 44–1. Regulation of blood pressure by the renin-angiotensin-aldosterone
system.
Physiology of the ReninAngiotensin-Aldosterone System
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Formation of angiotensin II by renin and
angiotensin-converting enzyme (ACE)
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Renin
• Catalyzes the formation of angiotensin I from
angiotensinogen
• Regulation of renin release
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Angiotensin-converting enzyme (kinase II)
• Catalyzes the conversion of angiotensin I (inactive) to
angiotensin II (highly active)
Physiology of the ReninAngiotensin-Aldosterone System
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Regulation of blood pressure by the reninangiotensin-aldosterone system
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Helps regulate blood pressure in the presence of
hemorrhage, dehydration, or sodium depletion
Acts in two ways
• Constricts renal blood vessels
• Acts on the kidney to promote retention of sodium and
water and excretion of potassium
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Tissue (local) angiotensin II production
Angiotensin-Converting
Enzyme Inhibitors
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Mechanism of action and overview of
pharmacologic effects
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Reducing levels of angiotensin II
Increasing levels of bradykinin
Pharmacokinetics
Angiotensin-Converting
Enzyme Inhibitors
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Therapeutic uses
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Hypertension
Heart failure
Myocardial infarction (MI)
Diabetic and nondiabetic nephropathy
Prevention of MI, stroke, and death in patients at
high cardiovascular risk
MI = myocardial infarction.
Fig. 44–2. Overview of ACE inhibitor actions and pharmacologic effects.
Angiotensin-Converting
Enzyme Inhibitors
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Adverse effects
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First-dose hypotension
Fetal injury
Cough
Angioedema
Hyperkalemia
Dysgeusia and rash
Renal failure
Neutropenia
Angiotensin-Converting
Enzyme Inhibitors
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Drug interactions
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Diuretics
Antihypertensive agents
Drugs that raise potassium levels
Lithium
Nonsteroidal anti-inflammatory drugs
Angiotensin-Converting
Enzyme Inhibitors
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Preparations, dosage, and administration
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Except for enalaprilat, all ACE inhibitors are
administered orally
All available in single-drug formulations
Except for captopril and moexipril, all oral
formulations may be administered without regard
to meals
Angiotensin II Receptor Blockers
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Mechanism of action and overview of
pharmacologic effects
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Block access of angiotensin II
Cause dilation of arterioles and veins
Prevent angiotensin II from inducing pathologic
changes in cardiac structure
Reduce excretion of potassium
Decrease release of aldosterone
Increase renal excretion of sodium and water
Do not inhibit kinase II
Do not increase levels of bradykinin
Fig. 44–3. Elevation of glomerular filtration pressure by angiotensin II.
Angiotensin II Receptor Blockers
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Therapeutic uses
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Hypertension, heart failure, myocardial infarction
Diabetic nephropathy
If unable to tolerate ACE inhibitors: protection
against MI, stroke, and death from cardiovascular
(CV) causes in high-risk patients
Migraine headache
May prevent development of diabetic retinopathy
New data show that ACE inhibitors and
angiotensin II receptor blockers (ARBs) are not
effective for primary prevention of nephropathy in
normotensive diabetic patients
Angiotensin II Receptor Blockers
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Adverse effects
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Angioedema
Fetal harm
Renal failure
Possibility of promoting cancer
Direct Renin Inhibitors
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Aliskiren (Tekturna)
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Binds tightly with renin and inhibits the cleavage
of angiotensinogen to angiotensin I
Side effects
• Angioedema, cough, GI effects, hyperkalemia,
fetal injury, and death
Aldosterone Antagonists
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Eplerenone (Inspra)
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Mechanism of action
• Selective blockade of aldosterone receptors
Therapeutic uses
• Hypertension
• Heart failure
Pharmacokinetics
• Absorption is not affected by food
Adverse effects
• Hyperkalemia
Aldosterone Antagonists
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Eplerenone (Inspra) (cont’d)
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Drug interactions
• Inhibitors of CYP3A4
• Drugs that raise potassium levels
• Use with caution when combined with lithium
Aldosterone Antagonists
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Spironolactone (Aldactone)
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Mechanism of action
• Blocks aldosterone receptors
• Binds with receptors for other steroid hormones
Therapeutic uses
• Hypertension
• Heart failure
Aldosterone Antagonists
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Spironolactone (Aldactone) (cont’d)
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Adverse effects
• Hyperkalemia
• Gynecomastia
• Menstrual irregularities
• Impotence
• Hirsutism
• Deepening of the voice