Lecture 17: Antihypertensives Flashcards
1
Q
Current Treatments
A
- First-line agents: ACE-inhibitors, ARBs, calcium channel blockers, thiazide diuretics
- Second-line agents: Beta-blockers, aldosterone antagonists
- Other agents: Loop diuretics, alpha-blockers, direct vasodilators, central alpha2-agonists, renin inhibitors
2
Q
Antihypertensives classes
A
- Inhibitors of angiotensin (ACE-inhibitors / ARBs / renin inhibitors)
- Calcium-channel blockers
- Diuretics
- Beta-adrenoceptor antagonists
- alpha-adrenoceptor antagonists
- Central alpha2 agonists
- Direct vasodilators
3
Q
ACE Inhibitors
A
- Captopril, Enalapril, Lisinopril
- First-line agents (in particular for diabetics and patients w chronic kidney disease)
- decr BP by decr peripheral vascular resistance
- INHIBIT ACE (angiotensin converting enzyme) that cleaves angiotensin I to form angiotensin II
- DECREASE Na+ & H20 retention
- INCREASE BRADYKININ levels
- DO NOT reflexively increase cardiac output, rate or contractility
Use
- Hypertension (most effective in white and/or young patients) + diuretic = effectiveness similar in white and black
- Preserve renal function in patients with either diabetic or non-diabetic nephropathy
- Effective in treatment of chronic HF
- Standard of care for patients following MI (started 24h after end of infarction)
Adverse
- Hyperkalemia
- Hypotension
- Persistent Dry cough
- Teratogenic
- Angioedema (rare but life-threatening)
- Acute renal failure (patients with bilateral renal artery stenosis RAS); However, ACE inhibitor is the drug of choice for unilateral
- Rash, fever, altered taste
- ABSOULTE contraindication in pregnancy
4
Q
Angiotensin Receptor Blockers (ARB)
A
- Block angiotensin-2 type 1 receptors
- BP by causing arteriolar & venous dilation
- Block aldosterone secretion -> decrease Na+ & H20 retention
- diabetic nephrotoxicity
- DO NOT INCREASE BRADYKININ levels
- Antagonism of aldosterone receptor -> inhibition of Na+ and H20 retention -> inhibition of vasoconstriction
- Reduces K+ excretion -> risk of hyperkalemia (more prominent in patients with chronic kidney disease or in patients taking concurrent ACEI, ARB or other K+-sparing diuretics)
- Used in the treatment of hypertension & heart failure
- Can be used as part of first-line therapy in patients with hypertension & severe left ventricular dysfunction
Adverse
- Similar to those of ACE inhibitors
- Dry cough does not occur (due to no effect on bradykinin levels)
- Angioedema risk is significantly lower than with ACEI’s
- contraindicated in pregnancy
- contraindicated in Pt w bialteral RAS
5
Q
Renin Inhibitor
A
- Ex. Aliskerin
- MOA: Inhibits enzyme activity of renin and prevents conversion of angiotensinogen into angiotensin I
- End result: Inhibits production of both angiotensin II and aldosterone
Adverse
- Similar to those of ACE inhibitors
- hyperkalemia
- Dry cough does not occur (due to no effect on bradykinin levels)
- Angioedema risk is significantly lower than with ACEI’s
6
Q
Ca2+ Channel Blockers (CCB)
A
- Verapamil, Diltiazem, Nifedipine, Amlodipine
- First-line agents
- Ca2+ CHANNEL CLASSES
- Non-dihydropyridines
- Verapamil
- Diltiazem
- Dihydropyridines
- Nifedipine, Amlodipine
Uses
- HPT
- have intrinsic natriuretic effect
- Useful in patients with asthma, diabetes, peripheral vascular disease
PK
- High-doses of short-acting dihydropyridine Ca2+- channel blockers can increase risk of MI (excessive vasodilation & reflex cardiac stimulation)
- Sustained release preparations are preferred
Adverse
- Verapamil: Constipation (~7 %), should be avoided in patients with CHF (-ve inotropic effects)
- Dihydropyridines: Hypotension, peripheral edema (esp. feet & ankles), dizziness, headache, fatigue, bradycardia, heart block, reflex tachycardia can occur, especially in short-acting preparations
7
Q
Verapamil
A
- Least selective of any Ca2+-blocker
- Significant effects in cardiac & vascular smooth muscle
- Used to treat angina, supraventricular tachyarrythmias, hypertension & migraine
8
Q
Dilitiazem
A
- Effects in both cardiac & vascular smooth muscle (less pronounced effect on heart than verapamil)
- Good side-effect profile
- Used to treat angina, hypertension & supraventricular tachyarrythmias
9
Q
Dihydropyridines
A
- 1st gen: Nifedipine
- 2nd gen: Amlodipine
- Greater affinity for vascular Ca2+-channels than for cardiac Ca2+-channels
- Reduce Ca2+ entry into smooth muscles to cause coronary & peripheral vasodilatation & lower BP
- Primarily used in treating hypertension
10
Q
Diuretics: Thiazides
A
- First-line agents (particularly black and/or elderly patients)
- Effective in lowering BP by 10-15 mmHg
MOA
- Lower BP by incr Na+ and H20 excretion -> decr in extracellular volume -> decr in cardiac output & renal blood flow.
- Long-term treatment = normal plasma volume but decreased peripheral resistance
Uses
- Counteract Na+ & H20 retention caused by other antihypertensive drugs -> useful in combination therapy
- Particularly useful in black & elderly (with normal renal & cardiac function)
Adverse
- Hypokalemia
- Hyperuricemia
- Hyperglycemia
- Hypomagnesemia
- Hypercholesterolemia
11
Q
Loop diuretics
A
- Act promptly in patients with poor renal function or heart failure
- More potent at inducing diuresis & can cause more side effects
- Used primarily in patients who do not respond to thiazide therapy adequately
- Cause decr renal vascular resistance & incr renal blood flow
12
Q
Potassium-Sparing
A
- decr K+ loss in urine caused by thiazide or loop diuretics
- Used in combination
13
Q
Beta-blockers
A
- Propranolol, Metoprolol, Atenolol, Pindolol
- Used only as add-on therapy to first line agents in primary prevention patients
- First-line therapy only for patients with coronary artery disease, heart failure or post-MI
14
Q
alpha1-blockers
A
- Prazosin, Doxazosin
- Na+ & H20 retention does occur
- Effective in lowering BP but more side effects than other antihypertensives
- Hypertension (due to side-effect profile, development of tolerance & advent of safer antihypertensives, alpha- blockers are seldom used in treatment of hypertension)
Adverse
- Orthostatic hypotension (which may lead to syncope) upon first-dose or large increases in dose
- Concomitant use of a Beta-blocker may be necessary to blunt short-term effect of reflex tachycardia
- Dizziness, drowsiness, headache, lack of energy, nausea, and palpitations,
- Doxazosin shown to incr rate of CHF
- reflex tachycardia
15
Q
Labetalol
A
- Oral & parenteral admin.
- Used in hypertension management (safe in pregnancy)
- IV labetalol = rapid reduction in BP -> useful in hypertensive emergencies
- Advantages: decr in BP associated with alpha1-blockade is not associated with reflex increase in HR or cardiac output