Beta-Adrenergic blocking Agents- Antianginal Drugs
Beta-Adrenergic blocking Agents- Antianginal Drugs
Beta-Adrenergic blocking Agents
• Prototype - Propranolol
• Prevent or inhibit sympathetic stimulation
– Reduces heart rate
– Myocardial contractility
– Reduce BP - decreases myocardial workload and O2 demand
• In long-term management used to decrease frequency and severity of anginal attacks
• Added when nitrates do not prevent anginal episodes
• Prevents exercise induced tachycardia
• Onset of action 30 min after oral dose. 1-2 min IV
• Block Beta adrenergic receptors in the heart and juxtaglomerular apparatus
• Decrease the influence of the sympathetic nervous system decreasing excitability of the heart
• Decrease cardiac output.
• Indicated for long term management of anginal pectoris caused by atherosclerosis
Atenolol, metoprolol, and nadolol have the same actions, uses, and adverse effects as propranolol, but they have long half-lives and can be given once daily. They are excreted by the kidneys, and dosage must be reduced in clients with renal impairment.
RENIN-ANGIOTENSIN SYSTEM INHIBITORS
The actions of Angiotensin II include an increase in blood pressure and a stimulation of the secretion of aldosterone (a hormone from the adrenal cortex) that promotes sodium retention. By preventing the formation of angiotensin II, blood pressure will be reduced. This is the strategy for development of inhibitors. Useful inhibitors of the renin-angiotensin system are the Angiotensin Converting Enzyme Inhibitors
First line treatment for: Hypertension , Congestive heart failure [CHF]
ACE-Inhibitor’s MOA (Angiotensin Converting Enzyme Inhibitors)
Renin-Angiotensin Aldosterone System:
. Renin & Angiotensin = vasoconstrictor
. constricts blood vessels & increases BP
. increases SVR or afterload
. ACE Inhibitors blocks these effects decreasing SVR & afterload
. Aldosterone = secreted from adrenal glands
. cause sodium & water reabsorption
. increase blood volume
. increase preload
. ACE I blocks this and decreases preload
Class I: captopril
Class II (prodrug) : e.g., ramipril, enalapril, perindopril
Class III ( water soluble) : lisinopril.
Mechanism of Action
Inhibition of circulating and tissue angiotensin- converting enzyme.
Increased formation of bradykinin and vasodilatory prostaglandins.
Decreased secretion of aldosterone; help sodium excretion.
- Reduction of cardiovascular morbidity and mortality in patients with atherosclerotic vascular disease, diabetes, and heart failure.
- Favorable metabolic profile.
- Improvement in glucose tolerance and insulin resistance.
- Renal glomerular protection effect especially in diabetes mellitus.
- Do not adversely affect quality of life.
- Diabetes mellitus, particularly with nephropathy.
- Congestive heart failure.
- Following myocardial infraction.
- Cough (10 - 30%): a dry irritant cough with tickling sensation in the throat.
- Skin rash (6%).
- Postural hypotension in salt depleted or blood volume depleted patients.
- Angioedema (0.2%) : life threatening.
- Renal failure: rare, high risk with bilateral renal artery stenosis.
- Contraindications include bilateral renal artery stenosis, pregnancy, known allergy, and hyperkalaemia.
- High serum creatinine (> 3 mg/dl) is an indication for careful monitoring of renal function, and potassium. Benefits can still be obtained in spite of renal insufficiency.
- A slight stable increase in serum creatinine after the introduction of ACE inhibitors does not limit use.
- ACE-I are more effective when combined with diuretics and moderate salt restriction.
ACE inhibitors drugs
Captopril 50-150 mg
Enalapril 2.5-40 mg
Lisinopril 10-40 mg
Ramipril 2.5-20 mg
Perindopril 2-8 mg
Angiotensin Receptor Blocker
Losartan 25-100 mg
Candesartan 4-32 mg
Telmisartan 20-80 mg
Mechanism of action
They act by blocking type I angiotensin II receptors generally, producing more blockade of the renin -angiotensin - aldosterone axis.
• Similar metabolic profile to that of ACE-I.
• Renal protection.
• They do not produce cough.
Patients with a compelling indication for ACE-I and who can not tolerate them because of cough or allergic reactions.
Sympatholytics And Alpha Adrenergic Blockers
1. Alpha 1-receptor blockers: prazocin,doxazocin.
2. Centrally acting alpha 2- agonists: methyldopa, clonidine.
3. Peripherally acting adrenergic antagonists: reserpine.
4. Imidazoline receptor agonists: rilmenidine, moxonidine.
- Alpha1- receptor blockers and imidazoline receptor agonists improve lipid profile and insulin sensitivity.
- Methyldopa: increases renal blood flow. Drug of choice during pregnancy.
- Reserpine: neutral metabolic effects and cheap.
- Diabetes mellitus: alpha1- receptor blockers, imidazoline receptor agonists.
- Dyslipidemia: alpha 1- receptor blockers, imidazoline receptor agonists.
- Prostatic hypertrophy: alpha 1- receptor blockers.
- When there is a need for rapid reduction in blood pressure: clonidine.
- Prazocin: postural hypotension, diarrhea, occasional tachycardia, and tolerance (due to fluid retention).
- Methyldopa: sedation, hepatotoxicity, hemolytic anemia, and tolerance.
- Reserpine: depression, lethargy, weight loss, peptic ulcer, diarrhea, and impotence
- Clonidine: dry mouth, sedation, bradycardia, impotence, and rebound hypertension if stopped suddenly.
- Prazocin, methyldopa, and reserpine should be combined with a diuretic because of fluid retention.
Direct Arterial Vasodilators
Types: hydralazine, diazoxide, nitroprusside, and minoxidil
The basis for the use of diuretics is to promote sodium depletion (and thereby water) which leads to a decrease in extracellular fluid volume.
An important aspect of diuretic therapy is to prevent the development of tolerance to other antihypertensive drugs.
TYPES OF DIURETICS
A. Thiazide Diuretics examples include chlorothiazide
a concern with these drugs is the loss of potassium as well as sodium
B. Loop Diuretics (High Ceiling Diuretics) examples include
these compounds produce a powerful diuresis and are capable of producing severe derangements of electrolyte balance
C. Potassium Sparing Diuretics examples include
unlike the other diuretics, these agents do not cause loss of potassium
Mechanism of Action
Initial effects: through reduction of plasma volume and cardiac output.
Long term effect: through decrease in total peripheral vascular resistance.
Documented reduction in cardiovascular morbidity and mortality.
Least expensive antihypertensive drugs.
Best drug for treatment of systolic hypertension and for hypertension in theelderly.
Can be combined with all other antihypertensive drugs to produce synergetic effect.
Metabolic effects (uncommon with small doses): hypokalemia,hypomagnesemia, hyponatremia, hyperuricemia, dyslipidemia (increased total
and LDL cholesterol), impaired glucose tolerance, and hypercalcemia (with thiazides).
Impotence in up to 22% of patients.
- Moderate salt restriction is the key for effective antihypertensive effect of diuretics and for protection from diuretic - induced hypokalaemia.
- Thiazides are not effective in patients with renal failure (serum creatinine > 2mg /dl) because of reduced glomerular filtration rate.
- Frusemide needs frequent doses ( 2-3 /day ).Thiazides can be given once daily or every other day.
- Potassium supplements should not be routinely combined with thiazide or loop diuretics. They are indicated with hypokalemia (serum potassium < 3.5 mEq/L) especially with concomitant digitalis therapy or left ventricular hypertrophy.
- Nonsteroidal antiinflammatory drugs can antagonize diuretics effectiveness.
Diuretics should be the primary choice in all hypertensives.
They are indicated in:
- Volume dependent forms of hypertension: blacks, elderly, diabetic, renal and obese hypertensives.
- Hypertension complicated with heart failure.
- Resistant hypertension: loop diuretics in large doses are recommended.
- Renal impairment: loop diuretics
Calcium Channel Blocking Agents
• Act on contractile and conductive tissues of the heart and on vascular smooth muscles
• Prevent movement of extracellular calcium into the cell
– Coronary and peripheral arteries dilate
– Myocardial contractility decreases
– Depress conduction system
• Inhibit movement of calcium ions across the membranes of myocardial and arterial muscle cells. Altering the action potential and blocking muscle cell contraction
• Depress myocardial contractility
• Slow cardiac impulse formation in the conductive tissues
• Cause a fall in BP
I. Diuretics to reduce blood volume
II. Drugs that interfere with the Renin-Angiotensin System
A. Converting enzyme inhibitors Captopril , enalapril, Lisinopril
B. Angiotensin receptor antagonists Saralasin Losartan
III. Decrease peripheral vascular resistance and/or cardiac output
A. Directly acting vasodilators
1. calcium channel blockers Nifedipine , Diltiazem, amlodipine
2. potassium channel activators Minoxidil
3. elevation of cGMP Nitroprusside
4. others Hydralazin e
B. Sympathetic nervous system depressants
1. α-blockers Prazosin, phentolamine, phenoxybenzamine
2. β-blockers Propranolol ,Metoprolol, atenolol
3. norepinephrine synthesis inhibitors Metyrosine
4. norepinephrine storage inhibitors Reserpine
5. transmitter release inhibitors Guanethidine
6. centrally acting: decrease
sympathetic outflow Clonidine , methyldopa