Upgrade to remove ads
Only $35.99/year

PHPY 304-Drugs for CAD/Angina

Terms in this set (54)

Angina
The result of decreased blood supply to meet the increased metabolic demands of the heart
Coronary Ischemia
Not having enough blood through the coronary arteries. Reduced O2 supply and increased O2 demand
Goals of Therapy;
1) Reduce O2 demand on work load on heart
2) Increase O2 supply to the heart
Nitrates
-Increase cGMP in arteries and veins
-potent and rapid vasodilator
-best for ACUTE angina
-can develop tolerance
Beta Blockers
-Decrease O2 demand of heart
-Decrease HR and contractility
-Best for long term chronic management of typical stable/exertional/exercise induced angina
-Use with caution in unstable prizmetal/vasospastic angina
Ca2+ Channel Blockers (CCBs)
-Inhibit Ca2+ influx via L-type channels in both heart and vessels
-Diltiazem and verapamil are the best choice
-Lowers load on heart and promotes coronary vasodilation
-Effective on exertional and vasospastic angina
Organic Nitrates
Prodrugs that release Nitric Oxide
-NO increases cGMP in smooth muscle cells
-Relax vascular smooth muscle. bronchial smooth muscle and GI tract smooth muscle
-***Dilate venous capacitance vessels and decrease preload and LV filling pressure in the heart.
- Nitroglycerin for acute anginal attack
-Higher doses it may also dilate resistance arterioles
Nitrates
-Mimic NO effect as a NO donor
-Dilate both resistance and capacitance vessels
-Decrease venous return and the filling pressures in the heart (decrease preload)
-decrease myocardial wall tension and O2 demand
Nitroglycerine and Isosorbide dinitrate
Given for Angina (enhance cGMP mediated vasodilation)
Sodium Nitroprusside
Given for hypertensive crisis (enhance cGMP mediated vasodilation)
Minoxidil and Hydralazine
Antihypertensives (enhance cGMP mediated vasodilation)
Drawbacks to Nitrates and Nitroglycerin
Tolerance, headache and flushing
Mechanism of action of Nitrates
Rapid relief of angina or ischemia is due to the decreased preload due to decreased venous return as a result of ventilation of the Capacitance Vessels
Rapid Relief of acute Angina
1) Increased Venodilatation
2) Decreased venous return to the heart
3) Decreased preload
4) Decreased work load on the heart resulting in decreased O2 consumption
Dominant Action of Nitrates
Decrease O2 demand by decreasing PRELOAD since the coronary vessel are already dilated maximally to compensate
Inactivation of Nitrates
Inactivated through first pass metabolism in the liver
- administration of nitroglycerin is often sublingually or transdermally via a patch
Short Acting Nitrates
1) Nitroglycerin (10-30 minutes)
- Sublingual administration
Long Acting Nitrates
1) Nitroglycerin, 2% ointment (3-6 hours)
2) Nitroglycerin, slow release, transdermal (8-10 hours)
3) Isosorbide dinitrate, oral (6-10 hours)
Pharmacokinetics; Nitroglycerin
-Sublingual administration peak at 4 min
-1/2 life= 1-3 min
Pharmacokinetics; Isosorbide Dinitrate
-Sublingual administration pear at 6 min
-1/2 life= 45 min
-active metabolitesisosorbide-2-mononitrate and isosorbide-5-mononitrate have longer t½ of about 3-6 h and contribute to the therapeutic utility of this drug
Pharmacokinetics; Isosorbide-5-mononitrate
No significant first pass metabolism (excellent bioavailability) so it can be given orally
Pharmacokinetics; Inhaled NO
Mainly effects pulmonary vasculature (pulmonary hypertension)
Organic Nitrates- Clinical Limitations
1) Frequent or continuous use of high doses of organic nitrates-->reduced pharmacological effects
2) Tolerance; due to reduced capacity of the vascular smooth muscle to convert nitroglycerin to NO
Isosorbide- Clinical Uses
Health Canada approved indications;
1) acute symptomatic relief of angina pectoris and prophylactic management in situations that provoke angina attacks
2) Long-term prophylactic management of stable angina
3) Preoperative hypertension
Sodium nitroprusside (SNP)
-SNP is a nitrovasodilator that acts by releasing NO
-involves both enzymatic and non enzymatic pathways
-SNP dilated both arterioles and venules
-limited use for rapid reduction of BP in HYPERTENSIVE EMERGENCY
Therapeutic Uses for SNP
-Reserved for hypertensive emergencies
-lower blood pressure during acute aortic dissection
-to improve CO in congestive heart failure
-decrease myocardial O2 demand after acute myocardial infarction
-can cause CYANIDE POISONING
Tolerance with Nitrates
-Need "drug holidays" or nitrate free intervals to maintain its advantage in overcoming acute ischemia
-less of an issue with isosorbide dinitrate
Beta Adrenergic Antagonists;
B1 Blockers
Metoprolol, Atenolol
Metoprolol and Atenolol
Compete w/ Epi and NE at B1 receptors
No effect on their own
Reduce HR
Reduce Contractility
Reduce renin release in kidney
Reduce after load
Reduce VR
Atenolol
Direct B1-R blocker; decrease BP
Aliskiren
Renin Inhibitor from Kidneys; decrease BP
Enalapril
ACE inhibitor in lungs; decrease BP
Losartan
AT1-R (ANGII) blocker (ARB) in renal cortex; decreased BP
Spironolactone and Eplerenone
K+ Sparing Diuretic; Decreased BP
Calcium Channel Blockers (CCBs)
Diltiazem, Verapamil, Dihydopyridines (DHPs)
- block L-type Ca2+ channels
-reduce HR, after load
-Negative force of contraction (inotropic)
CCBs 2;
Act on both vascular smooth muscle and the heart
Predominantly arteriolar dilators
Block the L-type Ca2+ channel
Relax GI (constipation) and bronchiolar smooth muscle
Arteriolar Dilators
Decrease in systemic blood pressure, reduce after load, increase stroke volume
DHP's
Amlopidine and Nifedipine have higher affinity for smooth muscle than cardiac muscle (HTN management)
- can cause reflex tachycardia
Adverse Effects of CCBs
Constipation, Urinary retention, Headache
Sites of Ca2+ Channel Blockers
1) Dilate coronary arteries, but NOT veins
2) decrease contractility, automaticity at the SA node, and conduction at AV node
3) Increase myocardial O2 supply, decrease myocardial O2 demand
3 Classes of CCBs
1) Dihydropyridines
2) Benzothiazepines
3) Phenylalkylamines
DHP; Nifedipine
Short 1/2 life (4h)- significant first pass metabolism, requires frequent dosing, rapid onset and intense fall BP
Causes reflex tachycardia, can worsen myocardial ischemia
DHP; Amlodipine
Higher bioavailability, longer longer 1/2 life (40h), once daily dosing
Significantly less tachycardia
MUCH safer to use as antihypertensive than Nifedipine
CCBs-Toxicity and AE
1) Flushing
2) Constipation
3)Bradycardia, AV block, heart failure
Diltiazem and verapamil not advised for addition use with B blockers (increase cardio depression)
Diltiazem and Verapamil
More useful in angina/CAD to decrease HR and contractility
DHPs (Nifedipine/Amlodipine)
Amlodipine is useful as antihypertensive
- causes tachycardia and constipation
- effective as peripheral vasodilators
-not used for angina b/c they cause reflex increase in HR
DHP Adverse Effects;
Constipation and flushing are major side effects of all CCBs particularly DHPs.
Treatment for Hypertension
AMLODIPINE (1st choice)
Nifedipine (2nd choice). Both are DHP's.
Treatment for Angina
Diltiazem (acts on coronary vessels); a Benzothiazepine
Treatment for Arrhythmia Atrial Flutter, Atrial fibrillation, Supra-ventricular Tachycardia
Verapamil (Phenylalkylamine)
Salient Features of CCBs (XXXX)
1) inhibit Ca2+ entry into blood vessels and Heart by blocking L-type Ca2+ channels; decrease work load on heart and cause vasodilation
2) AE may include cardiac depression, ankle edema and constipation
Beta blockers
Effective in STABLE ANGINA b/c they reduce myocardial O2 demand by decreasing HR and contractility
-suited for long term chronic prophylaxis of stable angina
Beta-1 Blockers
Use with caution when treating variant/vasospastic angina.
Exert much longer duration of action and less tolerance.
Amlopidine (DHP)
Preferred treatment of Essential Hypertension because of its selective effect on peripheral vasculature
Sets found in the same folder