Drugs for IHD Flashcards
IHD is characterized by what
partial occlusion of the coronary artery
What is classic angina?
=angina of effort/stable angina
CP during stress or exertion, caused by occlusion of coronary artery d.t a athersclerotic plaque.
What is variant (prinzmetal) angina?
How do we get it
CP d.t episodes of vasoconstriction of coronary arteries that occur when resting, often genetically inherited.
What type of angina is the most common?
Classic angina/stable angina
Angina is caused by imbalance of what?
Oxygen demand of the heart and oxygen supply via the coronary arteries
When do we experience CP in angina?
When the demand of the heart is GREATER than what can be supplied.
HEART is THIRTSTTTTYYY for blood.
Our heart wants blood, but our coronary arteries are having a heart time suppling it, causing our heart to hurt => angina.
What are two ways to solve this problem?
- 1. Decrease cardiac work => decrease myocardial O2 demand
- 2. Increase blood flow via CA
Name the 4 nonsurgical/surgical approaches to increasing blood to the heart?
- CABG
- PTCA (percutaneous transluminal coronary angioplasty)
- Atherectomy: catheter with a sharp blade removes plaque
- Stent
What is the problem with atherectomy?
Risk of reocclusion
What type of stent is preffered?
Drug eluting stent: stent that is covered with an antiproliferative medication, to prevent blockage in the future.
Vasodilators can be use to increase coronary blood flow and treat what kind of angina?
Variant (Prinzmetal angina) => relieves vasospasm => increases flood flow to the area.
Vasodilators shoud NOT be used for what types of angina?
- Classic angina (athersclerotic angina)
Vasodilators should not be used for classic angina. Why?
- Coronary steal phenomenon
- Vasodilators will dilate normal BV.
- BV with plaques, are, however, already maximally dilated. Thus, during excercise, vasodilators will SHUNT the little amount of blood passing the [plaque => ischemic tissue], and redirect it to the normal BV, which now is sending more blood than needed to NL tissue, which the ischemic tissue is getting even less.
Which vasodilator can cause coronary steal syndrome
Dipyramidole
What determines how much oxygen our heart needs?
- 1. HR
- 2. Contractility
- 3. Preload
- 4. Afterload
What causes the production of endogenous NO?
ACh, Bradykinin, Substance P or mechanical stress on the endothelial cell => makes NO => acts on smooth muscle by + GC (Guanylyl cyclase) => vasodilation
Describe the role of organic nitrates (nitroglycerin) in maintaining vascular tone?
- Organic nitrate is metabolically activated by thiol (ADH2) => NO activates GC (guanylyl cyclase) in vascular smooth muscle–> ↑ cGMP –> ↑ PKG (protein kinase G), which does 2 things:
- Dephosphoylates Myosin-LC –> smooth m. relaxation
- Open K+ channel => hyperpolarization and decreased Ca+ influx
Pharmacokinetics of Nitrovasodilators
First Pass Metabolism (amount of drug that reaches systemic circulation d/t some lost during absorption by gut wall and liver):
Administration:
- First Pass Metabolism: Significant, d/t high amount of nitrate reductase in the liver
- Administration: Sublingual, buccal or transdermal bc oral route decreases bioavailablity, thus, given though other mechanisms
Which nitrate is a poor substrate of nitrate reductase in the liver and therefore has higher bioavailability?
Isosorbide mononitrate
What is the crucial for the activation of nitrates to release NO?
Reduce VIA thiol (ADH2) => releases NO from nitrates
Which vessels are most sensitive => least sensitive to Nitrates?
Nitrates dilates vein and large artries BEST
Veins > large arteries > Small arteries and arteroles
What is the major effect of nitrates?
Relaxes vascular smooth muscle by:
-
Dilates veins**:
- increases venous capitance
- reduces pre-load => decreases O2 demand
- => treats stable angina
- With higher concentrations, dilates coronary arteries:
- reduces afterload
- stops spasm
- => treats variange angina
Nitrous oxide has effects beyond just vasodilation, describe some of the inhibitory effects.
- Inhibits platelet aggregation
- Does not cause coronary steal phenomenon
Major overall effect of nitrates is a decrease in?
Myocardial O2 demand
The development of tolerance to Nitrates is associated with what 4 events?
- Deplete thiol compounds, needed to metabolize NO
- Increased generation of superoxide radicas (O2-), which reacts with NO to make H2O2, depling NO.
- Reflex activation of sympathetic NS (=> tachycardia and decrease coronary BS)
- Hold in Na+ and water
The development of tolerance to Nitrates is associated with what 4 events?
Increased amount of superoxide radical depletes tissues of what?
NO
Nitrates can come in short-acting formulants and long-acting formulants.
What are the short acting nitrates, ROA, and what are they used for?
Short acting nitrates are used to relieve angina attack
- Nitroglycerin (sublingual or spray)
- Isosorbide dinitrate (sublingual or spray)
Nitrates can come in short-acting formulants and long-acting formulants.
What are the long acting nitrates, ROA, and what are they used for?
-
Long-acting nitrates are used to PREVENT attacks
- 1. Nitroglycerin (oral, ointment or a patch)
- 2. Isosorbide dinitrate (oral)
- 3. Isosorbid mononitrate (oral)
What are 4 adverse effects associated with Nitrates?
- HA
- Orthostatic hypotension (BP falls when standing up)
- Increased sympathetic activation (tachycardia and increased contractility)
- Increased renal Na+ and water reabsorption
Why are nitrates contraindicated if ICP is elevated?
Meningeal vessels can DILATE
Nitrate drugs should not be taken with what?
Drugs for ED:
- Sildenafil,
- Vardenafil
- Tadalafil
Why not to take nitrate drugs with drugs for ED
ED drugs inhibit PDE-5 => increase cGMP =>
- Dramatic drop in BP
- Can cause MI
What are the 3 non-cardioactive (dihydropyridines) calcium channel blockers used in angina?
1) Amlodipine
2) Nifedipine
3) Nicardipine
What are the 2 cardioactive calcium channel blockers used in angina?
- 1. Diltiazem
- 2. Verapamil
MOA: dihydropyridine calcium-channel blockers
Act mainly on peripheral vasculature and indirectly cause the heart not to work as hard :)
- Dilate peripheral arterioles
- Decrease PVR => decrease afterload => decrease BP
CCB can treat both athersclerotic angina and variant angina. How?
- Treats atherosclerotic angina by decreasing O2 demand
- Dihydropyrimidines (amlodipine, nifedipine and nicardipine) => dilating peripheral arterilioles => decrease PVR => decrease afterload => decrease BP
- Cardioreactive CCBs (verapimil and cardioreactive CCBs) decrease contractility and HR
- Treates variant angina by increase blood supply
- Dilates coronary arteries => relieves local spasm
Which non-cardioactive (dihydropyridine) is the longest-acting?
AMLODIPINE (30-50 hours)
Which non-cardioactive (dihydropyridine) is the shortest acting?
1. Nifedipine (4 hrs)
2. Nicardipine (2-4 hours)
Which group of CCB’s are more potent vasodilators?
Non-cardioactive (dihydropyridines)
Why is there less orthostatic hypotension as an AE when using CCB’s for angina?
- Dihydropyridines CCBs affect arterioles more
- Nitrates affect veins more.
Which CCB’s lead to ↓ cardiac contractility and HR?
- Cardioactive CCB’s (diltiazem and verapamil)
Which CCB causes the greatest ↓ cardiac contractility, ↓ SA and AV node conduction?
Verapamil
What are the major AE’s associated with cardioactive CCB’s?
1. Cardiac depression/arrest, acute HF
2. AV block and bradyarrythmia
Adverse effects associated with the short-acting dihydropyridine CCB’s?
Vasodilation => Reflex sympathetic activation
Nifedipine (immediate release) in should be used with caution in what patients?
Should use what type of dihydropyridine instead?
- Pts with HTN => increase risk of MI
- Slow-release or long-acting dihydropyridine are better tolerated.
What are the 4 beta-blockers indicated in tx of angina?
- Metaprolol
- Nadolol
- Atenool
- Propanol
mNAP
MOA of B-Blockers in treating Angina
Decrease myocardial O2 demand by
- Decrease HR => increase perfusion and the heart will need less o2 at rest and during XRCISE
- Decrease contractility
- Decrease BP => decrease afterload
What are 5 AE’s associated with beta-blockers?
- -↓ CO
- Bronchoconstriction
- - Impaired liver glucose mobilization
- (↓ HDL and ↑ VLDL)
- Sedation, depression
Which drugs cause withdrawal sx?
Why?
- B-blockers
- Sympathetic hyperrresponsiveness
CI of B-Blockers?
1. Asthma
2. Bradycardia
3. AV block
4. Peripheral vascular dise
5. Type 1 DB on insilin
B-Blockers should be taken with what drugs?
Nitrates
Why should B-Blockers should be taken with what Nitrates?
- Nitrates have reflex increase in HR: BB decrease
- Nitrates decrease EDV: BB increase
- Nitrates have reflex increase in contractility: BB have decrease
- Nitrates have decrease ejection time: BB have increase
How do we treat variant angina?
Mangement is focused on ______
- 1. Prevent episodes
- First drug of choice: CCB or, if contraindicated, LA-nitrate
How do we treat stable (atherosclerotic) angina?
- Lower lipids, modify lifestyle, immediate release nitrates, antiplate therapy (aspirin)
- BB or al
ALL OF THE FOLLOWING DRUGS MAY CAUSE ANGINA ATTACKS EXCEPT
A. ISOPROTERENOL
B. EPHEDRINE
C. PILOCARPINE
D. ATROPINE
E. PHENTOLAMINE
ASK; WILL IT INCREASE OXYGEN DEMAND VIA ONE OF THE 4 MECHANISMS.
