25. Drugs used for treatment of angina pectoris. Pharmacotherapy of ischemic heart disease. Flashcards
List the drug groups used to treat Angina Pectoris?
- Nitrates: mostly nitroglycerin
- Calcium channel blockers: nifedipine, verapamil
- β blockers: propranolol, carvedilol
- Metabolism modifiers: pFOX inhibitors (partial fatty acid oxidation inhibitors): ranolazine, trimetazidine
- Rate inhibitors: Ivabradine
What is the mechanism of action of Rate inhibitor?
Rate inhibitors like Ivabradine inhibits funny channels in SA node → hyperpolarization of pacemaker current → HR ↓ → workload ↓.
What are the side effects of using calcium channel blockers?
Mild:
- Constipation
- Pretibial edema
- Nausea
- Flushing
- Dizziness
Severe: (these are more common with verapamil)
- Heart failure
- AV block
- SA depression
What is the MOA of Nitrates?
Nitrates release nitric oxide in smooth muscle cells. NO activates guanylyl cyclase → cGMP ↑ → dephosphorylation of myosin light chain ↓ → smooth muscle relaxes (identical mechanism to nitroprusside).
What are the side effects of using nitrates?
Mostly related to vasodilation.
- Headache is extremely common
- Orthostatic hypotension - tachycardia from baroreceptor reflex (combine with β blockers to prevent)
- Methemoglobinemia (but this is useful in cyanide poisoning)
- Hypotension enhanced from erectile dysfunction meds like sildenafil citrate (viagra) - PDE5 inhibitors.
What is the route of administration of isosorbide dinitrate?
Isosorbide dinitrate used in sublingual or oral forms.
Why can calcium channel blockers be used for Angina?
Both dihydropyridines (vessel-selective, e.g nifedipine) and the non-dihydropyridines (non- selective / cardiac types - diltiazem, verapamil) are indicated for Angina. They block VG L-type Ca2+ channels, most important in cardiac and smooth muscle. Cardiac CCBs decrease rate and contractility of heart whereas dihydropyridine CCBs decreases workload via stronger vasodilation. Sympathetic reflex increases HR. Nifedipine has been used to abort acute anginal attacks and can be combined with nitrates in severe atherosclerotic angina.
What is angina pectoris and what are the different types of anginas?
Angina pectoris is a strangling, pressure-like pain caused by cardiac ischemia. There are 3 types. There is atherosclerotic angina which is an “effort” or “classic” angina, occurs due to atherosclerotic plaque(s) in coronary arteries. Occurs during exertion, but is relieved by rest. This is the most common type. Then there is unstable angina which is a “crescendo” angina, rapidly progressing atherosclerotic angina. Angina occurs even at rest, but is resolved before it can be considered an AMI. High likelihood to later have MI without intervention. Lastly there is the vasospastic angina also known as Prinzmetal angina / rest angina. Rarer and occurs due to reversible spasm of coronary arteries.
What is the MOA of Amyl nitrite?
Amyl nitrite is volatile and rapid-acting vasodilator, used to be an inhaled treatment for angina but rarely used now. It was also used as part of treatment for cyanide poisoning (along with IV sodium nitrite and IV sodium thiosulfate). Nitrates make more methemoglobin, which bonds stronger to cyanide ions and prevents them from blocking oxidative metabolism. Currently hydroxocobalamin (a form of vitamin B12) is preferred as cyanide poisoning treatment.
Why can Beta blockers be used in Angina pectoris?
- Beta blockers have beneficial antianginal effects (HR ↓, contractility ↓, blood pressure ↓) and detrimental effects (increased heart size, longer ejection period).
- Like nitrates and CCBs, they reduce cardiac workload/demand, used prophylactically for angina, no value in acute attack.
- They can help prevent exercise-induced angina, but not vasospastic form (Prinzmetal angina is a contraindication!)
- They also help prevent undesirable tachycardia from using nitrates.
What is the MOA of Trimetazidine?
Trimetazidine is an anti-ischemic (anti-anginal) metabolic agent, which improves myocardial glucose utilization through inhibition of long-chain 3-ketoacyl CoA thiolase activity, which results in a reduction in fatty acid oxidation and a stimulation of glucose oxidation. High fatty acid oxidation rates are detrimental during ischemia due to an inhibition of glucose oxidation leading to uncoupling of glycolysis and an increase in proton production, which has the potential to accelerate sodium and calcium overload in the heart, which leads to an exacerbation of ischemic injury and decreased cardiac efficiency during reperfusion.
What is the MOA of Ranolazine?
Ranolazine is an acetanilide and piperazine derivative that acts by inhibiting sodium and potassium ion channel currents. Ranolazine reduces fatty acid oxidation, but more importantly reduces sodium current in myocardial cells. Its decrease in intracellular Na → increased Ca2+ excretion via Na/Ca transporter → decreased contractility. It is moderately effective in angina prophylaxis.
What is the MOA of Nitroglycerine?
Nitroglycerine (proper name is glyceryl trinitrate) is potent venodilator and it decreases the preload. It is the most essential in treatment of chronic stable angina pectoris. What usually happens is that the preload leads to wall stress on the heart, more oxygen is needed and hypoxia → angina. This drug acts almost immediately to reduce the wall stress, takes 5-10 minutes.
What are the side effects of Nitroglycerin?
The side effects are mostly related to vasodilation.
- Headache: is extremely common
- Orthostatic hypotension: Tachycardia from baroreceptor reflex (combine with β blockers to prevent)
- Methemoglobinemia (but this is useful in cyanide poisoning)
- Hypotension enhanced from erectile dysfunction meds like sildenafil citrate (viagra) - PDE5 inhibitors.
What is the DOA of the sublingual form of Nitroglycerin?
The sublingual form for acute attacks has a duration of 10-20 minutes.
