Pharmacology Of Vasodilators Flashcards
Ischemia occurs when the work-load on the myocardium is ________ than its oxygen supply.
Greater
Anginal pain is usually due to release of bradykinin and adenosine onto _________ afferents
Nociceptive
Anginal pain can be counteracted by agents or procedures that improve ________ ________ or decrease its metabolic demands by improving ________ ________ or decreasing ________-________ of the myocardium.
Myocardial perfusion; oxygen delivery; work-load
What is the “Steal Phenomenon”?
The theoretical objection to vasodilator therapy that suggests macroscopic evaluation of the small coronary vessels demonstrate that they are already maximally dilated in chronic ischemic states (reactive hyperemia) and application of vasodilators may direct blood flow to other non-ischemic tissues by dilating larger distal vessels.
2 main mechanisms of vasodilator activity
- Blockade of endogenous vasoconstrictors: sympathetic nervous system (prazosin, etc.), humoral agents (angiotensin II, endothelin, etc.)
- Direct relaxation of vascular smooth muscle: endothelium-dependent vasodilators (ACh, BK), non-endothelium-dependent vasodilators such as NO-donators (nitrovasodilators), providing their own endothelium-derived relaxing factor (EDRF)
Sodium nitroprusside (MOA, PK, and Considerations)
MOA: Discussed in Antihypertensives. Primary cardiac effects to reduce both preload and afterload, thereby reducing myocardial oxygen demand.
PK: Emergency parenteral use only.
Considerations: Short-term intravenous use only because of toxicity from build-up of cyanide.
Nitroglycerin (General, Considerations, and MOA)
General: Organic nitrate (EDRF-donor). Drug choice for management of angina since 1879.
Considerations: Some indications that frequent dosing may result in tachyphylaxis (tolerance development).
MOA: NO-stimulated increase in guanylate cyclase activity and cGMP synthesis resulting in Ca2+ sequestration and extensive smooth muscle relaxation in both arteries (afterload) and veins (preload), thus reducing myocardial work-load by decreasing myocardial wall tension during diastole and systole.
Nitroglycerin (PK and ADRs)
PK: Several dosage forms and routes available. Fastest onset of action is sublingual; actual affects are within 1-3 minutes and some “psychological” relief within seconds.
ADRs:
- Hypotension, methemoglobinemia, tolerance
- Headache due to cerebral vasodilation (tolerance)
- Flushing of soft tissues
- Sublingual burning sensation (no tolerance)
Isosorbide dinitrate (ISDN) (General, MOA, and PK)
General: Compare to nitroglycerin. Used in treatment and prophylaxis of angina.
MOA: EDRF-donor
PK: PO and sublingual dosing with rapid onset of action
Nifedipine(General and MOA)
General: Discussed along with CCBs
MOA: Produces a coronary vasodilation in variant (vasospastic) angina, thus improving myocardial blood flow. Its use in stable angina is related to its effects to reduce afterload, this reducing myocardial oxygen demand.
Dipyridamole (General and MOA)
General: AKA Persantine.
MOA: Non-nitrate coronary vasodilator. Clinically no better than placebo in stable angina. Some use in coronary vasospastic angina. Purportedly stimulates an increase in coronary vessel adenosine, which acts at coronary alpha-2 receptors resulting in prompt dilation. Also inhibits platelet adhesion.
Other vasodilators (2 classes)
- ACE Inhibitors
2. Beta blockers
EDRF (General, MOA, and Considerations)
General: Soluble gas produced by vascular endothelial cells.
MOA: Produces a potent cGMP-mediated vasodilation.
Considerations: Inappropriate under-production may cause angina, vasospasm, hypertension, etc.
Endothelin (General, MOA, and Considerations)
General: Peptide produced by vascular endothelial cells.
MOA: Produces potent receptor-mediated (ETa) vasoconstriction.
Considerations: Inappropriate over-production may cause angina, vasospasm, hypertension, etc.
