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Pharm - Angina

Saba - Basic Sciences - Semester 4 - Pharm - Blk3 - Lect06

QuestionAnswer
Ischemic Heart Disease – 2 types Angina (Transient coronary ischemia, chieft manifestation) & Myocardial infarction (Complete occlusion) are the manifestations of this disease
Ischemic Heart Disease – Angina pectoris – Cause Imbalance between Oxygen supply & demand results in this cardiac condition
Ischemic Heart Disease – Angina pectoris – Stable MC Angina, occuring in effort or exericse d/t coronary atherosclerotic occlusion
Ischemic Heart Disease – Angina pectoris – Variant/Prinzmetal Vasospastic angina, due to a reversible decrease in coronary blood flow.
Ischemic Heart Disease – Angina pectoris – Risk Factors Risk factors for this cardiac condition include Hypertension, Diabetes, Hyperlipidemia, Smoking
Ischemic Heart Disease – Angina pectoris – Px This cardiac disorder is seen more commonly in adult males and in post-menopausal females
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy Incease oxygen delivery by reducing vasospasm (nitrates & CCBs). Decrease oxygen requirement by decreasing TPR/CO (+B-blockers)
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Types Classes of drugs used in this condition include nitrates, calcium channel blockers, and beta blockers.
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates Prodrugs of nitrous oxide that decreases pre-load & O2 requirement by dilating veins. Also reduces infarct size & improves post-MI mortality.
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates - Pathway In Endothelial cells, upon binding of ACh, bradykinin, 5-HT etc: L-arg → NO (NO Synthase). Smooth muscle cells: Nitroglycerin activates guanylyl cyclase with creates cGMP. This activates phosphatase which acts on MLCK, leading to vasodilatation.
Anti-Anginal Drugs – Nitrates – Effects Decrease pre-load (most import…(-) end-diastolic size and pr, (+) subendocardial perfusion), cardiac work & O2 demand by dilating VEINS. (+) coronary collateral circulation. Relieve vasospasm of coronary vessels. (-) infarct size, (+) post-MI mortality
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates -Types There are both nitrates and nitrites used in the treatment of this disorder
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates -Types - Classic - Subtypes "This class of antianginals includes nitroglycerin (GTN), isosorbide dinitrate, isosorbide mononitrate, Erithrityl tetranitrate
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates -Types - Nitrates This class of antianginals includes amyl nitrite
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates -Types- Classic - RoA (4) RoA's for this drug class include short acting: sublingual (GTN, Isosorbide dinitrate), long acting: oral (isosorbide mononitrate, isosorbide dinitrate, Erithrityl tetranitrate), and ointment and transdermal preparations.
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates -Types- GTN - This Nitrate is the DOC in acute anginal attack b/c it onsets in <1min d/t sublingual or spray RoA. Undergoes high first pass metab. transdermal or IV preparations are prophylactic
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates -Types-Isosorbide - Pharmacokinetics The dinitrate form of this drug onsets in 5 min, while the mononitrate in 30 min. Timed/Extended release formulas have d/a 8-12hrs.
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates - Indications In stable angina, these drugs are used synergistically w B blockers to improve exercise tolerance. In variant angina, they are used in combination with CCBs/
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates - Adverse Reactions Adverse reactions of this drug include tachyphylaxis w repeated use, For variant angina, morning is worst period d/t catecholamine surge, also headache, flushing, postural hypotension, reflex tachycardia and fluid retention, and metHBemia at large doses)
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates - Adverse Reactions - Tachyphylaxis - Antidote This adverse reaction to nitrates is overcome with a drug holiday of 10-12 hrs/overnight, when demand of heart is increased.
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates - Adverse Reactions - Drug Interactions - Drugs This drug class interacts with Sildenafil and Cocaine
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates - Adverse Reactions - Drug Interactions - Sildenafil Nitrates interact with this drug, aka Viagra, tor/I potentiation of their hypotensive effect, leads to SEVERE hypotension, tachycardia and heart attack
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrates - Adverse Reactions - Drug Interactions - cocaine the result of cocaines interact with this drug class includes increases oxygen demand by increasing HR & decreases O2 supply by vasoconstriction
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Nitrites - Nitrites - Amyl Nitrites This is an organic nitrite, not used for angina, but for tx of CN- poisoning (converts Hb to methemoglobin which has affinity for cyanide). Followed by administration of sodium thiosulfate for excretion. Not used as much dt unpleasant odour and short d/a.
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Ca2+ channel blockers This class of anti-anginals works by (-) after-load by arteriolar dilation
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Ca2+ channel blockers (CCBs) – Mechanism of Action This class of drugs blocks L-type channels in heart & blv's. This (-) contractile F and o2 reqmts. Lack of Ca2+ results in vasodilation. Predominantly, arteriolar dilation. Coronary dilation relieves vasospasm. Peripheral vasodilation reduces afterload.
Anti-Anginal Drugs – Ca2+ channel blockers (CCBs) – Indications All drugs of this class are indicated for angina pectoris. -Dipines better for vasospastic - good coronary dilators. They are usually give in combo w nitrate. Also used in HTN (even w PVD, DM, Angina, Asthma), peripheral vascular disease, arrythmia (V/D)
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Ca2+ channel blockers (CCBs) – Classification This class of drugs includes 1) Verapamil and Diltiazem – 2) DihydropyriDINES
Anti-Anginal Drugs – Ca2+ channel blockers (CCBs) – Verapamil/Diltiazem These anti-anginal drugs have effect on cardiac & vascular Ca channels, no change in preload & ventricular arrhythmias.
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Ca2+ channel blockers (CCBs) – 'Dines' These anti-anginal drugs, particularly dihydropyri - have much greater affinity for vascular Ca2+ channels only. Affect only afterload, O2 consumption, both anginas & HTN.
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Ca2+ channel blockers (CCBs) – Adverse Effects Adverse effects of these drugs include Constipation (Vera), Flushing, dizziness, headache & fatigue, peripheral edema, reflex tachy & gingival hyperplasia (-dipines), cardiac depression
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Ca2+ channel blockers (CCBs) – Contraindications Verapamil/Diltiazem should be used cautiously in patients w/ cardiac failure & heart blocks, as they increase supraventricular tachycardia (too much work, 02 demand). But before failure, they are very useful (increase work helps perfusion)
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - B-Blockers - Mechanism of Action This drug class works in the tx of angine by(-) HR (+ perfusion), F of Contraction, time to onset of angina → decrease O2 demand
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - B-Blockers - Indications Combo tx w nitrates and CCBs preferred for this drug class in txg classic angina d/t (-) adverse effects of both agents (inhibit reflex tachycardia). Carvedilol clinically equivt to isosorbide. also prophylactic of sudden death d/t arrhythmias (post-mi).
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - B-Blockers - Adverse Reactions Adverse effects of these drugs include fatigure, depression, insomnia, hallucinations, deranged lipid profile, bronchospasm, masking of hypoglycemic conditions of DM, and sexual dysfunction
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - B-Blockers - Adverse Reactions - Drug Interactions These should not be used with Verapamil/Diltiazem
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - B-Blockers - Contraindications These drugs are contraindicated in variant/prinzmetal angina and in CAD px w asthma, diabetes mellitus and HF.
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - Best combo for Vasospastic Nitrates increase preload while CCBs decrease afterload and so their combination is ideal for this condition
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - New This class of drugs includes potassium channel activators (nicorandil), dipyramidole, trimetazidine and ranolazine (cytoprotective antiischemic), ivabradine
Ischemic Heart Disease – Angina pectoris – Pharmacotherapy - New - Dipyramidole This drug results in coronary steal phenomenon, diverting flow to non-ischemic areas only, giving it pharmacological success but therapeutic failure. Further exacerbates angina.
Ischemic Heart Disease – MI – Pharmacotherapy Pharmacotherapy for this condition involves aspirin, oxygen, GTN, morphine (opiod analgesic), beta blockers (metoprolol), antiarrhythmics, thrombolytics and percutaneous coronary interventions, heparin, lipid lowering agents, ACE inhibitors if EF <40%
Created by: mprentic12