Angina Drugs Flashcards
Angina is caused by what?
CORONARY ISCHAEMIA which is the result of atherosclerosis by
Sudden ischemia is usually caused by
thrombosis and may result in infarction
-. Ca2+ overload results from
from ischemia
May be responsible for cell death, arrhythmias, diastolic dysfunction
ANGINA occurs when
the oxygen supply to the myocardium is insufficient for its needs
Three types of angina
1)Stable: predictable chest pain on exertion
Produced by increased demand on the heart usually caused by atheroma of coronary vessels or aortic stenosis
2) Unstable angina: pain that occurs with less and less exertion, culminating in pain at rest
Pathology is similar to myocardial infarction (MI)
but without complete occlusion of the vessel
3) Variant angina: relatively uncommon
Occurs at rest
Caused by coronary artery spasm, often in
association with atheromatous disease
TREATMENT APPROACH for angina
(inc./dec.)
•Decrease oxygen requirements
-Decrease total peripheral resistance (TPR)
-Decrease cardiac output (CO)
-Nitrates, calcium channel blockers (CCBs), beta-blockers
● Increase oxygen delivery
-Coronary artery vasodilation
-Opposes coronary spasm in variant angina -Nitrates and CCBs
Treatment for underlying atheromatous
disease
-Statins
-Prophylaxis against thrombosis with
antiplatelet drugs
BETA-BLOCKERS MoA
-SNS stimulation increases CO
Ventricle:
● Increased force of contraction
● Increased SV
SA and AV node: increases HR
-Reduce cardiac work and thus oxygen consumption of the heart
BETA BLOCKERS Clinical Use:
Clinical Use: Prophylaxis of stable angina (first- line) and treatment of unstable angina
Coronary diameter effects should be minor
Avoided in variant angina due to theoretical risk of
increasing coronary spasm
an alternative for patients that cannot use beta-blockers
Ivabradine
Three main L-type CCBs
For angina
Verapamil (heart)
Diltiazem (heart and smooth muscle vasculature)
Nifedipine (smooth muscle vasculature)
What do CCBs do in angina
•Dilate coronary vessels (effect on smooth muscle
vasculature)
•Decrease metabolic demands (effect on TPR and heart)= DECREASES TPR
Nitrates examples
•Glyceryl trinitrate (GTN): acute HF
•Isosorbide mononitrate: chronic HF
Clinical Use
Of CCBs
May be used in combination with beta-blockers (dihydropyridines;CCB), when monotherapy is insufficient, or as alternative in stable angina
Dihydropyridines: vasospastic angina
(DIHYDROPYRIDINES= vasodilation drug)
Therapeutic goal in angina
Of NITRATES
Improve perfusion of the myocardium
Reduce metabolic demands
NITRATES: MOA
•Venorelaxation -> central venous pressure (CVP) reduction i.e. reduced preload, reduced SV
•Effects on arteries: reduce afterload
-Myocardial oxygen consumption falls due to reduced afteload and preload
•Direct coronary vessel dilation increases oxygen content in coronary sinus blood
ADVERSE EFFECTS
Of nitrates
•(You build) Tolerance: d/t Depletion of –SH groups
Tolerance wears off after a brief nitrate-free interval
•Pronounced with long-acting nitrates or prolonged/frequent administration (IV infusion, transdermal patch)
•Postural hypotension- Contraindicated in hypotension
•Headache
•Reflex tachycardia
NITRATES
Clinical use in angina
•Stable: May be used in combination with beta-
blockers/CCBs
•Variant: May be used in combination with CCBs
•Unstable: In combination with other drugs e.g. anti-platelets
Nicorandil MoA
+ Adverse effects
•Potassium channel activator with nitrovasodilator activity
•Sometimes combined with other anti-anginal treatments in refractory angina resistant cases
•Both arterial and venous dilator
Adverse effects: headache, flushing, dizziness, hypotension
POTASSIUM CHANNEL ACTIVATION
Works how
•Relax smooth muscle
-Open KATP channels
-Hyperpolarization
-Switching off of VDCC
•Antagonize the action of intracellular ATP on these channels
RANOLAZINE MOA
-Ischemia causes increased Na+
-Prevents Ca2+ exit via Na+/Ca2+ exchanger (NCX)
!-Ranolazine inhibits late sodium current
!-Indirectly reduces intracellular Ca2+
!-Decreased EDP and thus improvement of diastolic coronary flow
Ranolazine Adverse effects
-Adjunct to other anti-anginal drugs
•Adverse effects: constipation, headache, dizziness, nausea, increased QT interval
-!Does not reduce blood pressure or heart rate
Ranolazine CI
Contraindicated in long QT syndrome or drugs which prolong the QT interval
Anti-psychotics, class Ia & III anti-arrhythmic drugs
Ex. Haloperidol
Stable angina: first-line+ alternative/ combination therapy
1.Beta blocker
2. CCB / long acting nitrates
Unstable angina tx
Anticoagulation, antiplatelets, β-blockers, ACE inhibitors,
statins Symptom control: nitroglycerin and morphine
