Antianginal Drugs Flashcards
most common factors that reduce supply of oxygen to myocardium
1) occlusive coronary artery lesions due to atherosclerosis
2) reversible narrowing due to coronary spasm or thrombi
Classic Angina ( angina of effort or exercise )
due to to coronary atherosclerotic occlusion
Variant angina ( Prinzmetal )
due to reversible decrease in coronary blood flow
Unstable Angina ( crescendo )
presents acute coronary syndrome with platelet aggregation
NO has been identified as
the endogenously released endothelium - derived relaxing factor
The formation of NO in endothelial cells can be triggered by
1) Ach
2) bradykinin
3) histamine
4) serotonin
Nitrates pathway
Nitrates -> S-nitrosothiols : are releasing NO which activates -> guanylyl cyclase within the the smooth muscle cell to form -> cGMP which effects -> relaxation of vascular smooth muscle
Nitrates from NO
1) causing marked dialtion of large veins -> decreasing of PRELOAD + CARDIAC WORK + DECREASE CARDIAC OXYGEN REQUIREMENT
2) Nitrates also improve collateral blood flow
3) Decrease coronary vasospasm
4) Inhibit platelet aggregation
5) At high doses , nitrates cause arteriolar dilation + decrease cardiac AFTERLOAD + cardiac oxygen requirement
Nitrates decrease _____ and _____
1) infarct size
2) post-MI mortality
Nitrates are considered as _____ and/or as ____ of ___
1) crisis therapy
2) prophylactic treatment
3) cardiac angina
When does tolerance to the effect of nitrates occur?
It occurs when chronic therapy is considered ( mainly for long acting preparations ) . Considering that , the current recommendation is to provide a nitrate free interval of 8-12 hours daily to prevent tolerance.
Side effects of nitrates
Most important
1) Hypertension
2) Headaches ( occurs at therapy initiation or in case of dose increase + decrease significantly after 1-2 weeks of therapy due to physiological tolerance ).
Other side efects of nitrates
3) flushing
4) reflex tachycardia
5) fluid retention ( possibly counteroroductive )
6) tachyphylaxia - require ‘’ rest periods ‘’ of more than 12 hours
7) methemoglobinemia ( more likely with nitrites , e.g , amyl nitrite )
How do the Calcium Channel blocking drugs act ?
they act by blocking of L and T type of membrane voltage activated calcium channels
Dihydropyridines ( e.g Nifedipine as slow release forms , amlodipine )
1 ) are largely vascular selective
2) Are used as prophylactic therapy in all types of cardiac angina and also as anti-HTN medication , treatment of migraine headaches and Raynaud’s disease
* * In prophylactic treatment of cardiac angina are administered orally
Side effects of Calcium Channel blocking drugs
Dihydropyridines
1) Hypotension
2) Reflex cardia tachycardia
3) Peripherical edemas
4) Headache
5) Constipation can be mentioned
Verapamil
Diltiazem
imropve oxygen delivery by
1) dilating coronary arteries and coronary resistance vessels
2) Reduce oxygen demand by reduction of heart rate and afterload
3) Produce vasodilation but also
4) Block Ca channels in the heart
5) Reduce cardiac output
They are less indicated as antianginal medication
Side effects of Calcium Channel blocking drugs
Verapamil and Diltiazem
( possible side effects that can be added to those associated to dihydropyridines treatment )
1) Severe bradycardia
2) AV block
3) Aggravation of congestive heart failure ( due to inotropic negative effect )
Beta Blockers
1) No direct actions on vascular smooth muscle in angina
2) act directly on the heart reducing : HR , force of contraction , and CO , oxygen requirement
3) Effectively prophylactically in angina of effort ( not vasospastic ) and offset reflex tachycardia caused by nitrates
4) are used also to treat hypertension and as antiarrythmic medication
Beta blockers act as
1) Beta receptors antagonists
2) competitive inhibition of the effect of circulating and locally released catecholamines.
3) Most beta blockers have been used (for other characteristics see sections on autonomic drugs and antihypertensive drugs).
beta blockers that are used as antianginal treatment
1) Non-selective beta blockers (propranolol), selective beta1 blockers (atenolol, metoprolol) and
2) beta blockers with intrinsic sympathomimetic activity (pindolol, acebutolol)
other compounds which associate an alpha and beta blocker effect (carvedilol) have been shown equivalent to
isosorbide
1) Such drugs are administered in therapy of cardiac angina in most of the cases orally, as once or twice daily preparation
2) They are well tolerated by the patients in most of the cases
Side effects of therapy with non- selective beta blockers
1) Depression of myocardial contractility
2) Bradycardia
3) Bronchoconstriction
4) Peripherical vasoconstriction
5) Sexual dysfunction
6) Depression
7) Sleep disturbances + nightmares
8) Decreasing of glucose tolerance in diabetics
Nicorandil
1) a vasodilator which reduce cardiac preload and afterload and decrease cardiac effort.
2) Is acting by activation of potassium channels.
Trimetazidine
1) is improving cardiac metabolism and
2) block ATP depletion in cardiac cells.
Ranolazine
decrease cardiac contractility by influencing of sodium influx.
Ivabradine
decrease cardiac frequency by direct inhibition of “funny” ion channels at sinusal node
