CR4 pharmacology Flashcards
Indications to the uses of Nitrates
All types of Angina, acute angina attack (immediate release), prophylactic treatment (long acting)
MOA low dose nitrates
Reduce preload but causing venous vasodilation (reduces the oxugen demand)
MOA high dose nitrates
Arterial dilation - reduces afterload and increases O2 supply
what enzyme converts Nitroglycerin to NO2
Aldehyde dehydrogenase - this is a problem in asians who do not have this enzyme- they cannot take nirtoglycerin
what enzyme converts NO2 to NO
P450 dehydrogenase
Acute AE of nitrates
headache, flushing, orthostatic hypotension, dizziness, syncope, REFLEX TACH, paradoxical bradycardia)
Chronic AE of nitrates
NITRATE TOLERANCE , dependence withdrawl, Methemoglobinemia
Nitrate DDI (major)
PDE inhibitors (-fils) - can cause major hypotension
Nitrate metabolism
high first pass metabolism (cant be taken orally)
Nitrate contraindications
Hypotension (SBP <100), elevated intracranial pressure
PDE inhibitor uses
Erectile dysfunction, Pulmonary HTN
MOA PDE inhibitor
enhabce the effect of NO on smooth muscle by allowing degradation of cGMP
PDE inhibitor AE
mainly due to vasodilatriy effects, visual disturbances
First line drug for stable angina
Beta blocker
First line drug for unstable angina
Beta blocker
First line drug for the prevention/decreasing frequencty of anginal attacks
Beta blocker- has survival benefits
drug for exercise induced angina
Beta Blocker (remember a side effect is exercise intolerance)
which BB have vasodilatory effects, what are these effects
Lebetilol and Cavedilol - block alpha receptors by reducing IP3 generation in vascular smooth muscle
Which BB have intrisic sympathomemetic activity, what are these effects
Pindolol, Acebutolol - partial B1 and B2 agonists (enough stimulation that they are tolerable)
Which BB has B3 receptor agonist activity
Nebivolol - enchances NO production (may relieve erectile dysfunction)
BB major DDI
Insulin, hyperglycemic agents, verapamil
Lipid soluble BB metabolism
Propranolol and Metoprolol are metabolized by the liver (CYP2D6)
Hydrophilic BB metabolism
Nadalol and atenolol - renal excretion unchanged
discontinuation of BB
over 2 week period to prevent refelex vasoconstriction that can worsen cardiac ischemia - can be mitigated by using a CaBlocker (dihydropyradine)
BB are contraindicated in what form of angina
Varient (Prinzmetal) - can potentiate vasoconstriction as a result of unopposed alpha adrenergic activity in coronary smooth muscle
BB Contraindications
variant angina, asthma, raynauds, AV block, Bradycardia, depression
Indications for the use of calcium channel blockers
1: Stable or variant angina 2: Can prevent angina but do not have the survival benefits that beta blockers do - used as a monotherapy when BB are contraindicated 3: Add on therapy to BB when theraputic goals are not being met (Dihdyrdopydradines) **THIS IS MORE EFFECTIVE THAN USING EACH DRUG ALONE
Non-dihydropyridines MOA
Dilt and Verapamil - Reduce voltage dependent L-type calcium channels in cardiac muscle - slow conduction through AV node (prevents Ca channel recovery) - decreased contractility due to decrease in calcium - relax nonvascular smooth muscle (Bronchial, GI, Uterine)
Dihydropyridine MOA
Pines - reduce voltage gated L-type calcium in smooth musle cells. effective vasodilatirs therfore decrease PR and BP (afterload)
Calcium channel blocker AE
Short acting result in HYPOTENSION, REFLEX TACH, RISK OF MI, peripheral edema, headache, flushing, nausea . Long term results in PERIPHERAL EDEMA
Non-dihydropyridines DDI
Beta blockers (can induce severe Bradycardia) , increase [Digoxin]
Dihydropyridine DDI
These drugs do not produced DDI because they are not block or induce CYP34A - other drugs can affect the concentrtaion of dihydropyradines
Non-dihydropyridines Metabolism
CYP3A4, block p-glycoprotein