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
Dihydropyridine Metabolism
CYP3A4
Non-dihydropyridine Contraindications
HF, AV conduction problems, Sick Sinus Syndrome, Hypotension, Aortic Stenosis
Dihydropyridine contraindications
Hyptension, aortic stenosis
Indication for use of Ranolazine
Stable angina as an add on agent if preventative goals have not been achieved. Combination therapy with nitrates, BB, or dihydropyradines. Can be used as BB alternative in contraindications and AE
Ranolazine MOA
blocks cardiac late Na channels - revereses the effect of Na buidup that occurs in ischemia and assures NCX goes in the correct direction (Na in Ca out)
Ranolazine AE
Long QT syndrome (due to block of Ikr)
Ranolazine DDI
Verapamil and Diltiazem, Ketoconazole (CYP34a blockers), Inhibits metabolism of digoxin and simvastatin (dose adjust these drugs)
in addition to anginal tretemt all patients should begin …
1: Antiplatelet (Asprin) 2: Antihypertensive (Atorvastatin)
what classes are used in unstable angina
Beta blockers and nitrates
What classes are used in variant angina
Nitrtes and Calcium channel blockers
ACE-I MOA
suppress RAAS systme – reduced preload and afterload (relaxation og blood vessels, reduce fluid and sodium retention) and inhibit remodeling
First choice treatment for CHF
ACE - used in all patients with HFrEF (reduces mortality up to 6 months)
ACE -I AE
GI, headache, dizziness, hypotension, HYPERKALEMIA, hypoglycemia, renal function impairment, ANGIOEDEMA, **COUGH
ACE-I CI
Pregnancy, bilateral renal stenosis - less effective in black population
Clinical use of ARB
used as an alternative only in patients who cannot tolerate ACE
Patient presents with NYHA II and EF 30%. Current medications include an ace and an a beta blokcer. The patinet remains symptomatic. What drug do you give to reduce mortality and cardiac remodeling
Aldosterone receptor antagonist (Spiralactone eperenone)
Patinet has syptoms of HF and LVEF < 40% with a history of diabetes what drug would you give
Aldosterone receptor antagonist (Spiralactone eperenone)
Aldosterone receptor antagonits major AE
HYPERKALEMIA, ACIDOSIS , gynecomatasia
Aldosterone receptor antagonist DDI
Oral K, other K sparing diuretics, NSAIDS
Aldosterone receptor antagonist CI
Renal isnufficiency, Serum K >5
BB MOA
reduced workload of the heart, decreased HR and contractility. Prevent RAAS activation- prevent fluid retention and remodeling. Reduce cardiac remodeling and mortality
BB Indication
Anyone with HFrEF on standard thearpy (ACE and diuretic as needed) who are hemodynamically stable (NO HYPOTENSION)
BB AE
Bradycardia (decreased HR), reduced exercise tolerance, fluid retention, worsening HF, hypotension
BB DDI
Digoxin
BB CI
Unstable HF, severe bradycardia, and heart block. Carvedilol should not be used in patients with asthma and COPD
Which drug can replace ACE in patient who can tolerate ARBs and are NYHA II or III
ARNI (sacubitril and valsartan: further reduce morbidity and mortality) Enhance the action of NP and supress the effect of Ang II
ARNI AE
Hypotension, Hyperkalemia, renal impairment
ARNI DDI
RAAS inhibitors
ARNI CI
pregnancy, bilateral renal stenosis , HX OF ANGIOEDEMA
47 year old african american female (ACE/ARB intoleranct) presents with NYHA III HFrEF who is symptomatic on standard therapy. What durg should be given
Hyrdralazine+ Isorbide (arteial and venous dilators)
Vasodilator CI
PDE inhibitors and Hypotension
Most common side effect of vasodilators
Flushing - also cause headache, postural hypotension, reflex tach, fluid retention and LUPUS ERYTHEMATOSUS LIKE SYNDROME
Loop diretic MOA
Relive pulmonary and peripheral congestion by inhibiting Na/K/2Cl in the thick ascending limb of the loop of henle and promoting renal loss of sodium and water
First line for rapid relief of congestion symptoms in HF
Loop Diuretic
Major AE of Loop Diuretics
Alkalosis, HYPOKALEMIA , Dilutional hyponatremia, ** Ototoxicity
Digoxin MOA
ionotropic drug. Inhibits Na/K ATPase – slows down the NaCa exchange thereby increasing the amount of Ca in the cell - increases contractility. At theraputic doses it slows HR and increases Contractility
Patient presents with symptomatic HFrEF. They are currently taking ACE, BB, aldosterone receptor blocker, and diuretic. What drug do you give
Digoxin
Patient presents with CHF and atrial fibrillation - what drug do you give
Digoxin
Patient complains of bludrred vision,altered color perception and hallows around dark objects- what drug are they taking
Digoxin
Digoxin DDI
Diuretics, CCB, BB
Patient is experiencing Digoxin toxicity - how do you treat
Lower or discontinue digoxin, correct electrolyte abnormalities (Mg, K) treat arrythmia with antiarrythmic, and give Digibind to reverse toxicity
Beta adrenergic receptors used in heart failure
Dopamine and dobutamine
Dopamine and dobutamine MOA
Ionotropic agent. Bind to B1 receptor and increase CAMP and PKA to promote Ca release to increase cardiac contractility
Dopamine and dobutamine indication
short term for treating end stage heart failure - patients with systolic dysfunction who don’t respond to other therapies and have organ hypoperfusion. Also increases contractility in acute HF
dopamine and dobutamine AE
tachycardia and Arrythmia (due to increased Ca)
PDE inhibitors
Milrinone and Imamirone
what drugs are indicated in end stage heart failure
PDE inhibitors and Vasodilators (dopamine and dobutamine)
PDE inhibior indication
Shor term use in treating end stage heart failure- systolic dysfunction who don’t respond to other therapies and have end organ hypoprofusion
Ivabradine MOA
Slows HR by blocking the cardica pacemaker If current (funny channel)
Ivabradine Indication
Worsening HF in patients with stable symptomatic HF, LVEF <35% who are in sinus whythm with a resting HR >70 bpm and who are on maximum tolerated doses of BB or have a contraindication to BB
