CV Drugs Flashcards
Mechanism(s) of Centrally-acting Agents
Stimulates the A2 receptor on SNS neurons, causing downregulation of norepinephrine release to systemic smooth muscle cells (clonidine)
Acts as a norepinephrine mimic that primarily acts on the brain to limit SNS outflow (methyldopa)
MAJOR EFFECT of both is to decrease systemic vascular resistance
How does increased SNS tone raise BP? There are 4 mechanisms
They cause vasoconstriction via A1-adrenergic signaling to smooth muscles, increasing systemic vascular resistance, and thus BP.
They act on B1-adrenergic receptors in the heart to increase CO and contractility, thus increasing BP.
They cause venous constriction via A1-adrenergic signaling to smooth muscles, increasing venous return/preload, causing increases in CO and contractility that lead to increased BP.
They stimulate renin release from the kidney, activating the RAA system, resulting in increased Na and water retention, thus raising BP.
Naming of Centrally-acting Agents
Clonidine and methyldopa
Clinical uses of Centrally-acting Agents
HTN: good adjunctive therapy (2nd line) due to having very few drug-drug interactions, w/methyldopa primarily used in pregnant women
Side Effects of Centrally-acting Agents
Both: sedation, depression, dry mouth (central acting agents can cause CNS problems, like depression)
Methyldopa: hepatotoxicity
Clonidine: bradycardia (unknown mechanism, perhaps due to increased vagal stimulation), clonidine withdrawal symptoms (HTN, headache, tremors, sweat)
Mechanism of A1-receptor Blockers
Block A1-adrenergic receptors on smooth muscle, preventing the action of norepinephrine, which normally causes smooth muscle contraction.
MAJOR EFFECT is decreased vascular resistance
Naming of A1-receptor Blockers
-zosin suffix (prazosin, terazosin, doxazosin)
Clinical uses of A1-receptor Blockers
HTN: adjunctive therapy (2nd line, NEVER a first line drug), good in patients w/enlarged prostates
Side Effects of A1-receptor Blockers
Orthostatic hypotension (due to all the vasodilation)
Mechanism(s) of Beta-Blockers
Block B1-adrenergic receptors on the heart and kidney, preventing norepinephrine from acting to increase CO/HR and renin release. Results in lower oxygen demand and decreased CO/HR/BP. Also results in greater diastolic filling time
Block B2-adrenergic receptors on smooth muscle cells, preventing epinephrine from acting to cause vasodilation and bronchodilation.
MAJOR EFFECT is to decrease CO/HR, vasoconstriction and bronchoconstriction are minor
Naming of Beta-Blockers
-olol suffix
B1-specific drugs: atenolol, metoprolol (LETTERS A-M)
B1 and B2 blocking drugs: propranolol, nadolol (particularly long half-life), timolol (LETTERS N-T)
B1, B2, and A1 blocking drugs: carvedilol, labetalol
B1 blocking and NO-activating drugs: nebivolol
Clinical uses of Beta-Blockers
HTN: adjunctive treatment (2nd line), HTN emergencies (labetolol can be administered IV)
HF: first line treatment, improves the heart’s sensitivity to SNS stimulation by inhibiting GPCR recycling via GRK2 and B-arrestin. ONLY THESE 3: metoprolol succinate, bisoprolol, carvedilol
CAD/IHD: acute (reduce ischemia by lowering oxygen demand), chronic (prevent recurrence), post-CABG
Arrhythmias: (FILL THIS IN)
Side Effects of Beta-Blockers
Bradycardia
Hyperkalemia (due to blocking of RAAS resulting in less Na/K antiport)
Fatigue (decreased CO)
Cold extremities and bronchospasm (due to B2-blockage causing vasoconstriction and bronchoconstriction)
Mechanism(s) of Ca-channel Blockers
Block L-type Ca-channels on smooth muscle, preventing Ca intake, thus inhibiting MLCK activity and smooth muscle contraction.
Block L-type Ca-channels in the heart, lowering HR and decreasing CO.
Naming of Ca-channel Blockers
Dihydropyridines (-dipine suffix, amlodipine, nifedipine) act only on VASCULATURE
Phenylalkylamines (verapamil) act only on HEART
Benzothiazepines (diltiazem) act on BOTH
Clinical Uses and Contraindications of Ca-channel Blockers
HTN: FIRST LINE drug, also good adjunctive drug; safe in diabetics, asthma, renal insufficiency, and lipid problems
CAD: slow down the HR/CO to decrease oxygen demand; acute (control spasm by inducing vasodilation)
Arrhythmias: (FILL THIS IN)
Contraindications: HF, do not give verapamil or diltiazem if pt is already on another HR slowing drug like a B-blocker
Side Effects of Ca-channel Blockers
Vasculature acting (dihydropyridines and diltiazem): edema (MOST COMMON SIDE EFFECT)
Central acting (verapamil and diltiazem): bradycardia (MOST COMMON SIDE EFFECT)
All 3: drug-drug interactions due to CYP3A4 metabolism (though dihydropyridines to a lesser extent), dizziness, nausea, headache, constipation
Mechanism(s) of Peripheral Vasodilators
Hydralizine: relaxes arterial smooth muscle to decrease vascular resistance (exact mechanism unknown)
Minoxidil: K-channel agonist that hyperpolarizes smooth muscle, leading to decreased vascular resistance
Nitroprusside and Nitrates: metabolized into NO, which increases cGMP in smooth muscle cells, activating PKG, resulting in more MLCP activity and less contraction, leading to decreased vascular resistance. This leads to decreased afterload. Nitrates also dilate the coronary arteries to allow for more blood flow.
Naming of Peripheral Vasodilators
Hydralizine, minoxidil, nitroprusside
Nitrates: “nitro” in the name (nitroglycerin, dinitrate, isosorbide mononitrate)
Clinical Uses of Peripheral Vasodilators
Hydralizine: HTN when other drugs don’t work due to side effects (can be administered PO or IV), HTN emergencies (IV administration); HF (combined w/isosorbide mononitrate)
Minoxidil: last resort for outpt HTN (PO only administration)
Nitroprusside: HTN emergencies (due to IV only administration)
Nitrates: acute MI (sublingual, control spasm), intermediate onset (topical, oral), long-term (transdermal, sustained release pills); HF (combined w/hydralazine)
Side Effects of Peripheral Vasodilators
Hydralizine: headache, nausea, dizziness, vomiting; edema, angina/heart failure
Minoxidil: Na/water retention (downregulation of SNS firing in kidney), tachycardia/angina/heart failure (faster repolarization in pacemakers due to increased K-channel activity)
Nitroprusside: hypotension, cyanide/thiocyanate toxicity (manifests as lactic acid, anorexia, fatigue, confusion, psychosis)
Nitrates: headache, nausea, dizziness, vomiting
What is the consequence of the body being quick to develop a tolerance for nitric oxide?
The dosing of nitrates and nitroprusside has to be spaced out, w/8 hour gaps where no drug is given in between each dose.
Mechanism of Ranolazine
Blocks the late inward Na-current that is present in ischemic cells. Normally, the increased Na due to this current increases the activity of the Na/Ca exchanger, causing Ca to move into the cell and increasing contractility, and thus increasing oxygen demand and preventing proper relaxation.
Ranolazine prevents all this and reduces oxygen demand in ischemic cells.
What is special about Ranolazine compared to anti-ischemic drugs?
Ranolazine does not lower BP or change HR since it only acts on ischemic cells. This allows it to be safely used in conjunction with nitrates, beta-blockers, and dihydropyridines
Clinical Uses of Ranolazine
CAD/IHD: reduces oxygen demand of ischemic cells and helps them relax properly, preventing further damage
Side Effects of Ranolazine
Potential drug-drug interactions since it is metabolized by CYP3A4
Mechanism(s) of Digoxin
Positive inotropic effect: blocks Na/K ATPase in the heart, partially dissipating the Na gradient. The lack of gradient prevents the Na/Ca exchanger from functioning, leaving more Ca inside the cell, thus increasing contractile force.
Vagomimetic effect: slows down phase 4 depolarization in pacemaker cells
Clinical uses of Digoxin
Arrhythmias: (FILL THIS IN)
HF: can help w/HF, but other medications are more popular
Side Effects of Digoxin
Super low therapeutic window
Nausea, diarrhea
Yellow vision
Pro-arrhythmic
How do you counteract the effects of severe Digoxin toxicity?
Monoclonal antibody fragments targeting digoxin
Mechanism of Ivabridine
Slows HR by blocking the inward Na (FUNNY) current in SA node
Clinical uses of Ivabridine
HF: only indicated if B-blockers have already been used and the pt’s HR is still too high (3rd/4th line drug)
Mechanism of B1 Agonists
Stimulate the B1 receptor on the heart, causing increased HR and contractility/inotropy/lusitropy
Naming of B1 Agonists
Dobutamine, norepinephrine, dopamine
Clinical uses of B1 Agonists
ADHF: inotrope for cold/wet
Mechanism of Milrinone
Inhibit phosphodiesterase 3 in the heart, preventing it from hydrolyzing cAMP. The increased cAMP results in increased HR and contractility/inotropy/lusitropy
Clinical uses of Milrinone
ADHF: inotrope for cold/wet
