CARDIO: PHARM Flashcards
What is responsible for the timing of “Monday disease”?
Nitrates are associated with the following adverse effects:
- Headache
- Hypotension
- Flushing
- Reflex tachycardia (which can be prevented/treated with β-blockers)
Monday disease occurs when tolerance develops to the vasodilatory effects of nitrates during the work week, which wears off during the weekend. Upon re-exposure on Monday, the vasodilation results in tachycardia, dizziness, and headache.
The compensatory vasoconstriction on weekends can result in non-atherosclerotic ischemia and possibly cardiac arrest, the most serious complication.
What are 2 key side-effects of methyldopa?
Two key side-effects of methyldopa include direct Coombs-positive hemolytic anemia and a SLE-like syndrome.
What other antiarrhythmic class properties does amiodarone have besides its role as a K+ channel blocker?
Amiodarone has class I, II, III and IV effects since it alters the lipid membrane.
What are the side effects of disopyramide?
Disopyramide—side effects:
- Anticholinergic symptoms (blurry vision, urinary retention, dry mouth);
- Heart failure
- Torsades de pointes due to increased QT interval
- Thrombocytopenia
What are the cardiovascular side effects of amiodarone?
The cardiovascular side effects of amiodarone include bradycardia, heart block, and congestive heart failure
What is the general mechanism of action of class IV antiarrhythmics? Name 2 examples of class IV antiarrhythmics.
Class IV anti-arrhythmic agents are non-dihydropiridine calcium channel blockers (e.g., diltiazem, verapamil), which exert their anti-arrhythmic effect mainly by slowing AV node conduction by inhibiting Ca2+ influx.
Describe the mechanism of action of resins (e.g., cholestyramine) in the treatment of hyperlipidemia.
The mechanism of bile acid resins is as follows:
- Positively-charged bile acid resins bind negatively-charged bile acids, forming a complex
- These complexes are excreted in stool, depleting the pool of bile acids (> 95% of bile acids are normally reabsorbed)
- Hepatic synthesis of bile-acids increases, depleting hepatic cholesterol (bile acids are made from cholesterol)
- Hepatocytes increase expression of LDL receptors
- Serum LDL is reduced due to increased hepatic LDL uptake
Side effects of bile acid resins include:
- GI discomfort (constipation, diarrhea, and flatulence)
- Malabsorption of fat-soluble vitamins and drugs
What is the mechanism of action of prazosin?
A:
Mechanism of prazosin: selective α1 receptor blockade which leads to vasodilation.
What is the cellular target of ranolazine?
Ranolazine inhibits the late inward sodium current (INa) on cardiac myocytes.
When taken with amiodarone, what cardiac drug shows markedly elevated levels due to decreased clearance?
Amiodarone decreases the clearance of digoxin leading to markedly elevated levels of digoxin when taken together.
Which electrolyte imbalances will increase digoxin toxicity? Which combination drug therapies will increase digoxin toxicity?
Risks of Toxicity increased by:
- Renal failure (only in digoxin)
- Hypokalemia from diuretics (digoxin competes with K+ for the same binding site on Na+/K+ ATPase)
- Hypomagnesemia
- Quinidine, Amiodarone
- Combination therapy with calcium channel blockers (especially Verapamil)
Note: Hyperkalemia indicates a poor prognosis in patient with digoxin toxicity.
What is/are the possible side effect(s) of ibutilide?
The side effect of ibutilide is torsades de pointes.
What are 3 commonly-tested Class IA antiarrhythmic agents?
Mnemonic: “Double Quarter Pounder”:
Disopyramide
Quinidine
Procainamide
What are Class IA antiarrhythmics used for?
Class IA antiarrhythmics: used for most atrial and ventricular arrhythmias
What do class III antiarrhythmics do?
Class III antiarrhythmics (AAs) block K+ channels and thus prolong repolarization.
What is the classic buzzword for quinidine toxicity?
Quinidine—side effects = 3 T’s + cardiac depression:
Thrombocytopenia, Tinnitus, Torsades
Severe hypotension with cardiac arrest
The classic “buzzword” for quinidine toxicity is cinchonism, often described as tinnitus, blurred vision, dizziness, nausea, and vomiting.
Name 3 different bile acid sequestrants.
Bile acid resins include:
Cholestyramine
Colestipol
Colesevelam
What is the mechanism for methyldopa as a treatment for hypertension?
Mechanism of clonidine/methyldopa: Central α2 agonist. Acts in the vasomotor center of the medulla to decrease presynapstic norepinephrine release.
What are some uses of minoxidil?
Minoxidil is a pro-drug that (upon sulfation by the liver) opens ATP-dependent potassium channels, causing hyperpolarization and subsequent relaxation of arteriolar smooth muscle. The net effect is arteriolar vasodilation.
Minoxidil is used in moderate to severe HTN. Because it causes hypertrichosis, or excessive hair growth, minoxidil is marketed as Rogaine.
Side effects of minoxidil and diazoxide include the following:
- Hypertrichosis (Minoxidil)
- Hyperglycemia (decrease insulin release from Diazoxide)
- Reflex tachycardia
- Edema
.
What are the 3 components of the treatment of β-blocker toxicity?
The treatment for beta blocker toxicity is:
Glucagon, which increases cAMP in cardiac tissue
Saline
Atropine
What ECG finding will be found following the administration of class II antiarrythmics (β-blockers)?
Class II antiarrythmics (β-blockers) decrease cAMP and Ca2+ currents, which leads to decreased SA and AV nodal activity.
Class II antiarrythmics (β-blockers) can be used to suppress abnormal pacemakers by decreasing the slope of phase 4 of the pacemaker cell action potential.
The AV node is particularly sensitive to the effects of class II antiarrythmics (β-blockers), thereby leading to an increased PR interval.
What 2 drugs are specifically recommended for the treatment of NYHA class IV congestive heart failure?
Treatment for NYHA class IV or moderate to severe CHF:
Add digoxin for symptomatic relief (no improvement in mortality)
Spironolactone can also be added for treatment of NYHA class IV, as it has been shown to improve mortality in these patients.
What are the side effects associated with dihydropyridine CCBs (calcium channel blockers)?
Side effects associated with dihydropyridine CCBs include:
Reflex tachycardia
Peripheral edema
Flushing
Dizziness
Constipation
Gingival hyperplasia
Name 2 clinical uses of class IV antiarrythmics.
Class IV antiarrythmics are used in the prevention of nodal arrhythmias, as well as rate control during atrial fibrillation.
Class IV antiarrythmics are used in the prevention of nodal arrhythmias, as well as rate control during atrial fibrillation.
Side effects associated with the prusside portion of nitroprusside include the following:
Rebound HTN
Cyanide toxicity (co-administered with nitrates and thiosulfate to decrease toxicity)
Name the class III antiarrhythmic drugs.
Class III antiarrhythmics include amiodarone, ibutilide, dofetilide, andsotalol
True or False: Digoxin binds to the intracellular subunit of the Na/K ATPase
Binds to extracellular α subunit of Na/K ATPase in myocytes
Name 2 important side effects of statins.
Side effects of statins include:
Myopathy/rhabdomyolysis, which is particularly common when used in combination with fibrates or niacin
Hepatotoxicity which can manifest with elevated LFTs
In the ER, a patient with coronary artery disease develops neck pain. An EKG reveals new ST depressions. In this patient, nitroglycerin administered sublingually reduces myocardial oxygen demand as a result of a reduction in which component?
A Blood pressure
B Intramyocardial tension
C Sulfydryl bonds
D Coronary vascular resistance
E Heart rate
Intramyocardial tension
Answer Explanation
Nitroglycerin reduces venous tone, causing pooling of peripheral blood in the venous circulation. This both lowers peripheral arterial resistance and decreases the preload returning to the heart. As such, left ventricular end diastolic volume and therefore left ventricular end diastolic pressure are decreased. There is less stretch of the myocardial tissues, and less demand tension.
What combination of drugs has been shown to benefit African-Americans in particular when treating congestive heart failure?
African American patients have also been found to benefit from hydralazine + nitrates.
What two pathological conditions are cardiac glycosides used to treat?
Cardiac glycosides: generally used to treat congestive heart failure andatrial fibrillation.
A patient comes into the ED with chest pain that is described as “squeezing.” An EKG is ordered STAT and shows S-T segment changes suspicious for myocardial infarction. The patient is given aspirin, oxygen, morphine, and a vasodilator. The most likely vasodilator used results in what changes at the cellular level?
A Block the efflux of potassium
B Increase intracellular cAMP
C Decrease intracellular calcium levels
D Increase intracellular cGMP
Increase intracellular cGMP
Answer Explanation
When a patient has a myocardial infarction (MI), or MI is suspected, remember the mnemonic
MONA: Morphine Oxygen Nitroglycerin Aspirin
Nitroglycerin works by increasing the levels of nitric oxide in smooth muscle cells, resulting in an increase in intracellular cGMP. The cGMP then causes smooth muscle relaxation and vasodilation. It is an important component to the initial treatment of ischemic heart disease, including MI.
Which of the following anti-arrhythmic drugs shows no change in the phase 0 upstroke but increases the effective refractory period of the action potential?
A Atenolol
B Adenosine
C Diltiazem
D Sotalol
E Quinidine
Sotalol
Answer Explanation
Sotalol is a class III antiarrhythmic that blocks K channels. Because it has no effect on Na channels, the phase 0 upstroke is unchanged. It increases action potential duration by increasing the effective refractory period.
Describe the effect that β-blockers have on:
- End-diastolic volume
- Blood pressure
- Contractility
- Heart rate
- Ejection time
- Myocardial oxygen consumption
β blockers have the following effects on cardiac function:
No impact or slight decrease in end diastolic volume
Decreased blood pressure
Decreased contractility
Decreased heart rate
Increased ejection time
Decreased O2 consumption
How does statin inhibition of HMG-CoA reductase decrease blood LDL levels?
Inhibition of HMG-CoA reductase results in:
- Impaired hepatic cholesterol synthesis
- Increased hepatic LDL receptor expression
- (A compensatory response to the reduced intracellular hepatocyte cholesterol)
- Serum LDL is reduced due to increased hepatic LDL uptake
Name 4 side-effects of class IV anti-arrhythmics.
Calcium channel blocker toxicities include:
Cardiovascular effects (CHF, AV block, sinus node depression)
Flushing
Constipation
Edema
What are the 3 Class IC antiarrhythmic agents?
The class IC antiarrhythmics include (mnemonic: More Fries Please):
Moricizine
Flecainide
Propafenone
What are Class IB antiarrhythmics used for?
Class IB antiarrhythmics: used for the termination of ventricular tachycardias and the prevention of ventricular fibrillation after cardioversion following MI (myocardial infarction)
Describe the mechanism of action of fibrates in the treatment of hyperlipidemia.
Mechanism: activation of nuclear transcription factor PPARα leads to upregulation of lipoprotein lipase. This causes increased clearance of triglyceride rich lipoproteins and increased HDL synthesis
What is the mechanism of action of Digitalis?
Digitalis inhibits the Na+/K+ ATPase by competing with K+ for binding to the extracellular alpha subunit.
Why is the use of Class II antiarrythmics contraindicated in cocaine users?
Contraindicated in cocaine users (risk of unopposed α-adrenergic receptor agonist activity)
Name 2 side effects of ezetimibe.
Side effects of ezetimibe include:
Hepatotoxicity (rare), which manifests as increased LFTs
Diarrhea
What are the main pharmacologic treatments for mild CHF (NYHA class II)?
reatment for NYHA class II or mild CHF:
Sodium restriction
Loop diuretic (furosemide) to achieve volume control
ACE inhibitor or ARB
A 69-year-old patient with a history of congestive heart failure presents to the ER with increasing shortness of breath and nausea. He vomited twice earlier in the day. While in the ER, he reports seeing blurry, yellow halos. An EKG shows shortened QT intervals and prolonged PR intervals. During your examination, his heart rhythm suddenly changes to a second degree AV block. All of the following drugs should immediately be used for treatment, except?
A Digitalis specific FAB antibody
B Lidocaine
C Potassium
D Quinidine
E Phenytoin
D Quinidine
Answer Explanation
The information not provided in the clinical stem is that the patient is on digoxin. However, given his CHF history and his presenting complaints, this should be suspected. Digoxin can produce various cardiac arrhythmias and cause vague abdominal and vision halo symptoms. These symptoms indicate digoxin toxicity; quinidine can actually increase the toxicity of digoxin. Quinidine slows the elimination of digoxin and simultaneously reduces digoxin’s apparent volume of distribution. As a result, serum digoxin levels may double or even triple. All of the other answers are treatments in digoxin toxicity.
What conditions are class III antiarrhythmics most often used to treat?
Class III AAs are often used to treat Wolff-Parkinson-White syndrome,ventricular tachycardia, atrial fibrillation, and atrial flutter.
A patient with end-stage liver disease from chronic hepatitis complains of increasing pruritus. Although you are not concerned about his lipid panel, you offer to treat his symptoms with which antihyperlipidemic drug?
A Lovastatin
B Gemfibrozil
C Niacin
D Cholestyramine
E Ezetimibe
Cholestyramine
Answer Explanation
Cholestyramine is a bile acid sequestrant that is used to prevent intestinal absorption of cholesterol. It is also a first line agent in cholestatic and liver disease pruritus. In hyperbilirubinemic patients, pruritus results from deposition of bile in the skin. Cholestyramine helps to sequester bile acids within the GI tract, aiding elimination. Because of this mechanism, these drugs also decrease the absorption of fat soluble vitamins. This effect may require dietary supplementation to prevent vitamin deficiency.
What agents are most effective at lowering triglyceride levels? Give three examples.
Fibrates are the most effective agents in reducing triglycerides. Four examples of fibrates are:
Gemfibrozil
Clofibrate
Bezafibrate
Fenofibrate
What are 4 side effects of Procainamide?
Procainamide—side effects:
Reversible systemic lupus-like syndrome (i.e., drug-induced lupus)
Agranulocytosis
Torsades de pointes
Thrombocytopenia
List 6 drugs commonly used in the treatment of CHF.
Basic treatment of CHF can be remembered with the mnemonic: β-SAD
β-blockers
Spironolactone
ACE inhibitors or ARBs (proven to improve mortality)
Diuretics (furosemide, HCTZ), Digoxin
