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Pharm 3 Test 1

What drugs are most effective for lowering LDL levels, have few adverse effects, and are most widely used? Produce more LDL receptors causing more LDL to be removed from the blood? HMG_CoA Reductase Inhibitors (Statins)
What are the uses of statins? hypercholesterolemia, dyslipidemia, dysbetalipoproteinemia, hypertriglyceridemia, prevention of coronary/CV event, increasing HDL levels, prevention of MI in those with type 2 DM
What are the potential uses of statins? Alzheimer's, kidney disease, MS, macular degeneration, glaucoma, RA, weak bones, and cancer (long-term use may decrease risk of colon cancer)
How long do statins take to work? LDL reduction takes 2 weeks and maximum effects in 4-6 weeks.
If statins are stopped, what happens? LDL levels will go back to pretreatment levels
List the adverse effects of statins. HA, rash, GI disturbance, myopathy, rhabdmyolysis, hepatotoxicity, peripheral neuropathy
What pregnancy category is statins in? X
If statins are given with fibrates or ezetimibe it increases the risk of? myopathy
If statins are given with other agents that inhibit CYP3A4 (cyclosporine, macrolides, azoles, HIV protease inhibitors) what will increase? Statin level
What are some names of statins available today? Atrovastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), prevstatin (Pravachol), rosuvastatin (Crestor), simvastatin (Zocor)
What is the pharmacokinetics of statins? PO, greatly affected by first pass through the liver, liver metabolism, excreted in bile. Take in the evening.
What drug reduces LDL and triglyceride levels and raise HDLs? Nicotinic Acid (Niacin)
What is the action of Niacin? decreases production of VLDLs. LDLs are a by-product of VLDL degradation--lower VLDLs=lower LDLs
Name the uses of Niacin. hypertriglyceridemia, hypercholesterolemia
When taking Niacin you should use caution with... PUD, asthma, arterial bleeding, hepatic dysfunction, glaucoma, DM, gout
Pharmacokinetics of Niacin? well absorbed PO, metabolized by liver, excreted in the urine, Reduces cholesterol level in days
What is the most common adverse effect of Niacin? face and neck flushing; others include itching, GI disturbances, hepatotoxic; severe liver damage has occurred (more common with long acting form). Possible hyperglycemia, gouty arthritis
When Niacin is used with vasodilators, what happens? may increase likelihood of flushing and postural hypotension Other drug interactions: oral hypoglycemic effects can be reduced, bile sequestrants can reduce absorption
When Niacin and Statins are used together what should you look out for? increase risk of rhabdomyolysis
What are the names of nicotinic acids? Niacor, Niaspan, Nicobid
This drug reduces LDLs, mainstay treatment in the past and now is usually used in adjunct with statins. Bile-Acid Sequestrants
Action of Bile-Acid Sequestrants. form an insoluble complex with bile acids in the intestines preventing reabsorption, and increasing excretion. This causes a demand for increased synthesis of bile acids in the liver.
What does synthesis of bile acid require? cholesterol provided by LDLs. Liver cells increase their LDL receptors thus taking more LDLs from circulation and reducing their numbers.
What are the uses of Bile-Acid Sequestrants? hyperlipidemia, hypercholesterolemia, diarrhea, antidote for negatively charged drugs by binding them in the gut before absorption (dig, PCN, tetracyclines, thyroid medications)
Pharmacokinetics of Bile-Acid Sequestrants... biologically inert, not absorbed from GI, pass through and excreted in feces
How long does it take for Bile-Acid Sequestrants to work? Cholesterol levels decrease in 1-2 weeks and may continue to drop for up to a year. If stopped, LDL levels return to pretreatment level in 3-4 weeks.
When should Bile-Acid Sequestrants be taken? Give before meals or with meals, mix well with a preferred liquid
What are the adverse effects of Bile-Acid Sequestrants? GI effects, constipation (most common), decreases fat absorption and uptake of the fat soluble vitamins D, A, K, E.
Bile-Acid Sequestrants decrease absorption of what medications? warfarin, digoxin, thiazides, propranolol, PCN G, tetracyclycines, thyroid medications. Take 1 hour before the sequestrant or 4 hours after.
Older Bile-Acid Sequestrants are? cholestryamine (Questran, Prevalite, LoCHOLEST) and colestipol (Colestid)
The new drug colesevelam (Welchol), a bile-acid sequestrant, is different from the others because? 1) causes less constipation, 2) does not reduce absorption of vitamins D, A, K, E, 3) does not significantly reduce levels of digoxin, warfarin, statins, and other drugs.
This drug is most effective for lowering triglycerides, can raise HDLs and has little or no effect on LDLs? Fibric Acid Derivatives (Fibrates)
How does Fibrates decrease triglycerides? by lowering VLDLs. Inhibit peripheral lipolysis and decrease the hepatic extraction of free fatty acids, which result in a reduction of triglyceride production.
What are the uses of fibrates? hypertriglyceridemia, can be used to raise HDLs
When does fibrates begin to work? Lowers VLDLs in 2-5 days, peaks in 4 weeks
Where is fibrates absorbed and excreted? absorbed in GI, metabolized in liver, excreted in urine
Which fibrate drug is excreted some in the feces? gemfibrozil
Fibrates have what adverse reactions? GI, gallstones, myopathy, liver injury. Fenofibrate also includes decreased libido, eye irritation, skin photosensitivity, rash, dizziness, flu-like symptoms, infections, pruritis.
Gemfibrozil displaces.. warfarin from plasma albumin, increasing anticoagulant effects; with statins increases risk of myopathy. Caution with cirrhosis, renal or liver dysfunction.
What fibrate drugs are available? gemfibrozil (Lopid), an fenofibrate (Tricor)
What drug decreases total cholesterol, LDL, triglycerides and acts on cells of the brush border of the small intestine to inhibit cholesterol absorption? Azetidinones Ezetimibe (Zetia)
Azetidinones are used for what purpose? total cholesterol reduction
Azetidinones is metabolized in what and excreted in... Metabolized to an active metabolite, most excreted in feces
Adverse effects of azetidinones include? GI, HA, possible myopathy, rhabdomyolysis, hepatits, pancreatitis, thrombocytopenia
Azetidinones and statins increase risk for what? liver damage
Azetidinone and fibrates increase risk for what? gallstones and myopathy
Azetidinone and bile-acid sequestrants decrease absorption of? ezetimibe
Azetidinone and cyclosporine can increase? ezetimibe levels
What do sodium channel blockers do? Block cardiac sodium channels and delay repolarization thereby decreasing conduction velocity in the atria, ventricles, and His-Purkinje system. Similar in action to local anesthetics.
What sodium channel block is the oldest and most studied, and most frequently used oral antidysrthymic? Quinidine Class IA
This drug is strong anticholinergic and blocks vagal input to the heart. Quinidine Class IA
This increase in SA nodal automaticity and AV conduction can drive the ventricles to a high heart rate. To prevent this high rate, usually pretreated with? digoxin, verapamil, or beta blocker
Quinidine has what on EKG? widens the QRS and prolongs the QT interval
What are the uses of Quinidine? supraventricular dysrhythmias, long-term suppression of SVT, A-fib, A-flutter. Some studies suggest increased mortality in A-fib and A-flutter. (Not first choice)
Adverse effects of Quinidine are? diarrhea and GI symptoms-immediate and intense, cinchonism (tinnitus, HA, N, vertigo, disturbed vision), cardiotoxicity (high doses-sinus arrest, AV block, v-tach, asystole-QRS and QT), arterial embolism (tx A-fib)
This drug can double digoxin levels by displacing dig on albumin and decreasing dig elimination? Quinidine
This drug is similar to quinidine but less desirable for long-term use? Can be used to terminate V-tach or V-fib Procainamide Class IA Sodium channel blocker
What are the adverse effects of Procainamide? systemic Lupus Erythematosus-like syndrome, blood dyscrasias (neutropenia, thrombocytopenia, agranulocytosis), cardiotoxicity (QRS and QT)
What drug is similar to quinidine but prominent side effects limit its use? Disopyramide
Adverse effects of Disopyramide include... anticholinergic effects, hypotension, heart failure. Indicated only for ventricular dysrhythmias. Reserved for those who cannot tolerate safer drugs (quinidine, procainamide)
This class of drug differs from IA agents by accelerating repolarization (IA drugs delay) and have little or no effect on the EKG Class IB Sodium channel blockers
IV agent used only for ventricular dysrhythmias-inactive or supraventricular dysrhythmias? Lidocaine (Xylocaine) Class IB
How does Lidocaine work? by blocking sodium channels thus slowing conduction in the atria, ventricles and His-Purkinje system, reduces automaticity, and accelerating repolarization
When using lidocaine will a small reduction occur in the QT interval with no widening of the QRS? yes, this may occur
Does Lidocaine have anticholinergic effects? NO
High doses of lidocaine can cause? CNS effects (drowsiness, confusion, paresthesias; toxic doses can cause convulsions and respiratory arrest)
What is the IV loading dose of lidocaine? 50 to 100 mg (1mg/kg) followed by infusion rate of 1-4 mg/min, usually D/C'd in 24 hours. IM: 300 mg in deltoid, can be repeated in 60-90 min, switched to IV ASAP
What drug is an antiseizure drug that is used to treat digoxin induced dysrhythmias? Phenytoin (Dilantin) Class IB
This drug reduces automaticity (esp in ventricles); little or no effect on EKG, increases AV nodal conduction Phenytoin (Dilantin)
This drug causes adverse effects that include sedation, ataxia, nystagmus, hypotension, dysrhythmias, cardiac arrest, and with long-term uses causes gingival hyperplasia Phenytoin (Dilantin)
Phenytoin IV is reserved for what severe, acute dysrhythmias (watch BP and EKG)
What drug is used to treat symptomatic ventricular dysrhythmias (PVCs, sustained V-tach)? Mexiletine (Mexitil) Class IB
What drug is used to alleviate persistent pain of diabetic neuropathy but not given to DM with heart disease> Mexiletine (Mexitil)
What drug is active against ventricular and supraventricular dysrhythmias and can prolong PR interval and widen QRS (dosage needs to be reduced)? Flecainide (Tambocor) Class IC
Flecainide (Tambocor) can exacerbate or precipitate what? heart failure.
Which drug should not be combined with other agents that decrease force such as beta blockers, verapamil, and diltiazem? Flecainide (Tambocor) Class IC
True or False. Propafenone (Rhythmol can widen QRS and prolong PR interval. True
Propafenone (Rhythmol) has beta-adrenergic blocking properties thus can? decrease myocardial contractility and promote bronchospasm (use caution in heart failure, AV block, and asthma). Reserved for those not responding to safer drugs.
This drug is a class I drug approved for life-threatening ventricular dysrhythmias, widens QRS and prolongs PR interval, reserved for those who have not responded to safer drugs? Moricizine (Ethmozine) Class IC
What classification of drugs are NOT interchangeable because they affect the heart in so many ways? Prolongs QT interval. Potassium channel blockers
What drug is used only for short-term therapy of severe ventricular dysrhythmias? Bretylium Potassium channel blocker
Effects of Bretylium? results in blockade of potassium channels in Purkinje fibers and ventricular muscle. When first administered it is taken up by sympathetic neurons and causes a transient increase in catecholamine release followed by blockade of further release.
The initial release of this drug can briefly exacerbate dysrhythmias? Bretylium
Adverse effects of Bretylium include? profound and persistent hypotension-results from blockade of norepinephrine release that promote contraction of vascular smooth muscle.
What drug requires continuous BP monitoring? May need to raise BP with dopamine or norepinephrine. Bretylium
This drug is highly effective against both atrial and ventricular dysrhythmias. Because of its toxicity, approved only for life threatening ventricular dysrhythmias that have been refractory to other safe agents. Amiodarone
What 2 life-threatening ventricular dysrhythmias are approved for oral amiodarone use? recurrent V-fib and hemodynamically unstable V-tach. Has been used with success to convert A-fib to NSR and to maintain NSR.
What is the half-life of oral amiodarone? 25-110 days, continues to act long after D/C'd (toxicity can continue for weeks or months)
Should amiodarone be given to a pregnant person? No, crosses placenta and enters breast milk
What tests should be done prior to starting amiodarone? Baseline chest x-ray and pulmonary function test are required with pulmonary function monitoring during treatment.
While taking amiodarone what tests would you do? periodic liver and thyroid tests due to hepatitis and thyroid dysfunction
Amiodarone can increase levels of what drugs? quinidine, procainamide, phenytoin, digoxin, diltiazem, warfarin, cyclosporine, lovastatin, simvastatin, atorvastatin (dosages may need to be decreased)
What can increase levels of amiodarone? Grapefruit juice
What decreases levels of amiodarone? cholestyramine, St. John's wort, rifampin
Combining amiodarone with a BB, verapamil, or diltiazem can lead to what? excessive slowing of the heart.
IV amiodarone, in contrast to oral, affects what primarily? AV node (slows AV conduction and prolongs AV refractoriness)
What classification slows ventricular rate in A-fib or flutter and can terminate SVT but has no effects for ventricular dysrhythmias? IV effects in 2-3 minutes. Calcium Channel blockers verapamil, diltiazem
Which drug is the drug of choice for acute angina attacks? Nitroglycerin
What is the action of nitroglycerin? vasodilation on vascular smooth doses. At usual doses, acts on veins; dilation arterioles is modest
In stable angina, nitroglycerin works by... decreasing O2 demand (decreases venous return to the heart - decreasing ventricular filling; this decrease in wall tension (preload) decreases O2 demand)
Does nitroglycerin relieve pain? No, pain relief is from effects on peripheral blood flow
In variant angina, nitroglycerin... relaxes and prevents spasm in coronary arteries-thus increasing O2 supply
Nitroglycerin's half life? 5-7 minutes
Adverse effects of nitroglycerin include.. HA, orthostatic hypotension fro relaxation of VSM resulting in pooling of blood in veins when standing (sit or lie down, elevating feet to promote venous return), reflex tachycardia (baroreceptor response)
Why should you pretreat with CCB and BB when a pt is on nitroglycerin? to prevent sympathetic stimulation of the heart
If nitroglycerin is used with phosphodiesterase type 5 inhibitors (Viagra, Cialis, Levitra) what can happen? intensify NTG effects - life threatening hypotension can occur- contraindicated with these drugs.
How fast can a person develop a tolerance to NTG? occurs rapidly (over 1 day) from depletion of sulfhydryl groups in VSM. Those who develop show a cross-tolerance to all nitrates. Most occurring with high-dose uninterrupted therapy.
How long should a person go without NTG to delay developing a tolerance? Use in lowest effective dose, try to allow 8 drug free hours a day, usually at night. Can add CCB and BB if angina is experienced during drug free time.
Absorbed directly through oral mucosa into blood stream. Very low doses. Effects rapid (1-3 min) and lasts up to 1 hour. Used for terminating ongoing attack and short-term prophylaxis when exertion is anticipated. Sublingual tablets of nitroglycerin
Sustained-release oral capsule are for... long term prophylaxis only. Cannot act fast enough for cute attack. Can cause tolerance, take once or twice a day.
Transdermal delivery system of NTG is.... patch for, absorbed through skin to blood, release is constant, begins in 30-60 min lasting for 14 hr. patch-free for 10-12 hr, put on in AM take off in PM. Not for acute attack.
NTG Translingual spray delivered to oral mucosa in a metered dose spray device, use like sublingual. Do NOT inhale spray.
Transmucosal (buccal) tablets between upper lip and gum or between cheek and gm. Dissolves over 3-5 hrs. Absorbed through oral mucosa ino blood. Has rapid onset (can be used for acute attack)
Topical ointment is placed on chest, back, abdomen, or anterior thigh. Effects begin in 20-60 min and last up to 12hrs. One inch equal 15 mg NTG
IV infusion of NTG is... rare for angina except with failure to respond to other medications. Used in MI, CHF, and production of controlled hypotension for surgery. Short duration of action. In glass bottle with special tubing.
Why should NTG be discontinued slowly To avoid vasospasm.
What is amyl nitrate? comes in ampule, broke and inhaled, effects in 30 sec and terminate in 3-5 min, intensifies sexual orgasm and has been abused for that purpose.
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