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A drug infused at a constant (IV) rate, eliminated via first order kinetics with a half life of 10hrs will take how long to reach 95% of steady state?

40 hrs; 1 half life = 50%, 2 = 75%, 3 = 87.5%, 4=95% of steady state

How do you calculate the volume of distribution?

Volume of distribution = amount of drug in body/plasma drug concentration

Define volume of distribution.

How much drug is in the body compared to how much drug is in the plasma (how far does it goooo)

How does kidney and liver disease impact Vd?

Plasma-protein bound drugs can be altered by liver and kidney disease. As protein drops, the volume of distribution will increase.

What is clearance?

How fast can the drug be eliminated divided by how much drug is in the plasma

How do you CALCULATE clearance?

CL = Vd x Ke where Ke is an elimination constant

How do you calculate half life?

t1/2 = (0.7 x Vd)/CL

What is the bioavailability (F) of a drug administered via IV?


How do you calculate loading dose?

LD = Target plasma concentration x the volume of distribution/ bioavailability

How do you calculate maintenance dose?

Target plasma concentration x the clearance/ the bioavailability

List the direct sympathomimetics

Epinephrine, Norepinephrine, Isoproterenol, Dopamine, Dobutamine, Phenylephrine, Metaproterenol, albuterol, salmeterol, terbutaline

On which receptors does Epinephrine work?

a1, a2, b1, b2 (less than the others)

On which receptors does Norepinephrine work?

a1, a2, b1 (less than the others). No action on B2

On which receptors does Isoproterenol work?

b1, b2

On which receptors does Dopamine work?

a1 and a2 in high dose, b1 and b2 in medium dose, and D1(in low dose)

On which receptors does Dobutamine work?

Mostly B1, some action at a1, a2

On which receptors does phenylephrine work?

Mostly a1, some a2

On which receptors do Metaproterenol, albuterol, salmeterol and terbutaline work?

Mostly B2, some B1 (think asthma). Metaproterenol and albuterol are shortacting, Salmeterol is long-term. Terbutaline is used to reduce premature contractions.

In what obstetric condition do we use Terbutaline?

Premature contractions

Terbutaline and what other sympathomimetic is used to reduce premature contractions?


On which receptors does Ritodrine work?


Name two indirect sympathomimetics that release stored catecholamines.

Amphetamine and Ephedrine

What are the indications for Amphetamine?

Narcolepsy, obesity, ADD

What are the indications for Ephedrine?

Nasal decongestion, urinary incontinence, hypotension

What is the MOA of cocaine?

uptake inhibitor, causes vasoconstriction and local anesthesia

What is the MOA of Clonidine and alpha-methyldopa?

Centrally acting a2-agonists, decrease central adrenergic outflow. Useful in HTN, esp. with renal disease.

Pt with HTN and renal disease, what is a sympathetic autonomic nervous system agent useful in treating this?

Clonidine or alpha-methyldopa.

What are the side effects of clonidine?

rebound HTN, dry mouth, sedation, bradycardia

What are the side effects of alpha-methyldopa?

sedation, +coombs test

Clonidine is used to treat what drug withdrawal?

Opiate withdrawal

What is an irreversible, nonselective alpha blocker?


What are the indications for phenoxybenzamine?

Pheochromocytoma (use before tumor removal)

What are the side effects of phenoxybenzamine?

orthostatic hypertension, reflex tachycardia

What is a reversible, nonselective alpha blocker?


What are the indications for phentolamine?

Used to treat pts on MAO inhibitors who eat tyramine. Side effects include decreased TPR and reflecx tachy.

What is the ending associated with a1 selective alpha blockers?


Name three a1 selective alpha blockers

Prazosin, terazosin, doxazosin

What is the indication for doxazosin?

HTN and urinary retention in BPH

Side effects of a1 selective alpha blockers?

1st-dose hypotension, dizziness, headache

What is Mirtazapine?

An a2 selective alpha blocker

What are the indications for Mirtazapine?


What are the side effects of Mirtazapine?

Sedation, increased serum cholesterol, increased appetite

What is the ending associated with b-blockers?


What are the indications for b-blockers?

Hypertension, Angina pectoris, MI, SVT, CHF, Glaucoma

Timolol is used to treat what condition?

Glaucoma by decreasing the secretion of aqueous humor

What drug class is associated with slowing the progression of compensated CHF?


What two b-blockers are indicated in the treatment of SVT?

Propranolol and esmolol

How do b-blockers treat angina pectoris?

inhibition of B1 receptors reduces heart rate and contractility, this decreases o2 consumption

How do b-blockers reduce renin secretion?

Decreased B receptor activation on JG cells reduces renin release

What are the side effects of metoprolol?

hyperlipidemia, AV-block

Why are we careful with b-blockers in diabetics?

can mask signs and symptoms of hypoglycemia

What are some CV side effects of b-blockers?

bradycardia, AV block, CHF

Do b-blockers or a-blockers cause impotence and exacerbation of asthma


What are the b1 selective antagonists?

Acebutolol, Betaxolol, Esmolol, Atenolol, Metoprolol

What are the nonselective antagonists?

Propanolol, Timolol, Nadolol, Pindolol

What are the nonselective (a and b) antagonists?

carvedilol (use for CHF) and labetalol

What are the partial b-agonists?

Pindolol, Acebutolol

What congenital cardiovascular malformation is associated with rupture of berry aneurysms?

Coarctation of the aorta, extreme hypertension makes aneurysms more likely to exist and rupture. NOTE: marfans, ED are associated with mitral valve prolapse, not congenital deformities (though kaplan says marfans is associated with ASD)

What antiplatlet agregation agent also vasodilates?

Cilostazol and dipyridamole: PDE III inhibitors that increase cAMP in platelets

What are the side effects of Aspirin?

Gastric ulceration, bleeding, hyperventilation, Reye's syndrome, tinnitus (CNVII), asthma, acidified urine

What is the MOA of ticlopidine?

Inhibits platelet agreggation by irreversibily blocking ADP receptors. Inhibits fibrinogen binding by preventing glycoprotein IIb/IIa expression.

What is the MOA of clopidogrel?

Inhibits platelet agreggation by irreversibily blocking ADP receptors. Inhibits fibrinogen binding by preventing glycoprotein IIb/IIa expression.

What toxicity is associated with ticlopidine?


Vein where the PO2 differs the most from the aorta?

Coronary sinus

23 year old male with recurrent epistaxis, skin discoloration, AVMs and telangiectasias. What is the inheritance of this condition?

Osler-Weber-Rendu syndrome or hereditary hemorrhagic telangiectasia is autosomal DOMINANT

Child with puritic xanthomas, pancreatitis and abdominal pain. What is the enzyme deficiency?

Lipoprotein Lipase or altered apolipoprotein C-II. No increased risk of atherosclerosis

Patient is given Niacin for hypercholesteremia. How would it effect their hypertension, DMII, and gout?

HTN: Niacin is vasodilatory, beware of orthostatic hypotension when used in conjunction with anti-hypertensives
DMII: Niacin increases insulin resistance, requiring higher doses of drugs
Gout: Niacin can cause hyperuricemia, beware in gout

Exposure to polyvinyl chloride, arsenic, and ThO2 (Thorotrast), and positive staining with CD31 (PECAM1)

Liver angiosarcoma. HIGHLY LETHAL

What are the major P450 inducers?

Quinidine, Barbituates, St. Johns wort, Phenytoin, Rifampin, Giseofulvin, Carbamazepine, Chronic alcohol use, Primidone, smoking
[Queen Barb Steals Phen-phen and Refuses Greasy Carbs]

What are the major P450 inhibitors?

Macrolides except azithromycin, Amiodarone, Grapefruit juice, Isoniazid, Cimetidine, Ritonavir, Acute alcohol abuse, Ciprofloxacin, Ketoconazole, Sulfonamides

Pharmacologic causes of hyperuricemia?

Hydrochlorothiazide, pyranzamine, niacin, cyclosporine

What is the MOA of Hydralazine?

Increases cGMP --> smooth muscle relaxation. Vasodilates arterioles MORE than veins to cause a reduction in afterload and subsequent increase in CO.

What are the indications for Hydralazine?

Severe HTN, CHF, FIRST LINE for HTN in pregnancy with methyldopa. Can be used to prevent reflex tachy. with beta blockers.

What are the toxicities of Hydralazine?

Compensatory tachy (contraindicated in angina/CAD), fluid retention, nausea, headache, angina, Lupus-like syndrome

What are the calcium channel blockers that impact vasculature more than cardiac muscle?

Nifedipine, verapamil, diltiazem, amlodipine, felodipine.

What calcium channel blocker is contrandicated in CHF?

verapamil, it increases the progression of CHF

What are the toxicities of anti-HTN calcium channel blockers?

Cardiac depression, AV block, peripheral edema, flushing, dizziness, constipation

What is Nifedipine?

Anti-HTN calcium channel blocker

What is Verapamil?

Cardiac calcium channel blocker

What is Amlodipine?

Anti-HTN calcium channel blocker

What is Diltiazem?

Anti-HTN calcium channel blocker

What three drugs are used for the treatment of Malignant HTN?

Fenlodipine, Nitroprusside, Diazoxide

What is the MOA of Fenlodipine?

Dopamine1 selective receptor antagonist. Three effects: decreases TPR, Increases sodium/water excretion, increases renal blood flow.

What is the MOA of Diazoxide?

K+ channel opener -->relaxes SM, also prevents release of insulin from b-islet causing hyperglycemia

what is the MOA of Nitroprusside?

Shortacting, increase cGMP via direct release of NO. CN toxicity can be treated with sodium thiosulfate, nitrite, or hydroxocobalamin.

What antimicrobials block cell wall synthesis by inhibition of peptidoglycan cross-linking?

Penicillin, Methicillin, ampicillin, piperacillin, cephalosporin, azetreonam, imipenem

What antimicrobials block peptidoglycan synthesis?

Bacitracin, vancomycin

What antimicrobials block nucleotide synthesis?

Sulfonamides, trimethoprim

What antimicrobials block DNA topoisomerase?


What antimicrobials block mRNA synthesis?


What antimicrobials damage DNA?


What antimicrobials block protein synthesis at the 30S subunit?

Aminoglycosides, tetracyclines

Patient with gram +, coagulase negative, catalase positive infective endocarditis post valve replacement. What do you treat with?

Infection is likely Staph. epidermidis, and is likely resistant since it was nosicomially acquired to all the major ones. Give Vancomycin.

What is the MOA of Penicillin G?

Binds penicillin-binding proteins, blocks transpeptidse cross-linking of peptidoglycan. Inactivates autolytic enzymes

What are the side effects Penicillin?

Hypersensitivity, hemolytic anemia

How are bugs resistant to penicillins?

beta-lactamase cleaves the b-lactam ring

Patient with methacillin sensitive staph. aureus. Treatment?

Penicillinase-resistant penicillins (nafcillin)

What is the mechanism of resistance in MRSA?

altered penicillin binding protein target site

Side effects of Dicloxacillin?

Hypersensitivity, methicillin-interstitial nephritis

Which has a greater bioavailablity: ampicillin or amoxacillin?


Bugs susceptible to ampicillin/amoxicillin?

Haemophilus influenzae, E.Coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci

Patient with painless lesion on genitalia, treated with penicillin. Presents with ecchymoses of skin, fever, and hypotension. Dx?

Syphilis treated with penicillins result in massive die-off = Jarish-Herxheimer rxn

What do we treat Klebsiella pneumonia with?

Cefotaxime: 3rd generation cephalosporin

What vitamin deficiency is associated with cephalosporin use?

Vitamin K

Patient treated with both cephalosporin and aminoglycosides. Hematuria, fatigue. Dx?

Increased nephrotoxicity of cephalosporins if used with aminoglycosides

Cefamandole and alcohol presentation?

Disulfiram-like rxn

What are the 1st generation cephalosporins?

Cefazolin and cephalexin; used to treat proteus mirabilis, e.coli, and klebsiella pneumonia

What are the 2nd generation cephalosporins?

Cefoxitin, cefaclor, cefuroxime: used to treat H. flu, Enterobacter aerogenes, neisseria, proteus, E. coli, klebsiella, Serratia.

Ceftriaxone is used to treat what conditions?

Meningitis and gonorrhea

Ceftaxidime is used to treat what conditions?


What are the 3rd generation cephalosporins?

Ceftriaxone, cefotaxime, ceftazidime

What are the fourth generation cephalosporins?


MOA of aztreonam?

Monobactam resistant to B-lactamases. Inhibits cell wall synthesis by binding PBP3. DOES NOT CROSS REACT WITH PENICILLINS

Spectrum of aztreonam?


MOA of Imipenem?

broad spectrum, b-lactamase resistant, carbapenem. administer with cilastain (inhibits renal dehydropeptidase I)

Why would we use meropenem instead of imipenem?

meropenem is stable to dehydropeptidase I and has a reduced risk of seizures

How is resistance conferred to Vancomycin?

amino acid change from D-ala D-ala to D-ala D-lac

What are the toxicities of Vancomycin?

Nephrotoxic, ototoxic, thrombophlebitis, diffuse flushing (redman) but generally well tolerated

Is vancomycin batericidal?


What are four K+ channel blockers (class III anti-arrhythmics)

Ibutilide, Sotaolol, Bretylium, Amiodarone, Dofetilide: K IS BAD

What is the MOA of Dofetilide?

K+ channel blocker: Increased AP duration Increased ERP, Used when other antiarrhythmiscs fail, increased QT interval --> risk of torsades

Which antiarrythmic carries a risk of pulmonary fibrosis?


What should you check if your patient is on K+channel blockers?


What are the two major functions of Digoxin?

1) Increased Inotropy by direct inhibition of the Na/K/ATPase and subsequent indirect inhibition of Na/Ca antiport which increases contractility.
2) Delayed AV conductance via increased parasympathetic tone and depression of SA node

Antidote to digoxin toxicity?

SLOWLY normalize K+, lidocaine, cardiac pacer, anti-dig Fab fragments, and Mg2+

Blurry yellow vision is associated with what cardiac drug?

Digoxin, also nausea, vomiting, and diarrhea

What ECG findings will you find in digoxin toxicity?

Increased PR, decreased QT, scooping and T wave inversion

What key electrolyte imbalance must be corrected slowly in digoxin toxicity?


Why does quinidine affect digoxin toxicity?

P450 inhibitor, displaces digoxin from tissue binding sites

What percent of digoxin is bound to protein?


What is the half life of digoxin?

40 hrs

How is digoxin eliminated?

Renal (urine)

Treatment for essential HTN?

Diuretics, ACE inhibitors, angiotension II receptor blockers, calcium channel blockers

Treatment for CHF?

Diuretics handle excess fluid, ACE inhibitors and b-blockers handle cardiac remodeling , potassium sparing diuretics

What is nesiritide?

An analong of BNP, increases cGMP used for CHF

What is contraindicated in decompensated CHF that is normally standard of care for CHF?

b-blockers, these decrease HR and CO from their effects on cardiac tissue

What diuretics are protective against diabetic nephropathy?

ACE inhintiors

In diabetics what pharmacotherapy is standard of care for treatment of hypertension?

First ACE inhibitors, ARBs, calcium channel blockers, diuretics, b-blockers (mask hypoglycemia), alpha blockers

What is the mechanism of action of hydralazine?

increased cGMP --> smooth muscle relaxation--> increase CO:: decreases afterload by preferentially vasodilating arterioles

Hypertension in pregnancy?


What drug class do we administer hydralazine with to prevent reflex tachy (side effect of hydralazine)


Side effects of hydralazine?

Compensatory tachycardia (contraindicated in angina/CAD), fluid retention, nausea, headache, angina. LUPUS like syndrome

List the first generation antihistamines.

diphenhydramine, chlorpheniramine, dimenhydrinate, hydroxyzine, meclizine

What are the side effects of first generation antihistamines?

sedation, antimuscarinic, anti-cholinergic (blurry vision from antimuscarinic loss of accomadation)
names all contain en/ine or en/ate

List the second generation antihistamines,

Loratidine, fenofexidine, desloratiadine, cetirizine (end in -adine)

What drugs should you avoid using with benzos?

Alcohol, barbituates, anti-epileptics, antihistamines, Q

Patient with excess orotic acid in urine and megaloblastic anemia. What do you supplement with?

uridine, this is orotic aciduria

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