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USMLE Pharmacology


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amount of drug in body/_______ = Vd
plasma drug concentration (note: Vd is Volume of Distribution)
rate of elimination of drug/[plasma drug] = ?
CL (Clearance)
(.7)(Vd)/CL = ?
T 1/2
A drug infused at a constant rate reaches about 94% of steady state after _______ t 1/2s.
Dosage Calculations
p. 288
A loading dose is calculated using this formula.
(Cp)(Vd)/F (note: Cp = target plasma concentration, and F = bioavailability)
A maintenance dose is calculated using this formula.
Elimination of Drugs
p. 288
Rate of elimination is proportional to _______ ______ in 1st order elimination.
drug concentration
In the case of EtOH, which is elimated by _____ order elimination, a constant amount of drug is eliminated per unit time.
Phase I vs. Phase II metabolism
p. 289
Phase ____ (I or II) reactions yield slightly polar metabolites that are often _____ (active or inactive)
I, active
Phase ____ (I or II) reactions yield very polar metabolites that are often _____ (active or inactive) and are excreted by the _______.
II, inactive, kidney
Phase II reactions are often of this type.
Cytochrome P-450 is involved in _____ phase (I or II) reactions.
Drug Development
p. 289
A patent lasts for _____ years after filing for application.
How many phases are there in drug development?
Drugs are first tested in patients in phase _____ of clinical testing, pharmacokinetic safety is determined in phase ______ of clinical testing, double blind tests are done in phase ____ and post-market surveillance is done in phase _____.
p. 289
In a dose response curve, a competitive antagonist shifts the curve _____, while a non-competitive antagonist shifts the curve ______.
right, down
What pharmacologic relationship would determine the existence of spare receptors?
EC50 < Kd
What does it mean if EC50 and Kd are equal?
The system does not have spare receptors
A partial agonist acts on the same receptor system as a full agonist? T/F
What's the main difference between a partial agonist and a full agonist?
A partial agonist has a lower maximal efficacy.
Is a partial agonist less potent than a full agonist?
Not necessarily. It can be less, more or equally potent as a full agonist.
Antimicrobial Tx -- Mechanism of Action
p. 291
The penicillin type drugs work by blocking ------ synthesis, specifically by inhibiting this molecule from cross-linking?
blocks bacterial cell wall synthesis by inhibition of peptidoglycan synthesis.
Which other drugs (aside from penicillin) have this same mechanism of action?
Imipenem, aztreonam and cephalosporins
Bacitracin, vancomycin and cycloserine block the synthesis of this molecule, preventing cell wall synthesis
These drugs block the 50s ribosomal subunit
clindamycin, chloramphenicol, erythromycin, lincomycin, linezolid, streptogramins "Buy AT 30, CELL at 50"
These drugs block the 30s ribosomal subunit
Aminoglycosides and tetracyclines "Buy AT 30, CELL at 50"
These drugs block nucleotide synthesis by interfering with the folate pathway
Sulfonamides (e.g. Bactrim), trimethoprim
These drugs block DNA topoisomerases
Quinolones (e.g. Cipro)
Which drug blocks mRNA synthesis
Which are the bacteriacidal Abx
Penicillin, cephalosporin, vancomycin, aminoglycosides, fluoroquinolones, metronidazole
These drugs disrupt the bacterial/fungal cell membranes
These specific disrupt fungal cell membranes
amphotericin B, nystatin, fluconazole/azoles (FAN the fungal cell membranes)
What is the mechanism of action of Pentamidine
p. 291
Which is the IV form and which is the oral form
G = IV, V=oral
Which of these is not a mechanism of penicillin action: (1) binds penicillin-binding protein, (2) blocks peptidoglycan synthesis, (3) blocks transpeptidase catalyzed cross-linking of cell wall and (4) activates autolytic enzymes
Penicillin does not block peptioglycan synthesis, bacitracin, vancomycin and cycloserine do that
T or F: penicillin is effective against gram pos and gram neg rods
False: penicillin is used to treat common streptococci (but not staph), meningococci, gram pos bacilli and spirochetes (i.e. syphilis, treponema). Not used to treat gram neg rods.
What should you watch out for when giving penicillin?
Hypersensitivity rxn (urticaria,severe pruritus) and hemolytic anemia
Methicillin, nafcillin, dicloxacillin
p. 291
These drugs are used mainly for what type of infection
Staphlococcal infection (hence very narrow spectrum)
T or F: these drugs have the same mechanism of action as penicillin
Are these drugs penicillinase resistant? If so why?
Bulkier R group makes these drugs resistant to penicillinase
What should you watch out for when giving these drugs?
Hypersensitivity rxn
Ampicillin and amoxicillin
p. 291
Which has greater oral bioavailability?
amOxicillin (O for Oral)
What do you use these for?
Ampicillin/amoxicillin HELPS to kill enterococci (H. influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella)
Can penicillinase effect these drugs efficacy?
Yes, they are penicillinase sensitive
Why not give these drugs with a penicillinase inhibitor. Name one.
clavulanic acid
Carbenicillin, piperacillin, ticarcillin
p. 292
Why are these considered to have an extended spectrum?
Because they are effective against pseudomonas and other gram neg rods (enterobacter and some species of klebsiella)
Why does concomitant administration with clavulanic acid increase the efficacy of these drugs?
Because they are penicillinase sensitive. (only piperacillin and ticarcillin)
p. 292
What is the mechanism of action of Cephalosporins?
inhibit cell wall synthesis
How are they similar/different from penicillin?
both have a beta-lactam ring structure but cephalosporins are less susceptible to penicillinases
What are the main similarities/difference between 1st and 2nd generation cephalosporins?
2nd gen has extensive gram neg coverage but weaker gram pos coverage
1st gen covers what bugs?
gram positives (staph and strep), Proteus mirabilis, E. coli, Klebsiella (PEcK)
2nd gen covers what bugs?
gram positives (staph and strep) though less so, H. influenzae, Enterobacter aerogenes, Neisseria, Proteus mirabilis, E. coli, Klebsiella (HEN PEcK)
What can 3rd generation drugs do that 1st and 2nd generation can't?
Cross the blood brain barrier
What are some other benefits of 3rd gen?
better activity against gram neg bugs resistant to beta-lactam drugs. Ceftazidime for Pseudomonas and ceftriaxone for N. gonorrhea
What are the benefits of 4th gen (e.g. Cefipime)?
increased activity against Pseudomonas, gram pos organisms and more beta-lactamase resistant (i.e. 4th gen combines 1st gen and 3rd gen characteristics into super drug)
What drugs should you avoid taking with cephalosporins?
Aminoglycosides (increases nephrotoxicity) and ethanol (causes a disulfiram-like rxn -- headache, nausea, flushing, hypotension)
p. 292
When would you use aztreonam?
Only to treat Klebsiella, Pseudomonas and Serratia spp.
Is it beta-lactamase resistant?
Yes, this is one of the huge benefits of the drug, and it is not cross-reactive with PCN!
Which population of pt. is this drug good for?
The PCN-allergic patient that can't take aminoglycosides b/c of renal insufficiency
Are there any toxicity issues with this drug?
Not really. Generally well tolerated with occasional GI upset. Vertigo, Headache and rare hepatotoxicity have been reported.
What is imipenem?
broad spectrum beta-lactamase-resistant abx
What do you always administer it with and why?
cilastatin -- it decreases inactivation of imipenem in renal tubules
What do you use it for?
Gram pos cocci, gram neg rods and anaerobes (broad spectrum)
What bug is it the drug of choice for?
What are its side-effects
GI distress, skin rash, seizures at high conc.
p. 293
Is it bactericidal or bacteriastatic and why?
Bactericidal because it blocks cross linkage and elongation of peptidoglycan by binding D-ala D-ala protion of cell wall.
How does resistance to Vanco occur?
D-ala D-ala is replaced with D-ala D-lactate which vanco does not block
What is it used for?
MTB, meningococcal prophylaxis
What are the important toxicities of vanco?
generally NOT many problems except, Nephrotoxicity, Ototoxicity and Thrombophlebitis
What can happen with rapid infusion of vanco?
"Red man's" syndrome. Diffuse flushing which can be controlled by pretreatment with anti-histamines and with slow infusion rate
Protein Synthesis Inhibitors
p. 293
Which drugs target bacterial protein synthesis by blocking the 30S unit vs 50S unit?
Buy AT 30, CELL at 50
What does AT stand for?
A = Aminoglycosides (streptomycin, gentamicin, tobramycin an damikacin. And T = Tetracyclines
What does CELL stand for?
C = Chloramphenicol, E= Erythromycin, L= Lincomycin and L= cLindamycin
Which of the above are bactericidal?
Only the aminoglycosides are, the rest are bacteriostatic
p. 294
Name some aminoglycosides?
Gentamicin, neomycin, amikacin, tobramycin and streptomycin
How do these drugs work?
inhibit protein synthesis
Why are they ineffective against anaerobes?
They require oxygen for uptake into bacteria
When would you use aminoglycosides?
against severe gram-negative rod infections
What drugs can you use aminoglycosides with for synergy?
the drugs that inhibit cell wall synthesis (e.g. penicillin and cephalosporins -- the beta-lactam antibiotics). Presumably this allows the drug to get in with out reliance on oxygen transport
What drug in this class is commonly used for bowel surgery?
What are the two major toxicities?
Nephrotoxicity (esp. when used with cephalosporins) and Ototoxicity (esp. when used with loop diuretics). amiNOglycosides
p. 294
Name some tetracylcines
Tetracycline, doxycycline, demeclocycline, minocycline
How does it work?
inhibits DNA-dependent RNA polymerase
Which tetracycline can you use in patients with renal failure and why?
Can use doxycycline because its elimination is fecal
Should you take these drugs with a glass of milk?
NO, because it intereferes with absorption in the gut as does antacids and iron-containing preparations
What are tetracyclines used for?
VACUUM your Bed Room -- Vibrio cholerae, Acne, Chlamydia, Ureaplasma, Urealyticum, Mycoplasma pneumoniae, Borrelia burgdorferi, Rickettsia, tularemia
What are the common toxicities
GI distress, teeth discoloration, inhibition of bone growth in children, Fanconi's syndrome and photosensitivity
p. 294
Name some macrolides?
Erythromycin, azithromycin, clarithromycin
What are they used for?
URIs, pneumonias, STDs -- gram pos cocci in patients that are allergic to PNC --- Mycoplasm, Legionella, Chlamydia, Neisseria.
Pneumonic for macrolide use?
Eryc's Nipple is at his Mid Clavicular Line (Eryc is brand name for erythromycin). Mycoplasm, Legionella, Chlamydia, Neisseria.
What are the major toxicities?
GI discomfort, acute cholestatic hepatitis, eosinophilia, skin rashes
What is the most common cause for non-compliance to macrolides?
GI discomfort
p. 294
How does this drug work?
inhibits 50S peptidyltransferase
Main use?
Meningitis (H. influenzae, N. meningitides, S. pneumo). Used conservatively b/c of toxicity
What are the main toxicities?
Anemia and aplastic anemia (both dose dependent), gray baby syndrome (in premes b/c they lack UDP-glucoronyl transferase)
p. 294
When do you use it?
Anaerobic infections (e.g. Bacteroides fragilis and C.perfringens)
Minor hepatotoxicity and increases P-450
p. 295
Name some sulfonamides
Sulfamethoxazole (SMX), sulfisoxazole, triple sulfa and sulfadiazine
What are its uses?
anti-protozoal: Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, anaerobes (bacteroides, clostridium)
p. 295
p. 295
What the most famous floroquinolone?
Ciprfloxacin (treatment for Anthrax)
What population is contraindicated for use?
pregnancy and children
What are its toxicities?
GI upset, superinfection, skin rashes, headache, dizziness and tendonitis and tendon rupture in adults. FluoroquinoLONES hurt attachment to BONES.
p. 296
What is the role of Metronidazole in H. pylori infection?
Used as part of triple therapy: bismuth, amoxicillin and metronidazole
Main toxicity?
disulfiram-like (antabuse) reaction to alcohol and headache
Which drug do you use to treat anaerobic infections above the diaphram and below the diaphram
anaerobes above diaphram: Clindamycin, and anaerobes below diaphram: metronidazole
p. 296
p. 296
What vitamin prevents neurotoxicity
Vitamin B6 (pyridoxine)
Why are toxicities particularly important to monitor in patients taking INH?
INH half-lives are different in fast versus slow acetylators!
P. 296
How can it be used for leprosy?
rifampin delays resistance to dapsone when used for leprosy
What would happen if you used rifampin alone?
get rapid resistance
What does it do to bodily fluids?
makes them red/orange in color
What are the 4 R's of Rifampin
RNA polymerase inhibitor, Revs up microsomal p-450, Red/Orange body fluids, Resistance is rapid
Anti-TB Drugs
p. 296
What are the anti-TB drugs?
Rifampin, Ethambutol, Streptomycin, Pyrazinamide, Isoniazid (INH) -- RESPIre
What do you use for TB prophylaxis?
What toxicity is common to all?
arachadonic acid products
pg 150
name the enzyme that liberates AA from the cell membrane
phospholipase A2
what does the lipoxygenase pathway yield
leukotrienes (L for Lipoxygenase and Leukotrienes)
LTB4 is a____
neutrophil chemotactic agent
which leukotrienes are involved in bronchoconstriction, vasoconstriction, smooth muscle contraction, and increased vascular permeability
LT C4, D4, E4 (SRS-A)
what are the 3 products of the cyclooxygenase pathway?
thromboxane, prostacyclin, prostaglandin
what are the 2 functions of TxA2
platelet aggregation, vasoconstricion
what are the 2 functions of PGI2
inhibition of platelet aggregation; vasodilation (Platelet Gathering Inhibitor)
pg 150
what are the shape and dimensions of a microtubule?
cylindrical, 24 nm in diameter, variable length.
what are the components of a microtubule
polymerized dimers of alpha and beta tubulin (+2 GTPs per dimer)
where are microtubules found
cilia, flagella, mitotic spindles, neuronal axons (slow axoplasmic transport)
antihelminthic drug that acts on microtubules
anti breast cancer drug that acts on microtubules (prevent disassembly)
antifungal drug that acts on microtubules
anti cancer drug that acts on microtubules (prevent assembly)
anti gout drug that acts on microtubules
Resistance mechanisms for various antibiotics
Most common resistance mechanism for penicillins / cephalosporins.
Beta-lactamase cleavage of beta-lactam ring.
Most common resistance mechanism for aminoglycosides.
Modification via acetylation, adenylation, or phosphorylation.
Most common resistance mechanism for vancomycin.
Terminal D-ala of cell wall component replaced with D-lac; decrease affinity.
Most common resistance mechanism for Chlorampenicol.
Modification via acetylation.
Most common resistance mechanism for macrolides.
Methylation of rRNA near erythromycin's ribosome-binding site.
Most common resistance mechanism for tetracycline.
Decrease uptake or increase transport out of cell.
Most common resistance mechanism for sulfonamides.
Altered enzyme (bacterial dihydropteroate synthetase), decrease uptake, or increase PABA synthesis.
Nonsurgical antimicrobial prophylaxis
Drug of choice for meningococcal infection.
Rifampin (drug of choice), minocycline.
Drug of choice for gonorrhea.
Drug of choice for syphilis.
Benzathine penicillin G.
Drug of choice for history of recurrent UTIs.
Drug of choice for Pneumocystis carinii pneumonia.
TMP-SMX (drug of choice), aerosolized pentamindine.
Anti-fungal therapy
Mechanism of action of the anti-fungal therapy polyenes.
Form artificial pores in the cytoplasmic membrane.
Mechanism of action of the anti-fungal therapies terbinafine and azoles.
Terbinafine blocks the conversion of squalene to lanosterol. Azoles block the conversion of lanosterol to ergosterol.
Mechanism of action of the anti-fungal therapy flucytosine.
Blocks the production of purines from the precurors.
Mechanism of action of the anti-fungal therapy griseofulvin.
Disrupts microtubles.
Amphotericin B
Mechanism of action of Amphotericin B.
Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes and disrupt homeostasis. "Amphotericin 'tears' holes in the fungal membrane by forming pores."
Clinical uses of Amphotericin B.
Used for a wide spectrum of sytemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not cross blood-brain barrier.
Symptoms of Amphotericin B toxicity.
Fever/chills ("shake and bake"), hypotension, nephrotoxicity, arrhythmias ("amphoterrible").
Mechanism of action of Nystatin.
Binds to ergosterol, disrupting fungal membranes.
Clinical use of Nystatin.
"Swish and swallow" for oral candidiasis (thrush).
Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole.
Mechanism of action for fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole.
Inhibits fungal steroid (ergosterol) synthesis.
Clinical uses of fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole.
Systemic mycoses. Fluconazole for cryptococcal meningitis in AIDS patients and candidal infections of all types (i.e., yeast infections). Ketoconazole for Blastomyces, coccidioides, Histoplasma, Candida albicans; hypercortisolism.
Symptoms of fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole toxicity.
Hormone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), fever, chills.
Mechanism of action of Flucytosine.
Inhibits DNA synthesis byconversion to fluorouracil, which competes with uracil.
Clinical uses of Flucytosine.
Used in sytemic fungal infections (e.g. Candida, Cryptococcus).
Symptoms of Flucytosine toxicity.
Nausea, vomitting, diarrhea, bone marrow suppression.
Mechanism of action for Caspofungin.
Inhibits cell wall synthesis.
Clinical use of Caspofungin.
Invasive aepergillosis.
Symptoms of Caspofungin toxicity.
GI upset, flushing.
Mechanism of action of Terbinafine.
Inhibits the fungal enzyme squalene epoxidase.
Clinical use of Terbinafinel.
Used to treat dermatophytoses (especially onychomycosis).
Mechanism of action of Griseofulvin.
Interfers with microtubule function; disrupts mitosis. Deposits in keratin-contianing tissues (e.g. nails).
Clinical use of Griseofulvin.
Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm).
Symptoms of Griseofulvin toxicity.
Teratogenic, carcinogenic, confusion, headaches, increase warfarin metabolism.
Antiviral chemotherapy
Viral adsorption and penetration into the cell is blocked by ---------.
Gama-globulins (non-specific).
Uncoating of the virus after its penetration into the cell is blocked by --------.
Amantadine (influenza A).
Early viral protein synthesis is blocked by --------.
Fomivirsen (CMV).
Viral nuclei acid synthesis is blocked by --------.
Purine, pyrimidine analogs; reverse transcriptase inhibitors.
Late viral protein synthesis and processing is blocked by --------.
Methimazole (variola); protease inhibitors.
Packaging and assembly of new viron is blocked by --------.
Rifampin (vaccinia).
Mechanism of action of Amantadine.
Blocks viral penetration/uncoating; may buffer pH of endosome. Also causes the release of dopamine from intact nerve terminals. "Amantadine blocks influenza A and rubellA and causes problems with the cerebellA."
Clinical uses of Amantadine.
Prophylaxis for influenza A; Parkinson's disease.
Symptoms of Amantadine toxicity.
Ataxia, dizziness, slurred speech. (Rimantidine is a derivative with fewer CNS side effects.)

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