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1/1186

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1186 Cards in this Set

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  • Back
  • 3rd side (hint)
amount of drug in body/_______ = Vd
plasma drug concentration

(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.
4
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.
(Cp)(CL)/F
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.
zero
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.
conjugation
Cytochrome P-450 is involved in _____ phase (I or II) reactions.
I
A drug patent lasts for _____ years after filing for application.
20
How many phases are there in drug development?
4
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 _____.
2,1,3,4
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 is lower then Kd
(EC50 is more to the left)
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
TRUE
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.
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 have the same mechanism of action as penicillin?
(3)
- Cephalosporins
- Imipenem
- Aztreonam
Bacitracin, vancomycin and cycloserine block the synthesis of this molecule, preventing cell wall synthesis
peptidoglycans
These drugs block the 50s ribosomal subunit
(4)
clindamycin
"buy at 30 CELL @ 50"
- Chloramphenicol
- Erythromycin
- Linezolid
- cLindamycin
These drugs block the 30s ribosomal subunit
(2)
"buy AT 30, cell @ 50"
- Aminoglycosides
- Tetracyclines
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
rifampin
Which are the bacteriacidal Abx
Penicillin, cephalosporin, vancomycin, aminoglycosides, fluoroquinolones, metronidazole
These drugs disrupt the bacterial/fungal cell membranes
polymyxins
These specific disrupt fungal cell membranes
(3)
FAN the fungal cell:
- Fluconazole/azoles
- Amphotericin B
- Nystatin
What is the mechanism of action of Pentamidine
Unknown
Which is the IV form and which is the oral form of Penicillin?
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, and dicloxacillin are used mainly for what type of infection?
Staphlococcal infection (hence very narrow spectrum)
T or F: Methicillin, nafcillin, and dicloxacillin have the same mechanism of action as penicillin
TRUE
Are Methicillin, nafcillin, and dicloxacillin penicillinase resistant? If so why?
Bulkier R group makes these drugs resistant to penicillinase
What should you watch out for when giving Methicillin, nafcillin, or dicloxacillin?
Hypersensitivity rxn (urticaria,severe pruritus); methicillin can cuase interstitial nephritis
T or F: Ampicillin/amoxicillin have the same mechanism of action as penicillin
TRUE
Which has greater oral bioavailability: Ampicillin or Amoxicillin?
amOxicillin (O for Oral)
What do you use Ampicillin/amoxicillin for?
Ampicillin/amoxicillin HELPS to kill enterococci (H. influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella)
Can penicillinase effect Ampicillin/amoxicillin efficacy?
Yes, they are penicillinase sensitive
since Ampicillin/amoxicillin are penicillinase sensitive, what inhibitor is used w/ them?
clavulanic acid
What should you watch out for when giving Ampicillin/amoxicillin?
(2)
Hypersensitivity rxn
(ampicillin rash)

Pseudomembranous colitis
Why are Carbenicillin, piperacillin, and ticarcillin considered to have an extended spectrum?
Because they are effective against pseudomonas and other gram neg rods (enterobacter and some species of klebsiella)
What should you watch out for when giving Carbenicillin, piperacillin, and ticarcillin?
Hypersensitivity rxn
Why does concomitant administration with clavulanic acid increase the efficacy of piperacillin and ticarcillin?
Because they are penicillinase sensitive
What is the mechanism of action of Cephalosporins?
inhibit cell wall synthesis
How are Cephalosporins 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 Cephalosporins cover what bugs?
gram positives (staph and strep) though less,
H. influenzae,
Enterobacter aerogenes, Neisseria,
Proteus mirabilis,
E. coli,
Klebsiella
(HEN PEcK)
What can 3rd generation Cephalosporin drugs do that 1st and 2nd generation can't?
Cross the blood brain barrier
What are some other benefits of 3rd gen Cephalosporins?
better activity against gram neg bugs;
resistant to beta-lactam drugs;

Ceftazidime for Pseudomonas;
Ceftriaxone for N. gonorrhea
What are the benefits of 4th gen Cephalosporins (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)
When would you use aztreonam?
(3)
Only to treat:
Klebsiella,
Pseudomonas,
Serratia spp.
Is Aztreonam 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 Aztreonam good for?
The PCN-allergic patient that can't take aminoglycosides b/c of renal insufficiency
Are there any toxicity issues with Aztreonam?
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 Imipenem with and why?
cilastatin -- it decreases inactivation of imipenem in renal tubules
What do you use Imipenem for?
Gram pos cocci, gram neg rods and anaerobes (broad spectrum)
What bug is Imipenem the drug of choice for?
Enterobacter
What are its side-effects of Imipenem?
GI distress,
skin rash,
seizures at high conc.
Is Vancomycin 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 Vancomycin used for?
Used for serious infection that is resistant to other drugs (e.g. gram pos multi-drug resistant organisms like S. aureus and C. difficile, methicillin resistant staph (MRSA))
What are the important toxicities of vanco?
generally NOT many problems except, Nephrotoxicity, Ototoxicity and Thrombophlebitis
What can happen with rapid infusion of Vancomycin?
Red man's syndrome.
Diffuse flushing which can be controlled by pretreatment with anti-histamines and with slow infusion rate
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 and damikacin)

T = Tetracyclines
What does CELL stand for?
C = Chloramphenicol,
E= Erythromycin,
L= Lincomycin,
L= cLindamycin
Which of the protein synthesis inhibitors are bactericidal?
Only the aminoglycosides are, the rest are bacteriostatic
Name some aminoglycosides?
Gentamicin, neomycin, amikacin, tobramycin and streptomycin
How do Aminoglycosides work?
They inhibit formation of the initiation complex in mRNA translation
Why are Aminoglycosides 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 the Aminoglycosides class is commonly used for bowel surgery?
Neomycin
What are the two major Aminoglycoside toxicities?
Nephrotoxicity (esp. when used with cephalosporins) and Ototoxicity (esp. when used with loop diuretics). amiNOglycosides
Name some tetracylcines
Tetracycline, doxycycline, demeclocycline, minocycline
How do Tetracyclines work?
Blocks t-RNA attachment to 30S subunit
Which tetracycline can you use in patients with renal failure and why?
Doxycycline

because its elimination is fecal
What drug class should you not take with a glass of milk?
Tetracyclines
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 of Tetracyclines?
(4)
Teeth discoloration,

inhibition of bone growth in children;

Fanconi's syndrome;

photosensitivity
Name (3) macrolides?
Erythromycin,

Azithromycin,

Clarithromycin
How do Macrolides work?
inhibit protein synthesis
What are Macrolides used for?
URIs, pneumonias, STDs -- gram pos cocci in patients that are allergic to PNC --- Mycoplasm, Legionella, Chlamydia, Neisseria.
Pneumonic for Macrolide use?
(4)*
Eryc's Nipple is at his Mid Clavicular Line:

Erythromycin tx:
Neisseria,
Mycoplasm,
Chlamydia,
Legionella
Eryc's Nipple is at his Mid Clavicular Line
What are the major toxicities of Macrolides?
(4)*
Macros make you GASE:

GI discomfort,

Acute cholestatic hepatitis,

Skin rashes,

Eosinophilia
Macros make you GASE
What is the most common cause for non-compliance to macrolides?
GI discomfort
How does Chloramphenicol work?
inhibits 50S peptidyltransferase
Main use of Chloramphenicol?
Meningitis
(H. influenzae, N. meningitides, S. pneumo)

Used conservatively b/c of toxicity
What are the main toxicities of Chloramphenicol?
Anemia and aplastic anemia
(both dose dependent),

Gray baby syndrome
(in premes b/c they lack UDP-glucoronyl transferase)
How does Clindamycin work?
blocks peptide bond formation at 50S
When do you use Clindamycin?
Anaerobic infections

(e.g. Bacteroides fragilis and C. Perfringens)
Toxicities of Clindamycin?
(3)
Pseudomembranous colitis,

fever,

diarrhea
MC sulfonamide
Sulfamethoxazole (SMX)
How do Sulfonamides work?
Inhibits bacterial folic acid synthesis from PABA

(by blocking dihydropteroate synthase)
What are its uses?
(4)
Gram-positive,
Gram-negative,
Nocardia,
Chlamydia

(simple UTIs)
Toxicities of Sulfonamides?
(5)
hypersensitivity rxn,

hemolysis if G6PD deficient,

nephorotoxicity
(tubulointerstitial nephritis),

kernicterus in infants,

displaces other drugs from albumin (e.g. warfarin)
How does Trimethoprim work?
inhibits folic acid pathway by blocking dihydrofolate reductase
What are Trimethoprim's uses?
(4)
used in combo with Sulfamethoxazole (TMP-SMX) for recurrent UTIs,

Shigella,

Salmonella,

prophylaxis for PCP in AIDS patients
Toxicities of Trimethoprim?
(2)
Megaloblastic anemia,

Pancytopenia

(may be alleviated with supplemental folic acid)
What the most famous floroquinolone?
Ciprfloxacin (treatment for Anthrax)
How do Fluoroquinolones work?
inhibits DNA gyrase (topoisomerase II)
What are Fluoroquinolones uses?
(3)
Gram neg,

First line for Pseudomonas UTI,

Neisseria
What population is contraindicated for Fluoroquinolone use?
(2)
pregnancy and children
What are Fluoroquinolone toxicities?
(2)
FluoroquinoLONES hurt attachment to BONES:

Cartilage damage;

Tendonitis and tendon rupture in adults
How does Metronidazole work?
forms toxic metabolites in the bacteria

(Bactericidal)
What are Metronidazole uses?
(6)
anti-protozoal:
Giardia,
Entamoeba,
Trichomonas,
Gardnerella vaginalis,

Anaerobes:
Bacteroides,
Clostridium
What is the role of Metronidazole in H. pylori infection?
Used as part of triple therapy:

Bismuth, Amoxicillin and Metronidazole
Main toxicity of Metronidazole?
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

Anaerobes below diaphram:
Metronidazole
How do Polymyxins work?
disrupts osmotic properties of bacteria, acts like a detergent
What are Polymyxins used for?
resistant gram negative infections
Toxicities of Polymyxins?
(2)
Neurotoxicity,

ATN
Isoniazid
p. 296
How does it work?
decreases synthesis of mycolic acid
What is it used for?
MTB (mycobacterium tuberculosis). The only agent used as solo prophylaxis against TB
Toxicities?
Hemolysis if G6PD deficient, neurotoxicity, hepatotoxicitiy, drug induced SLE. INH, Injures Neurons and Hepatocytes
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!
Rifampin
P. 296
How does it work?
inhibits DNA-dependent RNA polymerase
What is it used for?
MTB, meningococcal prophylaxis
Toxicities?
Minor hepatotoxicity and increases P-450
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?
INH
What toxicity is common to all?
hepatotoxicity
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)
microtubule
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
mebendazole/thiabendazole
anti breast cancer drug that acts on microtubules (prevent disassembly)
taxol
antifungal drug that acts on microtubules
griseofluvin
anti cancer drug that acts on microtubules (prevent assembly)
vincristine/vinblastine
anti gout drug that acts on microtubules
cholchicine
Resistance mechanisms for various antibiotics
p297
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
p297
Drug of choice for meningococcal infection.
Rifampin (drug of choice), minocycline.
Drug of choice for gonorrhea.
Cefriaxone.
Drug of choice for syphilis.
Benzathine penicillin G.
Drug of choice for history of recurrent UTIs.
TMP-SMX.
Drug of choice for Pneumocystis carinii pneumonia.
TMP-SMX (drug of choice), aerosolized pentamindine.
Anti-fungal therapy
p297
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
p298
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").
Nystatin
p298
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.
p298
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.
Flucytosine
p298
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.
Caspofungin
p298
Mechanism of action for Caspofungin.
Inhibits cell wall synthesis.
Clinical use of Caspofungin.
Invasive aepergillosis.
Symptoms of Caspofungin toxicity.
GI upset, flushing.
Terbinafine
p298
Mechanism of action of Terbinafine.
Inhibits the fungal enzyme squalene epoxidase.
Clinical use of Terbinafinel.
Used to treat dermatophytoses (especially onychomycosis).
Griseofulvin
p298
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
p299
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).
Amantadine
p299
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.)
Zanamivir
p299
Mechanism of action of Zanamivir.
Inhibits influenza neuraminidase.
Clinical use of Zanamivir.
Both influenza A and B.
Ribavirin
p299
Mechanism of action of Ribavirin.
Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase.
Clinical use of Ribavirin.
RSV (respiratory syncytial virus).
Symptoms of Ribavirin toxicity.
Hemolytic anemia. Severe teratogen.
Acyclovir
p299
Mechanism of aciton of Acyclovir.
Perferentially inhibits viral DNA polymerase when phosphorylated by viral thymidine kinase.
Clinical use of Acyclovir.
HSV, VZV, EBV. Mucocutaneous and genital herpes lesions. Prophylaxis in immunocompromised patients.
Symptoms of Acyclovir toxicity.
Delirium, tremor, nephrotoxicity.
Ganciclovir (DHPG dihydroxy-2-propoxymethyl guanine)
p300
Mechanism of action of Ganciclovir.
Phosphorlation by viral kinase; perferentially inhibits CMV DNA polymerase.
Clinical use of Ganciclovir.
CMV, especially in immunocompromised patients.
Symptoms of Ganciclovir toxicity.
Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir.
Foscarnet
p300
Mechanism of action of Foscarnet.
Viral DNA polymerase inhibitor that binds to the pyrophophate binding site of the enzyme. Does not require activation by viral kinase. "FOScarnet = pyroFOSphate analog."
Clinical use of Foscarnet.
CMV retinitis in immunocompromised patients when ganciclovir fails.
Symptoms of Foscarnet toxicity.
Nephrotoxicity.
HIV therapy
p300
Saquinavir, ritonavir, indinavir, nelfinavir, amprenavir are example of this type of anti-HIV drug.
Protease inhibitor.
Mechanism of action of protease inhibitors.
Inhibit assembly of new virus by blocking protease enzyme.
Symptoms of protease inhibitor toxicity.
GI intolerance (nausea, diarrhea), hyperglycemia, lipid abnormalities, thrombocytopenia (indinavir).
Reverse transcriptase inhibitors:
Zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), and abacavir are examples of --------- reverse transcriptase inhibitors.
Nucleoside.
Nevirapine, delavirdine, and efavirenz are examples of --------- reverse transcriptase inhibitors.
Non-nucleoside.
Mechanism of action of reverse transcriptase inhibitors.
Preferentially inhibit reverse transcriptase of HIV; prevent incorporation of viral genome into host DNA.
Symptoms of reverse transcriptase inhibitor toxicity.
Bone marrow supression (neutropenia, anemia), periphral neuropathy, lactic acidosis (nucleosides), rash (non-nucleosides), megaloblastic anemia (AZT).
Highly active antiretroviral therapy (HAART) generally entails combination therapy with ---------- and -----------.
Protease inhibitors, reverse transcriptase inhibitors.
When should HIV therapy be initiated?
When patients have low CD4 counts (<500 cells/mm3) or high viral load.
-------- is used during pregnancy to reduce risk of fetal transmission.
AZT.
Interferons
p300
Mechanism of action of Interferons.
Glycoproteins from human leukocytes that block various stages of viral RNA and DNA synthesis.
Clinical use of Interferons.
Chronic hepatitis B and C, Kaposi's sarcoma.
Symptoms of Interferon toxicity.
Neutropenia.
Antiparasitic drugs
p301
Clinical uses of Ivermectin.
Onchocerciasis "rIVER blindness treated with IVERmectin".
Clinical uses of Mebendazole / thiabendazole.
Nematode/roundworm (e.g., pinworm, whipworm) infections.
Clinical uses of Pyrantel pamoate.
Giant roundworm (Ascaris), hookworm (Necator/Ancylostoma), pinworm (Enterobius).
Clinical uses of Praziquantel.
Trematode/fluke (e.g., schistosomes, Paragonimus, Clonorchis) and cysticercosis.
Clinical uss of Niclosamide
Cestode/tapeworm (e.g., Diphyllobothrium latum, Taenia species) infections except cysticercosis.
Clinical uses of Pentavalent antimony.
Leishmaniasis.
Clinical uses of Chloroquine, quinine, mefloquine, atovaquone, proguanil.
Malaria.
Clinical uses of Primaquine.
Latent hypnozoite (liver) forms of malaria (Plasmodium vivax, P.ovale).
Clinical uses of Metronidazole.
Giardiasis, amebic dysentery (Entamoeba histolytica), bacterial vaginitis (Gardnerella vaginalis), Trichomonas.
Clinical uses of Pentamidine.
Pneumocystis carinii pneumonia prophylaxis.
Clinical uses of Nifurtimox.
Chagas' disease, American trypanosomiasis (Trypanosoma cruzi).
Clinical uses of Suramin.
African trypanosomiasis (sleeping sickness).
Pharmacology - CNS / Neurologic drugs
p301
Parasympathetic preganglionic neurons release the neurotransmitter -------- which act on -------- receptors.
Ach, nicotinic.
Sympathetic preganglionic neurons to sweat glands release the neurotransmitter ------- which act on ------- receptors.
Ach, nicotinic.
Autonomic drugs
p302
Cholinergic:
Ach is synthesized from acetyl-CoA and choline by the enzyme ---------.
Choline acetyltransferase.
Noradrenergic:
In the noradrenergic nerve terminal, tyrosine is hydroxylated to -------, which is decarboxylated to --------, which is finally hydroxylated to NE.
DOPA, dopamine.
The action of NE and DA is terminated by --------- and ----------.
Reuptake, diffusion (different than for Ach).
The drugs --------- and ---------- inhibit the reuptake of NE.
Cocaine, TCA.
Ach inhibits the release of NE from the noradrenergic nerve terminal by binding to --------- receptors.
M1.
Cholinomimetics
p303
Direct agonists:
Clinical application and action of Carbachol and Pilocarpine.
Glaucoma. / Activates ciliary muscle of eye (open angle), pupillary sphincter (narrow angle).
Indirect agonists (anticholinesterases):
Clinical application / action of Neostigmine.
Postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade (postoperative). / Increase endogenous Ach.
Clinical application / action of Pyridostigmine.
Myasthenia gravis. / Increase Ach; increase strength.
Clinical application / action of Physostigmine.
Glaucoma (crosses blood-brain barrier) and atropine overdose. / Increase endogenous Ach.
Clinical application / action of Echothiophate.
Glaucoma. / Increase endogenous Ach.
Symptoms of cholinesterase inhibitor poisoning.
Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, Salivation (also abdominal cramping). "DUMBBELSS".
Cholinesterase inhibitor poisoning may be caused by ---------.
Parathion and other organophosphates.
The cholinesterase regenerator ------- can be used as an antidote for cholinesterase inhibitor poisoning.
Pralidoxime.
Mechanism of action of Pralidoxime.
Regenerates active cholinesterase, chemical antagonist, used to treat organophosphate exposure.
Cholinoreceptor blockers:
p303
Clinical uses of the muscarinic antagonist Atropine.
Dilate pupils, decrease acid secretion in peptic ulcer disease, decrease urgency in mild cystitis, decrease GI motility, reduce airway secretions, and treat organophosphate poisoning. "Blocks SLUD: Salivation, Lacrimation, Urination, Defecation."
Side effects of Atropine.
Increase body temp, rapid pulse, dry mouth, dry/flushed skin, disorientation, mydriasis with cycloplegia, and constipation. "Atropine parasympathetic block side effects: Blind as bat, Red as a beet, Mad as a hatter, Hot as a hare, Dry as a bone."
Hexamethonium (ganglionic blocker) blocks -------- receptors.
Nicotinic.
antimuscarinic drugs
p. 304
"tropi" are anti-muscarinic
while vacationing in the tropics you lie on a beach and your muscles waste away!
benztropine is used to treat
Parkinson's disease
scopolamine is used to treat
motion sickness
scopolamine is an antimuscarinic that does not convert to the mnemonic!
name 2 antimuscarinic drugs that act on the CNS
benztropine, scopolamine
name a muscarinic used to treat motion sickness
scopolamine
name a muscarinic used to treat Parkinson's disease
benztropine
mechanism of action of benztropine
antimuscarinic
mechanism of action of scopolamine
antimuscarinic
name three antimuscarinics that act on eye
atropine, homatropine, tropicamide
the action of atropine is ______
produce mydriasis, cycloplegia
mechanism of atropine is
antimuscarinic
the action of homatropine is ______
produce mydriasis, cycloplegia
mechanism of homatropine is
antimuscarinic
the action of tropicamide is
produce mydriasis, cycloplegia
mechanism of tropicamide is
antimuscarinic
ipatropium is used to treat
asthma, COPD
mechanism of ipatropium is
antimuscarinic
name an antimuscarinic used to treat asthma and COPD
ipatropium
neuromuscular blocking drugs
p. 304
neuromuscular blocking drugs are used for
muscle paralysis in surgery or mechanical ventilation
name a depolarising neurmuscular blocking drug
succinylcholine
name 6 nondepolarizing neuromuscular blocking drugs
tubocurarine
*mnemonic -- the "cur" drugs are nondepolarizing neuromuscular blocking agents
atracurium
mivacurium
pancuronium
vecuronium
rapacuronium
is succinylcholine depolarizing or nondepolarizing?
depolarizing
is tubocurarine depolarizing or nondepolarizing?
nondepolarizing
is atracurium depolarizing or nondepolarizing?
nondepolarizing
is mivacurium depolarizing or nondepolarizing?
nondepolarizing
is pancuronium depolarizing or nondepolarizing?
nondepolarizing
is vacuronium depolarizing or nondepolarizing?
nondepolarizing
is rapacuronium depolarizing or nondepolarizing?
nondepolarizing
what is tubocurarine used for
nondepolarizing neuromuscular blockade
what agents are used to reverse neuromuscular blockade by succinylcholine?
cholinesterase inhibitors in phase II (ex -- neostigmine)
what phase of succinylcholine neuomuscular bloackade is reversible?
phase II (repolarized but blocked)
what agents are used to reverse pahse I neuromuscular blockade by succinylcholine?
phase I Succinylcholine neuromuscular blockade cannot be reversed
what phase of succinylcholine neuomuscular bloackade is irreversible?
phase I Succinylcholine neuromuscular blockade cannot be reversed
what is atracurium used for
nondepolarizing neuromuscular blockade
what is the effect of cholinesterase inhibitors on succinylcholine neuromuscular blockade?
phase I: cholinesterase inhibitors potentiates the blockade phase II: cholinesterase inhibitors reverse the blockade
what cholinesterase inhibitor is used to reverse phase II of succinylcholine neuromuscular blockade?
neostigmine
what is mivacurium used for
nondepolarizing neuromuscular blockade
Dantrolene
p. 304
what is dantrolene used for
treat malignant hyperthermia
what causes malignant hyperthermia
use inhalation anesthetics and succinylcholine together
what inhalation anesthetic DOES NOT cause malignanat hyperthermia?
N2O
what is dantrolene used for
neuroleptic malignant syndrome
what is neuroleptic malignant syndrome
a toxicity of antipsychotic drugs
what drug is used to treat malignant hyperthermia
dantrolene
what is the mechanism of dantrolene
prevents release of Ca++ from saarcoplasmic reticulum of skeletal muscle
Sympathomimetics
p. 305
epinephrine, NE, isoproterenol, dopamine, and dobutamine are all________________
catecholamines
catecholamines are_____________________
sympathomimetics
name 5 catecholamines
EPI, NE, Isoproterenol, dopamine, dobutamine
what receptors does epinephrine act on?
alpha-1, alpha-2, beta-1, beta-2 adrenergics
what receptors does NE work on?
alpha-1, alpha-2, beta-1 adrenergics
what receptors does isoproterenol work on?
beta-1 = beta-2 adrenergics
what receptors does dopamine work on?
D1 = D2, D1 and D2 more than beta, beta more than alpha
what receptors does dobutamine work on?
beta-1 > beta-2
which catecholamines are agonists to alpha-adrenergic receptors
EPI, NE > dopamine
which catecholamines are agonists to beta-1 adrenergic receptors
EPI, NE, Isoproterenol, dopamine, dobutamine
which catecholamines are agonists to beta-2 adrenergic receptors
EPI, isoproterenol, dopamine and dobutamine (less)
what is epinephrine used to treat?
anaphylaxis, open-angle glaucoma, asthma, hypotension
what is norepinephrine used to treat?
hypotension (but decreases renal perfusion)
what is isoproterenol used to treat?
AV block
what is dopamine used to treat
shock with renal failure, heart failure
what is dobutamine used to treat
shock, heart failure
what catecholamine is used to treat anaphylaxis
epinephrine ("EPI-pen")
what catecholamines are used to treat hypotension
EPI, NE
what catecholamine is used to treat asthma
epinephrine
what catecholamine is used to treat AV block
isoproterenol
what catecholamines are used to treat shock
doapmine, dobutamine
what is the action of amphetamine
indirect general adrenergic agonist, releases stored catecholamines
what is the action of ephedrine
indirect general adrenergic agonist, releases stored catecholamines
what is amphetamine used to treat
narcolepsy, obesity, attention deficit disorder
what is ephedrine used to treat
nasal decongestion, urinary incontinence, hypotension
name three sympathomimetic drugs used to treat hypotension
epinephrine, norepinephrin, ephedrine
what is the action of phenylephrine
adrenergic agonist, alpha-1 > alpha-2
what is the action of albuterol
adrenergic agonist, beta-2 >beta-1
what is the action of terbutaline
adrenergic agonist, beta-2 >beta-2
what is phenylephrine used for?
pupil dilator, vasoconstriction, nasal decongestion
what sympathomimetics are used to treat nasal congestion
ephedrine, phenylephrine
what is the mechanism of cocaine
indirect general adrenergic agonist, catecholamine uptake inhibitor
what is the action of cocaine
vasoconstriction, local anesthesia
what is the mechanism of clonidine
centrally acting alpha-adrenergic agonist, decreases central adrenergic outflow
what drug has the same mechanism as amphetamine
ephedrine
what is the mechanism of alpha-methyldopa
centrally acting alpha-adrenergic agonist, decreases central adrenergic outflow
what drug has the same mechanism as clonidine
alpha-methyldopa
what are clonidine and alpha-methyldopa used to treat
hypertension, especially in renal disease because they do not decreased blood flow to the kidney
what sympathomimetic is used to treat urinary incontinence
ephedrine
what sympathomimetic is used to treat attention deficit disorder
amphetamine
what sympathomimetic is used to treat narcolepsy
amphetamine
alpha-blockers
p. 306
name a nonselective irreversible alpha blocker
phenoxybenzamine
name a nonselective reversible alpha blocker
phentolamine
what is the mechanism of phenoxybenzamine
nonselective irreversible alpha blocker
what is the mechanism of phentolamine
nonselective reversible alpha blocker
what are phenoxybenzamine and phentolamine used for
pheochromocytoma
what are the side effects of nonselective alpha blockers
orthostatic hypotension, reflex tachycardia
name 3 alpha-1 selective adrenergic blockers
prazosin, terazosin, doxazosin
what is the mechanism of prazosin
alpha-1 selective adrenergic blocker
what is the mechanism of terazosin
alpha-1 selective adrenergic blocker
what is the mechanism of doxazosin
alpha-1 selective adrenergic blocker
what are alpha-1 selective adrenergic alpha blockers used for
hypertension, urinary retention in BPH
what are the side effects of alpha-1 blockers
orthostatic hypotension, dizziness, headache
what is prazosin used for?
hypertension, urinary retention in BPH
what drugs have the same action as prazosin
terazosin, doxazosin
what are the side effects of terazosin?
orthostatic hypotension, dizziness, headache
what selective alpha blockers cause orthostatic hypotension
phenoxybenzamine, phentolamine, terazosin, prazosin, doxazosin
name an alpha-2 selective adrenergic blocker
yohimbine
what is yohimbine used for
impotence (effectiveness controversial)
what alpha blockers are used to treat pheochromocytoma
phenoxybenzamine, phentolamine
beta-blockers ("lol"s)
p. 307
name some beta-blockers
propranolol, metoprolol, atenolol, nadolol, timolol, pindolol, esmolol, labetalol
what is the mechanism of propanolol
selective beta-adrenergic blocker
what is the mechanism of metoprolol
selective beta-adrenergic blocker
what is the mechanism of esmolol
selective beta-adrenergic blocker
what is the mechanism of pindolol
selective beta-adrenergic blocker
what are beta-blockers used to treat
hypertension, angina, MI, SVT, CHF, glaucoma
how do beta blockers treat hypertension
decrease cardiac output, decrease renin secretion
how do beta blockers treat angina
decrease heart rate, decrease cardiac contractility, decreased O2 consumption
why are beta blockers used to treat MI
decrease MI mortality
which beta blockers are used to treat SVT
propanolol, esmolol
how do propanolol and esmolol treat SVT
decrease AV conduction velocity
how do beta blockers treat CHF
slow progression of chronic failure
which beta blocker is used to treat glaucoma
timolol
what is timolol used to treat glaucoma
decrease secretion of aqueous humor
what are the toxic effects of beta blockers
impotence, exacerbation of asthma, caution in diabetes
what are the cardiovascular toxic effects of beta blockers
bradychardia, AV block, CHF
what are the CNS adverse effects of beta blockers
sedation, sleep alterations
which beta blockers are beta-1 selective
acebutolol, betaxolol, esmolol, atenolol, metaprolol (A BEAM of beta-1 blockers)
which beta-1 blocker is short-acting
esmolol
which beta blockers are non-selective
propanolol, timolol, pindolol, nadolol, labetalol
which beta blocker also blocks alpha receptors
labetalol (all others are spelled "olol")
glaucoma drugs
p. 307
which alpha agonists are used to treat glaucoma
epinephrine, brimonidine
which beta blockers are used to treat glaucoma
timolol, betxolol, carteolol
which cholinomimetics are used to treat glaucoma
pilocarpine, carbachol, physostigmine, echothiophate
which diuretics are used to treat glaucoma
acetazolamide, dorzolamide, brinzolamide
which prostaglandin is used to treat glaucoma
latanoprost
what classes of drugs are used to treat glaucoma
alpha agonists, beta blockers, cholinomimetics, diuretics, prostaglandins (*mnemonic -- treating glaucoma is easy as ABCD)
what is the effect of epinephrine in glaucoma
increase outflow of aqueous humor
what are the side effects of epinephrine treatment in glaucoma
mydriasis, stinging
what glaucoma should epinephrine NOT be used for
closed-angle glaucoma
what is the effect of brimonidine in glaucoma
decreased aqueous humor synthesis
what are the side effects of brimonidine treatment in glaucoma
no pupillary or vision changes
what is the effect of beta-blocker treatment in glaucoma
decrease aqueous humor secretion
what are the side effects of beta blocker treatment in glauzoma
no pupillary or vision changes
what is the effect of cholinomimetics in glaucoma
ciliary muscle contraction, opening of trabecular meshwork, increase outflow of aqueous humor
what are the side effects of cholinomimetics in glaucoma
miosis, cyclospasm
what is the effect of diuretic treatment in glaucoma
inhibition of carbonic anhydrase --> decrease HCO3 secretion --> decrease aqueous humor secretion
what are the side effects of diuretics in glaucoma
no pupillary or vision changes
what is the effect of prostaglandin (latanoprost) treatment in glaucoma
increase outflow of aqueous humor
what is the side effect of prostaglandin treatment in glaucoma
darkens color of iris (browning)
which drugs used to treat glaucoma increase outflow of aqueous humor
cholinomimetics, prostaglandin, epinephrine
can you use epinephrine in closed-angle glaucoma
NO
brimonidine is used to treat what eye disease
glaucoma
what kind of drug is latanoprost
prostaglandin
latanoprost is used to treat what eye disease
glaucoma
which glaucoma drugs decrease aqueous secretion
beta blockers, diuretics
L-dopa/carbidopa
p. 307
what does L-dopa stand for
levodopa
what is the mechanism of action of L-dopa/carbidopa
increase dopamine level in brain
what is L-dopa/carbidopa used to treat
Parkinson's disease
how is L-dopa different from dopamine
L-dopa can cross the blood-brain barrier, dopamine cannot
what happens to L-dopa after it crosses the BBB
converted to dopamine by dopa decarboxylase
what enzyme convertes L-dopa to dopamine
dopa decarboxylase
what is the function of carbidopa
peripheral decarboxylase inhibitor
why is carbidopa given with L-dopa
increase L-dopa availability in CNS by inhibiting decarboxylase in periphery, also limits peripheral side effects
what are the side effects of L-dopa.carbidopa treatment
arrhythmias, dyskinesias
why do patients taking L-dopa get arrhythmias
peripheral effects of dopamine
why do patients taking L-dopa get dyskinesias
excess dopamine stimulation in CNS
Parkinson's disease drugs
p.308
what drugs are used to treat Parkinson's disease
dopamine agonists, MAO inhibitors, antimuscarinics
specifically, which drugs are used to treat Parkinson's
Bromocriptine, Amantadine, Levodopa, Selegiline, Antimuscarinics (BALSA)
which dopamine agosts are used to treat Parkinson's
L-dopa/carbidopa, bromocriptine, pramipexole, ropinirole, amantadine
what is the action of bromocriptine in Parkinson's
ergot alkaloid, partial dopamine agonist
what is the action of amantadine in Parkinson's
enhances dopamine release
what MAOI is used to treat Parkinson's
selegiline
what is the mechanism of selegiline
selective MAO type B inhibitor
what antimuscarinic is used to treat Parkinson's
benztropine
what is the effect of benztropine in Parkinson's
improves tremor, rigidity, little effect on bradykinesia
Sumatriptan
p. 308
what is sumatriptan used for
acute migraine, cluster headache attacks
what is the mechanism of sumatriptan
5-HT1D agonist
what is the half life of sumatriptan
less than 2 hours
what are the side effects of sumatriptan
chest discomfort, mild tingling
what are the contraindications for sumatriptan
patients with CAD or Prinzmetal's angina
Epilepsy drugs
p. 308
which drugs are used for simple and complex partial seizures
phenytoin, carbamazapine, lamotrigine, gabapentin, topiramate, phenobarbital
what types of seizures is phenytoin indicated for
simple and complex partial, tonic-clonic, status epilepticus
what types of seizures is carbamazepine indicated for
simple and complex partial, tonic-clonic
what types of seizures is lamotrigine indicated for
simple and complex partial, tonic-clonic
what types of seizures is gabapentin indicated for
simple and complex partial, tonic-clonic
what types of seizures is topiramate indicated for
simple and complex partial
what types of seizures is phenobarbital indicated for
simple and complex partial, tonic-clonic
what drugs can be used for tonic-clonic seizures
phenytoin, carbamazapine, lamotrigine, gabapentin, phenobarbital, valproate
what drugs can be used for absence seizures
valproate, ethosuximide
what drugs can be used for status epilepticus
phenytoin, benzodiazapines (diazepam, lorazepam)
what types of seizure is valproate indicated for
tonic-clonic, absence
what types of seizure is ethosuximide inidcated for
absence
what type of seizure are benzodiazepines indicated for
status epilepticus
other than anti-seizure, what else is phenytoin used for
class 1B anti-arrhythmic
how should a patient taking carbamazepine be followed
monitor LFT's weekly
which seizure drugs have adjunct use
gabapentin, topiramate
which seizure drug is safest in pregnant women
phenobarbital
which seizure drug is used in Crigler-Najjar II
phenobarbital
what are the advantages of phenobarbital
can be used in pregnant women, Crigler Najjar II
Epilepsy drug toxicities
p. 309
what are the side effects of benzodiazepines
sedation, tolerance, dependence
what are the side effects of carbamazepine
diplopia, ataxia, CYP induction, blood dyscrasias, liver toxicity
what are the side effects of ethosuximide
GI distress, lethargy, headache, urticaria, Stevens-Johnson syndrome
what are the side effects of phenobarbital
sedation, CYP induction, tolerance, dependence
what are the side effects of phenytoin
nystagmus, diplopia, ataxia, sedation, ginigival hyperplasia, hirsutism, anemias, teratogenic
what are the side effects of valproate
GI distress, rare by fatal hepatotoxicity, neural tube defects (spina bifida)
what are the side effects of lamotrigine
life-threatening rash, Stevens-Johnson syndrome
what are the side effects of gabapentin
sedation, movement disorders
what are the side effects of topiramate
sedation, mental dulling, kidney stones, weight loss
which anti-epileptic drug is teratogenic
phenytoin
which anti-epileptic drug can cause dependence
benzodiazepines, phenobarbital
which anti-epileptic drug can cause neural tube defects
valproate
which anti-epileptic drugs can cause GI distress
valproate, ethosuximide
it is necessary to check LFT's with which anti-epileptic drugs
carbamazepine, valproate
which anti-epileptic drugs cause CYP induction
phenobarbital, carbamazepine
which anti-epileptic drugs can cause blood problems
carbamazepine, phenytoin
which anti-epileptic drugs can cause Stevens-Johnson syndrome
lamotrigine, ethosuximide
which anti-epileptic drugs can cause diplopia
carbamazepine, phenytoin
Phenytoin
p. 309
what is the mechanism of phenytoin action
use-dependent blockade of Na+ channels
what is the clinical application of phenytoin
grand mal seizures
what are the toxicities of phenytoin
nystagmus, ataxia, diplopia, lethargy
what are the chronic toxicities of phenytoin
gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic anemia, malignant hyperthermia (rare)
should pregnant women take phenytoin
NO -- teratogenic
why does phenytoin cause megaloblastic anemia
causes decreased vitamin B-12
Barbiturates
p. 309
name 4 barbiturates
phenobarbital, pentobarbital, thiopental, secobarbital
what is the mechanism of barbiturate action
increase duration of Cl channel opening --> decreased neuron firing --> facilitate GABA-A action
how do barbiturates facilitate GABA-A action
increase duration of Cl channel opening which decreases neuron firing (Barbidurate increases duration
is barbiturate action on the CNS stimulatory or inhibitory
inhibitory
what is the clinical application of barbiturates
sedative for anxiety, seizures, insomnia, anesthesia induction (thiopental)
which barbiturate is used for anesthesia induction
thiopental
what are the side effects of barbiturates
dependence, additive CNS depression effects with alcohol, respiratory or CV depression (death), drug interactions due to CYP induction
what should you find out before giving a patient barbiturates
what other medications they take, because of CYP induction and many drug interactions
what happens if you give barbiturates to a patient in alcohol-induced coma or DT's
they might DIE!! Because of additive effect of barbiturates and alcohol --> respiratory depression
when are barbiturates contra-indicated
porphyria
can barbiturates cause dependence
YES
My friend Barb was very anxious so her doctor gave her barbiturates to increase the duration of the time she could speak in public without freaking out and having a seizure. She became so dependent on it that she recommended it to her friend Portia who couldn't take it because of porphyria. One day Barb drank too much alcohol and took her barbiturates and never woke up! THE END
clinical pharmacology made ridiculous. Period
Benzodiazepines
p. 309
name a bunch of benzodiazepines
diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide (all have ZZZ in them)
what is the mechanism of benzodiazepines
increase frequency of Cl channel opening --> facilitate GABA-A action (Frenzodiazepines increase frequency)
which GABA receptors are facilitated by barbiturates and bezodiazepines
GABA-A
what are the clinical applications of benzodiazepines
anxiety, spasticity, status epilepticus (diazepam), detoxification (alcohol withdrawal, DT's)
which benzodiazepine can be used for status epilepticus
diazepam
what drugs can be used to treat alcohol withdrawal
benzodiazepines
which benzodiazepines are short-acting
TOM thumb: Triazolam, Oxazepam, Midazolam
what are the toxic effects of benzos
dependence, additive CNS depression effects with alcohol
how are benzos better than barbiturates
less respiratory depression and coma risk
how do you treat benzo overdose
flumazenil
what is flumzenil used for
benzo overdose
how does flumazenil work
competitive antagonist at GABA receptor
can a patient become benzodiazepine dependent
YES
are barbiturates or benzodiazepines used for alcohol withdrawal
benzodiazepines
Antipsychotics (neuroleptics)
p. 310
what is another name for antipsychotics
neuroleptics
name 4 antipsychotic drugs
thioridazine, haloperidol, fluphenazine, chlorpromazine
how do you keep benzos straight from antipsychotics
Benzos help 3rd year Jon Kazam be less anxious around patients: Shazam Kazam! Without antipsychotics patients talk like a crazy 'zine (well, not perfect, but I'm working on it)
what is the mechanism of most antipsychotics
block dopamine D2 receptors
what is the clinical application of antipsychotics
schizophrenia, psychosis
what are the side effects of antipsychotics
extrapyramidal side effects (EPS), sedation, endocrine, muscarinic blockade, alpha blockade, histamine blockade
what is a long-term effect of antipsychotic use
tardive dyskinesia
what is neuroleptic malignant syndrome
a side effect of antipsychotics; rigidity, autonomic instability, hyperpyrexia
how do you treat neuroleptic malignant syndrome
dantrolene, dopamine agonists
what is tardive dyskinesia
side effect of neuroleptics; stereotypic oral-facial movements, may be due to dopamine receptor sensitization
what is the "rule of 4" with EPS side effects from antipsychotic drugs
evolution of EPS side effects: 4 hours -- acite dystonia, 4 days -- akinesia, 4 weeks -- akasthesia, 4 months -- tardvie dyskinesia
is tardvie dyskinesia reversible
often irreversible
what is fluphenazine used for
schizophrenia, psychosis
Atypical antipsychotics
p. 310
name 3 atypical antipsychotics
clozapine, olanzapine, risperidone
what type of antipsychotic is clozapine
atypical
what type of antipsychotic is olanzapine
atypical
what type of antipsychotic is risperidone
atypical
what is the mechanism of atypical antipsychotics
block 5-HT2 and dopamine receptors
what is the mechanism of clozapine
block 5-HT2 and dopamine receptors
what is the mechanism of olanzapine
block 5-HT2 and dopamine receptors
what is the mechanism of risperidone
block 5-HT2 and dopamine receptors
what is the clinical application of clozapine
schizophrenia positive and negative symptoms
what is the clinical application of olanzapine
schizophrenia positive and negative symptoms, OCD, anxiety disorder, depression
what is the clinical application of risperidone
schizophrenia positive and negative symptoms
how are atypical antipsychotics different from classic ones
atypicals treat positive and negative symptoms of schizophrenia, fewer extrapyramidal and anticholinergic side effects than classic antipsychotics
which antipsychotics should be used to treat positive and negative symptoms of schizophrenia
atypical ones -- clozapine, olanzapine, risperidone
which antipsychotics should be used for fewer side effects
atypical ones -- clozapine, olanzapine, risperidone
what is a potential toxicity of clozapine
agranulocytosis
which antipsychotic drug can cause agranulocytosis
clozapine
what test must be done weekly on patients taking clozapine
WBC count because of potential agranulocytosis
Lithium
p. 310
what is the mechanism of action of lithium
unknown; may be related to inhibition of phosphoinositol cascade
what is the clinical application of lithium
mood stabilizer for bipolar disorder
how does lithium help people with bipolar disorder
prevents relapse and acute manic episodes
what are the side effects of lithium
tremor, hypothyroidism, polyuria, teratogenic
is it OK for women taking lithium to get pregnant
NO -- teratogenic
what does lithium cause polyuria
ADH antagonist --> nephrogenic diabetes insipidus
Antidepressants
pg 311
What do the following drugs inhibit: 1. MAO inhibitors, 2. Desipramine/maprotilline, 3. Mirtazapine and 4. Fluoxetine/trazodone?
1. MAO 2. NE reuptake 3. Alpha 2-R 4. 5HT reuptake
All of the above actions are ------synaptic
PRE
List the Tricyclic Antidepressants
pg 311 Imipramine, amitriptyline, desipramine, nortriptyline, clomipramine, doxepin
What are the three C's of their toxicity?
Convulsions, Coma, Cardiotoxicity (arrythmias). Also respiratory depression, hypyrexia.
How about toxicity in the eldery?
confusion and hallucinations due to anticholinergic SE
What is the mechanism of TCA?
block reuptake of NE and 5HT
What is the clinical uses of TCAs?
Endogenous depresion. Bed wetting - imipramine. OCD- clomipramine.
How are tertiary TCA's different than secondary in terms of side effects?
Amitriptyline (tertiary) has more anti-cholinergic effects than do secondary (nortriptyline). Desipramine is the least sedating.
what are the SE of TCAs?
sedation, alpha blocking effects, atropine-like anti cholinergic side effects (tachycardia, urinary retention)
Fluoxetine, sertraline, paroxetine, citalopram are what class of drugs?
pg 311 SSRI's for endogenous depression
How long does it take an anti-depressant to have an effect?
2-3weeks
How does the toxicity differ fromTCA's and what are they?
Fewer than TCA's. CNS stimulation - anxiety, insomnia, tremor, anorexia, nausea, and vomiting.
What toxicity happens with SSRI's and MAO inhibitors given together?
Seratonin Syndrome! Hyperthermia, muscle rigidity, cardiovascular collapse
What are heterocyclics?
pg 312 2nd and 3rd generation antidepressants with varied and mixed mechanisms of action. Used major depression.
Examples of heterocyclics?
trazodone, buproprion, venlafaxine, mirtazapine, maprotiline
Which one is used for smoking cessation?
Buproprion. Mechanism not known. Toxicity - stimulant effects, dry mouth, aggrevation of pyschosis
Which one used in GAD?
Venlafaxine - inhibits 5HT and DA reuptake. Toxicity - stimulant effects
which one blocks NE reuptake
maprotiline
Which one increases release of NE and 5HT via alpha 2 antagonism?
mirtazapine. Also potent 5HT Rantagonist. Toxicity - sedation, increase serum cholesterol, increase appetite
What is trazodone and it' SE?
primarily inhibits seratonin reuptake. Toxicity - sedation, nausea, priapism, postural hypotension
Give 2 examples of MAO
pg 312 phenelzine. Tranylcypromine
Mechanism and Clinical Uses?
non selevtive MAO inhibition. Atypical antidepressant, anxiety, hypochondriasis
What is the toxicity with tyramine ingestion (in foods) and meperidine?
Hypertensive crisis
Other toxicities?
CNS stimulation, contraindicated with SSRI's or B-agonists
What is the mechanims of selgiline (deprenyl)?
pg 312 Selectively inhibits MAO-B, increasing DA
what is the clinical use and toxicity?
adjunctive agent to L-dopa for Parkinsons. May enhance adverse effects of L-dopa
Analgesics/ Anesthetics
pg 312