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1211 Cards in this Set

  • Front
  • Back
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.
4
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.
(Cp)(CL)/F
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.
zero
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.
conjugation
Cytochrome P-450 is involved in _____ phase (I or II) reactions.
I
Drug Development
p. 289
A 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
Pharmacodynamics
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
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.
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
peptidoglycans
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
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
amphotericin B, nystatin, fluconazole/azoles (FAN the fungal cell membranes)
What is the mechanism of action of Pentamidine
Unknown
Penicillin
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
TRUE
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 (urticaria,severe pruritus); methicillin can cuase interstitial nephritis
Ampicillin and amoxicillin
p. 291
T or F: these drugs have the same mechanism of action as penicillin
TRUE
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
What should you watch out for when giving these drugs?
Hypersensitivity rxn (ampicillin rash), pseudomembranous colitis
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)
What should you watch out for when giving these drugs?
Hypersensitivity rxn
Why does concomitant administration with clavulanic acid increase the efficacy of these drugs?
Because they are penicillinase sensitive. (only piperacillin and ticarcillin)
Cephalosporins
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)
Aztreonam
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.
Imipenem/cilastatin
p.293
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?
Enterobacter
What are its side-effects
GI distress, skin rash, seizures at high conc.
Vancomycin
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?
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 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
Aminoglycosides
p. 294
Name some aminoglycosides?
Gentamicin, neomycin, amikacin, tobramycin and streptomycin
How do these drugs work?
They inhibit formation of the initiation complex in mRNA translation
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?
Neomycin
What are the two major toxicities?
Nephrotoxicity (esp. when used with cephalosporins) and Ototoxicity (esp. when used with loop diuretics). amiNOglycosides
Tetracyclines
p. 294
Name some tetracylcines
Tetracycline, doxycycline, demeclocycline, minocycline
How does it work?
Blocks t-RNA attachment to 30S subunit
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
Macrolides
p. 294
Name some macrolides?
Erythromycin, azithromycin, clarithromycin
How do these drugs work?
inhibit protein synthesis
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
Chloramphenicol
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)
Clindamycin
p. 294
How does it work?
blocks peptide bond formation at 50S
When do you use it?
Anaerobic infections (e.g. Bacteroides fragilis and C.perfringens)
Toxicities?
Pseudomembranous colitis, fever, diarrhea
Sulfonamides
p. 295
Name some sulfonamides
Sulfamethoxazole (SMX), sulfisoxazole, triple sulfa and sulfadiazine
How does it work?
Inhibits bacterial folic acid synthesis from PABA by blocking dihydropteroate synthase.
What are its uses?
Gram-positive, gram-negative, Nocardia, Chlamydia. Triple sulfas and SMX for simple UTIs
Toxicities?
hypersensitivity rxn, hemolysis if G6PD deficient, nephorotoxicity (tubulointerstitial nephritis), kernicterus in infants, displace other drugs from albumin (e.g. warfarin)
Trimethoprim
p. 295
How does it work?
inhibits folic acid pathway by blocking dihydrofolate reductase which humans have as well
What are its uses?
used in combo with Sulfamethoxazole (TMP-SMX) causing a sequential block of folate synthesis. Used for recurrent UTIs, Shigella, Salmonella, and prophylaxis for PCP in AIDS patients
Toxicities?
Megaloblastic anemia, pancytopenia (may be alleviated with supplemental folinic acid)
Fluoroquinolones
p. 295
What the most famous floroquinolone?
Ciprfloxacin (treatment for Anthrax)
How does it work?
inhibits DNA gyrase (topoisomerase II)
What are its uses?
Gram neg rods or urinary and GI tract (incl. pseudomonas), Neisseria, some gram pos spp
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.
Metronidazole
p. 296
How does it work?
forms toxic metabolites in the bacteria. Bactericidal.
What are its uses?
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?
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
Polymyxins
p. 296
How does it work?
disrupts osmotic properties of bacteria, acts like a detergent
What is it used for?
resistant gram negative infections
Toxicities?
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
General principles
pg 312
What is the significance of drugs with decreased solubility in blood?
rapid induction and recovery times . Ie. N20
What is the significance of drugs with increased solubility in blood?
increased potency = I/ MAC. Ie. Halothane
Inhaled Anesthetics
pg 312
list them
halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide
What is good about lower solubility?
the quicker the anesthetic response, and the quicker the recovery
What are these drug's effects?
myocardial depression, respiratory depression, nausea/emesis, increase cerebral blood flow
What toxicity mactches the following drugs 1. Halothane 2. Methoxyflurane 3. Enflurane 4. Rare
1. Hepatotoxcity 2. Nephrotoxicty 3. Proconvulsant 4. Malignant hyperthermia
IV anesthetics
pg313
What do barbituates, benzodiazepines, arylcyclohexylamines and narcotic analgesics have in common?
they are IV anesthetics
What the pharmacokinetics and uses of thiopental?
high lipid solubility, rapid entry into brain. Used for induction of anesthesia for short surgical procedures. Terminated by redistribution from brain. Decreased cerebral blood flow
Give an example of a benzo and what is this class's shortcoming?
midazolam used for endoscopy. Used with gaseous anesthetics and narcotics. May cause severe post-op respiratory depressio and amnesia
What does Ketamine (PCP analog and an arylcyclohexylamine) do?
dissociative anesthetic. Cardiovascular stimulant. Causes disorientation, hallucination, bad dreams. Increases cerebral blood flow.
How are narcotic analgesics used? Examples?
Morphone and fentanyl are used with CNS depressant during general anesthesia.
What is the advantage of propofol
used for rapid anesthesia induction and short procedures. Less post-op nausea than thiopental
Local anesthetics
pg 313
Name some esters?
procaine, cocaine, tetracaine,
Name some amides?
lidocaine, bupivacaine, (amides have two I's in name!)
What is the mechanism and clinical use?
bind receptor and block Na channels. Tertiary amine local anesthetics penetrate membrane in uncharge form, then bind charged form. Use for minor surgical procedures, spinal anesthesia.
How do you decide to use ester or amides?
if allergic to esters, give amides
what is the toxicity
CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, arrhythmias (cocaine)
In infected ________ tissue, anesthetics are charged and cannot penetrate membrane. Therefore, ______ anesthetics are needed.
acidic; more
What is the order of nerve blockade for size and myelination? Which factor predominates?
small diameter> large diameter. Myelinated fibers> unmyelinated fibers. Size factor predominates
what is the order of loss of sensation?
pain first, then temp, then touch, then pressure
Why would you give these drugs with vasoconstrictors?
to enhance local action
Opiod analgesics
pg 313
List as many as you can.
morphine, fentanyl, codeine, heroin, methadone, meperidine, dextromethorphan
Mechanism: They act as _____ for opiod receptors to modulate synaptic transmission
agonists
which drugs act at the mu, delta, kappa receptors?
morphine enkephalin, dynorphin
Clinical use?
pain, cough supression (dex), diarrhea (loperamide), acute pulmonary edema, methadone maintenance programs
What are the major toxicities?
addiction, respiratory depression, constipation, miosis, additive CNS depression wth other drugs
Tolerance does not develop to __________and ______
miosis and constipation
How would you treat toxicity?
naloxone, naltrexone (opiod R antagonist)
Other NSAIDS
pg 313
List three NSAIDS?
ibuprofen, naproxen, indomethacin
What is their mechanism?
reversibly inhibit COX 1 and 2. Blocks PG synthesis
What is their clinical use (3As)?
Antipyretic, analgesic, anti-inflammatory. Indomethacin is used to close a PDA.
What are common toxicities?
renal damage, aplastic anemia, GI distress, ulcers
COX 2 Inhibitors
pg 314
Where is cox2 found?
in inflammatory cells and mediates inflammation and pain
Why is cox2 inhibition better than cox1?
cox1 helps to maintain gastric mucosa, thus, should not have the corrosive effects of other NSAIDs on the GI lining (less incidence of ulcers and bleeding)
Clinical Use?
RA and osteoarthritis
Acetaminophen
pg 314
What is its mechanism and where does it work?
reversibly inhibits cox, mostly in CNS. Inactivated peripherally.
What are its 2 As?
antipyretic, analgesic but NOT anti-inflammatory.
Overdose effects?
hepatic necrosis, acetaminophen metabolites depletes glutathine and forms toxic tissue adducts in the liver
cardiovascular therapy
pg 314
Changes in CO affect two major pathways?
1. Carotid sinus firing, sympa discharge 2. Renal blood flow, renin-ang pathway
What is the effect of the following drugs: 1. Positive inotropic drugs 2. Beta blockers 3. Ace inhibitors 4. AII antagonists 5. Vasodilators and 6. Diuretics
1. Increases cardiac output. 2. Inhibit renin release. 3. Inhibit ACE 4. Inhibits effects of AngII including increasing the preload, increasing the afterload and remodelling. 5. Decrease the preload and afterload. 6. Decrease the preload and afterload
antihypertensive drugs
pg 315
What are the adverse effects of these two diueretics: hydrochlorothiazide, loop diuretics
1. Hypokalemia, hyperlipidemia, hyperuricemia, lassitude, hypercalcemia, hyperglycemia 2. Hypokalemia, met alk, hypotension, ototoxicity
These are wahat class of drugs: clonidine, methyldopa, ganglionic blockers, reserpine, guanethidine, prazosin, beta blockers?
sympathoplegics
Adverse effects of clonidine?
dry mouth, sedation, severe rebound HTN
Adverse effects of methyldopa?
sedation, positive coombs test
Adverse effects of ganglionic blockers?
orthostatic HTN, blurred vision, constitpation, sexual dysfuncction
Adverse effects of reserpine?
sedation, depression, nasal stuffiness, diarrhea
adverse effects of beta blockers?
impotence, asthma, cardiovascular, cns
Adverse effects of guanethidine?
orthostatic and exercise Hypotension, sex dysfxn, diarrhea
Adverse effects of prazosin?
1st dose orthostatic hypotension, dizzy, headache
The following are what class: hydralazine, minoxidil, nifedipine, verapamil, nitroprusside
vasodilators
which one causes lupus like syndrome? Other toxicities?
hydralazine, nausea, headache, reflex tachycardia, angina, salt retention
adverse effets of minoxidil?
hypertrichosis (hair growth - think Rogaine with minoxidil!), pericardial effusion, reflex tachycardia, angina, salt retention
Side effects of nifedipine, verapamil?
dizziness, flushing, constipation, nausea
which one causes cynide toxicity?
nitroprusside
Adverse effects of ACE-I Captorpil? Think CAPTOPRIL
C: cough, A: angioedema, P: proteinuria, T: taste changes, O: hypOtension, P: pregnancy problems like fetal renal damage, R: rash, I: increased renin, L: lower angiotensin. Also hyperkalemia.
Losartan is a ----------- R-Inhibitor? With ____-toxicity and ____kalemia
angiotensin II, fetal renal, hyper
Hydralizine
pg 315
Which two anti-htn drugs do you use with B blockers to prevent reflex tachycardia, diuretic to block salt retention?
hydralizine, minoxidil
What is hydralizine's mechanims and clinical use?
increase cGMP --> smooth muscle relaxation. Vasodilates arteries > veins. Reduces afterload. Used for severe HTN or CHF
Calcium channel blockers, name three
pg. 315 - nifedipine, verapamil, diltiazem
Mechanism: block _____ chanels of cardiac and smooth muscles to reduce contractility
voltage dependednt L type Ca
Rank their effects on vascular smooth muscle ad on the heart.
smooth muscle nifed> diltia > verapamil heart: vera> diltia> nifedepine
What is the calcium channel blockers use?
HTN, angina, arrythmias (not nifedipine)
ACE -I, name three
pg 316 - captopril, enalapril, lisinopril
Mechanim considering bradykinin and renin release?
reduce lvels of ang II, prevent inactivation of bradykinin, renin release is increased to to loss of feedback inhibition
what is the clinical use of these?
HTN, CHF, diabetic renal disease
Diuretics- site of action
pg 316
What is the site of action of 1. Acetazolamide, 2. Osmotic agents, 3. Loop agents, 4. Thiazides, 5. Potassium sparing, 6. ADH antagonists
1. PCT 2. PCT, thin desc limb, CD 3. Thick ascending limb 4. Distal conv tubule 5. DCT a bit later 6. CD in inner medulla
How does mannitol an osmotic diuretic work?
increase tubular fluid osmolarity, producing increased urine flow
what is the use and toxicity?
Use: shock, drug overdose, decrease intracranial pressure. Toxicity - pulmonary edema, dehydration. Contraindicated in anuria, CHF
Acetazolamide
pg 317
Is a ______inhibitor. Causes ______diuresis and _____ in total body HC03 stores.
Carbonic anhydrase, self-limited NaHCO3, reduction.
What electrolye disturbace does it treat? Does it cause?
treats met alk, causes in toxicity hyperchloremic met acidosis. ACIDazolamide caues ACIDosis.
Other toxicity?
neuropathy, NH3 toxicity, sulfa allergy
uses?
glaucoma, urinary alk, met alk, altitude sickeness
Furosemide
pg 317
This sulfonamide loop diuretic inhibits _______cotransport
NA, K, 2CL
Furosemide also works by?
abolishes hypertonicit y of medulla, prevent concentration of urine. Increase Caexcertion. Loops Lose calcium
The three uses for this loop diuretic?
edematous states, htn, hypercalcemia
Toxicity using the OH DANG?
ototoxicity, hypokalemia, dehydration, allergy, nephritis interstitial, gout
Ethacrynic Acid
pg 317
How is this drug different from furosemide? And how does that affect its use?
Although both have the same action, ethacrynic is a phenoxyacetic acid derivative not a sulfonamide. Therefore use this drug when you are allergic to sulfa.
What drug can be used to treat acute gout?
ethacrynic acid
Hydrochlorothiazide
p.318
Hydrochlorothiazide is a thiazide diuretic that inhibits the reabsorption of ----- in the ---- tubule
NaCl; early distal tubule
Does hydrochlorothiazide increase or decrease the excretion of calcium ion?
decrease
A toxic dose of hydrochlorathiazide will do what to the blood levels of these electrolites: potassium, sodium, glucose, lipid, uric acid, calcium
hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia (hyperGLUC)
K+-sparing diuretics
p.318
Spironolactone is a competitive antagonist to the --- receptor in the ---- tubule
aldosterone; cortical collecting tubule
Name two K+-sparing diuretics that block Na+ channels in the cortical collecting duct
Triamterine and amiloride
Besides causing hyperkalemia, a toxic dose of spironolactone will cause this endocrine effect
Gynecomastia (antiandrogen effect)
Name three K+-sparing diuretics
Spironolactone, Triamterene, Amiloride (The K+ STAys.)
Diuretics: electrolye exchange
p.318
Diuretics are classified as carbonic anhydrase inhibitors, loop diuretics, thiazides, and K+-sparing diuretics. Which of these causes in increase in urine NaCl?
All of them!
Which types of diuretucs increase urine K+?
All except K+-sparing diuretics. Carbonic anhydrase inhibitors, loop diuretics, thiazides.
Do carbonic anhydrase inhibitors increase or decrease blood pH?
Decrease, cause acidosis
Do K+-sparing diuretics cause acidosis or alkalosis?
Acidosis, decreases pH
Do loop diuretics cause acidosis or alkalosis?
Alkalosis, increases pH
Do thiazide diuretics cause an increase or decrease in blood pH?
Increase, cause alkalosis
Do loop diuretics increase or decrease levels of urine calcium ion?
Increase
Do thiazide diuretics increase or decrease levels of urine calcium ion?
Decrease
Antianginal therapy
p.319
Name four determinants of the level of myocardial oxygen consumption
There are five: end diastolic volume, blood pressure, heart rate, contractility, ejection time
Do nitrates affect preload or afterload?
preload
Do Beta-blockers affect preload or afterload?
afterload
What is the effect of nitrates on: diastolic volume, blood pressure, contractility, heart rate, ejection time?
decrease EDV, decrease BP, increase contractility (reflex response), increase HR (reflex response), decrease ejection time
What is the effect of Beta-blockers on: diastolic volume, blood pressure, contractility, heart rate, ejection time?
increase EDV, decrease BP, decrease contractility, decreased HR, increase ejection time
The effects of using nitrates and Beta-blockers together will: a) decrease myocardial oxygen demands by the same amount as using either alone, b) decrease myocardial oxygen demands by an amount greater than if each were used alone, or c) have no effect on myocardial oxygen demand
b) Decrease myocardial oxygen demands by an amount greater that if each were used alone
Nifedipine blocks -- channels
calcium
In its effects on myocardial oxygen consumption, is Nifedipine similar to Nitrates or B-blockers?
Nitrates (Nifedipine is similar to Nitrates)
In its effects on myocardial oxygen consumption, is Verapamil similar to Nitrates or B-blockers?
B-blockers
Nitroglycerine, isosorbide dinitrate
p.319
Dose nitroglycerin dilate arteries or veins more?
Veins>>arteries
Does nitroglycerin increase or decrease cGMP in smooth muscle?
Increase
In industrial exposure to nitroglycerine, weekend withdrawal is characterized by which three symptoms?
Tachycardia, dizziness , and headache ("Monday disease")
Toxic dosage of nitroglycerine causes which three symptoms?
Tachycardia, hypotension, headache
Cardiac drugs: sites of action
p.320
Digitalis has its action on which cell membrane transporter?
Na/K ATPase
Ryanodine has its action on which channel?
Calcium release channel in the sarcoplasmic receptor
Calcium enters cardiac cells through which channel?
Voltage-gated calcium channel
Cytoplasmic calcium concentrations in cardiac cells can be decreased by sequestering calcium in the sarcoplasmic reticulum. Calcium enters the SR through which transporter?
Calcium pump in the wall of the SR
Calcium channel blockers have their effect on which calcium transporters?
Voltage-gated calcium channel
Cardiac Glycosides
p.320
What is digoxin's effect on the intracellular Na+ level?
Increase
What is digoxin's effect on the intracellular calcium level?
Increase
Name two ECG changes ellicited by digoxin administration
There are 4: increase PR, decrease QT, scooping of ST segment, T-wave inversion
Name three symptoms of digoxin toxicity
Nausea, vomiting, diarrhea, blurry vision, arrhythmia
Which potentiates the effects of digoxin- hypo- or hyperkalemia?
hypokalemia
Antiarrhythmics- Na+ channel blockers (classI)
p.321
Which phase of the cardiac action potential do antiarrhythmics decrease the slope of?
Phase 4 depolarization
What type of antiarrhythmic is Amiodarone?
Class 1A (Class 1A includes Quinidine, Amiodarone, Procainamide, Disopyramide, "Queen Amy Proclaims Diso's pyramid."
Do class 1A antiarrhythmics increase or decrease the effective refractory period, AP duration, and QT interval?
Increase ERP, increase AP duration, increase QT interval
What do class 1B antiarrhythmics do to the AP duration?
Decrease AP duration
What type of antiarrhythmic is mexiletine?
Class 1B (includes Lidocaine, mexiletine, tocainide)
What type of antiarrhythmic is encainide?
Class IC (includes flecainide, encainide, propafenone)
What effect do class 1C antiarrhythmics have on the AP duration?
No effect!
Antiarrhythmics- Beta-blockers (classII)
p. 322
What does esmolol do to the cAMP in cardiac cells?
decreases cAMP (a beta-blocker)
What does atenolol do the calcium currents in cardiac cells?
decreases calcium current (beta-blocker)
Timolol decreases the slope of which phase of the cardiac AP cycle?
Phase 4 (a beta-blocker)
What does propanolol do the the PR interval?
Increases interval (beta-blocker)
Is esmolol a short- or long-acting beta blocker?
short-acting
Antiarrhythmics- K+ channel blockers (class III)
p. 322
Does amiodarone increase or decrease AP duration?
Increase (K+ channel blocker)
Does sotalol increase or decrease the effective refractory period?
Increase (K+ channel blocker)
Does bretylium increase or decrease the QT interval?
Increase (K+ channel blocker)
Name a symptom of sotalol toxicity.
Torsades de pointes (K+ channel blocker)
Name three of the symptoms of amiodarone toxicity.
Pulmonary fibrosis, corneal deposits, hepatoxicity, skin deposits resulting in photodermatitis, neurologic effects, constipation, bradychardia, heart block, CHF, hypothyroidism/hyperthyroidism. (Therefore, should check PFTs, LFTs, and TFTs)
Antiarrhythmics- Ca2+ channel blockers (class IV)
p. 323
Does verapamil increase or decrease the conduction velocity of the AV nodal cells?
Decrease (calcium channel blocker)
How does diltiazem affect the effective refractory period and the PR interval?
Increases ERP, increases PR (calcium channel blocker)
Other antiarrhythmics
p. 323
Name a potential use of Mg+ to treat arrhythmias.
To treat torsades de pointes and digoxin toxicity
Name a potential use of K+ to treat arrhythmias.
Depress ectopic pacemakers, especially in digoxin toxicity
Name a use of adenosine in treating arrhythmias.
To diagnose and abolish AV nodal arrhythmias.
Lipid-lowering agents
p. 324
What is the effect of cholestyramine on the serum triglyceride level?
Slight increase (cholestyramine is a bile acid resin)
What is the effect of colestipol on HDL?
No effect! (colestipol is a bile acid resin)
What is the effect of lovastatin on HDL?
Increase (lovastatin is an HMG-CoA reductase inhibitor)
Name 2 side effects of pravastatin.
Increase LFTs and cause myositis (prevastatin is an HMG-CoA reductase inhibitor)
What is the effect of Niacin on HDL?
Increase
What are the side effects of clofibrate?
Incease LFTs and cause myositis (Clofibrate is a "Fibrate")
Which increases HDL most: simvastatin, niacin, or gemfibrozil?
Niacin
Which decreases triglyceride level most: colestipol, Atorvastatin, niacin, or bezafibrate?
Bezafibrate
What is the main effect of ezetimibe?
decrease serum LDL (a cholesterol absorption inhibitor)
Gemfibrozil increases the activity of which enzyme?
Lipoprotein lipase (which converts VLDL to IDL)
Arachidonic acid products
p.325
What enzyme breaks down membrane lipid into arachidonic acid?
Phospholipase A2
What two enzymes are responsible for the production of Hydroperoxides (HPETEs) and Endoperoxidases, respectively from arachidonate?
Lipoxygenase= HPETE, Cyclooxygenases=endoperoxidases
What major class of products do HPETEs give rise to?
Leukotrienes
What are the 3 major products of Endoperoxidases?
Prostacyclin (PGI), Prostaglandins (PGE, PGF), Thromboxane (TXA)
In general what effect do leukotrienes have on bronchial tone?
Leukotrienes in general increase bronchial tone
In the arachodonic acid pathway, what two enzymes do corticosteroids block?
Phospholipase A2, COX-2
NSAIDs, Acetaminophen and COX-2 inhibitors block which arachadonic acid pathway enzymes
NSAIDs-non-selectively block COX-1 and COX-2, acetaminophen doesn't block COX-1 or COX-2, but instead it may block COX-3 in found in the brain, COX-2 inhibitors block COX-2
What are the 4 major effects of Prostacyclin
decrease platelet aggregation, decrease vascular tone, decrease bronchial tone, decrease uterine tone
What are the 3 major effects of Prostaglandins
increased uterine tone, decrease vascular tone, decrease bronchial tone
What are the 3 major effects of Thromboxane
increase platelet aggregation, increase vascular tone, increase bronchial tone
Zileuton is a ________ pathway inhibitor?
Lipoxygenase
Zariflukast is associated with what enzymes?
Lekukotrienes
Asthma drugs
p 326
Bronchodilation is mediated by what molecule
cAMP
Bronchoconstriction is mediated by _________ and ___________
Ach and adenosine
How many asthma drug categories are there?
7- (1) nonspecific B-agonists, (2) B2 agonists, (3) Methylxanthines, (4) muscarinic antagonist, (5) cromolyn, (6) corticosteroids, (7) Antileukotrienes
What is the only nonspecific B-agonist drug and what are its effects?
Isoprotenerol-relaxes bronchial smooth muscle (B2) and tachycardia (B1) (adverse effect).
What are the two B2 selective agonist asthma drugs?
Albuterol- relaxes bronchial smooth muscle (B2), Salmetrol
What are the indications for Albuterol and Salmetrol, respectively?
Albuterol- use during acute exarcebation, Salmetrol- long-acting agent for prophylaxis
what are the notable adverse effects of B2 agonist?
arythmias and tremor
B2-agonists activate this enzyme in bronchial smooth muscle that leads to an increase in ________ = bronchodilation
B2 agonists activate adenylate cyclase and increase conversion of ATP to cAMP
What are the likely mechanism of action theophylline?
bronchodialation by inhibition phosphodiesterase (PDE), decreasing cAMP hydrolysis and antagnonizing adenosine action
Why is usage of theophylline limited?
limited b/c narrow therapeutic index (cardiotoxicity, neurotxicity)
What kind of drug is Ipratropium?
muscarinic antagonist
How does mechanism of action of Ipratropium?
competitive block of muscarinic receptors= prevention of bronchoconstriction
cromolyn works by inhibiting the release of _______ from ______ cell?
prevents release of medicators from mast cells
Cromolyn is mainly used for the ______ of athsma and it is not indicated for _______ treatment of athsma?
Used only for prophylaxis, not effective during acute episode. Also, toxicity rare
__________and ________ are two major corticosteroids used for treatment of what kind of asthma?
Beclomethasone and prednisone are 1st line therapy for chronic asthma
What is the mechanism of action of corticosteroids?
inhibits the synthesis of virtually of cytokines-->inactivates NF-KB, the transcription factor that induces the production of TNF-a, amonth other inflammatory agents.
Zileuton blocks the conversion of _______ to ________.
zileuton is a 5-lipoxygenase pathway inhibitior. Blocks the conversion of arachidonic acti to leukotrienes