Term
| Cell wall synthesis interrupters |
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Definition
| Beta lactams, glycopeptides |
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Term
| Membrane potential disruptors |
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Definition
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Term
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Definition
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Term
| Nucleic acid biosynthesis disruptors |
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Definition
| Sulfonamides, trimethoprim |
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Term
| Minimum bacteriocidal concentration |
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Definition
| Lowest concentration to kill 99.9% of the culture |
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Term
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Definition
| Suppression of bacterial growth continues after the antibiotic concentration falls |
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Term
| Antibiotic protein binding |
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Definition
| Only the free antibiotic can have antimicrobial activity |
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Term
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Definition
| Concentration dependent effect, significant PAE; Lipopeptide daptomycin, aminoglycosides, ketolides, fluoroquinolones, nitroimidazole, rifamycin |
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Term
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Definition
Time-dependent effect, no PAE
Glycopeptides (selectively), beta-lactams (none for G-) |
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Term
|
Definition
Time dependent effect, moderate to prolonged PAE;
Glycopeptides (selectively), Beta lactams (selectively), Oxazolidinones, glycylcycline, tetracycline, chloramphenicol, macrolides, lincosamine, streptogramins, sulfonamides |
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Term
| Bacterial cell wall synthesis |
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Definition
Glucosamine-1-P=>UDP-NAG=>UDP-NAM=>add 5 amino acid tail
NAM-NAG transglycosylated to continuing chain of murein
Transpeptidase cross links the 5 amino chains to each other across fibers |
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Term
| Transglycosylase blockers |
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Definition
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Term
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Definition
| BETA LACTAMS, PENICILLINS, CEPHALOSPORINS, monobactams, carbepenems, carbacephem |
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Term
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Definition
INHIBIT BY BINDING THE ENZYME
Inhibit the cross links between cell wall subunits, ANALOG OF D-ALANYL-D-ALANINE SUBSTRATE, IRREVERSIBLY bind transpeptidase, activate/disinhibit autolytic enzymes to create weak points for cell membrane to extrude through |
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Term
| Beta lactam kinetics/resistance |
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Definition
Elim by renal excretion;
Resist by penicillinases (beta lactamase), decreased affinity of penicillin binding proteins, decreased cell membrane permeability, efflux pumps in bacteria; beat resistance by combining w/ suicide beta lactamase inhibitor |
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Term
Beta lactam adverse
[EXCEPT monobactams] |
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Definition
Allergic reactions (polymers and metabolites can react w/ bacterial or tissue proteins to form antigenic conjugates)
Diarrhea
Hallucinations/convulsions in large doses in renal failure pts (due to GABA binding inhib)
Coagulation defects (inhib platelet activation/converting fibrinogen to fibrin |
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Term
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Definition
| Good distribution except CSF, organic acids ionized at physiologic pH (poorly soluble, generally given in salt form); Renal secretion of unmetabolized, short serum half life |
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Term
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Definition
Thiazolidine ring fused to a beta lactam ring;
broad spectrum against GRAM POSITIVES, acid stable with good absorption after oral |
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Term
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Definition
| Acid labile, only 1/3 oral absorption; drug of choice for syphilis, more active against Neisseria/anaerobes than V) |
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Term
Penicillinase-Resistant Penicillins
METHICILLIN |
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Definition
Resist beta-lactamase by S. Aureus/S. epidermidis;
Initial therapy for G+ cocci making beta'ase;
NOT ACTIVE AGAINST G-!!
Not given orally |
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Term
Extended range penicillins
AMPICILLIN |
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Definition
GRAM NEGATIVE, more susceptible to G+ penicillinases
Active against E. COLI, P. MIRABILIS, H. FLU, SALMONELLA, SHIGELLA, NEISSERIA |
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Term
Anti-pseudomonal penicillins
TICARCILIN |
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Definition
| extended range of ampicillin to Pseudomonas, Proteus, and Enterobacter |
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Term
1st gen Cephalosporins
CEFAZOLIN |
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Definition
Narrow spectrum; surgical prophylax, not choice for active infxn; good for STAPH AND STREP;
DO NOT CROSS BBB; Good against most G+, ok for G-, not good for MRSA |
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Term
2nd gen Cephalosporin
CEFOTETAN |
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Definition
Increased activity against G-, decreased for G+;
Cefo=intra-abdominal surgery prophylax, good for B. fragilis/anaerobes |
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Term
3rd gen cephalosporin
CEFTAZIDIME
ceftriaxone |
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Definition
Good penetration of CNS/bone/lung/urinary tract
HIGH AGAINST GRAN NEGATIVE ENTERICS
Ceftaz=for multi-drug resist G- (mainly Pseudomonas)
Ceftri=choice for Neisseria/B. burgdorferi |
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Term
4th gen cephalosporin
Cefepime |
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Definition
| Pseudomonas/G- treat, better than 3rd against G+ (resist beta'ase), orally active |
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Term
|
Definition
Diarrhea, GI upset.
Bleeding (cefotetan)=hypoprothrombinemia/thrombocytopenia/platelet dysf'n in old/cancer, vitamin K defic from eradicate GI flora
Potential nephrotox (in combo w/ aminoglycosides)
Superinfxn
Hypersensitivity
Disulfiram-like alcohol rxn |
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Term
|
Definition
IV ONLY!
Extremely broad spectrum, resist beta'ase, rapid hydrolyze by renal tubule dipeptidase, NO RESIST TO METALLO-BETA-LACTAMASE; cause seizures/renal tox |
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Term
|
Definition
Excellent for G-
Poor for G+
ONLY NON-CROSS ALLERGY w/ other beta-lactams |
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Term
Glycopeptide antibiotics
VANCOMYCIN |
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Definition
Static G+ cocci
Cidal G+ rods
No G- effect
LAST RESORT IN C. DIFFICILE
Binds D-Ala-D-Ala terminus of murein monomer (BINDS SUBSTRATE!), prevents cell wall elongation |
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Term
|
Definition
Poor GI absorb, given by slow IV, NEVER IM
Renal elimination, treat resistant pseudomemb colitis/staph enterocolitis
No cross-resist/allergy w/ other Ab'otics; resist from replacing terminal D-Ala w/ D-lactate |
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Term
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Definition
Hypersensitivity (flushing, rash "red man syndrome")
Nephrotox, ototox, neutropenia, tissue necrosis by IM |
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Term
Lipopeptide antibiotic
DAPTOMYCIN |
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Definition
Complicated skin infxn/endocarditis by aerobic G+
Cidal against Vanc resistant enterobact
Static for Strep pneumo/staph aureus
Synergy w/ oxacillin against MRSA
Forms memb channels in Ca-dependent manner->rapid depol->inhib protein/DNA/RNA synth
IV inject, renal excrete, no BBB cross |
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Term
Cell membran disruption
polymyxins |
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Definition
| Disrupt membranes of G-, EXTREME nephrotox |
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Term
|
Definition
Prevent initiation complex formation by binding 50S
Static for G+, sometimes cidal
Treat E. faecalis, staph epi, staph aureus, staph haemo, strep pneumo
Good oral/IV, resist by mutate 23 S rRNA
Adv=Inhibits MAO, N/V/D, thrombocyto, anemia, myelosuppression |
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Term
| Tetracycline action/kinetics |
|
Definition
Prevent tRNA binding by binding 30S
Broad static (G+/-, aerobic/anaerob, ALL RICKETTSIAE)
Cross outer memb of G- by passive diffuse thru porin channel, active trans required thru plasma memb
Absorption impaired by food/dairy/antacids/alkaline |
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Term
| Tetracycline resist/adverse |
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Definition
Resist 1 cycline=likely resist others
Decreased influx/high efflux, ribosome protecting proteins, enzymatic inactivation
Adv=N/V/D, PSEUDOMEMB COLITIS, permanent tooth discolor/bone deform in child, venous thrombo, renal/hepatic tox, PHOTOSENSITIVITY |
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Term
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Definition
Prevent tRNA binding by binding 30S
Static G+/- (especially drug resist strains); SKIN INFXN=MRSA, E faecalis, E coli, strep pyogenes, B fragilis; INTRA-ABD INFXN=E coli, S anginosus, B fragilis, K pneumo
IV, excreted in feces/urine |
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Term
| Glycycline resist/adverse |
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Definition
No cross resist, substrate for TetX (gene product makes resistant), AcrAB transport system =reduced suscept to P. mirabilis
Adv=ADULTS ONLY, no preg; N/V/D, warfarin/OCP interx |
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Term
Aminoglycosides
STREPTOMYCIN |
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Definition
Interfere w/ initiation complex form/mRNA misread/premature dissociation
Broad cidal (mainly G-), cross by passive, then active trans; transport inhib by divalent cations/hyperosmol/low pH/anaerobic conditions
TRANSPORT O2 DEPENDENT, NO ANAEROBE ACTION |
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Term
| Aminoglycoside kinetics/resist/adverse |
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Definition
Poor oral absorb, low amt in CSF, rapid renal excrete, rapid absorb IV/IM
SYNERGY w/ beta-lactams!, post ab'otic effect
Resist=acetylases/adenylases/phosphorylases
Adv=ototox, nephrotox (AVOID LOOP DIURETICS), curare-like NM blockade (high dose->resp paralysis), allergic skin rxn/contact dermatitis |
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Term
|
Definition
NOT USED IN US, only where benefits outweigh tox
Inhib peptidyl transferase via 50S, prevent tRNA bind in A site
Broad static, cidal for H flu, strep pneumo, N meningitidis
Rapid GI abs, cross CNS/placenta; requires liver for urine excretion
Resist=decreased influx perm |
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Term
| Chloramphenicol adverse/interx |
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Definition
Adv=Dose related normocytic anemia (erythro suppress of marrow), allergic rxn->aplastic anemia, rash; inhib protein synth in host mito, Gray baby syndrome (vomit, flaccid, hypotherm, resp distress, pallor, shock) from inadequate glucuronic acid conjugation (bad liver conjugate/renal excrete)
Interx=Inhib P450s, prolong drug half-lives, antag macrolides/clindamycin |
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Term
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Definition
Inhib translocation by binding 50S
Static usually, cidal in high concent
Inactivated by gastric acid, absorbed in upper GI
Wide distrib EXCEPT CSF, liver elim
Resist by efflux, methylase production (modify target), MLS-B determinants, esterase hydrolysis
Adv=hypersensitivty, N/V/D, stim GI motility, cholestatic hepatitis, arrythmia, QT long w/ V tach
Interx=inhib hepatic enz, drug interx |
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Term
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Definition
Bind P/A sites of 50S
Static in G+ cocci, active against some macrolide resist strains, GOOD FOR ANAEROBES
Good oral absorb, wide distrib, CROSSES PLACENTA, NO CNS ENTRY; secreted in urine/bile
Resist=ribosomal methylation (MLS-B), not effected by efflux pumps
Adv= diarrhea, GI flora mod (C. difficile), skin rashes in HIV |
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Term
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Definition
Cidal in G+ cocci, inactive for G-; RESERVED FOR VANC-RESIST E FAECIUM/MULTI DRUG RESIST G+
grammin A bind 50S enhances B binding; B inhib translocation at macrolide site
ONLY IV, short half life, biliary excretion
Resist=active efflux/acetyltransferase, MLS-B, lactonases
Adv=infusion related pain/phlebitis, arthralgia, myalgia |
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Term
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Definition
Similar to macrolides, bind 50S; G+/- bacilli/cocci, mycobacteria; RESERVED FOR STREP PNEUMO, active against some erythromycin-resistant strains
Static mostly, cidal for strep pneumo
Resists efflux pump
Adv=N/V/D, dizzy, headache, LIVER TOX/FAILURE!! (jaundice, nausea, ab pain, dark urine)
Interx=CYP3A4 inhib |
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Term
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Definition
Works on E coli, staph aureus, E faecalis; not effective on acinetobacter, pseudomonas, proteus; causes DNA damage/inhibit bacterial enzymes
USE ONLY FOR UTI, cidal at urine concentration; good oral abs w/ food, metab by liver, distro only to bladder, pregnant safe for first 2 trimesters; BAD IN DECR KIDNEY F'N!
Adv=anorexia, N/V, hemolytic anemia |
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Term
Sulfonamides
SULFISOXAZOLE |
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Definition
Competitive antag/analogs of PABA @ dihydropteroate synthase (FOLIC ACID/DNA SYNTHESIS)
Static, broad spectrum; bacteria synth folic acid, mammals take from diet
Crosses BBB/placenta
resist=decr influx, efflux, increased PABA prod
Adv=crystalluria (precip drug/metabolites), hemolytic anemia, aplastic anemia, agranulocytosis, rashes, fever, malaise, pruritis, photosensitivity, Stevens-Johnson, N/V/D
Interx=oral anticoag potentiation |
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Term
Benzylpyrimidines
TRIMETHOPRIM |
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Definition
Dihydrofoloate reductase inhib; Broad spectrum static, usually oral; crosses BBB/placenta, TRAPPED IN PROSTATIC/VAGINAL FLUIDS
Resist=decreased influx/reductase production/decreased enzyme sensitivity
Adv=Megaloblastic anemia, leukopenia, granulocytopenia |
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Term
| Trimethoprim+Sulfamethoxazole(TMP-SMX) |
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Definition
| Synergistic, cidal instead of static; assoc w/ birth defects, NO PREGNANCY |
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Term
Fluoroquinolones
CIPROFLOXACIN |
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Definition
G-= inhib DNA gyrase (topoisomerase 2)
G+= inhib topoisomerase 4
Cidal, probably interferes w/ separation of replicated DNA into daughter cells;
good oral avail, impaired by dairy/antacids, broad distro, renal clearance
Resist=decr influx, decr affinity of gyrase/topo 4
Adv=Not used in pregnancy/nursing/children (cartilage damage), N/V/D, headache, dizziness, rash, seizure, insomnia, hepatitis, tendonitis, photosensitivity
Interx=Increased theophylline levels |
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Term
Nitroimidazoles
METRONIDAZOLE |
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Definition
Inhib DNA replication, causing breaks in DNA; Hits anaerobes, vanc-resist C. difficile, some aerobes
Used IV/oral, metab in liver/renal clearance
Adv=leukopenia, reduce dosing w/ reduced liver f'n, seizures, periph neuropathy w/ prolonged, barbiturates induce metab, interferes w/ alcohol metab |
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Term
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Definition
Inhib RNA synth, binds beta subunit of DNA-dep-RNA polymerase
G+, neisseria, mycobacteria, H flu.meningococci prophylax
Oral absorb, CNS penetrate, deacetylated in liver
Adv=induce CYP3A4, nausea, dermatitis, RED-ORANGE COLORED TEARS/SWEAT/URINE/FECES |
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Term
| Combo to inhib development of resistance |
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Definition
| Erythromycin + sulfisoxazole |
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Term
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Definition
| Chart showing the antibiotic sensitivity of the bugs seen at that hospital |
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Term
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Definition
Entamoeba histolytica
Sexual/fecal-oral transmission
Cysts in large intestine, amoeba invade mucosa (colitis=amoebic dysentery), invade extraintestinal tissue
Treat w/ iodoquinol/paromomycin (intestinal only), metronidazole (intestinal/extra) |
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Term
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Definition
Water borne protozoan, mainly in immunocompromised
Tx=nitazoxanide (80% effective, only over 12 months) |
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Term
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Definition
Diarrhea in AIDS pts
Tx=TMP-SMZ |
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Term
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Definition
Traveler's diarrhea from water (diarrhea, flatulence, nausea, weakness)
Tx=metronidazole (not FDA approved), nitazoxanide (pediatrics), paromomycin (pregnant) |
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Term
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Definition
Tropical/subtropical diarrhea
Tx=TMP-SMZ |
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Term
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Definition
Diarrhea, ab pain, weight loss in immunocompromised; hepatitis, sinusitis, myositis possible
Tx=albendazole may be effective |
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Term
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Definition
Urogenital tract infxn, inflammation, itching, tenderness, profuse frothy creamy discharge; self limiting, urethritis, prostatitis
Tx=Metronidazole, vinegar douches |
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Term
| Iodoquinol (Diiodohydroxyquin) |
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Definition
Treat E. histolytica (INTESTINAL ONLY); liberates iodine=kills amoeba
Not readily absorbed from GI=good for luminal bugs
Adv=headache, N/V/D, rash, anal pruritis, slight thyroid enlarge, loss of visual acuity, optical atrophy, blindness |
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Term
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Definition
Aminoglycoside ab'otic, intestinal amoebiasis/some intestinal cestodes;
Acts on protein synth; poorly absorbed (high in intestine)
Adv=ab pain, diarrhea, nausea, dizzy, can alter normal flora |
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Term
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Definition
Treat E. histo, T. vaginalis, G. lamblia, anaerobic bacteria (clostridia, bacteroides)
Works on anaerobe/microaerobe, acts as an electron sink to prevent re-oxidizing NADH/NADPH->DNA strand modifications
Well absorbed from GI, extensive metabolism, elim by kidneys
Adv=GI upset, metallic taste, disulfiram-like effect w/ alcohol, rare nervous system tox (weakness, paresthesias, vertigo, ataxia); AVOID IN PREGNANT |
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Term
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Definition
FDA approved for giardia/crypto in kids; inhib pyruvate-ferredoxin oxidoreductase (essential for anaerobic metab);
Absorbed from GI: 1/3 excrete in urine, 2/3 in feces; metabolite is active drug, extensive binding to plasma proteins
NO ADVERSE, MAY BE GOOD IN PREGNANT |
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Term
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Definition
Undercooked meat w/ cysts
Tx w/ folate antag PYRIMETHAMINE+SULFADIAZINE; must receive folinic acid supplements (LEUCOVORIN) to prevent marrow suppression; NEVER TAKE IF PREGNANT
Prophylax w. TMP-SMZ, PYRIMETHAMINE+DAPSONE+LEUCOVORIN |
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Term
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Definition
Respiratory illness (SOB, fever, non-prod cough)
Tx=TMP-SMZ, high adverse in AIDS; 2nd choice=PENTAMIDINE
Prophylax=TMP-SMZ, aerosol pentamidine |
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Term
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Definition
Treat PCP, toxo, microsporidiasis; inhibitory analog of ubiquinone->interferes w/ mitochondrial electron transport
Not well absorb, must give w/ fat; long half life, excrete unchanged, 99% protein bound
Adv=rash, fever, vomit, headache |
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Term
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Definition
Treat trypanosomiasis, leishmania, PCP; causes selective breaks in kinetoplast DNA of trypanosomes; given IM/IV, stored in tissues/excreted unchanged, no CNS penetration
Adv=VERY TOXIC, hypoTN, tachycardia, dizzy, faint, headache, vomit (rapid histamine release), reversible renal/liver damage, pancreatic beta cell selective toxicity (causes insulin release [hypoglycemia], then maybe irreversible diabetes) |
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Term
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Definition
Deer tick transmission, signs in immunocompromised/asplenic/elderly; causes hemolytic anemia w/ fever, weakness, jaundice, hepatospleno
Tx=CLINDAMYCIN, QUININE |
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Term
| Trypanosoma brucei gambiense |
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Definition
West/Central Africa tsetse fly, transmitted thru pigs; chronic disease, slow development
Tx=PENTAMIDINE initial, MELARSOPROL/EFLORNITHINE late stage |
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Term
| Trypanosoma brucei rhodesiense |
|
Definition
East Africa by tsetse fly, transmitted thru cows, acute disease , quick dev
Tx=SURAMIN initial, MELARSOPROL late stage |
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Term
|
Definition
Early=in blood and lymph; later stage=CNS penetration->meningoencephalitis->somnolence, coma, death
SURAMIN/PENTAMIDINE don't cross BBB, only good initially |
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Term
| American trypanosomiasis (Chagas disease) |
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Definition
T. cruzi, blood sucking kissing bugs (triatomids); acute=in blood (usually kids), goes to heart, reticulo-endothel system, autonomic NS->cardiac myopathy/chronic GI disease
Tx=NIFURTIMOX, BENZNIDAZOLE (neither good for chronic) |
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Term
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Definition
Sandfly vector, 3 types:visceral (kala azar), cutaneous, mucocutaneous
Visceral=invades macrophages/monos->intermittent fever, liver/spleen/marrow/nodal dysf'n
Tx=SODIUM STIBOGLUCONATE (antimonial), resistance rising; AMPHOTERICIN B good 2nd line for muco/visceral; PENTAMIDINE good 2nd line visceral |
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Term
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Definition
Late stage trypano treat; suicide inhib ornithine decarboxylase (needed for DNA synth/replication); well tolerated
Adv=diarrhea, ab pain, anemia |
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Term
|
Definition
Organic arsenical, only treat meningoencephalitic stages of sleeping sickness; react w/ sulfhydryl groups in proteins->inactivate many enzymes
Slow IV injection, very irritating
Adv=HTN, ab pain, vomit, proteinuria, periph neuropathy, rashes, reactive encephalopathy |
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Term
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Definition
Active against amastigote/extracell mastigote of T. cruzi; poorly effective; converted to superoxide redical/peroxide
Well absorbed from GI, extensive metab
Adv=CNS disturb, transitory convulsion, stiffness, limb weakness |
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Term
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Definition
All 3 leishmanias; prodrug, active inhibits parasite phosphofructokinase; highly toxic
Adv=muscle pain, joint stiff, nausea, flattened T-wave, weakness, liver damage, bradycardia, heart/renal damage, shock, sudden death |
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Term
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Definition
Early T. gambiense/rhodesiense infxn combined w/ diethylcarbamazine to treat O. volvulus
Can't cross mammal membranes
Slow IV injection, binds tightly to serum proteins
Adv=shock, coma, paresthesias, hyperesthesias, peripheral neuropathy, photophobia, nephrotoxic (proteinuria) |
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Term
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Definition
Mebendazole, albendazole, thiabendazole
Inhib microtubule polymerization by binding beta-tubulin |
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Term
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Definition
treat whipworm, mixed whipworm/ascaris/enterobius, ascaris, capillariasis, hookworm (americanus), visceral larva migrans; toxic to eggs, poorly absorbed.
Adv=ab pain, diarrhea
CONTRA IN PREGNANCY |
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Term
|
Definition
Broad spectrum, well tolerated, 4-fold better w/ fatty meal;
Adv=increased serum aminotransferase activity->jaundice, chemical cholestasis; CONTRA IN CIRRHOSIS/PREGNANCY/INFANTS |
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Term
|
Definition
| Strongyloides treatment (egg and larva); rarely used; adv=N/V, anorexia, dizzy, smelly sweat/urine |
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Term
|
Definition
Enterobius/hookworm treatment; depol NM blocker-> ACh release/nicotinic stim->worm paralysis
Adv=headache, dizzy, drowsy |
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Term
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Definition
W. bancrofti/loa loa treat, O. volvulus microfilariae; NEVER USED FOR ONCHO; unknown mech, may be surface coating, exposing antigens; readily absorbed;
Adv=nausea in uninfected, headache/nausea/vomit/anorexia/cough/joint pin/muscle pain in infected |
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Term
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Definition
Treat O. volvulus, W. bancrofti, B. malayi, strongyloides, ascaris, enterobiasis, trichuris; causes influx of negative Cl ions
Adv=lacks systemic tox, causes muscle paralysis, transient headache, mild itching, swollen nodes; CONTRA IN IMPAIRED BBB |
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Term
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Definition
Antischistosomal (s. mansoni/haemotobium/japonicum); choice for Clonorchis, faschiolopsis, paragonimus; INEFFECTIVE AGAINST FASCIOLA HEPATICA
Increase perm to Ca ions->vacuolization/contraction/paralysis, loss of immunological mask
Adv=colicky ab pain, dizzy, headache |
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Term
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Definition
Interfere w/ viral uncoating; prophylax influenza A
Block viral memb protein M2 proton channel
Rapid absorb
Amant=unmetab excrete in urine
Rimant=metab in liver, not good on H3N2/H5N1; SEASONAL H1N1 SENSITIVE, PANDEMIC H1N1 RESISTANT
Tox=dizzy, anxiety, insomnia, seizures |
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Term
|
Definition
| Blocks fusion of HIV to lymphocytes; adv=hypersensitivity rxn, pneumonia |
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Term
|
Definition
| CCR5 (HIV coreceptor) antag, block binding of HIV gp120 |
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Term
|
Definition
| Monoclonal Ab against F (fusion) protein of RSV preventing cell entry; prophylactic treat of RSV in high risk infants; adv=fever, pneumonia |
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Term
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Definition
Prophylax of flu A/B, can reduce duration; pandemic H1N1
Peramivir=emergency IV in H1N1
Inhibits viral neuraminidase->inhib sialic acid cleavage from glycoproteins/lipids, oligosacch=>BLOCKS NEW VIRUS BUDDING
Zanam=inhale, oselt=oral prodrug
Tox=Zanam=bronchospasm, decr lung f'n, neuropsych probs; oselt=nausea, vomit, headache, neuropsych |
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Term
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Definition
Synthetic nucleoside, treat RSV, combination w/ IFN alfa-2a/b for treat hepatitis C; perturb nucleotide pools (phospho'd form), inhib IMP dehydrogenase (GMP essential enzyme)(monophos form)
Tox=hemolytic anemia, conjunctival/bronchial irritation |
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Term
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Definition
Guanosine analogue, treat HSV-1/2, VZV; choice for herpes encephalitis, varicella;
phopho'd by thymidine kinase; potent inhib of DNA polymerase (chain termination)
ONLY INFECTED CELLS ACCUMULATE TRIPHOSPHATE DRUG
Tox=Gi distress, headache, renal dysf'n |
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Term
|
Definition
Val=Prodrug of acyclovir converted in first pass metab
Pen=acyclovir analogue, treat HSV-2 |
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Term
|
Definition
Acyclic guanine nucleoside analog, inhibs CMV DNA polymerase
Adv=granulo/thrombocytopenia
ONLY IN SEVERE INFXN IN IMMUNOCOMPRO/CMV RETINITIS |
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Term
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Definition
Synthetic thymidine analogue, treat AIDS; competes for dTTP for binding to reverse transcriptase->chain termination
Cleared rapidly after liver metab, 1 hour half life; slowed by probenecid/acetaminophen/aspirin, reaches in CNS
Tox=anemia, neutropenia, nausea, insomnia, POTENTIAL LACTIC ACIDOSIS FROM MITOCHONDRIAL TOX |
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Term
|
Definition
nucleoside Reverse transcriptase inhib
GI disturb, headache, fatigue, insomnia;
Lam=TREAT HEP B |
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Term
|
Definition
| Guanosine analog, less hematopoietic tox than AZT, inhib reverse transcript; adv=hypersensitivity, hepatomegaly |
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Term
|
Definition
Ente=Guanine nucleoside analog, weak anti HIV reverse transcriptase activity
Telb=thymidine analog
Both=inhib HBV RT/DNA polymerase |
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Term
|
Definition
Acyclic nucleoside phosphonate->diphosphate inhibts HIV reverse transcriptase
ANTIVIRAL IN RESTING CELLS, approved for HBV treat
Adv=hepatomegaly, Fanconi syndrome |
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Term
|
Definition
| Acyclic nucleoside phosphonate, treat ganciclovir/foscarnet resist CMV-retinitis; HIGHLY NEPHROTOXIC, treat smallpox |
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Term
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Definition
Treat Hep B, lower resistance than lamivudine;
Adv=nephrotoxic, withdrawl=hepatic flares |
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Term
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Definition
Non-nucleoside RTI
Adv=Hepatotox, toxic epidermal necrolysis, Stevens-Johnson
USE IN COMBO THERAPY |
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Term
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Definition
Single daily dose; adv=nightmares, neuropsych effects, NOT USED IN PREGNANCY
When co-admin w/ voriconazole, efav incr/voric decr;
USED IN COMBO THERAPY |
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Term
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Definition
Inhibits HSV/CMV DNA polymerase, HIV reverse transcriptase
Choice for acyclovir resistant HSV in AIDS; tox=nephrotox, symptomatic hypoCa |
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Term
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Definition
| HIV integrase strand transfer inhibitor; part of multi drug regimen; no mammalian analog |
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Term
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Definition
Forsamprenavir, atazanavir, darunavir, indinavir, lopinavir, ritonavir, saquinavir, tipranavir
Bind catalytic site of HIV protease, blocking cleavage of multiprotein gag-pol precursor into mature viral protein products; only used in combo therapy |
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Term
| HIV protease inhib resistance |
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Definition
Darunavir and tipranavir
Less cross-resistance, more effective in experienced pts |
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Term
| HIV protease inhibitor toxicities |
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Definition
Amprenavir/nelfinavir/ritonavir/saquinavir=diarrhea, ab discomfort, nausea, headache
Indinavir=incr bilirubin, renal tox, CYP3A4 inhibit
All=lipodystrophies (incr LDL/TG, decr HDL), hyperglycemia, MI risk
Atazanavir= LOWEST LIPODYSTROPHY RATE
Ritonavir=hepatitis w/ rifampin, intracranial hemorrhage w/ tipranavir |
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Term
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Definition
Chronic hep B, hep C (w/ ribavirin), various malignancies, condyloma acuminata
2b reduces frequency of chronic hep C infxn
Action=level of protein synth; dsRNA protein kinase & RNA depend 2-5 oligoadenylate synthetase=>activate potent RNase->degrades viral message
MUST BE IM/IV, pegylated=longer half life
Tox=marrow suppression (granulo/thrombocyto), neurotox, flu-like, alopecia, depression, GI distress |
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Term
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Definition
Polyene, treat Histo, Crypto, Blasto, Coccidiodes, Candida, Spororthrix; bind tightly to sterols in serum/membranes->perturb structure->leakage;
Targets ergosterol; poor oral absorb, works IV; urine excrete slowly
Tox=chills, fever, headache, vomit, impaired renal f'n |
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Term
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Definition
Fluconazole, itraconazole, posaconazole, voriconazole;
Inhibit 14-alpha-demethylase (P450 in ergosterol synth) |
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Term
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Definition
Itra=oral, nail infxn
Coricon=choice for aspergillosis
Flucon=oral, good CNS penetrate, AIDS crypto meningitis, choice for candida esophagitis
Posa=resistant candida, no renal tox |
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Term
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Definition
Nausea, vomit, rash, gynecomastia, hepatotox, inhibit CYP3A4 (incr cyclosporin, protease inhib, warfarin)
Itra=precipitate HF
Voricon=blurred vision, photophobia, altered color percept |
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Term
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Definition
| Allylamine, inhib fungal squalene epoxidase; topically for tinea cruris/pedis/corporis, oral for tinea capitis/cutaneous candida, treat nail infxn; liver metab; well tolerated, adv=local burning, pruritis, contact dermatitis, fatigue, alopecia, hepatotox (parenterally) |
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Term
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Definition
| Pyridones; inhib uptake of essential extracellular nutrients; treat dermatomycosis (tinea pedis, cruris, corporis, versicolor); only approved topically of hair/nails |
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Term
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Definition
| Echinocandin; noncompetitive beta(1,3)-D-glucan synthase inhibit (essential cell wall component, treat candida/invasive aspergillosis in refractory |
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Term
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Definition
Cytosine analog, treat candida/crypto/aspergillus/chromomycoses; frequent resistance, always used with amphotericin B;
Metab to 5-fluorouracil, incorporated into fungal RNA, blocking de novo dTMP synth;
Rapid GI absorb, excreted unmetab in urine, excretion slowed w/ amphotericin |
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Term
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Definition
Insoluble compound, treat skin/hair/nails by epidermophyton/micosporum/trichophyton; INEFFECTIVE AGAINST CANDIDA
Disrupt microtubule f'n->aberrant mitoses, limits ability of dermatophytes to infect new tissue;
External infxn most responsive to oral therapy, readily absorbed w/ fat, inhib by barbiturates;
Tox=well tolerated, induce porphyria, SLE similar syndrome, inhibits certain anticoagulants activity |
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Term
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Definition
| Suppress the immune system |
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Term
|
Definition
Made by fungus T. inflatum Gams;
Inhibits humoral/cell mediated immune response; inhib activation/prolif of CD4/CD8 T cells by inhib transcription of cytokine encoding genes (no IL-2, no activation); binds highly to cyclophilin->inhib it->blocks translocation of NF-ATc factor->no IL-2 expression;
Water insol, needs EtOH/oil IV to admin;
half life=6 hr, individual monitoring required;
Liver metab, incr clear w/ phenytoin/phenobarrbital, decr w/ erythromycin/amphotericin B/ST JOHN's WORT
Used in transplants/autoimmune disorders
Tox=nephro/neuro tox (tremor, seizure), HTN, hirsuitism, hyperlipidemia, gingival hyperplasia |
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Term
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Definition
50-100x potent than cyclosporine, less nephrotoc, prevent rejection, treat atopic dermatitis;
Acts identically to cyclosporine EXCEPT binds FKBP-12, not cyclophilin
Short half life, need IV load + 3x/day dosing, liver metab; RESCUE THERAPY FOR GRAFT REJECTION, used in kidney/liver transplant;
Tox=nephro/neurotox (tremor, headache, seizure, insomnia), HTN, inhib pancreatic beta cell f'n, increased malig lymphoma risk |
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Term
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Definition
Related to tacro, prevents acute rejection after renal transplant; little/none nephrotox, prevent neointimal prolif/restenosis after stent;
Binds FKBP-12, inhib activity of PI kinase-related protein kinase mTOR which modulates signal that reg transcrip/lation used in cell prolif; lack of response to growth stim signals/inhib T-B cell prolif
Liver metab, used in combo for renal transplant;
Tox=anemia, thrombocyto, hyperlipidemia; comtra after liver transplant |
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Term
|
Definition
Prodrug, becomes antimetabolite mycophenolic acid (MPA, combo w/ cyclosporine/tacrolimus;
hydrolyzed by liver esterases, INHIBITOR OF IMP DEHYDROGENASE REQUIRED FOR DE NOVO PURINE SYNTH (T/B cells reuire de novo purine synth)
Use=renal/heart transplant, don't admin w/ magnesium/aluminum hydroxide antacids (decr abs)
Tox=diarrhea, leukopenia |
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Term
|
Definition
Prodrug, INHIB DIHYDROOROTATE DEHYDROG'ASE (pyrimidine synth); treat active RA; long half life
Adv=diarrhea, nausea, hepatotox |
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Term
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Definition
| Treat erythema nodosum leprosum (type 2 leprosy); Tox=periph neuropathy (~irrev), TERATOGEN, NEVER IN PREGNANT/POTENTIAL |
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Term
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Definition
| Recomb monoclonal Ab against alpha chain (CD25) of IL-2 receptor, inhib IL-2 mediated T activation; REDUCES ACUTE REJECTION, may give acute hypersensitivity |
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Term
|
Definition
Ab against epsilon-chain of T-cell CD3; blocks engagement of T-cell receptor;
REVERSAL!!!!! OF REJECTION IN HEART, LIVER, KIDNEY |
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Term
|
Definition
Ab against TNF-alpha, treat Crohn's/UC/RA/psoriatic arthritis/plaque psoriasis/ankylosing spondylitis;
Incr infxn suscept (TB especially), Hep B reactive, malig, hepatotox;
May develop anti-inflix Ab=resistance |
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Term
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Definition
| p75-TNF receptor type 2/Fc chimera of human IgG; SOAKS UP FREE TNF, treat RA, anky spondy, plaque psoriasis; causes incr demyelinating disease incidence |
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Term
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Definition
| Ab against alpha-4 subunit of a4b1-integrin->inhibits lymphocyte migration to inflam sites; treat Crohn's/MS; incr risk of JC virus-induced pregressive multifocal leukoenceph |
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Term
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Definition
| Ab from CTLA-4/Fc of IgG, treat RA; Binds CD80/86, blocks binding to CD28 and T cell activation; WORKS UPSTREAM OF INFLIX/ETANER |
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Term
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Definition
Purine analog metab in vivo to 6-mercaptopurine; DISRUPTS DE NOVO PURINE SYNTH->INHIB TRANSCRIPTION; part of combo (prednisone/cyclospor/tacrolim) for RA;
Adv=Marrow suppress (leukopenia), GI distress |
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Term
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Definition
| Cytotoxic cancer chemo agent, used in low conc to treat autoimmune |
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Term
|
Definition
| Mixture of poly-L-alanine/glutamate/lysine/tyrosine, antigenically similar to myelin basic protein; treat remitting/relapsing MS |
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Term
| Lymphocyte Immune Globulin |
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Definition
Ab to numerous T-cell surface Ag, depletes periph T-cells by blocking surface recept/direct cytotox; used in combo to prevent rejection/aplastic anemia
Adv=fever, chills, leukopenia, thrombocyto, skin rxn's |
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Term
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Definition
| Purified IgG, replace Ab in immune deficient/block Fc receptors on macrophage (treat idiopathic throbocytopenic purpura) |
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Term
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Definition
| Analog of IL-1 receptor antag; treat RA in pts w/ IL-1 RA mutations; increased risk of serious bacterial infection |
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Term
|
Definition
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Term
|
Definition
2a=Treat Hept C, KS, CML, hairy cell leukemia
2b=hep B/C, malignancies
n1/alfacon-1=hep C
n3=chondyloma acuminata |
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Term
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Definition
| Treat chronic granulomatous disease/congen osteoporosis; exacerbates MS |
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Term
|
Definition
| recombinant erythropoeitin analog, stims RBC form in ANEMIC PTS |
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Term
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Definition
| Longer half life than epoetin, used in chemo-induced anemia; may stimulate tumor cell prolif |
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Term
| P. vivax/ P. ovale malaria |
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Definition
| Make hypnozoites in liver, makes dormant infection; use PRIMAQUINE to treat latent infxn |
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Term
|
Definition
| Affects liver stage of malaria only, kills bug BEFORE it causes illness |
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Term
|
Definition
| Kills parasites when in RBCs, treats disease form of malaria |
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Term
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Definition
| Kills/suppress malaria parasite in early erythrocytic stage (MEFLOQUINE, DOXYCYCLINE) |
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Term
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Definition
| P. falciparum often, medical emergency, treat IV quinine/quinidine |
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Term
Arylaminoalcohols
QUININE
QUINIDINE
MEFLOQUINE |
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Definition
Rapidly kills blood schizonts
Q's=oral for uncomplicated, IV complicated
Meflo=prophylax/treat uncomplicated, NOT FOR EMERGENCIES, treats quinine-resist P falcip.
Concentrates in parasite, blocks heme to hemazoin metab->toxic heme concentr in parasite |
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Term
| Quinine/Quinidine adverse |
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Definition
Binds a-1-acid glycoprotein (high during infxn), as infxn decreases the protein is reduced, releasing drug->toxicity
Cardiotoxicity (long QT)
Hypoglycemia (stim by insulin secretion, can be confused w/ cerebral malaria)
Thrombocytopenia
Cinchonism (tinnitus, blurred vision, headache, N/V, dysphoria)
Blackwater fever (massive hemolysis, hemoglobinemia, hemoglobinuria) |
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Term
|
Definition
| Cardiotox, sleep disturb, neuropsych concerns (rare, not given to pilots) |
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Term
Qunine/quinidine kinetics
Mefloquine kinetics |
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Definition
rapid, complete absorb, metab by P450, half life <12 hrs, resistance growing in SE Asia
Rapid, complete abs, half life 2-4 WEEKS, cross-resist w/ halopantrine |
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Term
4-aminoquinolines
CHLOROQUINE |
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Definition
Kills blood stage, treat/prophy Vivax/Ovale/Malariae, cheap cost; concentrates in RBC/food vacuoles of parasite->toxic heme levels
Adv=Mild GI disturb, bitter taste, retinal damage (high dose), seizure/nerve deafness;
Rapid complete abs, better tolerated than quinine
FALCIPARUM IS RESISTANT!! |
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Term
8-Aminoquinolines
PRIMAQUINE |
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Definition
Non-growing parasite stages (hypnozoites, NOT BLOOD)!
Terminal prophylax if returnign from endemic area
Adv=CONTRA IN G-6-PD, NOT IN PREGNANT/KIDS!!! |
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Term
|
Definition
Blood stage treat, slow acting, prophy of multidrug resist, combo w/ quinine/meflo; not used as single agent; inhib protein synth
Adv=interfere w/ bone/tooth dev-> CONTRA IN PREGNANT/KIDS!!, nausea, sun sensitive, superinfxn, esoph ulcers |
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Term
|
Definition
Uncomplicated MDR Falciparum, prophy
Atova=treat PCP/toxo as well; inhib mito electron transport at cytochrome bc1; KILLER
Proguan=safe antimalarial in young/pregnant; DHFR inhib, enhances atova ability to collapse membrane potentials; ENHANCER |
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Term
| Atovaquone + Proguanil kinetics/adv/resist |
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Definition
absorb better w/ food, peak of both at 8 hrs; Proguan=CYP2D19 metab, 12-21 hr clear; Atova=not metab, 31-84 hr clear
Adv=N/V/Ab pain, rare severe granulocyto/aplastic anemia
Atova Resist=point mutations in cytochrome B |
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Term
Uses:
QUININE
QUINIDINE
MEFLOQUINE
DOXYCYCLINE
PRIMAQUINE |
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Definition
Q'=1st line for uncomp MDR malaria, combo w/ doxycycline
Qd'=parenteral for severe/comp Falciparum
M=1st line PROPHYLAX MDR malaria, 2nd lien TREAT MDR uncomp
D=2nd line proph MDR malaria, 1st line PROPHY MDR in methoquine resistant areas
P=2nd line for all 4 species, acts on hypnozoites Vivax/Ovale |
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Term
| Flaciparum prophylaxis guidelines |
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Definition
| Atovaquone-proguanil. mefloquine, doxycycline |
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Term
| Problem areas for antibiotic delivery |
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Definition
Vegetations on endocardium, devitalized tissues, sequestrum of bone/eye/meninges.
Abscess=leukocyte f'n impaired, low oxygen, low pH can inactivate aminoglycosides; Hgb bind penicillin/tetracycline in hematomas |
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Term
| Antimicrobials that reach intracellular concentrations |
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Definition
| Erythromycin, rifampin, quinolones, tetracycline |
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Term
| Renal insufficient contras |
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Definition
| Tetracycline, long acting sulfonamides |
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Term
| Hepatic insuff contra/signif dose reduction |
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Definition
| Chloramphenicol, macrolides, tetracycline, clindamycin, metronidazole, rifampin |
|
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Term
| Why use multiple drugs simultaneously? |
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Definition
| Prevent emergence of resistant organisms, polymicrobial infxn, initial therapy in life threatening situations, synergy |
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Term
| Early goals of retroviral therapy |
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Definition
| Maximal durable suppression of replication, restore/preserve effective immune response |
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Term
| Recommendations for early antiretroviral treatment |
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Definition
| CD4<350, AIDS defining illness, AIDS nephropathy, Hep B co-infxn, pregnancy, viral load >100K, rapidly declining CD4 (>100/yr), acute opportunistic infxn |
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Term
| Opportunistic infxn and retroviral therapy? |
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Definition
| PCP=don't delay; cryptococcal meningitis=don't delay; no good therapy for OI; don't delay! |
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Term
|
Definition
Nucleoside Reverse transcriptase inhibitor
Thymidine analog
Adv=nausea, headache, myelosuppression, macrocytosis, lactic acidosis |
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Term
|
Definition
Nucleoside Reverse transcriptase inhibitor
Cytosine analog
Adv=Headache, lactic acidosis, considered safest NRTI |
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Term
|
Definition
Nucleoside Reverse transcriptase inhibitor
Cytosine analog
Adv=Hyperpigmentation of palms/soles |
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Term
|
Definition
Nucleoside Reverse transcriptase inhibitor
Adenosine analog
Adv=pancreatitis, neuropathy, lactic acidosis |
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Term
|
Definition
Nucleoside Reverse transcriptase inhibitor
Guanosine analog
Adv=Rash, anaphylaxis, DON'T RECHALLENGE
TEST FOR HLA B*5701 before starting |
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Term
| Non-Nucleoside Reverse Transcriptase Inhib |
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Definition
NEVIRAPINE
EFAVIRENZ
ETRAVIRINE |
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Term
|
Definition
NNRTI
Prevents maternal fetal transmission; decrease area under the curve of protease inhibitors
Adv=SERIOUS HEPATOTOX, may be related to BMI/P450 metab |
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Term
|
Definition
NNRTI
t1/2 40-55 hrs, crosses BBB, nightmares/vivid dreams |
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Term
|
Definition
NNRTI
Use for treatment refractory adults w/ resist to EFV, twice daily dosing w/ meals
Cyp3A4 substrate and inducer
Rash in 17% |
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Term
|
Definition
NucleoTide Reverse Transcriptase Inhibitor
Adenosine monophosphate analog, once a day dosing
Adv=hypophosphatemia, HA, N/V/D, anorexia, rarely lactic acidosis |
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Term
|
Definition
SAQUINAVIR, RITONAVIR, AMPRENAVIR, KALETRA, ATAZANAVIR, FOSAMPRENAVIR, TIPRANAVIR, DARUNAVIR
Highly protein bound, poor bioavailability, interact w/ P450-> MANY DRUG-DRUG INTERXN |
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Term
|
Definition
| PI, take w/in 2 hrs of meals |
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Term
|
Definition
| PI, w/ meals; adv=GI tox at full doses; used in low doses to ALTER KINETICS OF ANOTHER PI (blocks clearance, "ritonavir boosted") |
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Term
|
Definition
PI
don't take w/ fat, 30% get rash, OK to rechallenge after rash resolves; Adv=diarrhea, hyperlipidemia |
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Term
|
Definition
Lopinavir+ritonavir; PI
May SALVAGE saquinavir/nelfinavir failures |
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Term
|
Definition
| PI, DOES NOT CAUSE HYPERLIPIDEMIA; increases HDL; may not offer much if pt is PI resistant; Adv=asymp hyperbilirubinemia |
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Term
|
Definition
PI
Prodrug of amprenavir w/ less toxicity; adv=increased TG more than cholesterol |
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Term
|
Definition
PI
NON-PEPTIDIC, less suscept to resistance
2x/day w/ food, used in REFRACTORY PTS, contains sulfa, major Adv=GI |
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Term
|
Definition
PI
Superiority over lopinavir/ritonavir in experienced pts; Adv=diarrhea, HA, cold symptoms, overall well tolerated; taken w/ ritonavir boost |
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Term
|
Definition
Fuzeon by injection, blocks fusion of HIV into CD4 by binding HR1 region of Gp41; Adv=injection site irritation, bacterial pneumo, hypersensitivity, incr AST/ALT
NO P450 INTERXN |
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Term
|
Definition
Maraviroc
Only in treatment refractory, risk of selecting for CXCR4 tropic virus; metab via CYP 3A4 |
|
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Term
|
Definition
Raltegravir
Blocks virus cDNA integration; initial backbone of treatment in naive pts; metab by GLUCURONIDATION->NO LIPID TROUBLES |
|
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Term
| Resistance testing recommended on: |
|
Definition
Acute seroconverters
If treatment is delayed w/ acute illness
Chronic infxn on 1st visit
Changing therapy b/c of virologic failure |
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Term
| Naive pt initial retroviral regimen |
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Definition
NNRTI or PI or Integrase inhib; add 2 NRTI; used to use 3 NRTI
AVOID=monotherapy, efavirenz in pregnant, Indinavir+atazanavir (hyperbilirubin); Nevirapine never to low CD4 count (hepatitis risk) |
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Term
| Anti retrovirals and PREGNANCY |
|
Definition
antivirals interact w/ OCPs lots (NRTI, PI)
Therapy recommended for ALL pregnants
USE: AZT+3TC, Nevirapine (if present in labor); AVOID Efavirenz (terato), ddI (lactic acidosis), Nevirapine (hepatitis in low CD4); TREAT INFANT W/ AZT W/IN 6-12 HRS OF BIRTH FOR 6 WEEKS!! |
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Term
| Hep B coinfection w/ antiretrovirals |
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Definition
Interferon alpha 2a/b, 3TC (easy resist), tenofovir, entecavir (selects for resistance), adefovir (no HIV activity)
If treat Hep B but NOT HIV= ADEFOVIR/IFN (avoid ART resistance) |
|
|
Term
| Hep C and antiretrovirals |
|
Definition
Best in persons w/ CD4 >200
Pegylated interferon + ribavirin |
|
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Term
|
Definition
| High VL despite treatment, requires change in regimen |
|
|
Term
|
Definition
Failure to achieve/maintain CD4 despite low VL
Common in elderly, Hep C coinfection |
|
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Term
|
Definition
| Occur/recur HIV related event after 3 mo Rx |
|
|
Term
| Complications of long term antiviral Tx |
|
Definition
Lactic acidosis: obesity, femals, NRTI tx; ddC worst causer; NRTI affinity for DNA polymerase gamma->mitochondria dysf'n, maybe cardio/neuro/myopathy/pancreatitis
Diabetes mellitus: weeks-months, Indinavir worst from Beta cell dysf'n
Fat redistrtibution: months-years (NRTI/PI)->buffalo hump, periph wasting, central obese, breast enlarge, loss of facial fat; assoc w/ hyperlipid/insulin resist; common >40 yrs
Hyperlipidemia: Incr TG/cholesterol, Ritonavir worst; statins can be used (atorva/pravastatin) |
|
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Term
|
Definition
| Treat CMV retinitis/colitis; help w/ symptoms |
|
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Term
|
Definition
Late antiretroviral
Guanosine analog; undergoes tiPO4 by VIRAL kinases, competes w/ dGTP for DNA polymerase; very myelosuppressive; requires daily IV, may need ocular implant for CMV retinits |
|
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Term
|
Definition
Analog of inorganic phosphate; inhib viral replication by interfering w/ pyrophosphate binding site of CMV/HIV
VERY nephrotoxic, requires daily IV |
|
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Term
|
Definition
Late antiretroviral
Analog of cytosine
Intracellular triPO4-ing to compete for DNA polymerase; long half life, very nephrotox/myelosuppressive |
|
|
Term
| Sight threatening CMV retinitis Tx |
|
Definition
Combo ocular implant and oral valganciclovir
WATCH OUT for IRIS uveitis |
|
|
Term
|
Definition
| Nausea, anorexia, pain (neuropathy), myelosuppression (give folinic acid [ready for DNA synth], G-CSF, erythropoeitin) |
|
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Term
|
Definition
Similar to G-, has inner cytoplasmic memb/ MUREIN cell wall; outer membrane=thick, asymmetric, highly impermeable;
Mycolic acids make outer lipid layer, linked thru ester to middle component (ARABINOGALACTAN), which is linked to peptidoglycan inner layter;
Infxn tends to be chronic, intracellular, tend to get resistance |
|
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Term
|
Definition
|
|
Term
| First line mycobacterial agents |
|
Definition
| ISONIAZID, RIFAMPIN, ETHAMBUTOL, PYRAZINAMIDE |
|
|
Term
|
Definition
Primary TB treatment
Inhibits mycolic acid synth (unique to myco); STATIC for resting, CIDAL for dividing bugs
Readily GI abs, effective against intra-macrophage bugs, can cross BBB;
Inactivated by acetylation |
|
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Term
|
Definition
Treat clinically manifest disease/prophylax in persons converting from neg->pos PPD
Adv=Periph/central NEUROTOX (neuritis, insomnia, restlessness, twitching, [PREVENTED BY B6 ADMIN!]), Hepatotox, Allergic rxn
Interxn=Phenytoin inhibition
Resist=No cross resist, had to be activated by catalase peroxidase enzyme encoded by KatG gene |
|
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Term
|
Definition
Given in combo w/ INH as 1st line
Binds strong/inhibs bacterial DNA dep RNA polym; CIDAL for myco, penetrates phagocytic cells->kills intracell
Good GI abs, excreted in bile->ORANGE-RED URINE/FECES/SALIVE |
|
|
Term
| Rifampin use/adv/interx/resist |
|
Definition
TB 1st line combo, prophylax meningococcal disease/H. flu meningitis, certain Staph infxn (endocard, osteomyel, nasopharyn)
Adv=Jaundice, rash, thrombocyto, nephritis, hepatotox; less than 2x/week->flu-like
Interx=Induces P450, REDUCES MANY HALF-LIVES (always check when prescribing)
Resist=No cross resist; mutation in bacterial RNA polym->resist |
|
|
Term
|
Definition
Relatively low tox, used in combo 1st line
Inhib ARABINOGALACTAN SYNTH; STATIC myco, no effect on other bact
GI abs, excreted in urine (long t1/2 in renal fail); NO BBB CROSS (except in meningitis)
Adv=Very few, worst=OPTIC NEURITIS->vision loss of red-green differentiate
Rapid resist when alone, ALWAYS GIVE IN COMBO! |
|
|
Term
|
Definition
Inhib myco fatty acid synthase 1 gene->no mycolic acid synth
GI abs, excrete in urine; used short term (<6 mo) in combo, rapid resist by altering pyrazinamidase enzyme
Adv= HEPATOTOX |
|
|
Term
|
Definition
|
|
Term
Fluoroquinolones
LEVOFLOXACIN
MOXIFLOXACIN
OFLOXACIN |
|
Definition
| 2nd line multi-resist mycobacterial infxn, or in intolerant pts |
|
|
Term
|
Definition
doesn't enter readily, doesn't kill intracell; USE ONLY IN SEVERE CASES IN TRIPLE THERAPY
Adv=OTOTOX/NEPHROTOX! |
|
|
Term
|
Definition
Similar to INH, poorly tolerated->2nd line
Gastric irritation, metallic taste, neuro sympt; rapid resist, no cross resist w/ INH |
|
|
Term
| Aminosalicylic acid (PAS) |
|
Definition
STATIC for myco, abs from GI, excrete in urine
Adv=GI trouble (anorexia, nausea, diarrhea), drug fever, joint pain, rash, granulocyto |
|
|
Term
|
Definition
Irreversible inhib alanine racemase and D-Ala-D-Ala synthetase->no cell wall synth
Partial agonist at NMDA receptors
GI abs, excrete in urine
Adv=CNS trouble (somnolence, HA, tremor), psychotic rxn (suicide, paranoia) in 25%
No cross resist |
|
|
Term
|
Definition
| Treat 6 months, NEVER ADD SINGLE AGENT TO A FAILED REGIMEN |
|
|
Term
|
Definition
15-40% AIDS pts, need to use CLARITHROMYCIN or AZITHROMYCIN (macrolides) w/ ETHAMBUTOL to prevent resistance
May need to add RIFABUTIN, CLOFAZIMINE, or a quinolone |
|
|
Term
|
Definition
| Intracell, requires multi drug |
|
|
Term
|
Definition
<5 lesions and no orgs on smear (tuberculoid/borderline)
Tx=DAPSONE + RIFAMPIN
Single skin lesion=single dose RIFAMPIN, MINOCYCLINE, & OFLOXACIN |
|
|
Term
|
Definition
6+ lesions, possible bugs on smear
Tx=Dapsone + Rifampin + CLOFAZIMINE |
|
|
Term
|
Definition
Inhib folate synth; STATIC
GI abs, wide distrib; excrete in bile via enterohepatic recirc; acetylates in liver same way INH does; 70-80% excrete in urine
Adv=HEMOLYSIS ALMOST ALWAYS! over 200 mg/day, methemoglobin common; GI intol, fever, pruritis, erythema nodosum ;eprosum may develop
Resist pretty quickly |
|
|
Term
|
Definition
Very slow acting, may inhib template f'n of DNA?
GI abs variable, accum in tissue (t1.2 may be 2 months!), slow excretion into bile/urine
Adv=GI intol, red skin discolor |
|
|
Term
|
Definition
Sever birth defect!
Treats complications; MUST use 2 forms of contraception/monthly pregnancy tests |
|
|
Term
|
Definition
| All cells killed regardless of prolif state (nitrogen mustard, nonspecific alkylating agents) |
|
|
Term
|
Definition
| Cell cycle specific (vinblastine, methotrexate) |
|
|
Term
|
Definition
| Non-cycle specific but more effective against prolif cells (daunorubicin) |
|
|
Term
|
Definition
| Logarithmic, given dose kills constant FRACTION OF CELLS |
|
|
Term
|
Definition
| Transport defects, somatic mutation, gene amplification, "multi-drug resistance" (pumps drug out) |
|
|
Term
|
Definition
Nitrogen mustard, ethylenimines, alkylsulfonates, nitrosureas, triazines
Induce DNA damage pr can induce p53- mediated apop |
|
|
Term
|
Definition
| Alkylates DNA at N-7 position of guanine->misreading during DNA replication |
|
|
Term
|
Definition
mustard
Oral admin, t1/2 1.5-2.0 hrsEntry by active transport, excrete in stool |
|
|
Term
|
Definition
mustard
Similar to melphalan |
|
|
Term
|
Definition
mustard
Must be activated by P450 to aldophosphamide; hydrolyzed in target cells to active phosphamide mustard; Inactivated in liver->HEPATOTOX
Tox=Immunosuppress, pulm fibrosis, cystitis, water retention, alopecia, carcinogenesis |
|
|
Term
|
Definition
| Treat breast/ovarian cancer |
|
|
Term
|
Definition
| rapid oral abs, tox=myelosuppress, pulm fibrosis |
|
|
Term
Nitrosureas
CARMUSTINE (BCNU)
LOMUSTINE (CCNU) |
|
Definition
Capable of alkylation, DNA crosslink, carbamoylation of proteins
Lipid soluble, diasappear rapidly from plasma, distribute to lipid->long half life; rapid metab, readily cross BBB
Tox=-Delayed but SEVERE hemato depression, pulm fibrosis, renal insuff, alopecia, nausea, vomit |
|
|
Term
|
Definition
dacarbazine; RNA/protein synth inhib more than DNA (lack alkylating specificty)
tox=nausea, vomit, mild myelosuppress |
|
|
Term
|
Definition
Platinum coordination complexes; cis-dichloro form is active
Tx testicular/ovarian/head-neck cancers
Alkylating activity achieved by dissoc chloride ions leaving positively charged complex->variety of crosslinks form
Free drug active, rapid clear by renal
OXALIPLATIN=analog, not cross resist
Tox=Myelosuppress, nephro/ototox (nephro can be limited by amifostine admin [radical scavenger])
CARBOPLATIN=LESS RENAL TOX!; cause leuko/thrombocyto |
|
|
Term
|
Definition
Nonspecific alkylator, rapid metab by liver; TREAT HODGKIN'S
Tox=myelosupp, MAO inhib, carcinogenicity |
|
|
Term
|
Definition
| Decr cell perm, incr conjugation of electrophilic intermediates, incr DNA repair, incr metab |
|
|
Term
|
Definition
Bind tubulin->DISRUPT MICROTUBULE STRUCTURE
Spindle fiber formation/mitosis inhib
Cytoskeletal movement disrupted
Resist=pump out (MDR)
Rapid disappear from plasma, metab in liver, excrete in stool
Tox= Vincris-NEUROTOX, stimulate ADH release; Vinblas-myelosuppression, mucositis; both-dose limiting granulocyto |
|
|
Term
|
Definition
Treat breast/ovarian cancer when others fail
Promotes/stabilizes MICROTUBULE ASSEMBLY, BLOCKING SPINDLE FIBER REORG IN MITOSIS
Resist=MDR pump
Given by continued infusion, metab in liver
Tox=Neutropenia, mucositis, may cause ARRHYTHMIA in previous cardiotoxic pts |
|
|
Term
|
Definition
| Semisynthetic analog of paclitaxel |
|
|
Term
|
Definition
Binds beta-tubulin; promotes polymerization/stabilizes microtubules-> ARREST G2/M cell division
Treat taxane/anthracycline (daunorubicin) resistant breast cancer
Tox=dose neutropenia, cardiotox, periph neuropathy |
|
|
Term
Epipodophyllotoxins:
Etoposide
Teniposide |
|
Definition
Derivatives of podophyllotoxin, treat Hodgkin's, diffuse histiocytic lymphoma, small cell
INHIB TOPOISOMERASE 2
Resist=MDR
Tox=leukopenia, thrombocyto |
|
|
Term
Camptothecin derivatives
Irinotecan
Topotecan |
|
Definition
Irin=prodrug, treat meta colorectal
Topo=ovarian/small cell
INHIBIT TOPOISOMERASE 1
Resist=MDR
Tox (irin)=neutropenia, diarrhea (in UDP GRT 1A1*28 carriers) |
|
|
Term
Antibiotics in chemo
Actinomycin D |
|
Definition
Intercalates between G:C pairs; inhib RNA synth low, both RNA/DNA synth high dose
Tox=Myelosupp, GI, erythema, RADIATION SENSITIZATION |
|
|
Term
Anthracyclines:
Daunorubicin
Doxorubicin |
|
Definition
DNA intercalation, single strand breaks
Rapid uptake in heart/kidney/liver/lung/spleen; signif liver metab
Resist=MDR
Tox=myelosupp, mucositis, severe local rxn, CUMULATIVE CARDIOTOX (arrhythmia, CHF; form reactive species to attack heart especially)
DEXRAZOXANE=Iron chelator, inhib free radical formation, reduce damage |
|
|
Term
|
Definition
Peptide antibiotic w/ DNA binding & iron binding region
Oxidation->depurine/pyrimidization->single/double strand breaks
Concentrates in skin, lung, tumor; renal elim
Resist=increased inactive from overexpr. bleomycin hydrolase/incr DNA repair
Tox=subacute/chronic pneumonitis, skin lesions |
|
|
Term
|
Definition
FOLIC ACID ANALOG, COMPETITIVE INHIB DHF REDUCTASE!
block dUMP->dTMP, 2 other rxn's I won't spell out
Block pyrimidine biosynth 1 way, purine ring synth 2 ways
S phase cells can't make DNA!
High dose->excrete unchanged in urine; tight plasma bound, must monitor closely (only renally cleared), actively transport into cells
Resist=INCREASED DHFR, reduced transport
Tox=low-myelosupp, mucositis; high=fatal myelosupp, renal/hepato/neurotox, teratogen; leukoencephalopathy if intrathecal |
|
|
Term
|
Definition
| Rescue, aborts MTX toxicity by giving reduced folate to cells (bypass DHFR entirely); can potentiate 5-FU |
|
|
Term
Pyrimidine analogs
5-fluorouracil
Cytarabine
Capecitabine
Gemcitabine
Azacitidine |
|
Definition
| Uridine/cytidine analogs; block nucleic acid synth, metab to active inhibitors, incorporated into DNA (disruption) |
|
|
Term
|
Definition
Metab to 5-FdUMP->suicide inhib of thymidylate synthase, incorporate into RNA->defects
Resist=overexpress TS/mutations
Short t1/2, metab in liver/extrahepatic; extra effect AFTER MTX
Tox=Myelosupp, GI, acute/chronic conjunctivitis |
|
|
Term
|
Definition
| 5-FU prodrug; activated by thymidine phosphorylase=high in certain tumors->selective for tumor; metastatic breast/colon |
|
|
Term
|
Definition
Analog of cytidine (replace ribose w/ arabinose); TREAT HEMATOLOGIC MALIG
Phospho'd to Ara CTP->inhib DNA polymerase, incorporated in DNA
Resist=decr cytosine kinase/incr deaminase
Short half life (7-20 mins), longer w/ deaminase inhibitors
Tox=Myelosupp, nausea, vomit, ulcer, seizure |
|
|
Term
|
Definition
Good activity in breast/non-small cell lung/pancreatic/ovarian carcinoma
Deoxycytidine analog |
|
|
Term
|
Definition
Inhib DNA methyltransferase->hypomethylation; converted to 5aza CTP->enter RNA
Treat myelodysplastic syndrome |
|
|
Term
Purine analogs:
6-mercaptopurine
6-thioguanine |
|
Definition
Converted to nucleoside monophosphates by HPRT
Feedback inhib de novo purine synth, compete for rxns, incorporate into DNA/RNA
6-MP metab=S-methylation by TPMT, oxidation by xanthine oxidase (inhib by allopurinol)
Tox=myelosupp, hepatotox |
|
|
Term
|
Definition
Pentostatin=inhib adenosine deaminase, treat hairy cell
Fludarabine=adenosine analog, treat CLL
Nelarabine=treat ALL |
|
|
Term
|
Definition
Inhib ribonucleotide reductase, inhib DNA synth, blocks cells at G1/S border
Adv=leukopenia |
|
|
Term
|
Definition
Catalyzes conversion of asparagine to aspartate; lymphoid cells have low asparagine levels->becomes an essential amino acid; drug robs AA, inhibs protein synth
Tox=reduce secreted protein (clotters, insulin, albumin), hypersensitive, hepatotox |
|
|
Term
|
Definition
Competitively block ATP-binding site of c-abl kinase (bad regulation in CML)
Treat CML and Ph+ ALL; inhibs PDGF/c-kit-assoc tyrosine kinase
Treat GI stromal tumor
Adv=myelosupp, CHF!!! |
|
|
Term
|
Definition
Inhibit EGF receptor-assoc tyrosine kinase
Treat non-small cell lung carcin, pancreatic cancer
Adv=Increased risk of CHF |
|
|
Term
|
Definition
| Chimeric monoclonal Ab against EGF receptor; Use in head/neck/metastatic colorectal cancer |
|
|
Term
|
Definition
Treat p185-HER2 breast cancer; induces Ab-dependent cell mediated cytotoxicity
Adv=cardiotox (especially w/ anthracyclines) |
|
|
Term
|
Definition
Ab against VEGF, inhib angiogenesis
Treat lung/met colon/breast cancer
Adv=incr risk of thromboembolism |
|
|
Term
|
Definition
Anti CD-20 Ab, promotes complement mediated lysis of CD-20 positive B-cells in non-Hodgkin's and CLL
Adv=can reactivate HBV |
|
|
Term
|
Definition
Ab against CD33 (myeloid cell surface Ag)
Conjugated to calicheamicin (DNA cleaving antibiotic) |
|
|
Term
|
Definition
| Histone deacetylase inhibitor; treat cutaneous T cell lymphoma |
|
|
Term
|
Definition
| Protease inhibitor; treat multiple myeloma, mantle cell lymphoma |
|
|
Term
|
Definition
| Vitamin A; 1st line for promyelocytic leukemia |
|
|
Term
|
Definition
Bisphosphonates; Treat hyperCa, osteolytic lesions in multi myeloma/met breast cancer/bone mets from solid tumors
Inhib osteoclast activity, induce 'clast apop; prevents bone loss in men on leuprolide |
|
|
Term
|
Definition
Most common female cancer; assoc w/ increased estradiol and progesterone (early menarche, late menopause, obesity, hormone replacement)
p53 mutation (Li Fraumeni), BRCA1 (familial breast/ovarian), BRCA2 (familial male/female breast) |
|
|
Term
|
Definition
SERM, competitive partial agonist-inhib; PREVENTS ESTROGENS BINDING; ANTAG IN BREAST, AGONIST IN ENDOMETRIUM
Godo oral abs, fecal excrete; 1st phase 7-14 hr t1/2, 2nd phase 1-2 week t1/2; MUCH LONGER HALF LIFE THAN ESTRADIOL |
|
|
Term
| Tamoxifen use/adverse/benefits |
|
Definition
2x daily for 2-5 years; Most useful in postmenopause w/ estrogen recept positive breast cancer
ONLY USE UP TO % YEARS, after it may be a partial agonist in breast
Adv=Among least toxic antineo's; cause hot flash (prevent w/ megastrol or SSRI), N/V, vaginal bleed, dermatitis, ENDOMETRIAL CARCINOMA (E agonist in women w/ uterus), THROMBO EVENTS (decr antithrombin 3)
Reduces total cholesterol/preserves bone density in postmenopausal |
|
|
Term
|
Definition
SERM, works like tamoxifen w/ lower incidence of uterine cancer/fewer blood clots
Adv=hot flash, N/V, endometrial carcinoma (less than tamox), thrombo events (less than tamox) |
|
|
Term
|
Definition
Pure estrogen receptor antag, no agonist effects; 1 injection/mo IM;
Use in postmenopausal who progress on tamox or another antiestrogen |
|
|
Term
|
Definition
Aromatase inhib, use in postmeno who progress on tamox; inhibs P450 that onverts chol->pregnenolone; all steroid production is reduced
NOT WIDELY USED |
|
|
Term
ANASTROZOLE
LETROZOLE
EXEMESTANE |
|
Definition
Selective/irreversible aromatase inhib, ONLY FOR POST MENOPAUSE
Little/no effect on mineralo/glucocorticoid synth
Anas=fewer/less severe adv than tamox
All effective past 5 yrs, no endometrial cancer/thrombo risk
FIRST LINE ALTERNATIVES TO TAMOXIFEN |
|
|
Term
|
Definition
GRH agonists, induce initial flare release (prevented by E recept antag); Later, FSH/LH producing cells get desensitized
Estradiol/progesterone suppressed
Given in sustained microcapsule preparation, treat metastatic breast in PREMENOPAUSE, MAIN USE IN PROSTATE
Adv=ablation of sex steroids (hot flash, sweat, nausea), reversed w/ low level progestational analogs |
|
|
Term
|
Definition
Ab against HER2/erbB-2 receptor (epidermal growth factor family), overactive in breast cancer
Adv=cardiomyopathy (esp w/ anthacycline) |
|
|
Term
|
Definition
Treat advanced breast w/ high HER-2 levels that no longer respond to trastuzumab
ORALLY ACTIVE TYROSINE KINASE INHIB, targets both EGFR & HER2/neu receptors |
|
|
Term
|
Definition
Most common cancer in men, rare prior to 40
Prevent w/ lycopene (tomatoes), statins, finasteride (baldness/BPH treatment) |
|
|
Term
|
Definition
Prevents binding endogenous androgens; PURE ANDROGEN ANTAG w/o any intrinsic steroidal activity
Relatively short half-life
Treat met prostate cancer as initial therapy, often combo w/ GnRH agonists
Adv=Diarrhea most common, gynecomastia, hepatotox rarely |
|
|
Term
|
Definition
| Nonsteroid antiandrogen; more effective in treating prostate than flutamide; Less likely to have adverse effects |
|
|
Term
|
Definition
| GnRH antag, inhib LH/FSH release and inhib testosterone production w/o causing a flare |
|
|
Term
| Physiologic changes in pregnancy that effects drugs |
|
Definition
Altered absorption, distrib, and elim
Incr GFR
Incr abs of inhalants
Incr blood volume->dilutional hypoalbumin->decr drug binding |
|
|
Term
| 1st trimester drug use effects |
|
Definition
| Spontaneous abortion, potential teratogenesis |
|
|
Term
| 2nd/3rd trimester drug use effects |
|
Definition
| Growth restriction, sedation, altered metab |
|
|
Term
| Criteria for proof of human teratogenicity |
|
Definition
| Proven exposure, 2+ epidemiological studies, careful delineation, rare exposure linked to rare disease |
|
|
Term
|
Definition
Big before 9 weeks: CNS, heart, limbs, palate, pretty much everything
After 9 weeks:CNS, eyes, teeth, genitals |
|
|
Term
|
Definition
| Placental transfer, <600 daltons eaily cross, lipid soluble cross easy; higher protein binding ompedes crossing |
|
|
Term
|
Definition
| No fetal risks, tested on humans (vitamins) |
|
|
Term
|
Definition
Animal studies say safe for babies, no human studies either way
Penicillins |
|
|
Term
|
Definition
No adequate studies at all or bad in animals but no data for humans
Many pregnant drugs are here |
|
|
Term
|
Definition
Fetal risk, but benefits outweigh the risks
Carbamazepine, phenytoin |
|
|
Term
|
Definition
| Proven fetal risk, no good benefits |
|
|
Term
| Suspected/proven teratogens |
|
Definition
| ACEI, alcohol, aminopterin, androgens, busulfan, carbamazepine, chlorbiphenyls, coumarins, cyclophosphamide, danzol, diethylstilbestrol, etretinate, isotretinoin, lithium, methimazole, methotrexate, penicillamine, phenytoin, radioactive iodine, tetracycline, trimethadione, valproic acid |
|
|
Term
|
Definition
| Growth restriction, behavioral disturbances, brain/cardiac defects, craniofacial anomalies (flat philtrum, broad upper lip, flattened nasal bridge, micrognathia, micropthalmia) |
|
|
Term
| Antiseizure teratogenesis |
|
Definition
Congenital heart defects, oral-facial clefts, neural tube defect, microcephaly
Minor=mental subnormality, hypertelorism, palmar creases, digital hypoplasia |
|
|
Term
|
Definition
| Warfarin, ACEI, retinoids |
|
|
Term
|
Definition
| Azithromycin, Cephalosporin, Erythromycin, Metronidazole, Nitrofurantoin, Penicillins, Rifabutin, Sulfonamides |
|
|
Term
|
Definition
| ~Aminoglycosides, Aztreonam, Chloroquine, Fluoroquinolones, Imipenem, Quinolones, Trimethoprim, Vancomycin |
|
|
Term
|
Definition
| ~Aminoglycosides, Tetracycline |
|
|
Term
| Cardiovascular teratogenic agents |
|
Definition
| Digoxin, quinidine, propanolol, nifedipine, hydralazine |
|
|
Term
|
Definition
| Heparin, enoxaparin, coumadin |
|
|
Term
| Seizure disorders and teratogens |
|
Definition
| Malformation likely w/ decreased epoxide hydroxylase activity (responsible for phenytoin elim) |
|
|
Term
|
Definition
| May close ductus arteriosus and oligohydramnios |
|
|
Term
|
Definition
Treat severe HTN to prevent fetal damage, reduces BP slower than nifedipine->drug of choice for HTN w/ tachycardia;
can cross placenta, cause fetal bradycardia; long term oral=hypogly, bradycardia, hypoTN, pericardial effusion, myocardial hypertrophy
Useful in treating thyrotoxicosis |
|
|
Term
|
Definition
Milk is more acidic than plasma, affects actives and kinetics;
High lipid solubility passes into milk easy, high MW do not cross easy, high protein binding limits passage;
Contra in breast feeding=bromocriptine, cyclophosphamide, methotrexate, lithium, doxorubicin |
|
|
Term
| Drugs w/ pregnancy specific uses |
|
Definition
Tocolytics=prevent preterm birth
Oxytocin=labor stimulants
Prostaglandin E/F2 alpha=cervical ripening
Oxytocin/methergine/prostaglandin=prevent postpartum hemorrhage |
|
|
Term
| Dosing formula where peaks/troughs are desired |
|
Definition
| [C(peak)-C(trough)]xVd/F(bioavailability) |
|
|
Term
| Determining dosing interval in peak/trough drugs |
|
Definition
| Count # of half-lives required to peak to fall to trough and multiply by half life duration |
|
|
Term
| Loading dose in peak/trough |
|
Definition
| Desired peak x Vd x wt(kg) |
|
|
Term
| Maintenance dose in peak/trough |
|
Definition
| (Peak-trough) x Vd x wt(kg) |
|
|
Term
| Dose for constant concentration drugs |
|
Definition
|
|
Term
| Dose modification in peak/trough |
|
Definition
| Vd = F x Dose/(C[peak] - C[trough]) |
|
|
Term
| Actual t1/2 in individuals |
|
Definition
| Count how many times concentration halved between measured peak and trough, divide by elapsed time by the number of halvings |
|
|
Term
| General approach to poisoned patients |
|
Definition
| Patient stabilization, rapid patient eval, prevent reabsorption of agent, enhance elim, use specific antidote, supportive therapy |
|
|
Term
| Stabilizing depressed level of consciousness |
|
Definition
| Give naloxone, D50, Thiamine, and oxygen |
|
|
Term
| Approach to PE in poisoned pt |
|
Definition
Vital signs
Skin (warm/dry=anticholinergics; cyanosis=methemoglobin/hypoxia)
HEENT (Miosis=opiate/cholinergics, Mydriasis=sympathomimetic/anticholin., Vert/lat Nystagmus=PCP)
Cardiovascular (Tachy + S3=negative inotropics)
Abdomen (hypoactive=narcotic/antimuscarinic/sedative; hyperactive=organophosphate/theophylline)
Neurologic (Symmetric=encephalopathy, Incr muscle tone=sympathomim, tremor/seizure/brisk reflex=theophylline/lithium, Ataxia/dysarthria/nystagmus=phenytoin/ethanol/sedatives) |
|
|
Term
|
Definition
| Cholinergic, anticholinergic, narcotic, sympathomimetic |
|
|
Term
|
Definition
| NEVER DELAY THERAPY WHILE WAITING FOR LABS IN A POISONING! |
|
|
Term
| Possible Lab findings in poisoning |
|
Definition
| Salicylate, ethanol, acetaminophen, theophylline, digoxin, lithium, iron |
|
|
Term
|
Definition
| Na - HCO3 + Cl; normal 12 +/- 2 |
|
|
Term
| Elevated anion gap metabolic acidosis diseases |
|
Definition
Alcohol
Toluene
Methanol
Uremia
Diabetic Ketoacidosis
Paraldehyde
Iron, Isoniazid
Lactic acid
Ethylene Glycol
Salicylate |
|
|
Term
| Arterial blood gas findings in poisoning |
|
Definition
Hypoxia=pulmonary edema, lung injury
Hypercapnia=resp depression (any sedative)
Acidemia/Alkalemia=Primary resp/metab (commonly found in poisoned) |
|
|
Term
|
Definition
Measured - Calculated serum osmolarity
(2xNa) + (Glucose/18) + (BUN/2.8)
<10=normal
High in methanol, ethanol, ethylene glycol, isopropranolol |
|
|
Term
| EKG in tricyclic antidepressants |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Good for almost all ingestions; a cathartic (sorbitol/magnesium citrate) should be admin'd with it to make it go smoother |
|
|
Term
|
Definition
| Weak acids elim via alkalinizing urine thru sodium bicarb (works on salicylates) |
|
|
Term
|
Definition
| Favored in high water solubility/low volume of distribution, low MW, low protein binding; for severe salicylate intox, ethylene glycol, methanol, severe lithium, severe chloral hydrate |
|
|
Term
|
Definition
| Good for lipid soluble, high MW with low Vd; theophylline intox mainly; thrombocyto common in procedure |
|
|
Term
| Serial oral activated charcoal |
|
Definition
| Useful for drugs that undergo enterohepatic circulation; good for mild/moderate theophylline, selicylate digitoxin, phenytoin |
|
|
Term
|
Definition
| Only in severe poisonings of infants |
|
|
Term
| Immunologic antidote to digoxin |
|
Definition
| Fab fragments, bind the toxin and filtered by the kidney, not well reabsorbed, and excreted |
|
|
Term
| Chelator therapy in poison |
|
Definition
| Lead, iron, arsenic, gold, copper, mercury |
|
|
Term
|
Definition
Organophosphates=atropine
Beta-blocker OD=isoproterenol
Opiate OD=naloxine |
|
|
Term
|
Definition
| Provide substrates for detox of reactive intermediates (N-acetyl-cysteine for acetaminophen poison) |
|
|
Term
| Benzodiazepines in the elderly |
|
Definition
| Increased half-life/less predictable dynamics; assoc w/ falls/hip fractures |
|
|
Term
|
Definition
| Constipation, kinetic variability; elderly get undertreated commonly |
|
|
Term
| Antipsychotics in the elderly |
|
Definition
| Risk of stroke, MI and increased mortality |
|
|
Term
| Cholinesterase inhibitors in the elderly |
|
Definition
| Effects on cognition, behavior, and function; Diarrhea, bradycardia; DON'T PRESCRIBE ANTICHOLINERGICS |
|
|
Term
|
Definition
| Indication for severe dementia, blocks activation of N-methyl-D-aspartic acid |
|
|
Term
| BEERS criteria (full list) |
|
Definition
alprazolam (Xanax)
amiodarone (Cordarone)
amitriptyline (Elavil)
amphetamines
anorexic agents
barbiturates
belladonna alkaloids (Donnatal)
bisacodyl (Dulcolax)
carisoprodol (Soma)
cascara sagrada
chlordiazepoxide (Librium, Mitran)
chlordiazepoxide-amitriptyline (Limbitrol)
chlorpheniramine (Chlor-Trimeton)
chlorpropamide (Diabinese)
chlorzoxazone (Paraflex)
cimetidine (Tagamet)
clidinium-chlordiazepoxide (Librax)
clonidine (Catapres)
clorazepate (Tranxene)
cyclandelate (Cyclospasmol)
cyclobenzaprine (Flexeril)
cyproheptadine (Periactin)
dessicated thyroid
dexchlorpheniramine (Polaramine)
diazepam (Valium)
dicyclomine (Bentyl)
digoxin (Lanoxin)
diphenhydramine (Benadryl)
dipyridamole (Persantine)
disopyramide (Norpace, Norpace CR)
doxazosin (Cardura)
doxepin (Sinequan)
ergot mesyloids (Hydergine)
estrogens
ethacrynic acid (Edecrin)
ferrous sulfate (iron)
fluoxetine (Prozac)
flurazepam (Dalmane)
guanadrel (Hylorel)
guanethidine (Ismelin)
halazepam (Paxipam)
hydroxyzine (Vistaril, Atarax)
hyoscyamine (Levsin, Levsinex)
indomethacin (Indocin, Indocin SR)
isoxsuprine (Vasodilan)
ketorolac (Toradol)
lorazepam (Ativan)
meperidine (Demerol)
meprobamate (Miltown, Equanil)
mesoridazine (Serintil)
metaxalone (Skelaxin)
methocarbamol (Robaxin)
methyldopa (Aldomet)
methyldopa-hydrochlorothiazide (Aldoril)
methyltestosterone (Android, Virilon, Testrad)
mineral oil
naproxen (Naprosyn, Avaprox, Aleve)
Neoloid
nifedipine (Procardia, Adalat)
nitrofurantoin (Macrodantin)
orphenadrine (Norflex)
oxaprozin (Daypro)
oxazepam (Serax)
oxybutynin (Ditropan)
pentazocine (Talwin)
perphenazine-amitriptyline (Triavil)
piroxicam (Feldene)
promethazine (Phenergan)
propantheline (Pro-Banthine)
propoxyphene (Darvon) and combination products
quazepam (Doral)
reserpine (Serpalan, Serpasil)
temazepam (Restoril)
thioridazine (Mellaril)
ticlopidine (Ticlid)
triazolam (Halcion)
trimethobenzamide (Tigan)
tripelennamine |
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