Thorny Lecture Buzz Words Flashcards
Type C ADRs
associated with long term use involves dose accumulation
Drugs for Type 4
b-lactam antiB’s sulfonamides *also latex gloves and poison ivy are examples of these
Why is alcohol (elixir) contraindicated with metronidazole
Metronidazole blocks the bodies ability to metabolize alcohol resulting in high levels of acetaldehyde… leading the headache and facial flushing (asian flush)
What types of changes in DNA are the main focus to determine genetic variability and their corresponding changes in drug response?
SNPs
What foods should be avoided when taking warfarin?
those high in vitamin K
Isoniazid is a drug for TB… idiosyncratic differences in response to this drug makes 3 populations particularly slow metabolizers of isoniazid, potentially making it toxic… what is the enzyme responsible and what are the 3 groups?
enzyme = N-acetyltransferase 1) 80% egyptians are slow 2) 50% caucasians 3) 50% africans
Drugs causing Type 3
b-lactams sulfonamides NSAIDs hydralazine* procainamide* *implies causes a lupus-like reaction
cyp2D6 polymorphisms can have very different effects on metabolism… thus inhibitors of this enzyme can MIMIC a genetic polymorphism… what are examples of inhibitors?
cyp2D6 is inhibited by… fluoxetine, paroxetine, haloperidol, quinidine, ritonavir aka any drug that also requires cyp2D6 metabolism can decrease enzyme available to metabolize drug…
Type 1 Hypersensitivity MOA
Requires initial exposure to result in clonal expansion of B & T cells 2nd exposure results in rapid response.. T-cells activate B-cells which results in high [] of IgE causing mast cell degranulation and bronchospasm. Anaphylaxis is a sever type 1 response Re-challenge is OK after de-sensitization
Type A Adverse Drug Reactions
account for 2/3 of ADRs PREDICTABLE & Dose Dependent (include anaphylactoids) Preventable (propranolol & heart block)
Type D ADRs
delayed effects (dose INdependent) carcinogenicity teratogenicity
Difference between anaphylaxis vs anaphylactoid
Anaphylaxis is IgE-mediated histamine release (due to a severe type 1 hypersensitivity) Anaphylactoid is NON-IgE mediated histamine release
Antibiotics you gotta know frequently cause allergic reactions
b-lactams! (cephalosporins & penicillins) Sulfonamides Vancomycin
What foods should be avoided when taking diuretics?
foods high in salt
*sneaky important to know* Gotta remember these drugs are anaphylactoid… thus are DOSE-related, and have NO cross-reactivity within class (therefore using a different drug within the same class is okay)
1) codeine/morphine 2) Vancomycin 3) sulfites 4) Radiocontrast (also if you can member it… caspofungin)
Name 7 inducers of cyp450
1) EtOH 2) smoking cigarrettes 3) chewing tobacco 4) phenobarbital 5) phenytoin 6) rifampin 7) carbamazepine
Type B ADRs
idiosyncratic rare and not predictable
What is an example of an idiosyncratic response to general anesthesia?
Malignant hyperthermia
Type 1 HyperS MOA
Target organ = RBCs or platelets onset = immediate if 2nd exposure, otherwise 5-8 days for first time exposure Rechallenge NOT recommended Drug binds cell membrane (of RBCs or platelets) and antibodies are formed against the drug and attach resulting in toxicity… sometimes the anitbodies activate complement and cause cell lysis
Hypersensitivity vs Anaphylactoid
HyperS = immune-mediated, not dose related, cross-reactivity within class occurs, re-challenge only in type 1 & 4 Anaphylactoid = pharmacologically induced, IS dose related, NO cross-reactivity, and re-challenge is okay if pre-treated with antihistamine
Name a few drugs that can cause Type 1 HS
mAbs NMJ blockers quinolone antibiotics b-lactam antib’s Toluene diisocyanate (chemical factories) Apamin (evil Bee’s)
Big summary table of the 4 hypersensitivities
type 1 = IgE, onset in minutes, can desensitize drugs: b-lactams, quinolones (lone wolf = number 1), NMJ blockers type 2 = IgG, IgM, onset 5-8 days, No desensitization drugs: b-lactams and quinidine type3 = IgG, IgM, onset 10-14 days No desensitzation, drugs: b-lactams, hydralazine, procainamide, NSAIDs type 4 = *T-cell lymphocyte mediated*, usually 7-20 days for onset, can desensitize, b-lactams and *sulfa drugs*
Very low activity of thiopurine methyltransferase (TPMT) results in what?
Bone marrow toxicity (due to accumulation of thioguanine)
term for: study of relationship between individual gene variants and variable drug outcomes
Pharmacogenetics
MOA of type 3 HS
mostly the same as type 2… (a drug and antibody complex causes toxicity)… the KEY difference is that the complex fixes complement resulting in localized INFLAMMATION immediate onset if previous exposure or 10-14days for first time exposure! Target organ: Vascular endo = vasculitis kidney = glomerulonephritis skin = purpura joints = arthralgias *re-challenge not recommended
5 drug Inhibitors of cyp450 + 1 common juice that can also inhibit cyp450
1) clarithromycin 2) erythromycin 3) ciprofloxacin 4) cimetidine 5) omeprazole GRAPE FRUIT JUICE (know this!) + St. John’s Wort
Drugs causing Type 1 HS
b-lactam antiB’s - cause hemolysis Aspirin* quinidine* phenytoin* *implies cause thrombocytopenia —> purpura
Exprain why asian mares and femares get red frush in the face with arcohor?
45% of chinese have an auto. dom. trait leading to ALDH-2 deficiency… thus it can’t breakdown aldehyde causing hang-over feeling and facial flushing
what food should be avoided when taking tetracycline?
don’t drink MILK or MyLanta (for the love of liza)
GWAS… think what term?
Pharmacogenomics
A response to drug that is qualitatively different from normal and rare… due to hereditary factors… what term is best fits this?
Idiosyncratic Response.
what deficiency is an idiosyncratic response to oxidative drugs? (Primaquine, quinine, SULFA drugs)… what population is susceptible?
G6PDH deficiency… 1 in 10 africans
what is the term for: study of role of inherited and acquired genetic variation in drug response
Pharmacogenomics
Type 4 HyperS
“delayed-type”… most commonly causing a rash usually show up after 7-20 days Rechallenge can be done after de-sensitization *hapten-carrier mediated
which cyp450 polymorphism results in poor metabolism omeprazole resulting in greater cure rate for H. Pylori
CYP2C19
cyp2C9 & VKORC1
Warfarin
