| A | B |
|---|
| serious ADRs must be reported within * days | 15 |
| unexpected ADRs must be reported within * days | 3 |
| serious and unexpected ADRs must be reported to | FDA |
| Prohibits mislabeling and adulteration of drugs | Pure Food and Drug Act 1906 |
| new drugs must be safe and pure; did not have to show efficacy | Food Drug and Cosmetic Act 1938 |
| Proof of efficacy and safety; est guidelines for reporting ADR info | Kefauver Harris Ammendment 1962 |
| why did the kefauver harris ammendment become established? | Thalidomide and I-tryptophan -> kids without arms and eosinophillic myalgia |
| dechallenge | pt. stops med and ADR decreases |
| rechallenge | after resolution, med restarted -> ADR reoccurs |
| temporal sequence | s/s do not start prior to administration |
| Naranjo | probability; used most, add scores based on questions |
| ways to identify ADRs | literature citations, FDA programs, Manufacturer, Post marketing surveillance |
| FDA approval and phase III trials | may not enroll enough pt. or be carried out over along enough period of time to detect a rare ADR that may occur in <1000 pts. |
| felbamate (1993) | anticonvulsant ->aplastic anemia after 6 mo. on market |
| oral contraceptives | assd. with pulmonary embolism (3years) |
| slindamycin | assd. with pseudomembranous colitis (5years) |
| post marketing surveilance | need an inc. population to detect rare ADRs and high risk pops. not always studied in clinical trials |
| types of Predictable ADRs | direct extension, unwanted but inseparable, secondary or indirect |
| example of direct extension ADR | dec. blood sugar with sulfonylureas |
| example of umwanted but inseparable pharm. effect | dry mouth with anticholinergenic; sedation with antihistamine |
| example of secondary or indirect ADR; not related to primary action | candiasis with inhaled steroids |
| types of unpredictable ADRs | intolerance, allergic or hypersensitivity, idiosyncratic |
| example of intolerance | tinitus with aspirin; syncope with alpha blockers |
| example of immediate allergic or hypersensitive rxn | anaphylaxis, dec BP, edema (onset ,1hr) |
| example of accelerated allergic or hypersensitive rxn | uticaria, edema, wheezing (onset, 1-72hr) |
| example of late allergic or hypersensitive rxn | morbilliform rash (onset >72hr) |
| type of pseudoallergic ADR | NSAIDS -> aseptic neningitis; not assd with any known pharm effects or allergic mech. |
| example of genetic predisposition to ADR | G-6-PD, slow/fast acetylator (give less/more respectively) |
| example of opposite effect ADR | excitation with barbituates in peds.; seizures with antihistamines in peds |
| immuno classifications of ADRs | I. anaphylactic, II. cytotoxic, III. immunocomplex, IV. cell mediated |
| mediators of anaphylaxis | IgE Ab; mast cells (primarily) and basophils for chemotaxis |
| time of onset for anaphylaxis | <1hr |
| antigen stimulus for anaphylactic rxn | drug, metabolite, setum protein |
| actions of anaphylaxis | vasodil. enhanced perm. of cap. ->uticaria; sm. mm. contract. ->bronchospasm; vd ->dec BP -> shock |
| what causes sm. mm. contraction in anaphylaxis? | histamine |
| example of anaphylaxis | asthma |
| caused by mediators | anaphylaxis |
| IgG, IgM, or Complement assd; not caused by mediators | cytotoxic reactions |
| effects of cytotoxic reactions | damage directed toward cell membrane (eg. platelets, WBCs, RBCs) |
| what is the antigen stimulus for cytotoxic rxns | drug or metabolite, and protein and Ab; antigen + Ab complex = cell destruction |
| causes deposition of antigen-Ab complexes on the tissues | immunocomplex rxn |
| example of immunocomplex rxns | serum sickness; vasculitis; SLE; glomerular nephritis |
| delayed hypersensitivity; assd. with T-lymph -> rls lymphokines | cell-mediated reaction |
| example of cell-mediated rxn | contact dermatitis; photosensitivity |
| PPD (mantoux) test | based on CMI; how long takes cell to get there (48-72hr); cell-med. immun. |
| imability to respond to various stimulus | anergy |
| type A; Augmented | Predictable ADR |
| type B; Bizarre | unpredictable ADR |
