Gen Med midterm- ADR

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komail
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261093
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Gen Med midterm- ADR
Updated:
2014-02-09 17:51:59
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Gen med midterm
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Gen Med
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Gen Med midterm
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  1. Sulfanilamide caused; thalidomide caused; dethylstillbestol caused
    • renal impairment
    • phocomelia
    • vaginal carcinoma
  2. Define ADR
    noxious and intentended response to a drug which occurs at doses that are therapeutic (could be prophylaxis, diagnosis, therapeutic, disease modifying etc.)

    essentially: harm caused by drug at normal doses, expected or unexpected.
  3. Adverse drug event
    any harm caused by use of a drug (overdose, abuse, ADR etc. )
  4. Medication error
    inappropriate use of drug which may or may not result in harm to the patient (thus an adverse drug reaction is never a medication error)
  5. Impact of ADRs
    • common: 30% of hospitalizations due to ADR
    • expensive: 100 billion cost to U.S. annually (exceeds annual cost of medication)
    • Cause an average 2 day increase in hospital stays

    Fatal rxns are fifth leading cause of death and are preventable
  6. Factors to look at for causality assessment
    • onset of rxn
    • differential diagnosis
    • does rxn improve after withdrawal/decreased dose?
    • prior reporting of rxn with drug 
    • patient + drug rechallenge
  7. Naranjo causality scale
    • >9 definite ADR
    • 5-8 Probably ADR
    • 1-4 Possible ADR
    • 0 Doubtful ADR
  8. Two classifications of ADRs
    • Type A (predictable):
    • augmentation of drug pharmacology, dose dependent, no specific host factors, 80% of all ADRs

    • Type B: cannot be explained by drug pharmacology, no simple relationship between dose and toxicity 
    • 3 types (idiosyncratic, imunologic and pseudoallergic)
  9. What is DRESS
    • Is a Type B rxn
    • Drug reaction with eosinophelia and systemic symptoms 
    • tried of fever, skin eruptions and internal organ involvement (Increase in liver AST/ALT)
    • -occurs most frequently at first exposure, with initial symptoms starting 1-8 weeks after drug exposure.
  10. Drugs most often associated with DRESS?
    • anticonvulsants
    • sulfonamide antibiotics
    • dapsone
    • allopurinol
  11. Idiosyncratic Type B Rxns:
    • ex. DRESS, ehepatitis, nephritis
    • do not rechallenge a patient having this
    • ex. dapsone-> pneumonitis
    • valproic acid-> hepatitis
    • penicilins-> interstitial nephritis
    • clozapine-> agranulocytosis

    • extensive erythrodema,
    • bullae
    • painful skin
    • mucosal involvement
    • facial edema
    • lymphadenopathy
    • consitutional symptoms (faver, malaise, fatigue)
  12. What are Immunologic Type B rxns
    • does not occur on first exposure 
    • occurs at lower doses than required for pharmacologic effect
    • produces rxns characteristic of known immunologic rxns
    • symptoms subside within 3-5 days once drug d/c
  13. Types of immunologic Type B rxns (Type-> Description-> Primary effector 0> Clinical Rxn)
    • Type 1> Immediate-> IgE-> Anaphylaxis, urticaria
    • Type 2>Cytotoxic> IgG IgM> hemolytic anemia
    • Type 3>immune-complex disease> soluble immune complexes> serum sickness, drug fever
    • [most common type]Type 4> Delayed or cell-mediated (takes weeks!)>sensitized T-cells> Contact dermatitis
  14. Type B Pseudoallergenic Rxns
    • no antibody or T-cell response to antigen
    • symptoms resemble allergic rxn-> drug probably acting directly at the mast cell level, rather than antibody/T-cell (can rechallenge these patients)
  15. What's the difference between anaphylaxis and anaphylactoid?
    anaphylactoid produces a dose-dependent response in histamine and other mediators (usually caused by muscle relaxants-> opiates, barbiturates )

    anaphylaxis: histamine is involved, but not the most important mediator
  16. Pediatrics and ADRS
    children dont have higher risk of ADRs, but their immature enzymes makes them more susceptible to more serious ADRs (grey-baby syndrome-> chloramphenicol)
  17. Females and ADRs
    • Higher incidence of ADRs
    • kinetic differences, reporting bias, hormonal
  18. Geriatrics and ADRS
    normal elderly patient is at a higher risk of ADR, however with increasing meds they are increasingly predisposed to having higher ADRs.
  19. Genetic factors are important in what kinds of ADRs?
    IgE mediated rxns=genetic factors are not important

    Idiosyncratic rxns: genetic factors are important (Major histocompatibility complexes are usually tested before a drug is started; ex. carbamazepine and allopurinol cause toxic epidermal necrosis in han chinese but not caucasians)
  20. What kind of infections can cause drug-viral interactions?
    • Human herpes virus 6-> Hypersensitivity syndrome
    • Epstein-Barr virus and ampicillin
    • HIV infection and sulfamethoxazole
  21. Are past drug rxns predictive of future drug rxns?
    • Patients with a rxxn to sulfoneamides or penicillins are at an increased risk of rxn to other drugs
    • History of prior drug rxn is a risk factor for penicillin rxn
  22. Nocebo effect:
    • onset of bad reaction following administration of inert substance
    • usually subjective responses
    • 27% of patients reacted to placebo
  23. Panic attack symptoms:
    • unexpected, sudden overwhelming senseless terror
    • symptoms peak within 10 mins of onset
    • fear of dying
  24. Desensitization:
    • administration of a drug to a patient in whom allergy has been established, but patienrt requires drug (no substitute treatment)
    • -administer small doses to reuce antibody that is producing drug rxn

    Benefits: relatively safe; allows for drug readministration

    Disadvantages: termporary effect, doesnt determine if allergic to drug; not every drug can be desensitized
  25. What are some tests for ADRs?
    • -skin testing: only useful for IgE mediated (insulin, penicillin)
    • -patch testing: used for delayed-type reactions (Type 4) like contact dermatitis; also used for DRESS rxns
    • -oral provacation test: used if vague history, and drug s essential, and the risk of eliciting an actual reaction is known

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