Gen Med midterm- ADR

• renal impairment
• phocomelia
• vaginal carcinoma

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.

any harm caused by use of a drug (overdose, abuse, ADR etc. )

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)

• 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

• onset of rxn
• differential diagnosis
• does rxn improve after withdrawal/decreased dose?
• prior reporting of rxn with drug 
• patient + drug rechallenge

• >9 definite ADR
• 5-8 Probably ADR
• 1-4 Possible ADR
• 0 Doubtful ADR

• 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)

• 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.

• anticonvulsants
• sulfonamide antibiotics
• dapsone
• allopurinol

• 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)

• 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

• 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

• 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)

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

children dont have higher risk of ADRs, but their immature enzymes makes them more susceptible to more serious ADRs (grey-baby syndrome-> chloramphenicol)

• Higher incidence of ADRs
• kinetic differences, reporting bias, hormonal

normal elderly patient is at a higher risk of ADR, however with increasing meds they are increasingly predisposed to having higher 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)

• Human herpes virus 6-> Hypersensitivity syndrome
• Epstein-Barr virus and ampicillin
• HIV infection and sulfamethoxazole

• 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

• onset of bad reaction following administration of inert substance
• usually subjective responses
• 27% of patients reacted to placebo

• unexpected, sudden overwhelming senseless terror
• symptoms peak within 10 mins of onset
• fear of dying

• 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

• -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