Adverse Drug Reactions (Godofreda Vergeire-Dalmacion, MD) Flashcards
How many % of hospital admissions can be attributed to adverse drug reactions?
3 - 11%
ADRs are the (1) leading cause of death and (2) source of malpractice payouts in the US.
(1) 4th
(2) single largest
T/F: 4 out of 5 ADRs are dose-dependent.
False
3 out of 4!
T/F: ADRs may occur in standard doses.
True
Define: Adverse Drug Reaction (ADR)
Noxious and unintended response to a drug in recommended doses.
Overdose/toxicity goes beyond the recommended dose.
T/F: Causality has been determined in ADR.
True
T/F: In an adverse drug event, there is an unintended response in any dose and causality has been established.
False
Causality has not been established for an adverse drug EVENT.
Adverse drug event is the summation of what?
- ADR
- Unknown causes (preclinical trials or complication/side effect)
- Idiosyncratic causes (regardless of dose)
- Medication errors (information passing)
- Treatment failure (counterfeit drugs)
Lasix, a diuretic, is commonly confused with what drug?
Losec (Omeprazole)
What are the types of ADRs?
Dose-related and non dose-related
Dose-related ADRs are also known as?
Type A or Augmented
This category covers non-immune ADRs!
T/F: Non dose-related ADRs are due to pharmacokinetic and pharmacodynamic abnormalities that produce an excess of pharmacologic effect
False
Dose-related ADRs!
Define: Extension Effect
Predictable physiological changes beyond what is normal caused by following intended use
Solution is dose reduction or shifting to another drug.
What is the extension effect of taking aspirin?
GI bleeding and erosions due to inhibition of prostaglandins
Define: Side Effects
Predictable physiological changes caused by the drug other than intended use
Drug attacks different receptors
T/F: All beta-mimetics are cardiotoxic with the side effect of palpitation.
True
T/F: Anti-platelet action of aspirin prevents thrombus formation.
True
What is carbamazepine (tegretol) used for?
Controlling seizures
What are forms of pharmaceutical variation?
Changes in formulation
Outdated formulation
Presence of contaminants, pyrogens or bacteria
Describe the relationship between rate of acetylation and isoniazid side effects
Slow acetylators (caucasians): peripheral neuropathy (prescribe vitamin B6)
Fast acetylators (Filipinos): liver toxicity
What is succinylcholine used for?
Anesthesia
It induces prolonged apnea.
T/F: Pseudocholinesterase deficiency is a form of pharmacologic variation.
True
What are the forms of pharmacokinetic variation?
- Pharmacogenetic variation
- Hepatic disease
- Renal disease
- Cardiac disease
- Thyroid disease
- Decreased plasma albumin
T/F: Reduced clearance always results in increased adverse reactions.
False
Not if there’s compensatory excretion
What are the uses and side effects of theophylline?
Used for asthma
May cause hypotension and cardiac failure
What are the uses and side effects of phenytoin?
Anti-convulsant
Can induce sedation and coma
What are the uses and side effects of warfarin?
Anti-coagulant
Causes more bleeding
T/F: When there is decreased plasma albumin, drugs with low Vd are affected.
True
T/F: Warfarin, diazepam and salicylic acid are examples of protein-bound drugs.
True
What are the forms of pharmacodynamic variation?
Reduced blood clotting
Hepatic encephalopathy
Sodium and water retention
Altered fluid and electrolyte imbalance
When there is reduced blood clotting due to liver disease, these drugs should be avoided or changed in terms of dosage.
Anticoagulants
Aspirin, phenylbutazone, indomethacin and paracetamol
When there is hepatic encephalopathy, these drugs should be avoided.
Opiates Narcotic analgesics Barbiturates Chlorpromazine Short-acting benzos Diuretics
When there is sodium and water retention, these drugs should be avoided.
Corticosteroids
Carbenoxolone
Indomethacin
Antacids
T/F: In cases of hypokalemia and hypercalcemia, cardiac glycoside effects are depressed.
False
Potentiated! In fact, this leads to heart failure.
What drug effects are reduced when there is hypokalemia?
Class 1 anti-arrythmic effects (lignocaine, quinidine and procainamide)
What drug effects are prolonged when there is hypercalcemia?
Tubocurarine and succinylcholine
Describe: Cyclosporine
- Predisposing factor for renal transplant
- Increases potassium by impairment of excretion
- Immunosuppressant needs to be taken for life
When is the hypotensive effect of anti-hypertensives enhanced?
Fluid depletion
T/F: Non dose-related ADRs are explained by immunology or pharmacogenetic variation.
True
Non-dose related ADRs are described as Type B for?
Bizarre
Drug allergy or hypersensitivity reactions are elicited by?
High MW proteins
Polypeptides
Dextrans
Drug allergies occurs occur in what type of people?
Inherently atopic
Deficiency in MHC
What anti-retroviral drug is involved in the abacavir hypersensitivity reaction?
HLA B57
T/F: Drug allergies occur in incidental diseases.
True
Describe: Type I Reaction
IgE-mediated
Rapid
Give an example of a Type I reaction
Anaphylaxis from beta-lactam antibiotics
Describe: Type II Reaction
Cytotoxic
Give an example of a Type II reaction
Hemolytic anemia from penicillin
Describe: Type III Reaction
Immune-complex
Give an example of a Type III reaction
Serum-sickness from anti-thymocyte globulin
Describe: Type IV Reaction
Delayed and cell-mediated
Give an example of a Type IV reaction
Contact dermatitis from topical cell-antihistamine
What is it called when a single drug can cause more than one type of reaction?
Cross reaction or cross sensitivity
Give an example of specific T-cell activation
Morbilliform rash from sulfonamides
Give an example of Fas/Fas-Ligand-induced
Steven-Johnson syndrome apoptosis; toxic epidermal necrolysis
What family of molecules does the Fas ligand belong to?
Tumor necrosis factor (TNF)
Give examples of other types of reactions under the Gell-Coombs Classification.
Drug-induced lupus-like syndrome
Anticonvulsant hypersensitivity syndrome
What are the three different situations that can be identified based on the Gell-Coombs classification?
Pseudo-allergic reactions
Primarily antibody-mediated reactions
Cell-mediated reactions
What is the time of onset of the different hypersensitivity classifications?
Type I - immediate
Type II - within minutes or hours
Type III - within 1 - 3 weeks
Type IV - 2 to 7 days after cutaneous exposure (shorter when oral)
Differentiate Type IIA and Type IIB hypersensitivity reactions
Type IIA - cytotoxic
Type IIB - antibody-mediated cell stimulating
T/F: Grave’s disease and chronic idiopathic urticaria are examples of Type II hypersensitivity reactions.
False
They’re Type III!
Differentiate Types IVA - D
Type IVA - CD4+ Th1 w/ activation of macrophages
Type IVB - CD4+ Th2 w/ eosinophils
Type IVC - Cytotoxic CD8+ w/ perforin-granzyme B
Type IVD - T lymphocyte-driven neutrophilic inflammation
Give examples of Type IVA - D hypersensitivity reactions
Type IVA - granuloma and type I DM
Type IVB - persistent asthma and allergic rhinitis
Type IVC - Steven-Johnson syndrome and toxic epidermal necrolysis
Type IVD - pustular psoriasis and acute generalised exanthemous pustulosis
T/F: Clinical features of allergic drug reactions have correlations with known properties of the drug.
False
T/F: Allergy will only manifest on subsequent use of ciprofloxacin.
True
T/F: Allergic drug reactions can occur at doses below therapeutic range.
True
70% of patients with allergic rhinitis develop what?
Bronchial asthma
What is the typical manifestation of a type I reaction?
Urticaria
What is the most common dermatologic manifestation of a drug allergy?
Morbilliform rash
What are the most common drug causes of morbilliform rashes?
Beta-lactam antibiotics (penicillins and cephalosporins) Sulfonamide antibiotics Allopurinol Anti-epileptics NSAIDs
Type of rash caused by thiol and non-thiol-containing drugs (i.e. enalapril, cephalosporins and piroxicam)
Pemphigus
Caused by oestrogen in oral contraceptive pills
Melasma
Caused by omeprazole; can occur in bronchial passages and mucosal membranes
Angioedema
What is the only dermatologic emergency where all mucous membranes are affected?
Steven-Johnson Syndrome
Is contact dermatitis a manifestation of drug allergy?
No
Is viral exanthem a manifestation of drug allergy?
No
Drug allergies usually manifest as patches on the skin.
What are long term effects of drugs?
- Adaptive Changes
2. Rebound Phenomena
Describe the adaptive changes of the body to beta-blockers
Development of tachyphylaxis and eventually tolerance when all receptors are blocked.
RECALL: Beta-blocker in heart decreases blood pressure and cardiac output
Describe anti-hypertensives and rebound phenomena
There is extreme lowering then rising up again of blood pressure.
What are delayed effects of drugs?
- Carcinogenesis
2. Effects on Reproduction
Describe (1) carcinogenesis and anti-cancer drugs and (2) carcinogenesis and fertility drugs
(1) Anti-cancer drugs may produce a second cancer
(2) Ovulation induction drugs may cause ovarian cancer
Enumerate delayed effects of drugs in connection with reproduction
Impaired fertility
Teratogenesis
Drugs in breast milk
Enumerate common predisposing factors for immune and non-immune ADRs
Female gender
HIV
Systemic lupus erythematosus
Enumerate generic drug reaction (non-immune) risk factors
Serious illness Renal insufficiency Liver disease Polypharmacy Herpes infection Alcoholism
Enumerate immune hypersensitivity drug reaction risk factors
Age (adult) Concomitant viral infection Previous hypersensitivity to chemically-related drug Asthma Use of beta-blockers Specific genetic polymorphisms
T/F: Myocarditis is a common adverse drug reaction to Cefaclor.
False
It’s very rare.
