Adverse Drug Reactions (Godofreda Vergeire-Dalmacion, MD) Flashcards

1
Q

How many % of hospital admissions can be attributed to adverse drug reactions?

A

3 - 11%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

ADRs are the (1) leading cause of death and (2) source of malpractice payouts in the US.

A

(1) 4th

(2) single largest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

T/F: 4 out of 5 ADRs are dose-dependent.

A

False

3 out of 4!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

T/F: ADRs may occur in standard doses.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Define: Adverse Drug Reaction (ADR)

A

Noxious and unintended response to a drug in recommended doses.

Overdose/toxicity goes beyond the recommended dose.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

T/F: Causality has been determined in ADR.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

T/F: In an adverse drug event, there is an unintended response in any dose and causality has been established.

A

False

Causality has not been established for an adverse drug EVENT.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Adverse drug event is the summation of what?

A
  1. ADR
  2. Unknown causes (preclinical trials or complication/side effect)
  3. Idiosyncratic causes (regardless of dose)
  4. Medication errors (information passing)
  5. Treatment failure (counterfeit drugs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Lasix, a diuretic, is commonly confused with what drug?

A

Losec (Omeprazole)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the types of ADRs?

A

Dose-related and non dose-related

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Dose-related ADRs are also known as?

A

Type A or Augmented

This category covers non-immune ADRs!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

T/F: Non dose-related ADRs are due to pharmacokinetic and pharmacodynamic abnormalities that produce an excess of pharmacologic effect

A

False

Dose-related ADRs!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Define: Extension Effect

A

Predictable physiological changes beyond what is normal caused by following intended use

Solution is dose reduction or shifting to another drug.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the extension effect of taking aspirin?

A

GI bleeding and erosions due to inhibition of prostaglandins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Define: Side Effects

A

Predictable physiological changes caused by the drug other than intended use

Drug attacks different receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

T/F: All beta-mimetics are cardiotoxic with the side effect of palpitation.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

T/F: Anti-platelet action of aspirin prevents thrombus formation.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is carbamazepine (tegretol) used for?

A

Controlling seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are forms of pharmaceutical variation?

A

Changes in formulation
Outdated formulation
Presence of contaminants, pyrogens or bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe the relationship between rate of acetylation and isoniazid side effects

A

Slow acetylators (caucasians): peripheral neuropathy (prescribe vitamin B6)

Fast acetylators (Filipinos): liver toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is succinylcholine used for?

A

Anesthesia

It induces prolonged apnea.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

T/F: Pseudocholinesterase deficiency is a form of pharmacologic variation.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the forms of pharmacokinetic variation?

A
  1. Pharmacogenetic variation
  2. Hepatic disease
  3. Renal disease
  4. Cardiac disease
  5. Thyroid disease
  6. Decreased plasma albumin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

T/F: Reduced clearance always results in increased adverse reactions.

A

False

Not if there’s compensatory excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the uses and side effects of theophylline?

A

Used for asthma

May cause hypotension and cardiac failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the uses and side effects of phenytoin?

A

Anti-convulsant

Can induce sedation and coma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the uses and side effects of warfarin?

A

Anti-coagulant

Causes more bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

T/F: When there is decreased plasma albumin, drugs with low Vd are affected.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

T/F: Warfarin, diazepam and salicylic acid are examples of protein-bound drugs.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the forms of pharmacodynamic variation?

A

Reduced blood clotting
Hepatic encephalopathy
Sodium and water retention
Altered fluid and electrolyte imbalance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

When there is reduced blood clotting due to liver disease, these drugs should be avoided or changed in terms of dosage.

A

Anticoagulants

Aspirin, phenylbutazone, indomethacin and paracetamol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

When there is hepatic encephalopathy, these drugs should be avoided.

A
Opiates
Narcotic analgesics
Barbiturates
Chlorpromazine
Short-acting benzos
Diuretics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

When there is sodium and water retention, these drugs should be avoided.

A

Corticosteroids
Carbenoxolone
Indomethacin
Antacids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

T/F: In cases of hypokalemia and hypercalcemia, cardiac glycoside effects are depressed.

A

False

Potentiated! In fact, this leads to heart failure.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What drug effects are reduced when there is hypokalemia?

A

Class 1 anti-arrythmic effects (lignocaine, quinidine and procainamide)

36
Q

What drug effects are prolonged when there is hypercalcemia?

A

Tubocurarine and succinylcholine

37
Q

Describe: Cyclosporine

A
  1. Predisposing factor for renal transplant
  2. Increases potassium by impairment of excretion
  3. Immunosuppressant needs to be taken for life
38
Q

When is the hypotensive effect of anti-hypertensives enhanced?

A

Fluid depletion

39
Q

T/F: Non dose-related ADRs are explained by immunology or pharmacogenetic variation.

A

True

40
Q

Non-dose related ADRs are described as Type B for?

A

Bizarre

41
Q

Drug allergy or hypersensitivity reactions are elicited by?

A

High MW proteins
Polypeptides
Dextrans

42
Q

Drug allergies occurs occur in what type of people?

A

Inherently atopic

Deficiency in MHC

43
Q

What anti-retroviral drug is involved in the abacavir hypersensitivity reaction?

A

HLA B57

44
Q

T/F: Drug allergies occur in incidental diseases.

A

True

45
Q

Describe: Type I Reaction

A

IgE-mediated

Rapid

46
Q

Give an example of a Type I reaction

A

Anaphylaxis from beta-lactam antibiotics

47
Q

Describe: Type II Reaction

A

Cytotoxic

48
Q

Give an example of a Type II reaction

A

Hemolytic anemia from penicillin

49
Q

Describe: Type III Reaction

A

Immune-complex

50
Q

Give an example of a Type III reaction

A

Serum-sickness from anti-thymocyte globulin

51
Q

Describe: Type IV Reaction

A

Delayed and cell-mediated

52
Q

Give an example of a Type IV reaction

A

Contact dermatitis from topical cell-antihistamine

53
Q

What is it called when a single drug can cause more than one type of reaction?

A

Cross reaction or cross sensitivity

54
Q

Give an example of specific T-cell activation

A

Morbilliform rash from sulfonamides

55
Q

Give an example of Fas/Fas-Ligand-induced

A

Steven-Johnson syndrome apoptosis; toxic epidermal necrolysis

56
Q

What family of molecules does the Fas ligand belong to?

A

Tumor necrosis factor (TNF)

57
Q

Give examples of other types of reactions under the Gell-Coombs Classification.

A

Drug-induced lupus-like syndrome

Anticonvulsant hypersensitivity syndrome

58
Q

What are the three different situations that can be identified based on the Gell-Coombs classification?

A

Pseudo-allergic reactions
Primarily antibody-mediated reactions
Cell-mediated reactions

59
Q

What is the time of onset of the different hypersensitivity classifications?

A

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)

60
Q

Differentiate Type IIA and Type IIB hypersensitivity reactions

A

Type IIA - cytotoxic

Type IIB - antibody-mediated cell stimulating

61
Q

T/F: Grave’s disease and chronic idiopathic urticaria are examples of Type II hypersensitivity reactions.

A

False

They’re Type III!

62
Q

Differentiate Types IVA - D

A

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

63
Q

Give examples of Type IVA - D hypersensitivity reactions

A

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

64
Q

T/F: Clinical features of allergic drug reactions have correlations with known properties of the drug.

A

False

65
Q

T/F: Allergy will only manifest on subsequent use of ciprofloxacin.

A

True

66
Q

T/F: Allergic drug reactions can occur at doses below therapeutic range.

A

True

67
Q

70% of patients with allergic rhinitis develop what?

A

Bronchial asthma

68
Q

What is the typical manifestation of a type I reaction?

A

Urticaria

69
Q

What is the most common dermatologic manifestation of a drug allergy?

A

Morbilliform rash

70
Q

What are the most common drug causes of morbilliform rashes?

A
Beta-lactam antibiotics (penicillins and cephalosporins)
Sulfonamide antibiotics
Allopurinol
Anti-epileptics
NSAIDs
71
Q

Type of rash caused by thiol and non-thiol-containing drugs (i.e. enalapril, cephalosporins and piroxicam)

A

Pemphigus

72
Q

Caused by oestrogen in oral contraceptive pills

A

Melasma

73
Q

Caused by omeprazole; can occur in bronchial passages and mucosal membranes

A

Angioedema

74
Q

What is the only dermatologic emergency where all mucous membranes are affected?

A

Steven-Johnson Syndrome

75
Q

Is contact dermatitis a manifestation of drug allergy?

A

No

76
Q

Is viral exanthem a manifestation of drug allergy?

A

No

Drug allergies usually manifest as patches on the skin.

77
Q

What are long term effects of drugs?

A
  1. Adaptive Changes

2. Rebound Phenomena

78
Q

Describe the adaptive changes of the body to beta-blockers

A

Development of tachyphylaxis and eventually tolerance when all receptors are blocked.

RECALL: Beta-blocker in heart decreases blood pressure and cardiac output

79
Q

Describe anti-hypertensives and rebound phenomena

A

There is extreme lowering then rising up again of blood pressure.

80
Q

What are delayed effects of drugs?

A
  1. Carcinogenesis

2. Effects on Reproduction

81
Q

Describe (1) carcinogenesis and anti-cancer drugs and (2) carcinogenesis and fertility drugs

A

(1) Anti-cancer drugs may produce a second cancer

(2) Ovulation induction drugs may cause ovarian cancer

82
Q

Enumerate delayed effects of drugs in connection with reproduction

A

Impaired fertility
Teratogenesis
Drugs in breast milk

83
Q

Enumerate common predisposing factors for immune and non-immune ADRs

A

Female gender
HIV
Systemic lupus erythematosus

84
Q

Enumerate generic drug reaction (non-immune) risk factors

A
Serious illness
Renal insufficiency
Liver disease
Polypharmacy
Herpes infection
Alcoholism
85
Q

Enumerate immune hypersensitivity drug reaction risk factors

A
Age (adult)
Concomitant viral infection
Previous hypersensitivity to chemically-related drug
Asthma
Use of beta-blockers
Specific genetic polymorphisms
86
Q

T/F: Myocarditis is a common adverse drug reaction to Cefaclor.

A

False

It’s very rare.