Lecture 13

Question 1

Explain the types of ADRs

Answer 1

Type A (Augmented Dose related)
* Approximately 80% of ADRs→a consequence of the drug’s primary pharmacological effect (e.g., bleeding from warfarin) or low therapeutic index (nausea from digoxin) 

* Type A ADRs are predictable. 

* Dose-related and usually mild, may be serious or even fatal (e.g., intracranial bleeding from warfarin) 
→usually due to inappropriate dosage, especially when drug elimination is impaired 

* The term “side effects” is often applied to minor type A reactions. 


Type B (Bizarre non dose related)
* The reactions are not predictable from the drug’s main pharmacological action. 

* Not dose-related and are severe, with a considerable mortality 

* The underlying pathophysiology is poor→often has a genetic or immunological basis 

* The reactions occur infrequently (1:1,000-1:10,000 treated subjects being typical). 


Type C (Dose- and Time-Related)
* Continuous reactions (chronic) due to long-term drug use 

* E.g., neuroleptic-related tardive dyskinesia or analgesic nephropathy 



Type D (Time-Related)
* Delayed reactions 

* E.g., alkylating agents leading to carcinogenesis or retinoid-associated 
teratogenesis 


Type E 

* * End-of-use reactions
* E.g. a. Adrenocortical insufficiency following withdrawal of glucocorticosteroids

Question 2

DoTs Classifications

Answer 2

Dose-relatedness 

a. Supratherapeutic reactions

→occur at doses higher than recommended 

b. Collateral reactions

→occur at the recommended dose

c. Hypersensitivity reactions

→occur at lower doses than recommended

Time-relatedness
a. Fast reaction
→red man syndrome with vancomycin→pruritus and an erythematous
rash in the face, neck and thorax b. The first dose
→postural hypotension after administration of an ACE inhibitor c. Early→nitrate-induced headache
d. Intermediate→type II, III and IV hypersensitivity reactions
e. Late→typical antipsychotic-induced tardive dyskinesia
f. Delayed
→adenocarcinoma of the vagina associated with exposure in utero to diethylstilbestrol

Susceptibility
a. Genetic→e.g., patient bleeding with CYP2C9 polymorphism
b. Age→e.g., paediatric and older population
c. Gender→e.g., lupus erythematosus induced by drugs (more common in women)
d. Exogenous factor→e.g., drug interactions
e. Disease→e.g., hepatic or renal disease

Question 3

Prevention from Adverse effects

Answer 3

1. Identify the subgroup of patients who are likely to be susceptible to the adverse effect and modify the treatment choice accordingly

• Patients’ medication history will identify any previous ADRs and therefore preclude re-exposure to the drug
• Susceptibility factors→age, gender, pregnancy status and ethnicity can help predict the risk of ADR occurring
• Pharmacogenomic data?

2. Treatment plan mitigates any possible adverse effects
   * Prudent and safe prescribing is key to reducing errors that can contribute to ADRs
   * Prescribe two drugs to mitigate the ADRs that could be caused by one of the drugs

Question 4

The types of allergic reaction can be divided into

Answer 4

a. Type I: IgE-mediated drug hypersensitivity
* It is due to the production of reaginic (IgE) antibodies to an antigen.


b. Type II: IgG-mediated cytotoxicity
* It is due to antibodies of class IgG (predominating) and IgM


c. Type III: Immune-complex arthur reactions 

* Circulating immune complexes can produce several clinical allergic states

d. Type IV: T-cell-mediated drug hypersensitivity 

* The classical example of this reaction is contact dermatitis (e.g., topical antibiotics→penicillin and neomycin)

Question 5

Prevention of Allergic Adverse Drug Reactions

Answer 5

1. Taking a detailed drug history
   →prescription and over-the-counter drugs, drugs of abuse, nutritional and vitamin supplements and
   alternative remedies
2. Drugs given orally are less likely to cause severe ADRs than those given by injection.
3. Desensitisation (hyposensitisation)→applies only when continued use of the drug is essential
4. Prophylactic skin testing→not usually practicable, and a negative test does not exclude the possibility of an allergic reaction

Question 6

Examples of other allergic reactions other than ADRs

Answer 6

1. Rashes (Antimicrobial agents)
2. Lymphadenopathy (Phenytoin)
3. Blood Dyscrasias; Thrombocytopenia, anaemia (Heparin)
4. Systematic Lupus Erythematosus (Hydralazine)
5. Vasculitis (Acute = penicillins; Chronic = phenytoin)
6. Renal Dysfunction (penicillamine)