Adverse Drug Reactions

Predictable (Type A or Augmented) reactions ⁃ Augmented pharmacological properties of the drug 

 • These are common, dose related and mostly preventable & reversible  

Side effects: 

 • Unwanted often unavoidable Pharmacodynamic effects 

 ⁃ Predicted from the pharmacological profile of a drug

 ⁃ Reduction in dose, usually ameliorates the symptoms

 ⁃ e.g. atropine used as preanaesthetic medication for its antisecretory action. Produces dryness of mouth as a side effect. 

 -e.g. Promethazine antiallergic medication produces sedation, unrelated to its action   

Effect may be therapeutic in one context &  side effect in another context,  

e.g.Codeine used for cough produces  constipation as a side Effect, but the latter is its  therapeutic effect in Traveller's diarrhea  

⁃ Digoxin: Depression of A-V conduction,  desired in atrial fibrillation, but the same may  be undesirable When it is used for CHF  

 2. Secondary effects  ◦ Indirect consequences of a primary action of  the drug  

e.g.  1. Suppression of bacterial flora by tetracyclines  paves the way for superinfections;  

2. Corticosteroids weaken host defence  mechanisms so that latent tuberculosis gets  activated .

3. Toxic effects ⁃ Occurs as a result of excessive pharmacological action of the drug due to overdose or prolonged use. 

 ⁃ Clinical manifestations are predictable and dose related 

 Either due to functional alteration (high dose of atropine causing delirium) or ⁃ Drug induced tissue damage(hepatic necrosis from paracetamol overdosage)  

⁃ Extension of the therapeutic effect itself 

 e.g- Coma by barbiturates, Complete A-V block by Digoxin, Bleeding due to heparin 

Unexpected Undesirable Effects (TYPE-B) ADRs  

Arise unexpectedly even at therapeutic doses, mechanism not related to the main pharmacological effect of the drug, 

⁃ Either immunologically mediated reaction to the drug ⁃ Pharmacogenetically mediated adverse reaction or idiosyncratic reaction  

⁃ These are grouped as unpredictable reaction as no linear relationship with drug doses exists 

⁃ These are relatively uncommon but if occur, mortality rates are high. 

⁃ Reduction in dose does not reduce the risk of type B ADRS  

Drug allergy (hypersensitivity) 

◦ An immunologically mediated reaction producing symptoms unrelated to the pharmacodynamic profile of the drug ◦ symptoms may appear even with smaller doses ◦ This is also called drug hypersensitivity 

 ◦ target organs affected include; skin, airways, blood vessels, blood cells and gastrointestinal tract  

Mechanism and types of allergic reactions 

◦ Type-l (anaphylactic) reactions: 

 ⁃ (IgE) are produced which get fixed to the mast cells and basophils 

 ⁃ On exposure to the drug, ag: ab reaction takes place on the mast cell surface ⁃ Release mediators like histamine, 5-ht, leukotrienes prostaglandins, paf, etc. 

 ⁃ Manifest as urticaria, itching, angioedema, bronchospasm, rhinitis or anaphylactic shock. 

 ⁃ Need immediate intervention  

Usually with Penicillin group of drugs.

haptin ?