UNIT 3- Adverse Drug Reaction  

ADR:

 Adverse drug reactions (ADRs) are considered as one among the leading causes of morbidity and mortality 

 • The epidemiological importance of ADR is justified by its high prevalence rate since  

➢they cause from 3% to 6% of hospital admissions at any age, and up to 24% in the elderly population ➢they rank fifth among all causes of death 

➢they represent from 5 to 10% of hospital costs 21/09/2025 2 

• Every occasion when a patient is exposed to a medical product, is a unique situation and we can never be certain about what might happen. 

• A good example for this is thalidomide tragedy in late 1950s and 1960s. 

• Thalidomide prescribed as a safe hypnotic to many thousands of pregnant women caused severe form of limb abnormality known as phocomelia in many of the babies born to those women. 

• WHO defines ADR as ‘Any response to a drug which is noxious and unintended, and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function’. 

• serious adverse event (events relating to drugs or devices) as one in which “the patient outcome is death, life-threatening (real risk of dying), hospitalization (initial or prolonged), disability (significant, persistent, or permanent), congenital anomaly, or required intervention to prevent permanent impairment or damage.

Classification of ADRs 

Rawlins-Thompson classification 

 • Divides ADRs into two main groups 

 • Type A and Type B 

 • Type A ➢Normal, but quantitatively exaggerated, pharmacological effects of a drug 

 ➢ADRs caused by the antimuscarinic activity of tricyclic antidepressants. 

 ➢Type A reactions are most common, accounting for 80% of reactions. 

• Type B 

 ➢Type B reactions are qualitatively abnormal effects, which appear unrelated to the drug's normal pharmacology 

 ➢Example: hepatoxicity from isoniazid. 

 ➢They are more serious in nature, more likely to cause deaths, and are often not discovered until after a drug has been marketed. 

 • The Rawlins–Thompson classification has undergone further elaboration over the years to take account of ADRs that do not fit within the existing classifications

DoTS system 

 • DoTS system is based on Dose relatedness, Timing and patient Susceptibility 
 • In contrast to Rawlins–Thompson classification, which is defined only by the properties of the drug and the reaction, the DoTS classification provides a useful template to examine the various factors that both describe a reaction and influence an individual patient's susceptibility.  

1. Dose Related 

 • DoTS first considers the dose of the drug, as many adverse effects are clearly related to the dose of the drug used. 
 • For example, increasing the dose of a cardiac glycoside will increase the risk of digitalis toxicity. 
In DoTS, reactions are divided into 
➢Toxic effects (effects related to the use of drugs outside of their usual therapeutic dosage), ➢Collateral effects (effects occurring within the normal therapeutic use of the drug) and 
➢Hyper-susceptibility reactions (reactions occurring in sub-therapeutic doses in susceptible patients). 
• Collateral effects include reactions not related to the expected pharmacological effect of the drug or off-target reactions of the expected therapeutic effect in other body systems. 
• It is worth noting that approximately 20% of newly marketed drugs have their dosage recommendations reduced after marketing, often due to drug toxicity. 
• The time course of a drug's presence at the site of action can influence the likelihood of an ADR occurring. 
• For example, rapid infusion of furosemide is associated with transient hearing loss and tinnitus, and a constant low dose of methotrexate is more toxic than equivalent intermittent bolus doses