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Summary of Incompatibility :-

Definition - Incompatibility refers to interactions between two or more substances which lead to changes in chemical, physical, therapeutic properties of the pharmaceutical dosage form.

Classification of Incompatibilities :-
  1. Therapeutic Incompatibilities
  2. Physical Incompatibilities
  3. Chemical Incompatibilities

1. Therapeutic Incompatibility - It  is the modification of the therapeutic effect of one drug by the prior concomitant administration of another. It is also called drug interactions .  

Mechanisms - It divided into two groups :- 
  1. Pharmacokinetics Involve the effect of a drug on another from the point of view that includes absorption, distribution, metabolism and excretion.
  2. Pharmacodynamics  Are  related  to  the  pharmacological  activity  of  the  inter acting drugs. E.g.: synergism, antagonism, altered cellular transport, effect on the receptor site

Pharmacokinetic Interactions :- 
  • Altered GIT absorption  
  • Displaced protein binding  
  • Altered metabolism  
  • Altered renal execration  

  1. Altered GIT Absorption
    1. Altered pH  
    2. Altered bacterial flora  
    3. Formation of drug chelates or complexes  
    4. Drug induced mucosal damage and altered GIT motility  

A. Altered pH - non-ionized form of a drug is more lipid soluble and more readily absorbed from GIT than the ionized form does. 

B. Altered Intestinal Bacterial Flora - Eg : In 10% 0f patients receive digoxin:40% or more of the administered dose is metabolized by the intestinal flora. 

2. Displaced Protein Binding - It depends on  the  affinity of the  drug to plasma protein. The  most  likely bound  drugs  is  capable  to  displace  others.  The  free  drug  is  increased  by displacement by another drug with higher affinity.

3. Altered metabolism - The effect of one drug on the metabolism of the other is well documented. The liver is the major site of drug metabolism but other organs can also do.  
E.g.: WBC, skin, lung and GIT. CYP450 family is the major metabolizing enzyme in phase-I (oxidation process).

  • Additive Effect - Occurs when two or more drugs having the same effect are combined and the result is the sum of the individual effects relative to the doses used. This additive effect may be beneficial or harmful to the patients.  
  • Synergistic effect - Occurs when two or more drugs, with or without the same overt effect, are used together to yield a combined effect that has  an outcome greater than the  sum of the  single-drugs active components alone.