Combined drugs can have additive, supraadditive, or antagonistic effects. Additive effects occur when two drugs act in the same direction and their individual effects are added together without increasing side effects. Supraadditive effects happen when the combination is greater than the sum of the individual effects, such as when one drug inhibits the breakdown or metabolism of another. Antagonism occurs when one drug decreases or abolishes the effects of another drug through physical, chemical, physiological, or receptor-based mechanisms. Antagonism can be competitive or non-competitive depending on whether the drugs bind to the same receptor site.

1. Combined effect of drugs
Dr Harikrishnan A R

2. Synergism
• Action of one drug facilitated/increased by another
• Both drugs may have action in the same direction or one drug maybe
inactive when given alone
• Additive and Supraadditive

3. Additive
• Effect of two drugs adds up in the same direction
• Side effects do not add up
• Combination is better tolerated than higher dose of one compound
• Aspirin + Paracetamol  analgesic/antipyretic
• Nitrous oxide + Halothane  general anaesthetic
• Amlodipine + atenolol  antihypertensive

4. Supraadditive
• Effect of combination is greater than individual effect added
• One component inactive when given alone
• Acetyl choline + Physostigmine  inhibition of breakdown
• Levodopa + Carbidopa  inhibition of peripheral metabolism
• Adrenaline + Cocaine  inhibition of neuronal uptake

5. Antagonism
• One drug decreases or abolishes the action of another
• One drug is inactive which decreases the effect of another
• Physical , chemical, physiological, receptor

6. Physical
• Based on physical property of the drugs
• Charcoal adsorbs alkaloids and prevent their absorption

7. Chemical
• Two drugs chemically react to form an inactive product
• KMnO4 oxidizes alkaloids
• Tannins + alkaloids  insoluble alkaloidal tannate is formed
• Chelating agents  BAL, Calcium disodium edetate

8. Physiological/functional
• 2 drugs acts on different receptors or different mechanism but have
opposite effect on same physiological function
• Histamine and adrenaline on bronchial muscles and BP
• Hydrochlorthiazide and amiloride on urinary potassium excretion
• Glucagon and insulin on blood sugar level

9. Receptor antagonism
• One drug blocks the receptor action of another
• They are selective
• Anticholinergic only opposes the intestinal contraction by cholinergic
agonists but not of histamine or 5-HT
• Competitive and non competitive

10. Competitive
• Equilibrium type
• Antagonist chemically similar to agonist
• Binds to the same site
• Antagonist have affinity but no intrinsic activity
• Higher concentration of agonist progressively overcomes the block
• Parallel shift of DRC

12. Non competitive
• Chemically unrelated to agonist
• Binds to different site  allosteric site
• Allosteric antagonism
• Receptor is unable to transduce the response
• No competition
• Even at high doses agonist is unable to reverse the block
• Experimentally produced

14. Non equilibrium antagonism
• Antagonist binds with strong bonds
• Agonists are unable to reduce the receptor occupancy of antagonist
• Flattening of agonist DRC
• Phenoxybenzamine  adrenaline @ α receptor

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