Interactions between Two Drugs

? Additive effect: 1+1=2
? Synergistic effect: 1+1>2
? Antagonistic effect: 1+1<2
? Incompatibility & Indifference
Type of Antagonism According to Kinetics
Competitive Antagonism:
1. Reversible Antagonism
2. Irreversible Antagonism
Non Competitive Antagonism



DR/RT= [D]/[D]+Kd=Effect/Max. Effect
? k1
? D + R <======> DR
? k2
? By Law of Mass Action: [D]•[R]•K1= [DR]•K2
? Therefore K2 /K1= Kd = [D]•[R]/[DR]
? If RT = total # of receptors, then
? RT = [R] + [DR]
? Replace [R] by (RT-[DR]) and rearrange:
? Affinity: Ability of a drug to bind it receptor.
? Efficacy
? Degree to which a drug is able to produce the desired response. (measure to Emax.)


Potency
Amount of drug required to produce 50% of the maximal response of the drug effect. Used to compare compounds within

classes of drugs. Measure of the dose.





Effective Concentration 50% (ED50)
Concentration of the drug which induces a specified clinical effect in 50% of subjects


Lethal Dose 50% (LD50): Concentration of the drug which induces death in 50% of subjects.
Therapeutic Index
Measure of the safety of a drug: Ti Calculation: LD50/ED50
Margin of Safety
Margin between the therapeutic and lethal doses of a drug.
The lowest toxic dose(LD1)/ The maximal effective dose (ED99)
Dose-Response Relationship
Drug induced responses are not an “all or none” phenomenon
Increase in dose may:
Increase therapeutic response
Increase risk of toxicity
Tolerance:
Decreased sensitivity to a drug.
Tacchyphylaxis:
Rapidly developed tolerance.
Idiosynecracy:
Abnormal response to drug action.
Iatrogenic diseases:
Drug induced diseases. Physician induced diseases.
Side Effects: An avoidable unwanted secondary drug effects.




It is an endogenous property of the drug. Some times drugs are used because of their side effects. It could be related to the

usual drug effect. E.g. atropine has anticholinergic antispasmodic effect but because of its anticholinergic effect it can

produce Xerostomia (dryness of the mouth). It could be not related to the usual drug effect. E.g. Minoxidil a vasodilator can

induce hair growth, corticosteroids can induce hyperlipedmia.
Toxic effects:
Unwanted but avoidable adverse effect of a drug. It is determined by the dose. It has a wide spectrum from simple allergic

reactions to mutagenesis, carcinogenesis and teratogenesis during pregnancy.