DRUG INTERACTIONS

Types of Agonists

1. Full Agonists

-  If a drug binds to a receptor and produces a maximal response that mimics the response to the endogenous ligand.

2.Partial Agonists

-  Produces a partial response that mimics the response to the endogenous ligand.

3.Inverse Agonists 

-  Produce a response below the baseline response measured in the absence of drug. - Decreases the number of activated receptors.

 

Regulation of receptors:-

•       Continuous stimulation of receptors with agonists à Decrease number of receptors and decrease sensitivity   à    Down regulation. 

•       Continuous blocking of receptors with antagonists à Increase number of receptors and Increase sensitivity à                       Up regulation.

DOSE

-Def. The amount of drug given to the patient at a time.

-Types of dose :- 

ü  Therapeutic dose:                The average dose that produce therapeutic effect.

ü  Maximum tolerated dose:  The largest dose of a drug that can be taken safely.

ü  Initial dose:                            The dose used at start of treatment. 

ü  Maintenance dose:              The dose required to maintain the therapeutic effect.

ü  Lethal dose or Fetal dose:  The dose that produce death.

Therapeutic Index (TI):-

Def. It is the ratio of the dose that produces toxicity in half the population (TD50)  to the dose that produces a clinically desired or effective response in the half of population (ED50).

TI = TD50/ED50                                            

Therapeutic index used for Measure of drug safety.                                         

                                                                                                                                                                           

N.B: Quantal dose response curve gives information about differences in the sensitivity of individuals to increasing doses of drugs.

 

Standard margin of safety (SMS) 

• Def. = The ration of the dosage required to kill 1% of population compared to the dosage that is effective in 99% of population. 

The higher margin of safety the better and safer.

 

Factors affecting the dosage and action of the drug :-

1: Age, weight and body surface area:

 Adult dose (20 - 60 years of age) and weight about 70 kg.

-Elderly required small dose (due to decrease renal excretion and decrease hepatic metabolism). 

-Children required small dose (due to immature kidney and liver and decrease plasma protein).

 

2: Sex: 

Female need smaller dose than male due to :

a.High fat content à Increase fate in the body à Slow rate of oxidation decrease metabolism à Increase drug effect. 

b.Effect of sex hormone (Estrogen) on liver Microsomal enzyme (LME). * Some drug avoided during pregnancy, lactation and menstruation. 3: Routes of administration: • IV > IM > SC > Oral 3: Genetic abnormality.

 

 

 

 

4: Tolerance :-

Def. Failure of responsiveness to the usual dose. 

Types of tolerance: 

a.Congenital Tolerance .

b. Acquired Tolerance 

ü  Cross Tolerance: Between Nicotine and Lobeline (similar). 

ü  Tachyphylaxis  : rapidly diminishing response to successive doses of a drug, rendering it less       effective. e.g. Ephedrine Sudden increase blood Pressure then decrease (Gradually). 

ü  Bacterial resistance to antibiotics.

Mechanism of acquired tolerance (Drug desensitization)

Receptor Mediated	Non-Receptor Mediated
Reduction of receptor numbers. (Down-regulation of receptor)	Physiological adaptation Reduction of receptor-coupled signalling component. Change in kinetics of drugs.

 

 

Drug dependence:-

 It usually occurs with CNS acting drugs. 

It is a phenomena related to tolerance. 

It involves a certain degree of tissue adaptation. 

Withdrawal of the drug could produce certain unpleasant symptoms. Types of dependence:-

Habituation	Addiction
-                      Mild degree of drug dependence.  - Psychic dependence.  -When drug stopped develop some emotional distress for a relative short period.  -                      E.g. Smoking and Coffee.	More serious form of drug dependence. -                      Psychic and physical dependence.  -                      When drug stopped Withdrawal symptoms reverse the normal pharmacological action.  -E.g. Morphine and Heroin.

 

 

DRUG INTERACTIONS

A- Pharmacokinetics Interactions

B-Pharmacodynamics Interactions.

	Increase in drug effects
Addition (Summation) Algebraic sum of the 2 drug effect.  1+1 = 2               E.g. Acetylcholine + Histamine in contraction of intestine.	Potentiation - Drug which increase the effect of other drug.  0 +1 >1   E.g. Physostigmine +Acetylcholine	Synergism  - The combination effect more than algebraic sum .  1 + 1 > 2

 

 

Decrease in drug effect (Antagonism)
Chemical  antagonism   - Chemical interaction between 2 drugs decrease absorption. - E.g. Heparin + Protamine sulfate	Pharmacological antagonism - 2 drugs act on the same receptor but one of them is ü  Non-competitive ü  Competitive	Physiological (Functional) antagonism - 2 drugs act on 2 different receptors Different mechanism of action → Different effect.

 

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