introduction

INTRODUCTION

Types of antagonist(Mechanisms of receptor antagonism)
1- Pharmacological A- Competitive. The antagonist reversibly competes or displaces the agonist from the receptor. Since occupancy by an antagonist produces no response, the action of the agonist is blocked. Higher concentrations of agonist, however, can overcome this competition and restore the full response.

Competitive antagonism : occurs when the agonist (A )and antagonist (I)compete for the same binding site on the receptor. Response curves for the agonist are shifted to the right in a concentration- related manner by the antagonist.

B-Non-CompetitiveThe antagonist changes the receptor to decrease the efficacy of the agonist or irreversibly blocks the agonist from combining with the receptor. If the antagonist binds to the same site as the agonist but irreversibly (slow dissociation but no covalent bond), it causes a shift of the dose–response curve to the right, with further depression of the maximal response.

* Competitive non competitive

1- antagonist binds with the same receptor as the agonist 2-antagonist resembles chemically with agonist 3-antagonist reduces affinity of agonist 4-intensity depend on conc. Of both agonist and antagonist 5-e.g. Ach - atropine
1- bind to another 2- not 3-antagonist reduces efficacy of agonist 4-intensity depend only on conc. Of antagonist 5- Aspirin with cyclooxygenase

2- Physiologic ANTAGONIST (functional antagonist ) A drug that binds to a non-related receptor, producing an effect opposite to that produced by the drug of interest. histamine induced bronchoconstriction, antagonist by epinephrine

Its intrinsic activity is = 1, but on another receptor

Glucocorticoid Hormones  Blood SugarInsulin  Blood Sugar


3- Chemical ANTAGONIST A chelater of similar agent that interacts directly with the drug being antagonized to remove it or prevent it from binding its receptor.
Heparin, an anticoagulant, acidicIf there is too much dose  bleeding and hemorrhagingProtamine sulfate is a base. It forms a stable inactive complex with heparin and inactivates it.

* synergism

Synergism in a Greek mean : work togetherWhen the action of one drug is facilitated or increased by the other It can be: 1- Additive e.g. aspirin + paracetamol drug A+ drug B = effect of A + effect of B 2- supra – additive (potentiation):the effect of combination is greater than individual effect e.g .adrenaline + cocaine (as a vasoconstrictor )Effect of drug A+B > effect of drug A or effect of drug B when given each drug alone

Drug Concentration

DOSE-RESPONSE CURVE
DOSE-EFFECT RELATIONSHIP
The intensity and duration of a drug’s effects. i:e relation of the drug dose , drug concentration and the effect.

Drug Concentration

Response
DOSE-RESPONSE CURVE
ED50
50% Effect
Maximal Effect
Effect or

Types of Dose-Effect (response)

Graded
Quantal
•Continuous scale (­dose ® ­effect)•Relates dose to intensity of effect •All-or-none pharmacologic effect••Relates dose to frequency of effect


Therapeutic index
Is the ratio of the dose that produce toxicity to the dose that produce effective response Therapeutic Index = LD 50 ED 50

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Affinity When a drug molecule moves so close to it is receptor by attractive force between them i:e (the drug binds to the receptor) Types of reaction between drug and receptor 1- noncovalent binding. 2- covalent binding. 3- hydrogen binding. 4- electron transfer 5- enzyme reaction - Efficacy of a drug refers to the maximal effect produced by a drug, it depend on the number of drug-receptor complexes formed.

Drug effects cont.

Potency of a drug is the dose of drug which required to produce response. Potency is influenced by absorption, distribution, biotransformation, excretion, and ability to combine with receptors. Or defined as the relative pharmacological activity of dose of drug compared with a dose of a different drug producing the same effect

Comparison of different drugs at the same dose to determine which is stronger

* Note: potency is related to affinity of drug to it is receptor , where as efficacy is related to the intrinsic activity of the drug once a drug-receptor complex is formed

Other Dose-related Terms

Maximal Effect: greatest response that can be produced by a drug, above which no further response can be created (sometimes called “peak effect”.Onset: how long time before a drug is able to exert a therapeutic effectDuration: how long a drug effect lasts.

Factors affecting the safety and effectiveness of drug

A-host related factor B-drug related factor


A-host related factor
1-biological variation include tolerance cross-tolerance Tolerance : is characterized by the need to increase the dose continually to achieve the desired effect due to decrease response by the time.

2- age (weight and surface area) In children Size of body are small Have lower albumin and renal blood flow Have lower GFR In old age - decrease in body weight - Low blood flow - Impaired hepatic function

3-bioavailability 4-allergy Is an immunological mediated adverse reaction to chemical resulting from previous sensitization to that chemical . Allergy not doses related because allergic reaction may result from exposure to relatively low doses .

5- Idiosyncrasy idiosyncratic response Some people has deficient in G 6 phosphate dehydrogenase so when taken antimalarial drug (primaquine) cause genetic abnormality and result hemolytic anemia . 6-Sex generally, men metabolize faster than women (ex: alcohol)

B-drug related factor

1-side effect 2-secondary effect 3-toxic effect 4-interaction with other drug

* Adverse drug effects

Is any undesirable effects of drug administration. Predictable (type A ):depend on pharmacological properties of drug ( include side effect, toxic effects and consequence of drug withdrawal) Unpredictable (type B):depend on patient (include allergy and idiosyncrasy)

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* Severity of adverse effects graded as:

Minor : no therapy Moderate:change the drug therapy Sever : need medical Rx Lethal : lead to death