Pharmacokinetic parameters & Pharmacodynamics

Pharmacokinetic parameters

1) Bioavailability :-

Def. The amount of administered drug that reaches the systemic circulation.

Oral bioavailability (F) = AUCOral /AUCIV X 100

AUC = Area under curve

> Factors affecting bioavailability:-

• First pass effect  Decrease bioavailability.

• Physicochemical properties of the drug. (Polarity – solubility – Particle size)

 Nature of formulation. (Solution > Suspension > Tablet)

2) Plasma half-life (t1/2) :-

Def. Time needed by the body to decrease a plasma concentration of drug to its half.

(It depend on clearance and Vd)

3) Clearance (Cl) :-

Def. - It is volume of plasma cleared from the drug per unit time (ml/min).

Cl total = Cl hepatic + Cl Renal + CI Pulmonary + Cl others

4) Elimination Kinetics:-

Zero-order elimination First-order elimination

Def. - Elimination of the drug which is

independently of the drug conc.

For example: 1.2 mg are climinated-

every hour.

Elimination of the drug which is

dependently of the drug conc.

For example: increase drug conc. lead

to increase rate of drug elimination.

Elimination

rate

Elimination rate saturates with higher

drug concentration.

Elimination rate is proportional to

drug concentration.

term Non-linear (Saturation) Elimination Linear Elimination

Curve

Log c

time

log c

Example A few substances are eliminated by

zero-order elimination kinetics

- 95% of the drugs in use at

therapeutic concentrations are

eliminated by first order climination

kinetics.

time

Pharmacodynamics

Def. What the drug does to the body (Mechanism of action of drugs).

Drug-Receptor interactions

D+R=DR

D=Drug R=Receptor DR = Drug-Receptor complex

-Biological effect increase when the drug receptor complex increases.

What is a Receptor?

Any biological molecule to which a drug binds and produces response.

Drug or any substance (activate or inactivate receptor) called Ligand.

Major classes of receptors:-

1_Ligand-gated and voltage-gated ion channels ( E.g. cholinergic nicotinic receptors)

2_G-protein-coupled receptors

3_Enzyme linked (Tyrosine kinase-linked) receptors (E.g. insulin receptors)

4_Intracellular receptors (e.g. Steroid receptors)

G-protein-coupled receptors (GPCRS)

G-protein and second messengers:-

• G-protein → Protein located in the cytoplasm between receptor and cell.

Main types:

I. Gs (Stimulatory):- Activate adenylate cyclase  Increase cyclic adenosine monophosphate

(cAMP) that activate protein kinasethen open Calcium channels and Increase Ca* influx

from sarcoplasmic reticulum (SR).

II. Gi (Inhibitory) :- Inactivate adenylate cyclase  Decrease cAMP  Decrease Calcium

influx.

III. Gq (Stimulatory):- Increase phospholipase-C (PLC)  PLC break phosphatidylinositol

bisphosphate (PIP2) into Inositol triphosphate (IP3) and Diacylglycerol (DAG)  IP3 increase

Calcium influx.

Ligand-receptor interaction (Lock and key theory) :-

What is a Ligand? Any substance combines with receptor.

Types of Ligand:-

• Ligand has affinity and efficacy to Receptor  Agonist

• Ligand has affinity and not have efficacy to Receptor  Antagonist or Blocker

Dose Response Curve:

Emax: maximum response) effect ) produced by the lowest dose.

ED50: The conc. of drug producing 50% of the maximum effect. Usually used to determine potency.

Potency:-

 Potency is a measure of the amount of drug necessary to produce an effect of a given

magnitude.

 Drug A is more potent than Drug B, because a lesser amount of Drug A is needed when

compared to Drug B to obtain 50% effect.

Efficacy:-

 Efficacy is the magnitude response a drug causes when it interacts with a receptor.

 Drug A is more potent than Drug B, but both show the same efficacy. Drug C shows lower

potency and lower efficacy than Drugs A and B.

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