1. Introduction to Pharmacology

2. Overview The aim of drug therapy Drug target tissue
Absorption Distribution Metabolism Elimination
The route of administration is determined by the properties of the drug and by the therapeutic objectives. Enteral and parenteral

4. enteral Oral: the most common route
Sublingual: allows the drug to diffuse into the capillary network
Rectal: Fifty percent of the drainage of the rectal region bypasses portal circulation

5. parenteral
Intravascular: IV injection is the most common route used for drugs that are not absorbed orally.
Intramuscular: can be aqueous solutions or specialized depot preparations
Subcutaneous: slower than the IV route and minimizes the risks associated with IV.

6. Other
Inhalation: provides the rapid delivery across the surface area of the mucous membranes of the respiratory tract.
Intranasal: desmopressin in the treatment of diabetes insipidus.
Intrathecal/intraventricular: to introduce drugs directly into the CSF.
Topical: the application is used when a local effect of the drug is desired.

8. Absorption of drugs
Absorption is the transfer of a drug from its site of administration to the blood stream.
The rate and efficiency of absorption depend on the route of administration.

9. Transport of drug from the GI tract
Passive diffusion: moves from a region of high concentration to one of lower concentration.
Active transport: involves specific carrier proteins. Energy-dependent. Against a concentration gradient.

10. Effect of pH on drug absorption
Weak acids or weak bases
HA H++A +
BH B+H+
the effective concentration of the permeable form of each drug at its absorption site is determined by the relative concentrations of the charged and uncharged forms.

12. Physical factors influencing absorption
Blood flow to the absorption site
Total surface area available for absorption
Contact time at the absorption surface

13. Bioavailability
Bioavailability is the fraction of administered drug that reaches the systemic circulation.
Bioavailability is determined by comparing plasma levels of a drug after a particular route of administration with plasma drug levels achieved by IV injection

15. Factors that influence bioavailability
First-pass hepatic metabolism
Solubility of drug
Chemical instability
Nature of the drug formulation

16. Drug distribution
Drug distribution is the process by which a drug reversibly leaves the blood stream and enters the cells of the tissues.

17. Depends on Binding of drugs to proteins Blood flow
Capillary permeability
capillary structure
drug structure
Binding of drugs to proteins

19. Volume of distribution
The volume of distribution (Vd) is a hypothetical volume of fluid into which the drug is disseminated.
A. water compartments in the body
1. Plasma compartment
2. Extracellular fluid
3. Total body water
4. other sites
B. the apparent volume of distribution

20. Determination of Vd Distribution of drug in the absence of elimination
Distribution of drug when elimination is present
Calculation of drug concentration if distribution were instantaneous

21. Binding of drugs to plasma proteins
Binding capacity of albumin
Competition for binding between drugs

22. Drug metabolism Kinetics of metabolism First-order kinetics
zero-order kinetics

24. Reaction of drug metabolism
Phase I: Phase I reaction function to convert lipophilic molecules into more polar molecules by introducing or unmasking a polar functional group
Phase II: This phase consists of conjugation reaction.

25. Pharmacokinetics
Quantitative, time dependent

26. Kinetics of intravenous infusion
With continous intravenous infusion, the rate of drug entry into the body is constant.
Steady-state drug levels in blood
Influence of the rate of drug infusion on the steady-state

27. Time required to reach the steady state drug concentration
Exponential approach to steady state
The sole determinant of the rate that a drug approaches steady state is the t1/2

29. Kinetics of fixed-dose,fixed time interval regimens
Single intravenous injection
Multiple intravenous injection

31. Dose-response quantitation
Drug receptor
Graded dose-respose
An agonist
Efficacy maximal response
ED50=drug dose that shows 50% of maximal response
Potency effective dose concentration

32. Therapeutic index
Therapeutic index=toxic dose/effective dose

33. Drug elimination Renal elimination of a drug glomerular filtraton
proximal tubular secretion
Distal tubular reabsorption