Introduction to Pharmacology

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

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

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.

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.

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.

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.

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.

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

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

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

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

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

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

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

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

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

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.

Pharmacokinetics Quantitative, time dependent

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

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

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

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

Therapeutic index Therapeutic index=toxic dose/effective dose

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