INTRODUCTION TO PHARMACOLOGY

SAMUEL AGUAZIM ( MD)

WHAT IS PHARMACOLOGY?

The study of the interaction between chemicals and living systems

Pharmacology is the science that deals with the study of therapeutic agents.

What is drug?

A drug is broadly defined as any chemical agent that affects biologic systems

What is Pharmacology ?

Pharmacology

Pharmacokinetics Pharmacodynamics

What the body does to drug What the drug does to body

Pharmacotherapeutics Pharmacocognosy

The study of the use of drugs Identifying crude materials as drugsToxicology

Four Major subdivisions of Pharmacology

Pharmacokinetics- describes “ what the body does to the drug.” this includes topics such as absorption, distribution, metabolism and excretion of drugs.

Pharmacodynamics- describes “ what the drug does to the body.” specifically, it deals with the biochemical and physiological effects of drugs and their mechanisms of action

Pharmacotherapeutics- describes the use of drugs for the prevention, diagnosis and treatment of disease.

Toxicology- describes the undesirable effects of therapeutic agents, poisons and pollutants on biologic systems

Pharmacokinetics

Pharmacokinetics describes actions of the body on drugs, including the principles of drug absorption, distribution, biotransformation (metabolism) and excretion

Absorption

Absorption is the rate at which and extent to which a drug moves form its site of administration

What does the rate and efficacy of absorption depend on?

Route of administration- the intravenous route is most effective.

Blood flow- highly vascularized organs such as the small intestine have the greatest absorbing ability

Surface area available- absorption of a drug is directly proportional to the surface area available

Solubility of a drug- the ratio of hydrophilic to lipophilic properties that a drug has will determine whether the drug can permeate cell membranes

Drugs-drugs interaction- when given in combination, drugs can either enhance or inhibit one another’s absorption.

pH- a drug’s acidity or alkalinity affects its charge which affects absorption

How does the pH of a drug affect its charge?

Many drugs are either weak acids or weak bases. Acidic drugs are uncharged when protonated while

Basic drugs are charged when protonated

How does charge affect a drug’s ability to permeate a cell membrane

Generally, a drug will pass through cell membranes more easily if it is uncharged. Therefore, the amount of drug absorbed depends upon its ration of charged to uncharged species, which is determined by the ambient pH at the site of administration and the pKa(negative log of dissociation constant) of the drug

Define biovailability.

The fraction of administered drug that gains access to its site of action or a biologic fluid that allows access to the site of action.

Bioavailability

What is the bioavailability of an intravenously injected drug?

100%- because all of the drug enters the systemic circulation

what is the bioavailability of any drug that is not intravascularly injected?

Less than 100%- because some of the drug may not be absorbed or it may become inactivated.

Factors Affect Bioavailability

1. first pass hepatic metabolism 2. all of the factors that affect

absorption (i.e., blood flow, drug solubility, drug-drug interactions, route of administration)

Routes of Drug Delivery

Parenteral(IV)

Inhaled

Oral

Transdermal

Rectal

TopicalParenteral(SC, IM)

Routes of drug administration

Alimentary Parenteral Inhalation Topical Transdermal subcutaneous

Four types of alimentary routes

Oral-commonest routeAdvantages: convenience/patient

compliance and the utilization of the small intestine, which is specialized for absorption because of its large surface area.

Buccal( between gum and cheeks).Advantages: allows direct

absorption into the venous circulation

Sublingual( under the tongue) Nitroglycerin is often given by this

route.Advantage: allows the drug to drain

into the superior vena cava, thus bypassing hepatic first-pass metabolism

Rectal (suppository)-useful when the oral route is unavailable due to vomiting or loss of consciousness:

Advantages: approximately 50% of drug absorbed from the rectum will bypass the liver

Four Parenteral routes of administration and state the advantage of each

1. intravenous- direct injection into the vascular system.

Advantage: most rapid and potent mode of administration, because 100% of drugs enters circulation

Intramuscular Advantages: usually more rapid and

complete absorption than with oral administration.

Minimizes hazards of intravascular injection

Location important Deltoid - rapid Thigh - moderate Buttocks - slowest Difference in blood supply & distance

Subcutaneous-under skinAdvantages: same as intramuscular

Intrathecal- under sheath of nerve fibers, spinal cord, or brain

Advantage: in cases of acute CNS infections or spinal anesthesia, drugs can be more effective if injected directly into the spinal subarachnoid space.

Inhalation drugs

What category of drugs is commonly administered by inhalation?

Answer: pulmonary agents How are inhaled drugs administered? By machine aerosolization or

vaporization

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Topical drugs

When is topical administration used?

Usually for treatment of localized disease( e.g psoriasis, acne, eye infections)

When is transdermal administration used?

For sustained release of a drug- for example nicotine patches.

Distribution

Is define as the process by which a drugs leaves the bloodstream and enters the interstitium or the cells of the tissue

Three Biochemical mechanism of drugs absorption into cells

1. Passive diffusion: it is the most common mode of drug transport which makes a drug move from higher concentration to one of low concentration

2. Transport by special carrier proteins-

3. Active transport. The energy for this mechanism comes from dephosphorylation of adenosine triphosphosphate

What does distribution depend upon?

Blood flow Capillary permeability- the structure of

capillaries varies depending on the organ. E.g. in the brain the junction between cells is very tight. In the liver and spleen, the junction between endothelial cells is wide. Which allows large molecules to pass through.

Binding to plasma proteins such as albumin- this will limit access to cellular compartments

Drug structure- small lipophilic molecules will be able to distribute to more compartments than will large polar molecules

BIOTRANSFORMATION

Why does the body biotransform drugs?

The lipophilic properties of drugs that allow them to pass through the cell membranes hinder elimination. Therefore, drugs are modified to become more polar so that elimination can occur more quickly.

Two main modification occur in biotransformation:

Phase 1: oxidation, reduction(dehydrogenation) and hydrolysis

occur in endoplasmic reticulum Phase 2: formation of a covalent linkage

between functional groups on the parent drug and another substrate(i.e glucuronate, acetic acid, glutathione and sulfate)

Occur in cytosol they both occur in the LIVER

FACTORS THAT AFFECT DRUG BIOTRANSFORMATION

Genetic differences Induction of the cytochrome P-

450( increase biotransformation) Inhibition of the cutochrome P-

450 system Disease of the liver Age and gender

Are the rates for drug biotransformation predictable

Yes. In general, drugs will be inactivated or biotransformed according to one of two general chemistry principle.

First order kinetics Zero-order kinetics

FIRST ORDER KINETICS

Process by which a constant percentage of substrate is metabolized per unit time.

The higher the concentration of drug, the greater the absolute amount of drug biotransformed or excreted per unit of time

ZERO-ORDER KINETICS

Process by which a constant amount of drug is metabolized per unit of time regardless of the drug concentration.

Alcohol is metabolized according to zero order kinetics.

EXCRETION

Is define as the process by which a drug or metabolite is removed from the body

What is the difference between excretion and secretion

Excretion is the removal of a drug from the body

Secretion occurs when the drug is actively transported from one compartment into another.

( for example: drugs are secreted into the renal tubule from the medullary capillaries)

Major routes of excretion Renal- urine is one of the most

common routes of elimination Fecal Respiration- primarily for anesthetic

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