Introduction

PHARMACOLOGY

INTRODUCTION Lecture one

Introduction

What is pharmacology? Why do we need to take pharmacology? Significance of pharmacology to Dentistry

History of Pharmacology

worldwide, and remains an important drug today. (Interestingly, it was not until 1971 that Sir John Vane discovered the mechanism of action of aspirin, a feat that earned him the 1981 Nobel Prize for Medicine.)

Pharmacology

DEFINITIONS: Pharmacology : is the science dealing with interactions between chemicals ( drugs ) and living systems. pharmakol : medicine Logia: study

DEFINITIONS:

Drug: chemical substances that, when introduced into the body, alters the body's function by interactions at the molecular level.Prodrug: a chemical that is readily absorbed and distributed and then converted to the active drug by biologic processes—inside the body.


DEFINITIONS:
Medical pharmacology : is the science of materials used to prevent, diagnose, and treat disease. Toxicology : IS that branch of pharmacology that deals with the undesirable effects of chemicals in biological system.

DEFINITIONS:

Pharmacogenomics (or pharmacogenetics) is the study of the genetic variations that cause individual differences in drug response. Responses that are not found in the general population, such as general toxic effects, allergies, or side effects, but due to an inherited trait that produces a diminished or enhanced response to a drug. Differences in Enzyme Activity Acetylation polymorphism Butylcholinesterase alterations Cytochrome P450 aberration

General Concepts

Drug Dose Administration
Drug Effect or Response
Pharmaceutical
Pharmacokinetics
Pharmacodynamics
Pharmacotherapeutics
Disintegration of Drug
Absorption/distribution metabolism/excretion
Drug/Receptor Interaction

Pharmaceutical Phase

-describes the stage during which the medication enters the body in one form and changes into another form to be utilized.


Pharmacokinetics
Is what the body does to the drug. The magnitud of the pharmacological effect of a drug depends on its concentration at the site of action. Absorption Distribution Metabolism Elimination

Pharmacodynamics

Is what the drug does to the body. Interaction of drugs with cellular proteins, such as receptors or enzymes, to control changes in physiological function of particular organs. Drug-Receptor Interactions Binding Dose-Response Effect Signal Transduction Mechanism of action, Pathways

Drugs

Drugs can be defined as chemical agents that uniquely interact with specific target molecules in the body, thereby producing a biological effect. Drugs can be stimulatory or inhibitory

How are Drugs Administered?

Routes of Drug Delivery
Parenteral (IV)
Inhaled
Oral
Transdermal
Rectal
Topical
Parenteral (SC, IM)

Routes of Administration

ENTERAL(GI route) ORAL- most absorbed from small intestine. Pay close attention to presence or absence of food or antacid. Rectal - highly vascular-at times excellent site absorbs quickly. Sublingual- are valuable in administering drugs subject to a high degree of first-pass Metabolism.

Routes of Administration

Parenteral route: IV, IM, SC most common IV provides immediate availability IM/SC-must rely on vascular system perfusion to site to be absorbed-if poor circulation use cautiously

The ROA is determined by the physical characteristics of the drug, the speed which the drug is absorbed and/ or released, as well as the need to bypass hepatic metabolism and achieve high conc. at particular sites
Important Info

No single method of drug administration is ideal for all drugs in all circumstances

Very Important Info!

What Happens After Drug Administration?

Drug at site of administration
Drug in plasma
Drug/metabolites in urine, feces, bile
Drug/metabolites in tissues
1. Absorption
2. Distribution
4. Elimination
3. Metabolism

We are now talking about … Pharmacokinetics

Drug Absorption
Absorption: is the process by which a drug enters the bloodstream without being chemically altered or The movement of a drug from its site of application into the blood or lymphatic system

Introduction

Steps in appearance of intact drug in circulation

pH = 1 - 3

pH = 5 - 7
disintegration
disintegration
disso- lution
disso- lution
absorption
intestinal metabolism
absorption
hepatic metabolism
clearance
faeces
Pharmacological effect
gastric emptying rate
intestinal transit rate

Schematic diagram of an absorption membrane

Lattice of protein
Lattice of protein
Inner lipoidal matrix
Aqueous pores
Hydrophilic tail
Hydrophobic head

Mechanisms for drug transport across membranes

Pharmacokinetics
I. Absorption A. Passive (simple) diffusion 1. Rate of transfer of substances are directly proportional to the concentration gradient on both sides of the membrane 2. Rapid for lipophilic, nonionic, small molecules 3. No energy or carrier required

Mechanisms of transport across the GIT/blood barrier

A- Passive diffusion
Drug in solution
GIT fluid
GIT membrane
Blood
Drug in solution carried away by blood
h
K1
K2
D
(unionized concentration)

Pharmacokinetics

B. Pore transport (Aqueous channels) 1. Small hydrophilic drugs (<200 MW) diffuse along conc gradient by passing through pores (aqueous channels) 2. No energy required

B_ Pore transport

Intestinal lumen
Apical cell membrane
Cell interior
Drug
Drug
Examples: water, urea, low weight sugars, organic electrolytes, etc.
High concentration
Lower concentration

Pharmacokinetics

C. Facilitated diffusion – drugs bind to carrier noncovalently.No energy is required

Facilitated transport

Intestinal lumen
Apical cell membrane
Cell interior
Drug
Drug + Carrier
Carrier
Drug
Carrier
Carrier
Examples: thymine etc.
High concentration
Lower concentration

Pharmacokinetics

D. Active transport – identical to facilitated diffusion except that ATP (energy) powers drug transport against conc gradient

Active transport

Intestinal lumen
Apical cell membrane
Cell interior
Drug
Drug + Carrier
Carrier
Drug
Carrier
Carrier
Examples: 5-fluorouracil, levodopa, riboflavine, body nutrients, l - amino acids, thiamine, nicotinic acid, vit B6, etc.
Higher concentration
Low concentration
ATP

Pharmacokinetics

E. Pinocytosis and phagocytosis Engulfing of drug For large substances to enter the cells Ex: iron and vitamin B12 Each complexed with appropriate binding proteins


E- Pinocytosis
Intestinal lumen
Apical cell membrane
Cell interior
Drug
Drug
Not important for drug absorption
High concentration
Lower concentration
vacoule

THAT’S IT!!