INTRODUCTION TO PHARMACOLOGY

Renato I. Dalmacio, RPh Pharmacology 325 College of Pharmacy

1

Pharmacology
study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes. studies the effects of drugs and how they exert their effects.
2

History of Pharmacology
Pan Tsao Ayurveda Ebers Papyrus Hippocrates Theophrastus Galen Paracelsus Dioscorides
3

Drug
is any substance which is used for the following purposes: Prevention of the disease Diagnosis of the disease Mitigation of the disease Treatment or palliation (relief of symptoms) of disease Maintenance of optimal health
4

Sources & Nature of Drugs

Natural sources Animal sources Microbiological sources Mineral sources Semi-synthetic sources Synthetic sources Biosynthetic sources
5

Classification of Drugs According to General Use

1. Functional Modifiers alters the normal functions. Examples: Analgesics Antipyretics Anti-Inflammatories

physiologic

Classification of Drugs According to General Use

2. Replenishers Supplement endogenous substances that are lacking or deficient. Examples: Insulin Water Electrolyte
7

Classification of Drugs According to General Use

3. Diagnostic Agents Agents used to determine the presence or absence of a condition or disease. Examples: Edrophonium Histamine Technetium 99m
8

Classification of Drugs According to General Use

4. Chemotherapeutic Agents Agents used to kill or inhibit growth of cells or nucleic acid considered as foreign to the body. Examples: Anti-infectives Antineoplastics

Branches of Pharmacology

1.Pharmacokinetics 2.Pharmacodynamics

10

Pharmacokinetics
study of how the drugs move into, through and out of the body including delivery to their target sites. deals with LADMER System.

11

Pharmacodynamics
study of biochemical and physiological effects of drugs and the mechanism by which they produce such effects. deals with Mechanism of Action (MOA).

12

Pharmacokinetic Principles
1. Permeation 2. Ionization 3. Ionization Increases Renal Clearance of drugs 4. Order of Reactions

13

Fate of Drug In-Vivo

1. 2. 3. 4. 5. 6. 7. L-iberation A-bsorption D-istribution M-etabolism E-xcretion R-eabsorption (T)-oxicity
14

1. Liberation
release of the active ingredient (drug) from its dosage form Pharmacotechnical Factors Affecting Liberation: 1. Pharmaceutic Factors Tablet disintegration Inert ingredient / Solvent effects Solubility Drug pH Concentration
15

2. Patient Factors Absorbing surface Blood flow Environmental pH Disease states Interactions with food, other drugs
Rate Limiting Factors in Drug Liberation: 1. Disintegration 2. Dissolution
16

2. Absorption
The drugs uptake from the site of administration to the systemic circulation. Factors Affecting Drug Absorption: Dose size administered pH of absorbing environment Area of absorbing surface Degree of perfusion Gastric emptying time Dosage Form Drug Solubility First Pass Effect Enterohepatic Recycling

17

Factors that Increase Gastric Emptying Time: 1. Stress 2. Heavy Exercise 3. Gastric Ulcers 4. Hot Food (Protein Rich, Lipid-Rich Foods) 5. Lying on the left side 6. Drugs that inhibit gastric motility

18

Factors that Decrease Gastric Emptying Time: 1. Mild Exercise 2. Gastrectomy 3. Cold Foods/Drinks 4. Lying on the right side 5. Use of motility enhancing drugs

19

Modes of Drug Transport

means of movement of drug molecule across cell membrane. Examples of Transport Mechanism 1. Passive Transport 2. Carrier-Mediated Transport 3. Convective Transport 4. Vesicular Transport 5. Ion-Pair Transport
20

1. Passive Transport higher concentration to lower concentration. movement of small lipophilic molecule along a concentration gradient. non energy requiring only nonionized molecules can pass through cell membranes weakly acidic drugs can only be absorbed through the stomach which is acidic. Weakly alkaline drugs can be absorbed through the intestine, which is alkaline.
21

2. Carrier Mediated Transport A process that accounts for passage through the membrane of large, lipid-insoluble molecules and ions. All use carrier systems, i.e., special carrier molecules are required to be present in the membrane to help in the movement of the transported molecules. These carrier systems all show three properties: specificity, saturation and competition.
22

2 Types of Carrier Mediated Transport 1. Facilitated Transport a passive process requiring no cellular energy drug moves along a concentration gradient saturable and structurally selective 2. Active Transport from lower concentration to higher concentration pushing a rock uphill requires cellular energy
23

3. Convective Transport small drug molecules simply move along with fluid through the pores in cell walls mediated through water-filled pores/channels/aquaporins. Characteristics: a. Pore size/Diameter b. Charge of pore lining c. Solvent Drag d. Movement is governed by electrochemical gradient
24

4. Vesicular Transport An active process in which materials move into or out of the cell enclosed as vesicles. Vesicles are bubble-like structures surrounded by a membrane. They can form at the cell membrane or can fuse with the membrane. Vesicular transport is also known as bulk transport because large quantities of materials can be transported in this way.

25

2 Basic Types of Vesicular Transport 1. Endocytosis- It is a process by which cells absorb molecules (such as proteins) by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane. 2. Exocytosis- It is a process in which an intracellular vesicle (membrane bounded sphere) moves to the plasma membrane and subsequent fusion of the vesicular membrane and plasma membrane ensues.
26

5. Ion-Pair Transport Occurs when ionized drug is linked up with an opposite charged ion, an ion pair is formed in which the overall charge of the pair is neutral. Drugs like quaternary ammonium compounds and sulphonic acids, which ionise under all pH conditions, is ion-pair transport. Ex. Propranolol - membrane neutral ion pair complex GI lumen.
27

3. Distribution
The extent to which the drug passes into different tissues and fluid compartments in the body. Physiologic Factors Affecting Distribution Cardiac Output Regional Blood Flow Parameters Volume of Distribution Protein Binding BBB and Placental Barrier
28

Volume of Distribution (VD) The hypothetical volume of body fluid necessary to dissolve a given amount or dose of a drug to achieve a concentration equal to that of the drug plasma concentration.
High VD -basic drugs -examples: -atropine, chloroquine -Digoxin, B-Blockers Low VD -acidic drugs -examples: -chlorpropamide -tolbutamide -warfarin -furosemide
29

Protein Binding It is the phenomenon that occurs when a drug combines with plasma (particularly albumin) or tissue protein to form a reversible complex. 2 Types of Protein Binding 1. Reversible Drug-Protein Binding implies that the drug binds the protein with weaker chemical bonds such as hydrogen bonds or Van der Waals forces. 2. Irreversible Drug Protein Binding is usually a result of chemical activation of the drug, which then attaches strongly to the protein or macromolecule by covalent chemical bonding.
30

Protein Binding Site 1. Albumin Major plasma protein component Reversible drug binding Binds with acidic drugs 2. Alpha-Acid Glycoprotein Nonselective Binds with basic drugs 3. Globulin Specific, and Responsible for transport of certain endogenous substances Binds with basic drugs
31

4. Lipoproteins Macromolecular complexes of lipids and proteins Responsible for the transport of plasma lipids Responsible for binding if albumin is saturated. 5. Erythrocytes (RBC) May bind to both exogenous and endogenous compounds. Penetration is dependent on the free concentration of the drug. Binding does not significantly affect distribution.
32

1. 2. 3. 4. 5.

Factors Affecting Protein Binding The drug The protein Affinity between drug & protein Drug Interaction Physiologic Condition of the patient.

33

Special Barriers: Placental: most small molecular weight drugs across the placental barrier, although fetal blood levels are usually lower than maternal.
Blood-Brain: permeable only to lipid-soluble drugs or those of very low molecular weight.

34

4. Metabolism
a.k.a. Biotransformation the drugs conversion metabolites. Phases of Drug Metabolism 1. Phase I Metabolism 2. Phase II Metabolism

to

active

35

Drug Biotransformation Reactions

1. 2. 3. 4. 5. Active Drug to Polar Metabolite Active Drug to Inactive Metabolite Active Drug to Active Metabolite Inactive Drug to Active Metabolite Active Drug to Reactive Metabolite

36

1. Phase I Metabolism
a.k.a. Functionalization. Unmasking or addition of functional group. Oxidation Reduction Hydrolysis

37

2. Phase II Metabolism
a.k.a. Conjugation. these groups are relatively polar and make the product less lipid-soluble than the original drug molecule. Liver is the most important organ for drug metabolism. Glucuronidation, Acetylation, Glutathione conjugation, Glycine conjugation, Sulfate conjugation, Methylation
38

5. Excretion
the drugs removal from the body. polar, water-soluble drug or metabolite. Route of Drug Excretion Kidney Biliary excretion Skin Tears Mammary gland Lungs Saliva Feces
39

Factors Affecting/Influencing Drug Effects

Weight Age Gender Pathological Factors Genetic Factors

40