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Renato I. Dalmacio, RPh Pharmacology 325 College of Pharmacy
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.
History of Pharmacology
Pan Tsao Ayurveda Eber’s Papyrus Hippocrates Theophrastus Galen Paracelsus Dioscorides
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
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. Examples: Analgesics Antipyretics Anti-Inflammatories physiologic 6 . Functional Modifiers alters the normal functions.
Classification of Drugs According to General Use 2. Replenishers Supplement endogenous substances that are lacking or deficient. Examples: Insulin Water Electrolyte 7 .
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 3.
Examples: Anti-infectives Antineoplastics 9 . Chemotherapeutic Agents Agents used to kill or inhibit growth of cells or nucleic acid considered as foreign to the body.Classification of Drugs According to General Use 4.
Branches of Pharmacology 1.Pharmacokinetics 2.Pharmacodynamics 10 .
11 . deals with LADMER System. through and out of the body including delivery to their target sites.Pharmacokinetics study of how the drugs move into.
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 .
Ionization 3. Order of Reactions 13 . Ionization Increases Renal Clearance of drugs 4.Pharmacokinetic Principles 1. Permeation 2.
7. 4. 6. 3. 2.Fate of Drug In-Vivo 1. 5. L-iberation A-bsorption D-istribution M-etabolism E-xcretion R-eabsorption (T)-oxicity 14 .
1. Pharmaceutic Factors • Tablet disintegration • Inert ingredient / Solvent effects • Solubility • Drug pH • Concentration 15 . Liberation • release of the active ingredient (drug) from its dosage form Pharmacotechnical Factors Affecting Liberation: 1.
other drugs Rate Limiting Factors in Drug Liberation: 1.2. Dissolution 16 . Disintegration 2. Patient Factors • Absorbing surface • Blood flow • Environmental pH • Disease states • Interactions with food.
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 . Absorption The drug’s uptake from the site of administration to the systemic circulation.2.
Gastric Ulcers 4. Hot Food (Protein Rich.Factors that Increase Gastric Emptying Time: 1. Drugs that inhibit gastric motility 18 . Stress 2. Lipid-Rich Foods) 5. Lying on the left side 6. Heavy Exercise 3.
Mild Exercise 2. Use of motility enhancing drugs 19 .Factors that Decrease Gastric Emptying Time: 1. Lying on the right side 5. Gastrectomy 3. Cold Foods/Drinks 4.
Vesicular Transport 5. Convective Transport 4. Passive Transport 2. Examples of Transport Mechanism 1. Ion-Pair Transport 20 . Carrier-Mediated Transport 3.Modes of Drug Transport means of movement of drug molecule across cell membrane.
21 . non energy requiring • only nonionized molecules can pass through cell membranes • weakly acidic drugs can only be absorbed through the stomach which is acidic. movement of small lipophilic molecule along a concentration gradient.1. which is alkaline. Passive Transport higher concentration to lower concentration. • Weakly alkaline drugs can be absorbed through the intestine.
e. i.2. Carrier Mediated Transport A process that accounts for passage through the membrane of large.. All use carrier systems. lipid-insoluble molecules and ions. These carrier systems all show three properties: specificity. 22 . saturation and competition. special carrier molecules are required to be present in the membrane to help in the movement of the transported molecules.
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 .2 Types of Carrier Mediated Transport 1.
Characteristics: a. Movement is governed by electrochemical gradient 24 . Pore size/Diameter b. Charge of pore lining c.3. Solvent Drag d. Convective Transport • small drug molecules simply move along with fluid through the pores in cell walls • mediated through “water-filled pores/channels/aquaporins”.
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. Vesicles are bubble-like structures surrounded by a membrane.4. Vesicular Transport An active process in which materials move into or out of the cell enclosed as vesicles. 25 .
2. 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. Exocytosis.It is a process by which cells absorb molecules (such as proteins) by engulfing them. 26 .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.2 Basic Types of Vesicular Transport 1. Endocytosis.
5. Ion-Pair Transport Occurs when ionized drug is linked up with an opposite charged ion. Drugs like quaternary ammonium compounds and sulphonic acids. 27 . an ion pair is formed in which the overall charge of the pair is neutral. is ion-pair transport.membrane neutral ion pair complex GI lumen. Ex. which ionise under all pH conditions. Propranolol .
3. Physiologic Factors Affecting Distribution Cardiac Output Regional Blood Flow Parameters Volume of Distribution Protein Binding BBB and Placental Barrier 28 . Distribution The extent to which the drug passes into different tissues and fluid compartments in the body.
High VD -basic drugs -examples: -atropine. chloroquine -Digoxin.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. 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. 30 . 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.
Protein Binding Site 1. and Responsible for transport of certain endogenous substances Binds with basic drugs 31 . Globulin Specific. Albumin Major plasma protein component Reversible drug binding Binds with acidic drugs 2. Alpha-Acid Glycoprotein Nonselective Binds with basic drugs 3.
• Binding does not significantly affect distribution. • Penetration is dependent on the free concentration of the drug. 32 . Lipoproteins Macromolecular complexes of lipids and proteins Responsible for the transport of plasma lipids Responsible for binding if albumin is saturated.4. 5. Erythrocytes (RBC) • May bind to both exogenous and endogenous compounds.
4. 5. 2.1. Factors Affecting Protein Binding The drug The protein Affinity between drug & protein Drug Interaction Physiologic Condition of the patient. 3. 33 .
34 . although fetal blood levels are usually lower than maternal.Special Barriers: Placental: most small molecular weight drugs across the placental barrier. Blood-Brain: permeable only to lipid-soluble drugs or those of very low molecular weight.
a. Phases of Drug Metabolism 1. Phase I Metabolism 2.k. Phase II Metabolism to active 35 .4. “Biotransformation” the drug’s conversion metabolites. Metabolism a.
3. 5.Drug Biotransformation Reactions 1. 2. 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 . 4.
“Functionalization”.1.k. Oxidation Reduction Hydrolysis 37 . Unmasking or addition of functional group. Phase I Metabolism a.a.
Glycine conjugation.a. these groups are relatively polar and make the product less lipid-soluble than the original drug molecule. Glutathione conjugation. Liver is the most important organ for drug metabolism. “Conjugation”.2.k. Glucuronidation. Acetylation. Methylation 38 . Phase II Metabolism a. Sulfate conjugation.
5. Excretion the drug’s removal from the body. water-soluble drug or metabolite. Route of Drug Excretion Kidney Biliary excretion Skin Tears Mammary gland Lungs Saliva Feces 39 . polar.
Factors Affecting/Influencing Drug Effects Weight Age Gender Pathological Factors Genetic Factors 40 .