prelims - intro to pharmacology

INTRODUCTION TO INTRODUCTION TO PHARMACOLOGYPHARMACOLOGY

Renato I. Dalmacio, RPh

Pharmacology 325

College of Pharmacy

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PharmacologyPharmacology

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.

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History of PharmacologyHistory of Pharmacology

Pan TsaoAyurvedaEber’s PapyrusHippocratesTheophrastusGalenParacelsusDioscorides

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DrugDrugis 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

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Sources & Nature of DrugsSources & Nature of DrugsNatural sourcesAnimal sourcesMicrobiological sourcesMineral sourcesSemi-synthetic sourcesSynthetic sourcesBiosynthetic sources

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Classification of Drugs Classification of Drugs According to General UseAccording to General Use

1. Functional Modifiers alters the normal physiologic

functions. Examples:

Analgesics Antipyretics Anti-Inflammatories

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2. Replenishers Supplement endogenous substances

that are lacking or deficient. Examples:

Insulin Water Electrolyte

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3. Diagnostic Agents Agents used to determine the

presence or absence of a condition or disease.

Examples: Edrophonium Histamine Technetium 99m

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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

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Branches of PharmacologyBranches of Pharmacology

1.Pharmacokinetics

2.Pharmacodynamics

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PharmacokineticsPharmacokinetics

study of how the drugs move into, through and out of the body including delivery to their target sites.

deals with LADMER System.

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PharmacodynamicsPharmacodynamics

study of biochemical and physiological effects of drugs and the mechanism by which they produce such effects.

deals with Mechanism of Action (MOA).

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Pharmacokinetic PrinciplesPharmacokinetic Principles

1. Permeation

2. Ionization

3. Ionization Increases Renal Clearance of drugs

4. Order of Reactions

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Fate of Drug In-VivoFate of Drug In-Vivo

1. L-iberation

2. A-bsorption

3. D-istribution

4. M-etabolism

5. E-xcretion

6. R-eabsorption

7. (T)-oxicity

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1.1. LiberationLiberation• 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

• Concentration15

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

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2.2. AbsorptionAbsorption The drug’s uptake from the site of administration

to the systemic circulation.

Factors Affecting Drug Absorption:Dose size administeredpH of absorbing environmentArea of absorbing surfaceDegree of perfusionGastric emptying timeDosage FormDrug SolubilityFirst Pass EffectEnterohepatic Recycling

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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

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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

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Modes of Drug TransportModes of Drug Transportmeans 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

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1.1. Passive TransportPassive 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.

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2.2. Carrier Mediated TransportCarrier 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.

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22 Types of Carrier Mediated TransportTypes 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

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3.3. Convective TransportConvective 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/Diameterb. Charge of pore liningc. Solvent Dragd. Movement is governed by electrochemical

gradient

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4.4. Vesicular TransportVesicular 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.

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2 Basic Types of Vesicular Transport2 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.

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5.5. Ion-Pair TransportIon-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.

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3.3. DistributionDistribution

The extent to which the drug passes into different tissues and fluid compartments in the body.

Physiologic Factors Affecting DistributionCardiac OutputRegional Blood Flow

Parameters Volume of Distribution Protein Binding BBB and Placental Barrier

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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 Low VD-basic drugs -acidic drugs-examples: -examples:

-atropine, chloroquine -chlorpropamide -Digoxin, B-Blockers -tolbutamide -warfarin -furosemide

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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.

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Protein Binding Site1. AlbuminMajor plasma protein componentReversible drug bindingBinds with acidic drugs2. Alpha-Acid GlycoproteinNonselectiveBinds with basic drugs3. GlobulinSpecific, and Responsible for transport of certain

endogenous substancesBinds with basic drugs

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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.

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Factors Affecting Protein Binding

1.The drug

2.The protein

3.Affinity between drug & protein

4.Drug Interaction

5.Physiologic Condition of the patient.

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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.

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4.4. MetabolismMetabolism

a.k.a. “Biotransformation”the drug’s conversion to active

metabolites.

Phases of Drug Metabolism

1.Phase I Metabolism

2.Phase II Metabolism

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Drug Biotransformation Reactions1.Active Drug to Polar Metabolite

2.Active Drug to Inactive Metabolite

3.Active Drug to Active Metabolite

4.Inactive Drug to Active Metabolite

5.Active Drug to Reactive Metabolite

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1.1. Phase I MetabolismPhase I Metabolism a.k.a. “Functionalization”. Unmasking or addition of functional group.

Oxidation Reduction Hydrolysis

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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

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

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Factors Affecting/Influencing Drug Effects

Weight Age Gender Pathological Factors Genetic Factors

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prelims - intro to pharmacology

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