Pharmacology

Review

• Pharmacology – (pharmakon) = drug, (logia) = study – study of drugs– pharmacodynamics, pharmacotherapeutics,

pharmacokinetics

• Drug – chemical substances that are used for the diagnosis,

prevention or treatment of disease and the prevention of pregnancy

• MIMS – Master Index of Medical Specialties

– I. Review of Drug Index (MIMS)

• a. Drug Classification

• b. Drug Regulation

• c. Pregnancy Safety Index

• d. Drug Administration

• e. Drug Nomenclature

– II. Routes of Drug (Enteral and Parenteral)

– III. Dosage Forms (Liquid, Semi solid, Solid)

Parts of a Drug Index:

Generic Name

Indications

Dosage/Direction for Use

Pre and Post-PrandialAdvice

Contraindications

Special Precautions

Adverse Reactions

Drug Interactions

Presentation and Packing

USFDA Pregnancy Category

Brand Name

Manufacturer

Drug Classification

• Gastrointestinal and Hepatobiliary system• Cardiovascular and Hematopoetic system• Respiratory system• Central Nervous system• Musculo Skeletal system• Hormones• Contraceptive Agents• Anti-Infectives• Oncology

• Genito-Urinary system

• Endocrine and Metabolic system

• Allergy and Immune system

• Nutrition

• Dermatological therapy

• Anesthetics

• Vitamins and Minerals

Drug Regulation

– DD, Rx –Dangerous Drug as listed in the Comprehensive Dangerous Act of 2002 supplied only on Special DOH Prescription Form (Yellow Rx) by a licensed PDEA prescribing physician.

– EDD, Rx – medicine containing any amount of prohibited or regulated drugs, supplied on ordinary prescription forms with S-2 license number by a licensed PDEA prescribing physician.

– Rx – prescription medicine; supplied on prescription only.

– Non-Rx – non-prescription medicine; supplied without need for prescription.

• Example of Yellow Prescription:

Pregnancy Safety Index (Preg-Cat)

• a guide to the safe prescribing of drugs in pregnancy based on the United States Food and Drug Administration (US FDA) Pregnancy Categories.

U.S Food and Drug Administration Pregnancy Risk Categories

(Preg-Cat)

• Category A – Adequate and well-controlled studies have failed to show a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters). Ex: Levothyroxine, magnesium sulfate(injectable), sodium fluoride

• Category B – Either (1) adequate and well-controlled studies have failed to show a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters, but animal reproduction studies have shown an adverse effect on the fetus; or (2) human studies are lacking, but animal studies have failed to show a risk to the fetus. Ex: Acetaminophen,* amoxicillin and clavulanate, cefaclor, erythromycin, lidocaine, naproxen, penicillin V

• Category C – No adequate and well-controlled studies have been performed in pregnant women, but animal reproduction studies are lacking or have shown an adverse effect on the fetus. Potential benefit may warrant use of the drug in pregnant women despite potential risk. Ex: Atropine, bupivacaine, butorphanol, codeine, diflunisal, epinephrine, hydrocortisone (topical), mepivacaine, morphine, thiopental

• Category D – Positive evidence exists of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans. Potential benefit may warrant use of the drug in pregnant women despite potential risk. Ex: Aspirin, hydrocortisone (systemic), lorazepam, midazolam, pentobarbital, valproic acid

• Category X - Studies in animals or humans have shown fetal abnormalities, or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, or both, and the potential risk of the drug in pregnant women clearly outweighs the potential benefit. Ex: Ergotamine, estradiol, isotretinoin, temazepam, triazolam, warfarin.

Preg-Cat Summary:

– Category A - (-) risk to human fetus

– Category B - (-) risk to fetus, (+) adverse effects on animal fetus / (lacking) study on human fetus, (-) risk on animal fetus

– Category C - (-) study on pregnant women, (lacking) study on animal fetus, (+) adverse effect on animal fetus, potential benefit > potential risk on pregnant women

– Category D - (+) fetal risk and adverse reaction on human fetus, potential benefit > potential risk on pregnant women

– Category X - (+) fetal risk and adverse effect on both human and animal fetus, potential risk > potential benefit on pregnant women

• Administration of Oral Drugs

– Take with food

– Take on an empty stomach

– Take with or without food

Drug Administration

• Government Agencies– US

• Food and Drug Administration (FDA)

• Federal Trade Commission

• Drug Enforcement Administration (DEA)

– Philippines• Bureau of Food and Drugs (BFAD)

• Philippine Drug Enforcement Agency (PDEA)

• Department of Trade and Industry (DTI)

• Various Police Anti-drug task forces

• Properties of Drug

– 1) Selectivity – the ability of drug molecules to choose which cell type it will influence physiologically.

– Ex: Caffeine – stimulates CNS

– 2) Potency – strength of a drug in relation to its dosage

– 3) Reversibility of Action – results in temporary drug effect

– 4) Chemical ability to interact with a biologic system –due to water and lipid solubility

• Characterizationof Drug Action:

– 1. Potency

• Strength of a drug in relation to its dosage

– 2. Efficacy/Maximal Effect

• Inherent ability of a drug to effect a physiologic change

• Effect of a drug attained at a certain dose that cannot be further increased even if there is a progressive increase in dose

– 3. Median effective dose (ED50)• Pertains to the amount of dose of a drug which produce

specific intensity of effect in 50% of test subject

– 4. Median lethal dose (LD50)• Pertains to the amount/dose of a drug which produce lethal

effect in 50% of test subject

– 5. Therapeutic index (TI)• Denotes the margin of safety of a particular drug

• TI= LD50ED50

• Factors that characterize the action of all drugs/determine the effective level of a drug– Route of a drug administration

• Enteral• Parenteral

– Passage of drugs across body membrane• Passive transfer• Specialized transport

– Absorption• Absorption in the GIT• Absorption at the injection site

– Transport and distribution

• Plasma protein binding

• Cellular binding

• Blood brain barrier/ Blood placental barrier

– Molecular mechanism of action

• Drug-receptor interaction

• Physiochemical mechanisms

– Drug metabolism

• Liver microsomal drug metabolizing system

• Other mechanisms

• Non-microsomal

• Non-hepatic

– Excretion

• Renal

• Extra-renal

Passage of drug across body membranes

• Passive Transfer– 1. simple diffusion

• Molecules from higher concentration goes to lower concentration

• Lipid solubility of drug molecules

• Degree of ionization = pKA of a drug, higher pKA lower lipid solubility

• Higher PH, higher ionization, lower lipid solubility

– 2. filtration• Ability to filter depends on filtering membrane

• Specialized Transport

– Active transport

• Blockade of metabolic inhibitors

– Facilitated diffusion

– Pinocytosis

• Cell engulf drug molecules

Absorption of Drugs

• Absorption in GIT

– Drugs absorb in the GIT with the help of gastric enzymes

• Absorption at the injection site

– Vascularity of the injection site

– Solubility of the drug

Transport and Distribution

• Factors that contribute to unequal distribution of drugs– Plasma protein binding

• Some drugs can displace other drugs from their protein binding sites

• Ex:ASA +MTX

– Cellular binding• Ex: tetracycline – hard tissues of the body

– Blood brain barrier• Restricts passage of drugs into the CNS

– Blood placental barrier

Drug Metabolism

• Liver microsomal drug metabolizing enzymes– If liver cannot process drug, drug will stay in the body,

suffer toxicity

• Other Mechanisms– Conjugation– Hydrolysis– Reduction– Dehalogenation

• Non-microsomal• Non-hepatic

Excretion

• Renal– Through the kidneys

– Glomerular secretion, active tubular secretion and passive tubular secretion

• Extra-renal– Lungs

– Bile and GIT

– Sweat

– Saliva

Drug Nomenclature

• Chemical Name– Conveys the chemical structure of the compound or drug.– If the structure is not yet known, a code number may be

assigned to the compound.

• Brand/Trade Name/Proprietary Name– Given if the chemical is determined to be therapeutically

useful and is to be marketed commercially

• Generic Name/Non-proprietary Name– The official name of the drug and is the one used in the

USP-NF (United States Pharmacopeia-National Formulary)

• Examples:– Chemical Name: 2-diethylamino-2, 6-acetoxylidide

– Generic Name: Lidocaine

– Brand Name: Xylocaine/Octocaine

– Chemical Name: 2-(2,3-dimethylphenyl)aminobenzoic acid

– Generic Name: Mefenamic Acid

– Brand Name: Ponstan/Mefenax