This document summarizes general principles of pharmacology including pharmacokinetics and pharmacodynamics. It discusses drug absorption, distribution, metabolism, excretion and factors affecting these processes. It also covers drug targets like receptors, enzymes, ion channels and carriers. Finally, it provides an overview of the drug development process from lead compounds to clinical testing and marketing.

1. GENERAL PRINCIPLES http://crisbertcualteros.page.tl

2. GENERAL PRINCIPLES PHARMACOLOGY DRUG MEDICAL PHARMACOLOGY PHARMACY PHARMACOGNOSY PHARMACOKINETICS PHARMACODYNAMICS

3. PHARMACOKINETICS ABSORPTION DISTRIBUTION BIOTRANSFORMATION/ METABOLISM EXCRETION

4. FACTORS AFFECTING ABSORPTION I. DRUG II. TYPES OF TRANSPORT 1. SIMPLE DIFFUSION 2. FILTRATION 3. ACTIVE TRANSPORT 4. FACILITATED DIFFUSION 5. PINOCYTOSIS

5. FACTORS AFFECTING ABSORPTION FICKS LAW OF DIFFUSION: Permeability Coefficient RATE = (C1-C2) ------------------------------ X AREA THICKNESS III. DEGREE OF IONIZATION Protonated form Log ----------------------------- - = pKa – pH Unprotonated form

6. DEGREE OF IONIZATION RNH3 -------------------> RNH2 + H Protonated Unprotonated Proton Weak Base Weak base Charged more Uncharged more Water soluble lipid soluble RCOOH --------------  RCOO - + H Protonated Unprotonated Proton Weak Acid Weak Acid Uncharged more Charged more Lipid soluble warer soluble

7. FORMULA I 10 pH - pKa Weak Acid = ----- = ----------- U 1 I 10 pKa - pH Weak Base = ----- = ----------- U 1

8. EX OF WEAK ACID WITH PKA OF 8 I 10 pH - pKa Weak acid = ------ = -------------- U 1 Stomach pH = 2 Plasma pH = 7.4 10 2 – 8 10 7.4 - 8 = ------------------ = -------------------- 1 1 10 - 6 10 - 0.6 = ---------------------- = -------------------- 1 1 0.000001 0.25 = --------------- = ----------------- 1 1 TOTAL DRUG IN STOMACH TOTAL DRUG IN PLASMA 1.000001 1.25

9. EXAMPLE OF A WEAK BASE WITH PKA OF 8 I 10 pKa - pH Weak Base = ----- = -------------- U 1 Stomach pH = 2 plasma pH = 7.4 10 8-2 10 8 - 7.4 = ------------------ = -------------------- 1 1 10 6 10 0.6 = ---------------------- = -------------------- 1 1 1000000 4 = --------------- = ----------------- 1 1 TOTAL DRUG IN STOMACH TOTAL DRUG IN PLASMA 1,000,001 5

10. ROUTES OF ADMINISTRATION I. ENTERAL 1. ORAL 2, SUBLINGUAL & BUCCAL 3. RECTAL II. PARENTERAL A. INJECTIONS 1. INTRAVENOUS ` 2. INTRAMUSCULAR 3. SUBCUTANEOUS B. INHALATION C. TOPICAL D. TRANSDERMAL

11. DISTRIBUTION OF DRUGS SIZE OF THE ORGAN BLOOD FLOW LIPID SOLUBILITY TISSUE BINDING Vd = VOLUME OF DISTRIBUTION

12. METABOLISM/ BIOTRANSFORMATION OF DRUGS NEED FOR DRUG METABOLISM > TERMINATION OF DRUG > ACTIVATION OF DRUGS . SITES OF DRUG METABOLISM . FACTORS AFFECTING METABOLISM > GENETIC FACTORS > ENVIRONMENTAL FACTORS . TYPES OF METABOLIC REACTIONS > PHASE I REACTION > PHASE II REACTION

13. PHASE I METABOLISM OXIDATION A. OXIDATION P450 DEP HYDROXYLATIONS:barbiturates, phenytoin, amphetamines N - ALKYLATIONS: morphine,caffeine, theophyllline O --DEALKYLATION: codeine N -OXIDATION: acetaminophen, nicotine S-OXIDATION: cimetidine, chlorpromazine B. OXIDATION P450 INDEPENDENT AMINE OXIDATION: epinephrine DEHYDROGENATION: ethanol, chloral hydrate

14. PHASE I METABOLISM REDUCTION: chloramphenicol, naloxone HYDROLYSIS A. Esters: procaine aspirin B. Amides: lidocaine, indomethacin

15. PHASE II METABOLISM GLUCORONIDATION : morphine. Diazepam, digitoxin ACETYLATION : sulfonamides, isoniazid GLUTATHIONE CONJUGATION : ethacrunic acid GLYCINE CONJUGATION : salicylic acid, nicotinic acid SULFATE CONJUGATION : acetaminophen, methyldopa METHYLATION : dopamine. epinephrine

16. DRUG METABOLISM INDUCER DRUG INDUCED PHENOBARBITAL Chloramphenicol, Digoxin, Phenytoin, Coumarin Quinine, Testosterone RIFAMPIN Coumarin, Digitoxin, Oral Contraceptives Metoprolol, Quinine PHENYTOIN Cortisol, Dexamethazone Digitoxin, Theophylline GRISEOFULVIN Warfarin

17. DRUG METABOLISM INHIBITORS CIMETIDINE Diazepam, Warfarin Chlordiazepoxide ISONIAZID Antipyrine, Dicoumarol, Probenecid PHENYLBUTAZONE Phenytoin, Tolbutamide

18. EXCRETION GLOMERULAR FILTRATION TUBULAR EXCRETION TUBULAR REABSORPTION ELIMINATIION ZERO ORDER KINETICS FIRST ORDER KINETICS

19. QUANTITATIVE PHARMACOKINETICS VOLUME OF DISTRIBUTION amount of drug in the body Vd = ------------------------------------- plasma concentration HALF LIFE 0.693 x Vd 0.693 t ½ = ---------------- or- -------------- Cl k CLEARANCE 0.693 x Vd Cl = ------------------------------ or Vd X k t 1/2

20. DOSAGE REGIMEN LOADING DOSE = Vd X desired plasma concentration MAINTENANCE DOSE = Cl X desired plasma concentrationn STEADY STATE PLASMA CONCENTRATION, OR PLATEAU 1 ST HALF LIFE= 50% 2 ND HALF LIFE = 75 %

21. PHARMACODYNAMICS RECEPTORS AGONIST PARTIAL AGONIST ANTAGONIST A. PHYSIOLOGIC ANTAGONISM B. PHARMACOLOGIC ANTAGONISM > COMPETITIVE ANTAGONIST > IRREVERSIBLE ANTAGONIST C CHEMICAL ANTAGONISM

22. PHARMACODYNAMICS POTENCY EFFICACY GRADED DOSE RESPONSE CURVE QUANTAL DOSE RESPONSE CURVE BIOAVAILABILITY BIOEQUIVALENCE THERAPEUTIC INDEX TD50 OR LD50 T.I. = ----------------------- ED50

23. TARGET FOR DRUG ACTION RECEPTOR ENZYME ION-CHANNELS CARRIER MOLECULES

25. RECEPTORS Agonist Antagonist Beta adrenoreceptor Norepi- nephrine Propranolol Opiate (mu) Morphine Naloxone Dopamine (D2) Dopamine Bromocrip- tine Chlorpro- mazine Insulin insulin None known Estrogen receptors Ethinyl- estradiol Tamoxifen

26. ENZYMES INHIBITORS FALSE SUBSTRATE Cyclooxy- genase Aspirin Carbonic Anhydrase Acetazola- Mide Dihydrofolate reductase trimetoprin Monoamine oxidase B Selegiline Angiotensin convering enzymes Captopril

27. ION CHANNELS BLOCKERS MODULATORS Renal tubule Sodium channels Amiloride Aldosterone ATP sensitive K + channels ATP Cromokalin sulfonylureas GABA gated chloride channels Picrotoxin Benzodiazepines Voltage gated Ca ++ channels Divalent cations Beta-adrenoreceptor agonists

28. CARRIERS INHIBITORS FALSE SUBSTRATE Na + K + Cl co transporter Loop diuretics Na + K + pump Cardiac glycosides Proton pump Omeprazole Weak acid carrier(renal tubule) Probenecid

29. OVERVIEW OF PRODUCT DEVELOPMENT Lead Compound Efficacy Selectivity Mechanism Phase 1 Phase 2 Phase 3 Drug metabolism, safety assessment Phase 4 In vitro studies Animal Studies Clinical Testing Marketing 0 2 4 8 – 9 20 YEARS

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