Gen Prin Sp Class

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Gen Prin Sp Class

  1. 1. GENERAL PRINCIPLES Zenaida N. Maglaya, MD; FPSECP Department of Pharmacology
  2. 2. GENERAL PRINCIPLES <ul><li>PHARMACOLOGY </li></ul><ul><li>DRUG </li></ul><ul><li>MEDICAL PHARMACOLOGY </li></ul><ul><li>PHARMACY </li></ul><ul><li>PHARMACOGNOSY </li></ul><ul><li>PHARMACOKINETICS </li></ul><ul><li>PHARMACODYNAMICS </li></ul>
  3. 3. PHARMACOKINETICS <ul><li>ABSORPTION </li></ul><ul><li>DISTRIBUTION </li></ul><ul><li>BIOTRANSFORMATION/ METABOLISM </li></ul><ul><li>EXCRETION </li></ul>
  4. 4. FACTORS AFFECTING ABSORPTION <ul><li>I. DRUG </li></ul><ul><li>II. TYPES OF TRANSPORT </li></ul><ul><li>1. SIMPLE DIFFUSION </li></ul><ul><li> 2. FILTRATION </li></ul><ul><li>3. ACTIVE TRANSPORT </li></ul><ul><li>4. FACILITATED DIFFUSION </li></ul><ul><li>5. PINOCYTOSIS </li></ul>
  5. 5. FACTORS AFFECTING ABSORPTION <ul><li>FICKS LAW OF DIFFUSION: </li></ul><ul><li>Permeability Coefficient </li></ul><ul><li>RATE = (C1-C2) ------------------------------ X AREA </li></ul><ul><li>THICKNESS </li></ul><ul><li>III. DEGREE OF IONIZATION </li></ul><ul><li>Protonated form </li></ul><ul><li>Log ----------------------------- - = pKa – pH </li></ul><ul><li>Unprotonated form </li></ul>
  6. 6. DEGREE OF IONIZATION <ul><li>RNH3 -------------------> RNH2 + H </li></ul><ul><li>Protonated Unprotonated Proton </li></ul><ul><li>Weak Base Weak base </li></ul><ul><li>Charged more Uncharged more </li></ul><ul><li>Water soluble lipid soluble </li></ul><ul><li>RCOOH --------------  RCOO - + H </li></ul><ul><li>Protonated Unprotonated Proton </li></ul><ul><li>Weak Acid Weak Acid </li></ul><ul><li>Uncharged more Charged more </li></ul><ul><li>Lipid soluble warer soluble </li></ul>
  7. 7. FORMULA <ul><li>I 10 pH - pKa </li></ul><ul><li>Weak Acid = ----- = ----------- </li></ul><ul><li>U 1 </li></ul><ul><ul><ul><ul><ul><li> I 10 pKa - pH </li></ul></ul></ul></ul></ul><ul><li>Weak Base = ----- = ----------- </li></ul><ul><li>U 1 </li></ul>
  8. 8. EXAMPLE OF WEAK ACID WITH PKA OF 8 <ul><li> I 10 pH - pKa </li></ul><ul><li>Weak acid = ------ = -------------- </li></ul><ul><li>U 1 </li></ul><ul><li>Stomach pH = 2 Plasma pH = 7.4 </li></ul><ul><li>10 2 – 8 10 7.4 - 8 </li></ul><ul><li>= ------------------ = -------------------- </li></ul><ul><li>1 1 </li></ul><ul><li>10 - 6 10 - 0.6 </li></ul><ul><li>= ---------------------- = -------------------- </li></ul><ul><li>1 1 </li></ul><ul><li>0.000001 0.25 </li></ul><ul><li>= --------------- = ----------------- </li></ul><ul><li>1 1 </li></ul><ul><li>TOTAL DRUG IN STOMACH TOTAL DRUG IN PLASMA </li></ul><ul><li>1.000001 1.25 </li></ul>
  9. 9. EXAMPLE OF A WEAK BASE WITH PKA OF 8 <ul><li> I 10 pKa - pH </li></ul><ul><li>Weak Base = ----- = -------------- </li></ul><ul><li>U 1 </li></ul><ul><li>Stomach pH = 2 plasma pH = 7.4 </li></ul><ul><li>10 8-2 10 8 - 7.4 </li></ul><ul><li>= ------------------ = -------------------- </li></ul><ul><li>1 1 </li></ul><ul><li>10 6 10 0.6 </li></ul><ul><li>= ---------------------- = -------------------- </li></ul><ul><li>1 1 </li></ul><ul><li>1000000 4 </li></ul><ul><li>= --------------- = ----------------- </li></ul><ul><li>1 1 </li></ul><ul><li>TOTAL DRUG IN STOMACH TOTAL DRUG IN PLASMA </li></ul><ul><li>1,000,001 5 </li></ul>
  10. 10. ROUTES OF ADMINISTRATION <ul><li>I. ENTERAL </li></ul><ul><ul><li>1. ORAL </li></ul></ul><ul><ul><li>2, SUBLINGUAL & BUCCAL </li></ul></ul><ul><ul><li>3. RECTAL </li></ul></ul><ul><ul><li>II. PARENTERAL </li></ul></ul><ul><ul><li>A. INJECTIONS </li></ul></ul><ul><ul><li>1. INTRAVENOUS </li></ul></ul><ul><ul><li>` 2. INTRAMUSCULAR </li></ul></ul><ul><ul><li>3. SUBCUTANEOUS </li></ul></ul><ul><ul><li>B. INHALATION </li></ul></ul><ul><ul><li>C. TOPICAL </li></ul></ul><ul><ul><li>D. TRANSDERMAL </li></ul></ul>
  11. 11. DISTRIBUTION OF DRUGS <ul><li>SIZE OF THE ORGAN </li></ul><ul><li>BLOOD FLOW </li></ul><ul><li>LIPID SOLUBILITY </li></ul><ul><li>TISSUE BINDING </li></ul><ul><li>Vd = VOLUME OF DISTRIBUTION </li></ul>
  12. 12. METABOLISM OR BIOTRANSFORMATION OF DRUGS <ul><li>NEED FOR DRUG METABOLISM </li></ul><ul><li>> TERMINATION OF DRUG </li></ul><ul><li> > ACTIVATION OF DRUGS </li></ul><ul><li>. SITES OF DRUG METABOLISM </li></ul><ul><li>. FACTORS AFFECTING METABOLISM </li></ul><ul><li>> GENETIC FACTORS </li></ul><ul><li> > ENVIRONMENTAL FACTORS </li></ul><ul><li>. TYPES OF METABOLIC REACTIONS </li></ul><ul><li>> PHASE I REACTION </li></ul><ul><li>> PHASE II REACTION </li></ul>
  13. 13. PHASE I METABOLISM <ul><li>OXIDATION </li></ul><ul><li>A. OXIDATION P450 DEP HYDROXYLATIONS:barbiturates, phenytoin, amphetamines </li></ul><ul><li>N - ALKYLATIONS: morphine,caffeine, theophyllline </li></ul><ul><li>O --DEALKYLATION: codeine </li></ul><ul><li>N -OXIDATION: acetaminophen, nicotine </li></ul><ul><li>S-OXIDATION: cimetidine, chlorpromazine </li></ul><ul><li>B. OXIDATION P450 INDEPENDENT AMINE OXIDATION: epinephrine </li></ul><ul><li>DEHYDROGENATION: ethanol, chloral hydrate </li></ul><ul><li>REDUCTION: chloramphenicol, naloxone </li></ul><ul><li>HYDROLYSIS </li></ul><ul><li>A. Esters: procaine aspirin </li></ul><ul><li>B. Amides: lidocaine, indomethacin </li></ul>
  14. 14. PHASE II METABOLISM <ul><li>GLUCORONIDATION: morphine. Diazepam, digitoxin </li></ul><ul><li>ACETYLATION: sulfonamides, isoniazid </li></ul><ul><li>GLUTATHIONE CONJUGATION: ethacrunic acid </li></ul><ul><li>GLYCINE CONJUGATION: salicylic acid, nicotinic acid </li></ul><ul><li>SULFATE CONJUGATION: acetaminophen, methyldopa </li></ul><ul><li>METHYLATION: dopamine. epinephrine </li></ul>
  15. 15. DRUG METABOLISM <ul><li>INDUCER DRUG INDUCED </li></ul><ul><li>PHENOBARBITAL Chloramphenicol, Digoxin, Phenytoin Coumarin, Quinine, Testosterone </li></ul><ul><li>RIFAMPIN Coumarin, Digitoxin, Oral Contraceptives </li></ul><ul><li> Metoprolol, Quinine </li></ul><ul><li>PHENYTOIN Cortisol, Dexamethazone </li></ul><ul><li>Digitoxin, Theophylline </li></ul><ul><li>GRISEOFULVIN Warfarin </li></ul><ul><li> </li></ul>
  16. 16. DRUG METABOLISM <ul><li>INHIBITORS </li></ul><ul><li>CIMETIDINE Diazepam, Warfarin </li></ul><ul><li>Chlordiazepoxide </li></ul><ul><li>ISONIAZID Antipyrine, Dicoumarol, Probenecid </li></ul><ul><li>PHENYLBUTAZONE Phenytoin, Tolbutamide </li></ul>
  17. 17. EXCRETION <ul><li>GLOMERULAR FILTRATION </li></ul><ul><li>TUBULAR EXCRETION </li></ul><ul><li>TUBULAR REABSORPTION </li></ul><ul><li>ELIMINATIION </li></ul><ul><li>ZERO ORDER KINETICS </li></ul><ul><li>FIRST ORDER KINETICS </li></ul>
  18. 18. QUANTITATIVE PHARMACOKINETICS <ul><li>VOLUME OF DISTRIBUTION </li></ul><ul><li>amount of drug in the body </li></ul><ul><li> Vd = ------------------------------------- </li></ul><ul><li>plasma concentration </li></ul><ul><li>HALF LIFE </li></ul><ul><li>0.693 x Vd 0.693 </li></ul><ul><li>t ½ = ---------------- or- -------------- </li></ul><ul><li>Cl k </li></ul><ul><li>CLEARANCE </li></ul><ul><li>0.693 x Vd </li></ul><ul><li>Cl = ------------------------------ or Vd X k </li></ul><ul><li>t 1/2 </li></ul>
  19. 19. DOSAGE REGIMEN <ul><li>LOADING DOSE = Vd X desired plasma concentration </li></ul><ul><li>MAINTENANCE DOSE = Cl X desired plasma concn </li></ul><ul><li>STEADY STATE PLASMA CONCENTRATION, OR PLATEAU </li></ul><ul><li>1 ST HALF LIFE= 50% 4 th half life = 94% </li></ul><ul><li> 2 ND HALF LIFE = 75 % 5 th half life = 97% </li></ul><ul><li>3 rd half life = 88% 6 th half life = 99% </li></ul>
  20. 20. DRUG EVALUATION <ul><li>I. PRECLINICAL PHASE </li></ul><ul><li>A. SAFETY & EFFICACY </li></ul><ul><li>B. ANIMAL TESTING: Acute, Subacute, Chronic </li></ul><ul><li>C. TYPES OF ANIMAL TEST: Pharmacologic Profile, Reproductive Toxicity, Carcinogenesis </li></ul><ul><li>II. CLINICAL PHASE </li></ul><ul><li>a. PHASE I </li></ul><ul><li>b, PHASE II </li></ul><ul><li>c. PHASE III </li></ul><ul><li>d. PHASE IV </li></ul>
  21. 21. Thank You! <ul><li>If any of you lacks wisdom, let him ask of God, who gives to all, liberally and without reproach, and it will be given </li></ul><ul><li>to him. </li></ul><ul><li>James 1: 5 </li></ul>

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