gen prin sp class
TRANSCRIPT
![Page 1: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/1.jpg)
GENERAL GENERAL PRINCIPLESPRINCIPLESGENERAL GENERAL
PRINCIPLESPRINCIPLESZenaida N. Maglaya, MD; FPSECPZenaida N. Maglaya, MD; FPSECP
Department of PharmacologyDepartment of Pharmacology
![Page 2: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/2.jpg)
GENERAL PRINCIPLES• PHARMACOLOGY• DRUG• MEDICAL PHARMACOLOGY• PHARMACY• PHARMACOGNOSY• PHARMACOKINETICS• PHARMACODYNAMICS
![Page 3: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/3.jpg)
PHARMACOKINETICS• ABSORPTION
• DISTRIBUTION
• BIOTRANSFORMATION/ METABOLISM
• EXCRETION
![Page 4: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/4.jpg)
FACTORS AFFECTING ABSORPTION
• I. DRUG• II. TYPES OF TRANSPORT
1. SIMPLE DIFFUSION 2. FILTRATION3. ACTIVE TRANSPORT4. FACILITATED DIFFUSION5. PINOCYTOSIS
![Page 5: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/5.jpg)
FACTORS AFFECTING ABSORPTION
• FICKS LAW OF DIFFUSION: Permeability CoefficientRATE = (C1-C2) ------------------------------ X AREA THICKNESS
III. DEGREE OF IONIZATION Protonated form Log ----------------------------- - = pKa – pH Unprotonated form
![Page 6: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/6.jpg)
DEGREE OF IONIZATION
RNH3 -------------------> RNH2 + H • Protonated Unprotonated Proton• Weak Base Weak baseCharged more Uncharged more Water soluble lipid soluble
RCOOH -------------- RCOO - + H Protonated Unprotonated
Proton Weak Acid Weak AcidUncharged more Charged more Lipid soluble warer soluble
![Page 7: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/7.jpg)
FORMULA• I 10 pH - pKa • Weak Acid = ----- = -----------• U 1
I 10 pKa - pH • Weak Base = ----- = -----------• U 1
![Page 8: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/8.jpg)
EXAMPLE 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
![Page 9: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/9.jpg)
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
![Page 10: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/10.jpg)
ROUTES OF ADMINISTRATION• I. ENTERAL
1. ORAL2, SUBLINGUAL & BUCCAL3. RECTAL
II. PARENTERALA. INJECTIONS 1. INTRAVENOUS` 2. INTRAMUSCULAR
3. SUBCUTANEOUSB. INHALATIONC. TOPICALD. TRANSDERMAL
![Page 11: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/11.jpg)
DISTRIBUTION OF DRUGS
• SIZE OF THE ORGAN• BLOOD FLOW• LIPID SOLUBILITY• TISSUE BINDING
• Vd = VOLUME OF DISTRIBUTION
![Page 12: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/12.jpg)
METABOLISM OR 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
![Page 13: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/13.jpg)
PHASE I METABOLISM• OXIDATIONA. OXIDATION P450 DEP
HYDROXYLATIONS:barbiturates, phenytoin, amphetamines
• N - ALKYLATIONS: morphine,caffeine, theophyllline• O --DEALKYLATION: codeine• N -OXIDATION: acetaminophen, nicotine• S-OXIDATION: cimetidine, chlorpromazineB. OXIDATION P450 INDEPENDENT AMINE OXIDATION:
epinephrine• DEHYDROGENATION: ethanol, chloral hydrate• REDUCTION: chloramphenicol, naloxone• HYDROLYSISA. Esters: procaine aspirinB. Amides: lidocaine, indomethacin
![Page 14: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/14.jpg)
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
![Page 15: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/15.jpg)
DRUG METABOLISM•
INDUCER DRUG INDUCEDPHENOBARBITAL Chloramphenicol,
Digoxin, Phenytoin Coumarin, Quinine, Testosterone
RIFAMPIN Coumarin, Digitoxin, Oral Contraceptives
Metoprolol, QuininePHENYTOIN Cortisol, Dexamethazone Digitoxin, TheophyllineGRISEOFULVIN Warfarin
![Page 16: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/16.jpg)
DRUG METABOLISM• INHIBITORS• CIMETIDINE Diazepam, Warfarin• Chlordiazepoxide• ISONIAZID Antipyrine,
Dicoumarol, Probenecid
• PHENYLBUTAZONE Phenytoin, Tolbutamide
![Page 17: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/17.jpg)
EXCRETION
• GLOMERULAR FILTRATION• TUBULAR EXCRETION• TUBULAR REABSORPTION
• ELIMINATIION• ZERO ORDER KINETICS• FIRST ORDER KINETICS
![Page 18: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/18.jpg)
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
![Page 19: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/19.jpg)
DOSAGE REGIMEN LOADING DOSE = Vd X desired plasma concentration MAINTENANCE DOSE = Cl X desired plasma concn
STEADY STATE PLASMA CONCENTRATION, OR PLATEAU 1ST HALF LIFE= 50% 4th half life = 94%
2ND HALF LIFE = 75 % 5th half life = 97% 3rd half life = 88% 6th half life = 99%
![Page 20: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/20.jpg)
DRUG EVALUATIONI. PRECLINICAL PHASE
A. SAFETY & EFFICACYB. ANIMAL TESTING: Acute, Subacute, ChronicC. TYPES OF ANIMAL TEST: Pharmacologic Profile, Reproductive Toxicity, Carcinogenesis
II. CLINICAL PHASEa. PHASE Ib, PHASE IIc. PHASE IIId. PHASE IV
![Page 21: Gen Prin Sp Class](https://reader034.vdocuments.us/reader034/viewer/2022051617/55b17a12bb61eba8268b4677/html5/thumbnails/21.jpg)
Thank You!If any of you lacks wisdom, let him ask of God, who gives to all, liberally and without reproach, and it will be
givento him.
James 1: 5