PHBP | Part 2 & 3 Flashcards
The enzymatic or biochemical transformation of the drug substance to (usually less toxic) metabolic products, which may be eliminated more readily from the body
METABOLISM
Principal site of metabolism
Both synthesizing and eliminating organ
LIVER
Basic unit of liver
Liver Lobule
A network of interconnected lymph and blood vessels
PARENCHYMAL CELLS
Perfused blood in the liver
Hepatic artery
Carries oxygen in the liver
Hepatic artery
Collects blood from various segments of GIT that perfuse in the liver
Hepatic Portal Vein
Carries nutrient to the liver
HEPATIC PORTAL VEIN
Large vascular capilaries
SINUSOIDS
Facilitates drug and nutrient removal before the blood enters the general circulation
SINUSOIDS
Endothelial lining of the sinusoids
Part of the Reticulo Endothelial system
Kupffer cells
Phagocytic macrophages
Kupffer cells
secreted by the liver
Bile Acids
3 Major Components of a drug biotransformation
Reactant (Drug/Xenobiotics)
Product (Metabolite)
Reaction catalyst (Enzymes)
5 Types of Metabolites
Inactive Metabolite
Retain Similar Activity
Altered Activity
Bioactivated Metabolite
Reactive Metabolite
Birth
Sulfation
1st Week
Reduction. Oxidation
1 month
Acetylation
2 months
Glucoronidation
3 months
Glycine, Glutathione, Cysteine Conjugation
Presystemic metabolism
First Pass Effect
Initial Biotransformation of an active drug BEFORE reaching the systemic circulation
FIRST PASS EFFECT
the final LOSS of the drug substance or its metabolites from the body
EXCRETION
Are excreted mainly by renal excretion, into the urine
NONVOLATILE DRUGS
Gaseous anesthetics, or drugs with high volatility, are excreted via lungs into expired air
VOLATILE DRUGS
Excretion Pathway
Anion, cations, non-ionized molecules with lipophilic polar groups & those with MW > 500
Biliary Excretion
Excretion Pathway
For drugs poorly absorbed in the intestines
Biliary Excretion
Excretion Pathway
Organic acids & organic bases - active transport
Consider ___________
Biliary Recycling
Excretion Pathway
via different transport mechanism
Salivary Excretion
Excretion Pathway
Nursing mothers should avoid taking drugs
Mammary Excretion
Excretion Pathway
Passive diffusion of the non-ionized moiety
Drug Excretion into Sweat
Excretion Pathway
Less soluble anesthetics
Soluble gases
Drug Excretion Into Expired Air
Excretion Pathway
Prostate secretions
Genital Excretion
Excretion Pathway
Verified by the presence of drugs in the gut lumen after IV adminstration
Intestinal Excretion
Excretion Pathway
Major Route
Non-volatile, water-soluble, low MW Drugs
Renal Drug Excretion
Kidney is located in the ______
Peritoneal Cavity
Most imp organ for excretion
Kidney
secretion of _____ (regulates BP)
Renin
secretion of _______ (RBC production)
Erythropoetin
Basic unit of kidney
Nephron/Malphigian Bodies
Filtration of LMW molecules
Glomerular filtration
Normal GFR:
125mL/min (180 L/day)
tells how healthy the kidney is
GFR
Average urine:
1-1.5L (99% are reabsorbed)
Pressure of artery
100mmHg
Pressure on glomerulus
45-65 mmHg
fulfills most of the criteria needed
standard reference
Inulin
used most extensively as a measurement of GFR
Clearance of Creatinine
Byproduct of muscle metabolism
Creatinine
Occurs in PCT
Active Tubular Secretion
Reabsorption of water and active secretion of some weak electrolytes esp weak acid
Active Tubular Secretion
occurs in DCT
reabsorption of water and passive excretion of lipid soluble drugs
Tubular Reabsorption
Depends on urine pH based on Hendersson-Hasselbalch equation
Tubular Reabsorption
The maximum amt of drug in the body following a single rapid _____ is equal to the dose of the drug
IV Injection
For a one-compartment open model, the drug will be eliminated acc to
First-order kinetics
Is a drug product that contains the same active drug substance in the same dosage form and is marketed by more than one pharmaceutical manuf
Multi Drug Product
Patent has not be expired or has ceratin exclusivities so that only one manufacturer can make it
Single Source Drug Products
Identifies drug products approved on the basis of safety and effectiveness by the FDA
Approved Products with Therapeutic Equivalence Evaluations (Orange Book)
same active ingredients, salt, dosage form and strength, ROA, content uniformity
Pharmaceutical Equivalent
same therapeutic moiety but…as different salt, dosage form and strength
Pharmaceutical Alternative
Safe and effective pharmaceutical equivalent, bioequivalent, adequately labeled, complied with CGMP
Therapeutic Equivalent
Contains different active ingredients indicated for the same therapeutic use
Therapeutic Alternative
Tmax, Cmax, AUC
Plasma Drug Concentration
Du, dDu/dt, t
Urinary Drug Excretion
Emax
Acute Pharmacodynamic Effect
Well controlled clinical trials
Clinical Observations
Drug Dissolution
In-Vitro Studies
Based on aqueous solubility of drug and the permeation of the drug through GI tract
Biopharmaceutics Classification System (BCS)