Drug Absorption Chapter 4 - MADAN Flashcards
(15 cards)
The lack of availability of the drug being absorbed
1- incomplete dissolution of the drug from the dosage form
2- partial or slow activation of drug in the gastric environment
routes that by pass the GI tract
IV
IM
SQ
SL
RECTAL
SKIN - transdermal patch
example nitroglycerin
if we want immediate absorption into the systemic circulation give it SL!
transdermal patch - is for sustained release of frugs
drugs with a high MWT cannot be given transdermal because they cannot diffuse through the skin
true!
drugs unstable in solution form are what
they are reconstitutions just before administration
oral administration
drug release depends on 3 factors -
1- physicochemical properties of the dosage form
2 - physiochemical factors of the human body at site of admin/absorption
3-physiochemical properties of the dosage form
biopharmaceutics classification system
Class 1 - High membrane permeability high aq. solubility
Class 2- High membrane permeability LOW aq. solubility
Class 3- low membrane permeability high aq. solubility
Class 4- low membrane permeability low aq. solubility
pharmakinetics process
drug at site of admin (Extravascular) then absorption then bound drug to plasma or unbound/free drug is distributed at the target site is clinical effect and then it is elimination as excreted unchanged or as metabolized and then metabolites are excreted
routes of drug admin
Intravascular - no ABOSRPTION AT IV!!
Extravascular
1 - PARENTERAL - IM/SC
2 - NONPARENTERAL - oral, rectal, vaginal, dermal (painless, less expensive, compliance, self medication) - PREFERRED!
Topical absorption - absorption not good!
- stratum coreum 3-5x LESS permeable than dermis
- 1.73m^2 vs. 120-200m^2 in small intestine
- statuem coreum in phase 2 lipid/protein heterogenous membrane in which lipid is continuous
PASSIVE DIFFUSION
***1.73m^2 is the SA of a normal adult BSA at 65kg **
***1.73m^2 is the SA of a normal adult BSA at 65kg **
true
120-200m^2 is BSA if the GI tract
true
topical administration
concentration in delivery system
drug affinity for vehicle
surface area for film
film thickness
permeation enhancers
Nature of skin - anatomical region; age of patient; sex of patient; thickness if skin; multiple application ; psoriasis dermatitis, hydration, metabolism of drug in skin; binding of drug in epidermis
advantages -
avoids biochemical degradation in the GI tract
avoids presystemic metabolism in the gut wall and liver (AVOID 1ST PASS EFFECT)
provide long period of drug action for short acting drugs
transdermal is recommend for potent lipophilic drugs with SHORT half lives
disadvantages -
metabolism of drug in skin
binding to epidermis
blood supply affected by drug
TRANSDERMAL patch helps so you dont need to give the drug as often.
statuem coreum to the viable epidermis to the dermis **CAPILLARY NETWORK to intracellular pathway or transcellular pathway
intracellular - is between the space of dead cells
transcellular - is across the cells (small and lipophilic)
transdermal we want ZERO ORDER KINETICS
Passive diffusion
high to low concentration
dc/dt = DAKC/h –> Fick first law
Henderson/Hasselback equation
ph =pka +log (ionized/unionized)
this equation is good for solubility not PERMEABILITY
Transport through a semi permeable membrane. it is transport mechanism where drug first dissolve in aqueous portion of membrane and then dissolution in the lipid portion of membrane, the solubility of the drug in the aqueous portion and the lipid is governed by partition coefficient of drug. after entering the membrane the drug leaves the lipid portion of membrane and dissolve again in aqueous portion (ON OTHER SIDE OF MEMBRANE) - based on concentration gradient
conc OF DRUG AT ABSOPRTION SITE is greater than conc of drug in the BLOODSTREAM. so the conc gradient always favors absorption.
dc/dt = DAKC/h –> Fick first law
D= diffusion coefficient of drug
A is SA of the absorbing membrane
K is partition coefficient of drug
c is conc gradient
h is thickness of absorbing membrane
rest is on google doc
