Routes Of Admin Lec 2 PDB Flashcards
List three reasons what we prefer oral administration
1) Convenient
2) Well accepted by patients
3) Cheap
Where does drug and nutrient absorption take place?
Small intestine
The stomach secretes what two substances?
What happens to these two substances?
1) Hydrochloric acid
2) Pepsinogen
The hydrochloric acid stimulates the conversion of pepsinogen to pepsin by acidic hydrolysis.
Pepsin is a potent proteolytic enzyme
What happens to polypeptides and short peptides in the stomach?
Polypeptides are broken down by pepsin whereas small peptides can pass through unchanged
The small intestine has a huge surface area due to 3 things… what are they?
1) Folds of Kerckring
2) Villi
3) Microvilli
The large intestine is also known as the what?
Colon
The colon contains WHAT that can metabolise certain drugs?
Anaerobic and aerobic bacteria
Can metabolise drugs such as L-dopa
Strongs acids (pKa 10) are…
WELL or POORLY absorbed?
POORLY absorbed as a high percentage of molecules are ionised at pH of 6.5
What happens if movement of a drug through the GI tract is too fast?
The drug may pass through the system without being absorbed
What happens if movement of a drug through the GI tract is too slow?
The drug may be degraded or the epithelium may be irritated
The larger the meal, the __ the initial emptying rate
quicker
First pass effect results in a net __ of drug which reaches systemic circulation
loss
Amount of drug reaching systemic circulation depends on:
3 things…
1) Release from dosage form
2) Stomach, intestinal and hepatic 1st pass effects
3) Absorption across GI membrane
What is enterohepatic recycling?
- Drug eliminated by biliary secretion into small intestine
- Reabsorbed and reaches systemic circulation
Presence of food can have a complex effect on the abs and BA or drugs.
It can reduce, ___, ___ or have __ ____ on abs rate depending on drug
delay, increase or have no effect
Food can have complex effects on abs and BA of drugs by many mechanisms. List 8
1) Delayed gastric emptying time
- damage to protein or acid labile drugs
2) Stim bile secretion
- inc solubilisation and abs of lipophilic drugs
3) Inc viscosity of luminal contents
4) Stim hepatic blood flow
- effects on first pass metab
5) pH changes in GO tract
- decreased pH may aid dissolution of basic drugs - ionise
6) Change in luminal metab
- some foods activate/inhibit enzymes in GI
7) Interaction of drug and food
- e.g chelation
8) Competition for uptake transporter
- e.g L-Dopa, abs by AA transporter so compete protein
Statins cannot be taken with grapefruit juice for what reason?
Grapefruit juice inhibits CYP3A enzymes increasing BA of statin (reduces degradation) and can lead to muscle toxicity
What is P-gp and where is it found?
An efflux pump found in the apical membrane of cells in the small and large intestine (also BBB and liver etc…)
P-gp is known as an MDR protein. What does this stand for?
Multi drug resistance protein
List 4 advantages to oral drug delivery…
1) Convenient (accessible, good compliance)
2) Large surface area and rich blood supply
3) Prolonged retention and potential for 0 order release
4) Cheap
List 7 disadvantages to oral drug delivery…
1) Highly variable
2) Adverse reactions (gastro-toxicity)
3) High metabolic activity and hepatic 1st pass effect
4) pH extremes
5) Efflux pumps e.g P-gp
6) Intestinal motility
7) Impermeability of epithelium e.g large, hydrophobic peptides
Name 5 strategies for improving oral drug delivery…
1) Increasing drug lipophilicity - prodrugs
2) P-gp inhibitors
3) Cytoadhesion - target drugs to specific areas or cells in GI tract
4) Mucoadhesive patches
5) New delivery systems e.g protective coatings, micro and nanoparticles (micelles, vesicles etc)
How can membrane permeability be improved e.g in Ampicillin?
- Ampicillin is chemically modified to make more fatty prodrug
- Increases drug absorption as can cross lipid membrane
- Metabolised by esterase’s, cleaving the ester bond
- Leaves the parent drug
P-gp inhibitors are extremely useful at increasing bioavailability by preventing the efflux of which group of oral agents?
- Chemetherapeutics
