Gastrointestinal Absorption Lecture 2 Flashcards Preview

PM2B: Journey Through the GI tract > Gastrointestinal Absorption Lecture 2 > Flashcards

Flashcards in Gastrointestinal Absorption Lecture 2 Deck (16):
1

Describe the process of oral drug administration?

1. Disintegration and dissolution (luminal degradation)

2. Diffusion through GI fluids

3. Membrane permeation, active transport (travel through efflux pump and uptake) (metabolism in enterocytes)

4. Uptake into portal vein blood headed to the liver (First pass hepatic extraction)

5. Onwards to systemic circulation, binding to albumin

2

What are the 5 barriers to GI drug absorption?

1. Lumen

2. Mucous membrane

3. Not properly crossing membrane: bile salts change charge so drug cannot cross

4. Metabolism before the drug reaches the plasma:

5. Diseased states that can effect each of the above barriers

3

Describe the chemical degradation involved in the lumen that acts as a barrier?

1. pH in the stomach when fasted or fed

2. Drug stability often affected by pH

3. Drugs such as erthyromycin, methypenicillin and omeprazole depend on the pH to metabolise them

4. Enteric coated tablets can be used to bypass the stomach and prevent gastric irritation

4

Describe the enzymatic degradation involved in the lumen that acts as a barrier?

1. Stomach: pepsin which will cleave amino acids such as cyclosporin

2. Small intestines: lipases, amylases and proteases
- Stimulated by presence of food

3. Drugs which resemble nutrients will be cleaved by these enzymes

4. Colon has many bacterial enzymes that cleave molecules: sulfazalzine is broken down to treat ulcerativie colitis

5

Describe the complexation involved in the lumen that acts as a barrier?

1. Lifestyle factors: Milk and antacids neutralise the effect of tetracycline

2. Secretions: Bile salts stimulated by food, generally solubilise poorly water soluble drugs
- Can also form insoluble complexes with drugs such as nystatin

6

Describe the adsorption involved in the lumen that acts as a barrier?

1. Drug can bind to food molecules due to ions having high energy

2. Rarely happens, however, charcoal is used to absorb toxins

7

Describe the two separate structures of the mucus layer?

1. One firmly attached to the endothelial cells

2. One loosely attached that can slough off and transit with/lubricate food

8

Describe how drug absorption may be effected by the mucus?

1. Has to cross the mucous to reach the membranes

2. If high viscosity of mucous there is less absorption

9

Describe the functions of the epithelial cells and where they are found in the small intestine?

1. Found on the basal membrane that are joined together by tight junctions (contains brush border)

2. They express:
- ABC transporters: efflux cells back into lumen
- Cytochrome P450 enzymes: metabolise some drugs

10

Explain the transcellular route of absorption through the GIT?

Major route of absorption

1. Passive diffusion: no energy needed

2. Ficks law: concentration gradient driven, dependent on partition co-efficient

3. Apical membrane phospholipid: lower permeability than basolateral membrane

4. Molecules partition and diffuse into membrane and interior to reach basolateral membrane

11

Explain the paracellular route of absorption through the GIT?

1. Absorption by travelling through tight junctions between cells

2. Moderately sized molecules

3. Passive diffusion mechanism

4. Generally for molecules like Ca2+, amino acids

12

Explain the carrier mediated route of absorption through the GIT?

1. Between many transporters (proteins) in apical cell membrane

2. Examples:
- Peptide, nucleotide, sugar, amino acid, bile

3. Drug properties that are similar to natural substrates are binded and carried through apical membrane AGAINST concentration gradient

13

Define what transcytosis is?

Vesicle with internalised material is transported through to the other side of the cell and secreted on the opposite basolateral cell

14

Describe the function of counter transport efflux proteins?

1. Highly expressed on apical membrane

2. Efflux (re-transport) back into the lumen

3. Nifedipine

15

Describe the pre systemic circulation?

1. Starting from the stomach/intestines/colon, drug travels from the hepatic portal vein to the liver before reaching systemic circulation

2. Cytochrome P450 metabolism

16

What are the local food effects that may effect the GIT?

1. Drug complications with pH, transit time, stimulating secretions

2. Completion for absorption mechanism
- active transport mechanisms

3. Higher viscosity slows dissolution

4. Grape fruit juice inhibits Cytochrome P450 so increased bioavailability

5. Food change alters blood flow
- Increases after food
- Faster rate of drug arriving at liver, saturates metabolising enzyme so more drug escapes first pass so bioavailability increases