Flashcards in Gastrointestinal Absorption Lecture 1 Deck (22):
What are the drug properties that affect solubility in the GIT?
1. Drug forms (salts)
2. pH (Ionisation): acidic environment will let it get ionised
3. Surfactants (Bile Salts)
4. Must have some solubility to liberate molecules
5. Molecules must pass through membranes (not particles)
What are the drug properties that affect dissolution in the GIT?
1. Particle size
4. Noyes whitney equation: IMPORTANT
- (Rate of diffusion + Rate of area)/area of thickness
Diffusion co-efficient/ Movement of molecules to membrane
Describe partitioning in terms of a weakly acidic drug with a pKa of 3?
1. Stomach at pH 1.2 = mostly unionised (98.4%)
2. Intestinal fluid at pH 6.8 = totally ionised (99.98%)
Describe partitioning in terms of a weakly alkaline drug with a pKa of 5?
1. Stomach at pH 1.2 = mostly ionised
2. Intestinal fluid at pH 6.8 = nearly totally unionised
What is the generic meaning of the pH partition hypothesis?
1. Weakly acidic drugs are likely to be absorbed in the stomach where it's unionised
2. Unionised bases are likely to be absorbed in intestines
Describe why the intestines may absorb weakly acidic drugs better than the stomach?
1. Larger surface area- compensates for ionisation
2. Longer residence time for ionisation
3. Microclimate differences in pH
4. Mucous layer must be crossed: especially water
5. Ionised form could react with other ions to form neutral one- aids lipophillicity
6. Connective flow of water through membrane could have carrier ions across epithelium
How does change in GI physiology affect the absorption?
1. Various pH's
2. Variations in transit times
3. Variations in enzymes present, bile acids, bacteria and number of bacteria/types
4. Variable if fed or fasted
5. Pressure and peristalsis
Describe the region of the mouth when administering medication?
1. Usually first site of entry for tablets, capsules, solutions and suspensions
2. Rich in oxygenated blood
3. Can be used for sublingual methods as it has a lot of blood vessels: GTN spray to cause vasodilation
4. Allows for a fast onset of action
Describe the region of the oesophagus when administering medication?
1. Must stand up right and straight when swallowing medication to allow proper metabolism
2. Epithelial cells with simple mucous glands secrete mucus to lubricate
3. Peristalsis wave moves the content down o oesophagus
4. Assisted by gravity
Describe the role of gastrin in the stomach and how its released?
1. Stimulated by peptides, amino acids and muscle distention
2. Gastrin stimulates acid production and is released by G cells
3. Pepsins break proteins to peptides
4. Mucous secreted to lubricate
Describe the role of the stomach in the GIT?
1. Contains stomach acid which removes bacteria and pathogens
2. Turns solid into chyme for digestion
3. Reservoir for ingested food and APIs- controlled release to the intestines- sphincter delivers to small intestine
4. Not major site for absorption- relatively small surface area
5. Gastric emptying can affect absorption (later), varies between fed and fasted, type of dosage form etc
7. Degrades noxious agents away from small intestines
Describe what the small intestine comprises of and its main role?
1. Duodenum: buffers contents down
4. Drug and nutrient absorption
- Rich in blood and lymph supply
- Long residence time
- Large surface area
5. Enzymatic digestion
Describe what the large intestine (colon) comprises of and its main role?
2. Ascending colon
3. Transverse colon
4. Descending colon
6. No villi but does have microvilli and folds
7. Very long residence time
8. Storage of faeces and waste products
Explain the transit of a tablet through the oesophagus and how it should be down?
1. Tablet should be swallowed up right to allow for it to pass through quickly- if not done, can lead to capsule/tablet adhering to the oesophagus wall to form gel
2. Liquids transit the fastest
3. When tilting head back, this actually closes up the oesophagus which can lead to difficulty swallowing
Explain what gastric emptying time is and how it's affected?
1. Time to pass through the stomach
2. Highly variable
- 5 to 2 hours fasted
- 12 hours or more fed
3. Dosage forms: Large dosage forms and floating ones
4. Poorly soluble drugs: taken better with food to increase time in body
5. Drugs you want to act quickly, take when fasted, sumatriptan
What are the four phases of electrically stimulated contractions of the stomach?
1. Occasional contractions 40 to 60 mins
2. Stronger contractions 40 to 60 mins
3. Power peristalsis, pylorous opens and stomach empties
4. Short transition back to step one
After the stomach is fed, what happens in the electrical stimulated contractions of stomach?
1. Proximal tubule relaxes to allow food in
2. Contractions move food distally, mix it up and break it down
3. Liquid and food particles seep through pyloric sphincter
4. Next peristaltic wave expels digested food
How does the composition of food effect tablet absorption?
Fattier the food, the longer it takes for the tablet to be absorbed into the small intestine
Explain what the transit time is like in the small intestine?
1. Different from stomach as it's the same fed or fasted
2. All it depends is on residence time, the longer the more absorption
3. Can use enteric coated to reach intestines straight away
What are the drugs that must be looked out for when it comes to transit time?
1. Aspirin, taken with or after food as it can cause irritation and ulcers in stomach lining
2. Tetracycline: contraindicated in children as can bind with calcium to form oxalates which altogether affects growth
3. Statins: do not take with grape fruit juice: affects bioavailability
How does age affect transit time?
1. Older: Increase gastric pH and transit time
- Decrease GI blood volume
- Vitamin D, folate and B12 absorption reduced
2. Neonates: Less bile salts: Less drug absorption