Flashcards in 6.0 Pharmacokinetics Deck (17)
What type of drug is preferentially absorbed in the stomach?
Weak acids (pH of stomach = 1)
Most drugs are absorbed in non-ionized forms
What type of drug is preferentially absorbed in the intestine?
Weak bases (pH or intestine = 7)
What factors affect oral bioavailability?
1) Degree of ionisation (↑ → drug doesn't get into plasma)
2) Digestion (some drugs are broken down in stomach)
3) Metabolism of drugs by enzymes in gut wall
4) First pass metabolism
6) Food in the gut (normal food → ↓ absorption, but poor water solubility drugs show ↑ absorption following high-fat meal)
What plasma proteins can drugs bind to?
- Makes up 50% of plasma protein
- Each one has multiple binding sites
- Binds most weak acids, neurals and some weak bases
- Most weak bases bind to this
- Single high affinity site
- Levels ↑ with age/injury/surgery
What factors affect the rate of drug entry into tissues?
1) Fraction of drug molecules bound to plasma
2) Relative rates of blood flow through capillary beds
3) Permeability of capillaries for free drug molecules
What can cross the blood brain barrier?
1) Lipid soluble molecules
2) Small polar essential nutrients
What organs are involved with drug metabolism?
What routes are available for excretion?
Where in the cell are the cytochrome enzymes found?
Smooth Endoplasmic reticulum (smooth ER)
What are the two phases of drug metabolism?
1) Phase I
Catalysed by CYP enzymes
(oxidation, reduction, hydrolysis, hydroxylation)
Products of this phase can still be active
2) Phase II
Catalysed by transferases
Rate limiting step
Products are nearly always inactive (exception = morphine)
What factors can cause the rate of drug elimination to vary between individuals?
1) Metabolism is poorly developed in neonates
2) Metabolism is ↓ in aged population
3) Different between males/females
4) Depressed by chronic hepatitis/cirrhosis
5) Genetic variation
6) Altered by drug-drug interactions
What drugs induce CYP metabolism with multiple administration (i.e. can induce tolerance)?
4) Cigarette smoking
What drugs inhibit CYP metabolism?
2) Imidazole containing drugs
What three processes determine the rate of excretion?
Rate = Filtration - reabsorption + secretion
What drugs show zero order elimination?
What factors affect rate of absorption of oral drugs?
1) Physical state of drug
2) Water solubility
3) Lipid solubility
4) Effect of pH
5) Chemical stability
6) Motility of gut