Pharmacology
Pharmacokinetics
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Get access- Volume of distribution = dose/plasma concentration at time of administration
With repeated administration, the plasma concentration is a function of the rate of administration and the rate of elimination
- Achieves steady state within 3-4 half-lives
- Steady state can be achieved faster by using a loading dose
- Drug half-life determines the frequency of subsequent doses
Bioavailability: the amount of oral dose that reaches the systemic circulation and is available to the site of action
- May be limited by first-pass metabolism
- Gut motility
- Intestinal pH, bile salts
- Enterohepatic circulation
- Intestinal blood flow
- Intestinal microflora
Hot Topic
Ocular topical drugs have higher bioavailability as they are absorbed via nasal mucosa and so avoid first-pass metabolism
- Drug kinetics
- First-order: linear increase in rate with increased drug concentration
- Zero-order: saturation at high drug concentrations
- Eg. when the capacity of liver enzymes is consumed
- Drug penetration of cells
- Diffusing through lipid (depends on lipid solubility)
- Diffusion through aqueous pores
- Via carrier molecules
- Pinocytosis
- Drug distribution
- Binding affinity for plasma proteins eg. albumin
- Highly bound drugs tend to remain in the plasma
- Binding to tissue proteins
- Blood flow to different tissues
Hot Topic
The blood-retinal and blood-aqueous barriers limit drug distribution in the eye. Usually only lipid-soluble drugs move between the blood and the retina. Systemically administered drugs do not necessarily produce high intraocular levels
- Drug metabolism
- Occurs almost entirely in the liver
- Increases drug solubility for excretion
- Might activate a prodrug to its active form
- May inactivate others
- Phase I: oxidation
- Performed by cytochrome p450
- This group of enzymes also exists in the eye
- Numerous inducers and inhibitors (including chloramphenicol)
- Phase II: conjugation
- Drug excretion
Renal excretion: varies widely between drugs depending on the kidneys capacity to handle the drug’s properties
- Glomerular filtration (if not protein-bound and small enough ie. <20,000Da)
- Tubular secretion into the glomerular filtrate
- Reabsorption
- Biliary excretion
- Conjugated drugs are concentrated in the bile and delivered to the intestine
- Drug may be released and re-absorbed (enterohepatic circulation)