Pharmacokinetics I Flashcards
Define adsorption
Movement of a drug from its site of administration into the blood
How are most drugs absorbed?
By passive absorption, some drugs need carrier mediated transport
Describe the rate of diffusion by small molecules and lipid soluble non-ionised drugs
Small molecules diffuse more rapidly than larger
Lipid drugs are absorbed faster
What are the different absorption processes?
Gastric emptying, colonic transit, via small intestine
Describe the effects of gastric emptying
Biological variability, greater motility with increased absorption, drugs taken with food to prevent gastric irritation
Describe the causes of gastric emptying
Increase in large liquid volumes, physical activity, emotional state
Decrease in ingestion of food, physical inactivity, depression
Describe what factors affect oral absorption
Drug chemical stability, motility/mixing in GI, type of food, passage across GI, blood flow to GI
What is the law of mass action?
Rate of ADME of drug occurs is proportional to its concentration in the body
Describe the first order process in terms of drug absorption
Rate of drug absorption is proportional to amount remaining to be absorbed
What is absorption half-life?
Time needed to increase plasma drug concentration by 50%
What is elimination half-life?
Time needed to reduce plasma drug concentration by 50%
Describe plasma membrane permeation of cells by drugs
Direct diffusion through lipid - Ionisation
Carrier-mediated transport - Uphill transport, Finite number of receptors leads to saturation/competition between drugs for transport
Diffusion through aqueous pores
Pinocytosis
Describe the effects of ionisation in terms of oral drugs
Mouth - Neutral
Stomach - Acid
Intestines - Alkaline
Many drugs are weak electrolytes so ionise to greater/lower in terms of pH
Degree of lipid solubility determined by ionisation
Describe the characteristics of GI tract
Oesophagus: pH5-6
Stomach: pH2-6 (fasting), pH1.5-2 (presence of food)
Small intestine: pH6-6.5 (duo/jej), pH7-8 (ileum)
Colon: pH5.5-7
Describe the factors affecting absorption in terms of oral drugs
Passive transfer relies on ionisation/lipid solubility of drugs
Non-ionised forms soluble in membrane lipids to cross
Strong bases poorly absorbed
Strong acids fully ionised
Describe the physiochemical properties of drugs
Too hydrophilic, unable to pass through membrane lipids
Too lipophilic, not soluble enough to penetrate intercellular media
What does ionisation depend on?
pH of the aqueous environment and drug dissociation constant
eg strong acid low pka vv
Describe aspirin in the body
Stomach: Aspirin unionised so lipid soluble/diffusible
Enters gastric epithelial cells, its ionised/localised there
Metabolised tp salicylic acid in body
pH 7.4: Highly ionised stays in extracellular fluid
Describe aspirin in overdose cases
Removal of salicyclic acid helped make urine more alkaline so aspirin’s more ionised so stays lipid insoluble, passes into urine
Describe amfetamine
Acidifying urine increases elimination
What is bioavailability?
Fraction of drug dose that reaches blood stream in an active form
What is bioavailability affected by?
First pass effect
Metabolism in gut wall
Hepatic disease
Drug formulation
Describe what bioavailability is dependent on
Amount of drug absorbed Route of administration Food intake Disease Drug interactions
Describe the extent of absorption
Due to bacterial metabolism in small intestine
Issue in elderly where bacterial overgrowth is pathological condition
