ADME Of Drugs Flashcards
What does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
What routes of administration are there?
Oral - most favourable
Sublingual - absorption under tongues “angina spray”
Rectal - diazepam
Injection & inhalation
Other epithelial surfaces:
Skin
Cornea
Vagina
Nasal mucosa
What is topical and systemic administration?
Topical is onto the skin
Systemic is into the body
What’s the difference between enteral and parenteral administration?
Enteral is via the GI-tract
Parenteral is Non-GI tract route
What’re the benefits of oral administration?
Easy for patients to take - high patient compliance
Formulation can be manipulated to alter rate of absorbance
Require gastrointestinal absorption
When is rectal administration used?
Used for drugs to produce a local effect
Useful method when patients are unable to take medication orally - post op or due to vomiting
Con - cannot be administered intravenously
What’s the benefits of sublingual administration?
Gives rapid response - angina attack
Good for drugs which are unstable at gastric pH or are metabolised rapidly
What does the rate of absorption depend on for intravenous administration?
Diffusion through local tissue
Removal by local blood flow
(Want little tissue with good blood flow)
What is a Bolus injection?
IV injection, fastest and most certain route
Rapidly produces a high concentration in the right heart, pulmonary vessel and systemic circulation - morphine/adrenaline
What is IV infusion?
A steady intravenous infusion avoids peaks of systemic concentrations and uncertainty over absorption
What’re the benefits of administration by inhalation?
Achieves high local drug concentration - minimises systemic effects
Administration of volatile and gaseous anaesthetics - nitrous oxide
Large SA and high blood flow in lungs allow rapid changes in systemic concentration
What is cutaneous administration?
Used when a local effect on the skin is required - topical steroid creams
Significant absorption can occur leading to systemic effects - transdermal patches / voltarol
Why is the small intestine so efficient?
Micorvilli provide very large surface area ≈ 200m^2
High blood flow
Bile help solubilise some drugs
What is transcellular absorption?
Passive and facilitated diffusion as well as active transport pathways through the phospholipid bilayer
What is paracellular absorption?
For non-lipophilic drugs, pass between cells into blood capillary
What factors affect GI absorption?
Physiochemical factors
- water solubility
- lipophilicity
- ionisation
Formulation
- solution > emulsion > suspension > capsule > tablet
Interaction with food - chelation of tetracycline with calcium milk
Drug-drug interactions
What is the rate determining step in drug absorption?
Gastric emptying - hence time taken can be used for estimating dose absorption
What drug-drug interactions influence GI absorption?
Stomach emptying time - anticholinergics
Gut motility - laxatives
Decreased blood circulation - CV drugs
Adsorption by antacids
Adsorption by ion exchange resins
What is partition coefficient P?
Conc in organic solvent / conc in aqueous phase
What does Log P indicate? What does a greater Log P mean?
Log of partition coefficient P indicates the lipohilicity of the drug
A greater Log P means greater lipophilicity
How does the lipophilicity of a drug affect how it is administered?
A higher lipophilicity means administration absorption should be lower to avoid unwanted effects / toxic build up in fatty tissues
What is the definition of pKa?
The pH of an acid/base when it is 50% dissociated
What absorbs better weak acid and bases or strong acids and bases?
Weak acids and bases absorb better
pH ≈ 5 is optimal
What is pH partition theory?
Ionisation also affects the steady state distribution of drug molecules between two aqueous compartment if a pH difference exists
