Drug Absorption Flashcards
What is bioavailability?
Fraction of unchanged drug that reaches the systemic circulation.
What is bioequivalence?
- Equivalence to medication they are currently on.
- Two types - Generic substitution (same drug, different brand/way of making it) or Therapeutic substitution (alternative molecular make-up but has same assumed therapeutic effect. Can be from same class of drug).
- Generics must have between 80-125% bioavailability of reference medication.
How do physicochemical properties of a drug influence drug absorption?
-drug ionisation - weak bases ionised in acidic pH are absorbed in small intestine, ionised in plasma? Weak acids are un-ionised in acidic pH but also absorbed in small intestine due to large surface area.
How does oral routes of administration influence drug absorption?
- Buccal/sublingual mucosa - direct absorption into bloodstream, avoids first pass metabolism (bypasses liver), not ideal surface for absorption.
- Gastric mucosa - enteric coating.
- Small intestine - main site of drug absorption. Large surface area, more neutral pH.
- Large intestine - poor absorption, long transit times.
- Rectal mucosa - direct to systemic circulation.
How does drug formulation influence drug absorption?
- particle size & make-up: diffuses directly through the lipid (lipid solubility highly important), diffusing through aqueous pores (gases), transmembrane carrier proteins (e.g. solute carriers), pinocytosis (mostly macromolecules).
- binding agents
- excipients
- lubricants
- enteric coatings and sustained release formulations. Time retained in acid may aid dissolution.
How does gastrointestinal motility influence drug absorption?
- Effect of food on drug absorption - in general food tends to slow the rate of gastric emptying.
- Decreased absorption - intestinal motility, interactions with food and acids, presystemic metabolism.
- Delayed absorption - gastric emptying, Cmax is decreased, clinically important.
- Increased absorption - poorly water soluble drugs, increased solubilisation, decreased presystemic metabolism.
- Additional considerations - type of meal (solid v liquid, protein and fat content, other dietary factors?), is the drug a GI irritant?
- Effect of intestinal disease - alters rate of drug absorption due to disease state. Increased GI motility, compromised GI integrity. Reduced motility can be due to diabetic gastroparesis.
How does first pass metabolism influence drug absorption?
- Levodopa uptake
- Prodrug, treatment of parkinson’s disease
- Rapidly taken up from stomach and small intestine - large neutral amino acid transport carrier (LNAA).
- DOPA decarboxylase present in gastric mucosa - effect of retention in stomach?
How do drug interactions influence drug absorption?
Can be direct or indirect. Can change pH, motility, perfusion. Interfere with mucosal function. Chelation. Resin binding. Adsorption.
What are the advantages of administering drugs via the oral route?
- cheap
- safe
- convenient
What are the disadvantages of administering drugs via the oral route?
- patient compliance
- variation in bioavailability of drug between patients.
What are the advantages and disadvantages of using the inhalation route?
- Advantages - can locally and systemically affect. Good for volatile and gaseous anaesthetics, can be rapidly broken down in circulation.
- Disadvantages - can be a route for drugs of abuse amd accidental poisoning.
What are the advantages and disadvantages of using the topical route of administration?
- Advantages - can locally and systemically effect, large surface area/volume ratio
- Disadvantages - healthy skin can be a barrier for absorption, can accidentally gp through (accidental poisoning via AChEsterase insecticides).
What are the advantages and disadvantages of injecting drugs?
- Subcutaneous- slow absorption due to blood flow
- intramuscular - lipophilic drugs absorbed rapidly, polar drugs taken via bulk flow and endothelial cell junctions, and high MWT or very lipophobic drugs via lymphatics. Allergic?
- Rate of onset depends on extent of capillary perfusion, drug vehicle and can be affected by factors which alter perfusion.
Advantages and disadvantages of intranasal route?
- advantages - avoids hepatic first pass metabolism, ease, convenience, safety
- disavantages - limited drugs suitable as it requires concentrated drug
