Drug Absorption Flashcards
Bioavailability
Fraction of unchanged drug that reaches the systemic circulation
IV injection gives 100% bioavailability
Bioequivalence
Generics vs therapeutic substitutions
Generics must have a bioavailability of
80-125% compared to the reference product (EU reg.)
Generic substitution
when a different formulation of the same drug is substituted
Therapeutic substitution
the replacement of the originally-prescribed drug with an alternative molecule with assumed equivalent therapeutic effect. The alternative drug may be within the same class or from another class with assumed therapeutic equivalence.”
Advantages of oral route
– Cheap
– Safe
– Convenient
disadvantages of oral route
– Patient compliance
– Variation in bioavailability of drug
Journey of an oral drug
oral dose destroyed in gut not absorbed destroyed by gut wall destroyed by liver
Buccal / sublingual mucosa
– Direct absorption in to bloodstream
– Avoids first pass metabolism
– Not ideal surface for absorption
Gastric mucosa
– Enteric coating
Small intestine
– Main site of drug absorption
– Large surface area, more neutral pH
Large intestine / colon
– Poor absorption, long transit times
rectal mucosa
- direct to systemic circulation
Four ways small molecules cross cell membranes
- diffusing directly though the lipid
- lipid solubility is important - diffusing through aqueous pores
- more likely for diffusion of gases - transmembrane carrier protein
- solute carriers - pinocytosis
- mostly macromolecules
Weak bases
– Ionised in acidic pH
– Absorbed in small intestine – Ionisation in plasma?
Weak acids
– Unionised in acidic pH
– BUT also absorbed in small
intestine
• Large surface area
what is the general rule when it comes to food and drug absorption
slows down the rate of gastric emptying
why would food cause decreased absorption
intestinal motility
interactions with food, acids and presystemic metabolism
why would food delay absorption
gastric emptying, Cmax may be decreased (maximum concentration that a drug achieves in tested area after the drug has been administrated)
why would food cause increased absorption
poorly water soluble drugs
- increased solubilisation
- decreased presystemic metabolism
what things should you consider when thinking about the interaction between drugs and food
is the drug an irritant?
- solid vs liquid
- protein and fat content
- other dietary factors
Levodopa uptake
- Prodrug, treatment of Parkinson’s disease
- Rapidly taken up from stomach and small intestine by LNAA transport carrier
- HOWEVER DOPA decarboxylase is present in the gastric mucosa and this causes the DOPA > dopamine reaction and then dopamine is hydrolysed and doesn’t last long so this medication is normally taken with something which inhibits this enzyme
Altered rate of drug absorption due to disease state
increased = crohns decreased = coeliac disease
factors that affect oral absorption
Particle size and formulation
GI motility
First pass metabolism
– First pass metabolism by gut wall or hepatic enzymes Physicochemical factors
– Direct drug interactions, dietary factors, varying pH
Subcutaneous
– Slow absorption due to blood flow
Intramuscular
– Lipophilic drugs rapidly
– Polar drugs via bulk flow and endothelial cell junctions
– High MWT or very lipophobic drugs via lymphatics
Rate of onset
– Extent of capillary perfusion
– Drug vehicle
– Affected by factors that alter perfusion
Inhalation
Alveolar epithelium and bronchial mucosa Systemic effects • Lipid-solubledrugs – Volatile / gaseous anaesthetics • Drugs of abuse • Accidental poisoning
inhalation local effects
– Modify structure (ipratropium)
– Particulate size (salbutamol)
– Selectivity for receptors (salbutamol)
– Rapid breakdown in circulation (fluticasone)
Intranasal advantages
Easily accessible, rich vascular plexus
• Avoids hepatic first pass metabolism
• Ease ,convenience, safety
Intranasal limitations
• Limited drugs suitable
– Requires concentrated drug
Topical route
Healthy skin is a barrier
– Stratified, squamous epithelium
– Keratinised layer
– Sebaceous gland secretions
local effects of topical route
– Corticosteroids for eczema (hydrocortisone)
– Antihistamines for insect bites (mepyramine)
– Local anaesthetics (EMLA)
systemic effects of topical route
– Transdermal patches (HRT, GTN, nicotine)
– Accidental poisoning (AChEsterase insecticides)
