Drug Absoprtion Flashcards
What is bioavilability?
Fraction of unchanged drugs that reaches the systemic circulation
What gives 100% bioavaiability?
IV injection
What must generics have a bioaviability of?
must have a bioavailability of 80-125% compared to the reference product (EU regulation)
What is generic substiution?
occurs when a different formulation of the same drug is substituted. All generic versions of a drug are considered by the licensing authority to be equivalent to each other and to the originator drug
What is therapuetic substitution?
is 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 of from another class with assumed therapeutic equivalence
What are the advantages of the oral route of administration of drugs?
- cheap
- safe
- convienent
What are the disadvantages of the oral route of drug administration?
- patient compliance
- variation in the bioaviability of the drug
What are the main contributors to particle size and formulation of oral drugs?
Excipients, binding agents, lubricants and coatings
What are the 5 main oral routes?
- Buccal/sublingual mucosa
- Gastric mucosa
- Small intestine
- Large Intestine/colon
- Rectal mucosa
describe the buccal/sublingual mucosa route
- Direct absorption into blood stream
- Avoids first pass metabolism
- Not ideal surface for absorption
How are drugs adapted to by-pass the gastric mucosa?
Enteric coating
What is the main site for drug absoprtion?
- Small intestine
- Main site of drug absorption
- Large surface area, more neutral pH
How do drugs enter the systemic circualtion via the rectal mucosa?
Direct entry
What are the 4 ways small molecules cross the cell membrane?
- Diffusing directly through the lipid
- Lipid solubility highly important
- Diffusing through aqueous pores
- More likely important for diffusion of gases
- Transmembrane carrier protein
- E.g. solute carriers
- Pinocytosis
- Mostly macromolecules, not drugs
What are the 2 main methods that drugs cross cell membranes?
- Diffusing directly through the lipid
- Lipid solubility highly important
- Transmembrane carrier protein
- E.g. solute carriers
Describe the drug ionisation of weak bases
- Ionised in acidic pH
- Absorbed in small intestine
- Ionisation in plasma?
Describe the drug ionisation of weak acids
- Unionised in acidic pH
- BUT also absorbed in the small intestine
- Large surface area
Draw the henderson-hasselbach for a weak base
compartment 1 = blood
compartment 2 = SI
Draw the henderson-hasselbach equation for a weak acid
How does food affect the rate of gastri emptying?
generally slows rate
What can cause decreased absoprtion?
- intestinal motility
- interactions with food, acids
- presystemic metabolism
What can cause delayed absoprtion?
- gastric emptying
- Cmax may be decreased
What can cause increased absoprtion?
- poorly water soluble drugs
- increase solubilisation
- decrease presystemic metabolism
How do antacids and proton pump inhibitors affect absoprtion?
changes in gastric or intestinal pH
How do Laxatives and anticholinergics alter absoprtion?
Changes in gastrointestinal motility
How do vasodilators alter absoprtion?
changes in Gi perfusion
How does neomycin alter absoprtion?
interference with mucosal function (decrease in SA)
How do teracycline, calcium and magnesium alter absoprtion?
chelation (binding)
How does cholestyramine alter absoprtion?
resin binding
how does charcoal alter absoprtion?
adsoprtion
What 2 diseases commonly affect GI motility?
Crohn’s and coeliac
What are the main factors that affect oral absoprtion?
- Particle size and formulation
- GI motility
- First pass metabolism
- First pass metabolism by gut wall or hepatic enzymes
- Physiochemical factors
- Diet drug interactions, dietary factors, varying pH
- Splanchnic blood flow
- Increased flow increases drug absorption
- Efflux pumps
- P-glycoprotein
Describe the subcutaneous route
Slow absorption due to blood flow
Describe the intramuscular route
- Lipophilic drugs rapidly
- Polar drugs via bulk and endothelial cell junctions
- High MWT or very lipophobic drugs via lymphatics
Describe the rate of onset in parenteral routes
- Extent of capillary perfusion
- Drug vehicle
- Affected by factors that alter perfusion
What are the systemic effects of inhalation of drugs?
- Lipid-soluble drugs
- Volatile/gaseous anaesthetics
- Drugs of abuse
- Accidental poisoning
What are the local effects of inhalation of drugs?
- Modify structure (ipratropium)
- Particulate size (salbutamol)
- Selectively for receptors (salbutamol)
- Rapid breakdown in circulation (fluticasone)
What are the advanyahes of intranasal drugs?
- Avoids hepatic first pass metabolism
- Ease, convenience, safety
What are the disadvantages of intranasal drugs?
Limited drugs suitable - Requires concentrated drug
Describe healthy skin
- Stratified, squamous epithelium
- Keratinised layer
- Sebaceous gland secretions
What are the local effects of the topical route ?
- Corticosteroids for eczema (hydrocortisone)
- Antihistamines for insect bites (mepyramine)
- Local anaesthetics (EMLA)
What are the systemic effects of the topical route?
- Transdermal patches (HRT, GTN, nicotine)
- Accidental poisoning (AChEsterase insecticides)
What must be closely checked when using the topical route?
surface area to volume ratio
What are the key drug factors influencing route of administration?
lipid-solubility, weak acid/base, charge and size
What are the key bioloigcal factors influencing drug absoprtion?
blood flow, surface area, metabolic enzymes and compartment pH
