Drug Absorption Flashcards
What is the bioavailability of IV injection?
100%
What is bioavailability?
Fraction of unchanged drug that reaches the systemic circulation
What does the area under a palsma concentration against time curve represent?
The overall exposure to the patient
What must generics’ bioavailibility be in comparison with the reference product *EU reg.)?
80 - 125%
What is a generic subsitution?
Occurs when a different formulation of the same drug is substituted
What is 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
What class of drug can have its affects greatly altered by generic substitution?
Antipsychotics
What are the advantages of the oral route?
- Cheap
- Safe
- Convenient
What are the disadvantages of the oral route?
- Patient compliance
- Variation in bioavailability of drug
What factors can cause an oral drug to not reach systemic circulation?
- Destroyed in gut
- Not absorbed
- Destroyed by gut wall
- Destroyed by liver
Describe the features of the buccal / sublingual mucosa?
- Direct absorption into blood stream
- Avoids first pass metabolism
- Not ideal surface for absorption
Where is the main site of drug absorption?
SI
What is the advantage of absorption via the rectal mucosa?
Direct to systemic circulation
What are the 4 ways small molecules cross cell membranes?
- Diffusing directly through lipid
- Diffusing across aqueous pores (more likely important for diffusion of gases)
- Transmembrane carrier protein (e.g solute carriers)
- Pinocytosis (mostly macromolecules, not drugs)
What are the feautures of weak bases?
- Ionised in acidic pH
- Absorbed in SI
- Ionisation in plasma?
WHat are the features of weak acids?
- Unionised in acidic pH
- BUT also absorbed in SI
Large surface area
What is the HEnderson-Hasselbach equation?
pKa - pH = log10([BH+]/[B])
What is the difference between the HH eqn when using a weak acid vs a weak base?
- Acid = ionised form goes on bottom of eqn
- Base = ionised form goes on top
- H always stays on top
Will a weak acid more likely be more ionised or unionised form in the SI?
Unionised form - more likely to cross across the membrane into blood, more likely to become ionised in blood due to high pH which traps it in the blood
In general how does food affect gastric emptying?
Tends to slow the rate of gastric emptying
What can happen as a result of food being prsesent in the GI tract?
- Decreased absorption
- Delayed absorption
- Increased absorption
What drugs can have an increased absorption as a result of food?
Poorly water soluble drugs
- Increased solubilisation
- Decreased presystemic metab
- e.g propranolol
What additional considerations should you think of in relation to the affects of food on drug absorption?
Type of meal - Solid v liquid - Protein and fat content - Other dietary factors Is the drug a GI irritant?
What is the problem with taking levadopa and how is this problem fixed ?
Metabolised in GI (SI lumen) converted into dopamine which is very rapidly degraded and excreted (low bioavailability)
- Carbadopa inhibits DOPA decarboxylase (inhibits presystemic metabolism of levadopa) which then allows for more levadopa to be absorbed and finally into dopanergic neurons
- Increases pharmacological benefit
What effect do antacids and ppis have which can affect drug uptake?
Change in gastric or intestinal pH
What affect can laxatives and anticholenergics have which can affect drug uptake?
Change GI motility
What affect can vasodilators have which can affect drug uptake?
Changes in GI perfusion
What affect can neomycin have which can affect drug uptake?
Interferences with mucosal function (blunting ends of villi)
What affect can tetracycline, calcium, magnesium have which can affect drug uptake?
Chelation (can bind to other drugs e.g biphsophonates and calcium)
What affect can cholestryamine have which can affect drug uptake?
Resin binding
What affect can charcoal have on drug uptake?
Adsorption
How can coeliac disease affect drug absorption?
Blunting of villi less surface for uptake reduced uptake of drug
How can ulcerative colitis affect drug absorption?
Can increase absorption
What factors can affect oral absorption?
- Particle size and formation
- GI motility
- First pass metabolism
- Physicochemical factors
- Splanchnic blood flow
- Efflux pumps (P-glycoprotein)
What are parenteral routes?
- Subcutaneous
- Intramuscular
What is absorption like for drugs administered via the subcutaneous route?
Slow due to poor blood flow
What drugs are absorbed rapidly via IM route?
- Lipophilic drugs rapidly
- Polar drugs via bulk flow and endothelial cell junctions
- High MWT or very lipophobic drugs via lymphatics
What affects rate of onset of the parenteral route?
- Extent of capillary perfusion
- Drug vehicle
- Affected by factors that alter perfusion
What barriers do drugs which are inhaled bypass?
Alveolar epithelium and bronchial mucosa
What do you need to take into account when prescribing inhaled medication?
Whether you want the effects of the drug on just the lungs or if you want them to reach the systemic circulation
What drugs do you want to just have an effect on the lungs and not enter the systemic circulation?
- Ipratropium
- Salbutamol
- Fluticasone
What are the ways in which drugs will have a local affect and not affect systemic circulation?
- Modified structure (become ionised)
- Particle size
- Selectivity for lung receptors
- Once in the systemic circulation rapidly broken down
What types of drugs do usually have a systemic affect but are inhaled?
- Lipid soluble drugs
Volatile / gaseous anaesthetics - Drugs of abuse
- Accidental poisoning
What are the advantages of the intranasal route?
- Avoids hepatic first pass metabolism
- Ease, convenience, safety
What are the limitations of the intranasal route?
- Limited drugs available
- Requires concentrated drug
What barriers are present in healthy skin?
- Stratified, squamous epithelium
- Keratinised layer
- Sebaceous gland secretions
Give some examples of some medications which are given topically
- Corticosteroids for eczema (hydrocortisone)
- Antihistamines for insect bites (mepyramine)
- Local anaesthetics (EMLA)
What are some of the ways / some examples of topical medications which can have a systemic effect?
- Transdermal patches (HRT, GTN, nicotine)
- Accidental poisoning (AChEsterase insecticides)
What must you remeber when applying topical medication which is likely to have a systemic effect?
SA to Volume ratio
