L31 - Absorption: Physiological Factors Affecting Drug Absorption 2 Flashcards
What does bile facilitate?
Excretion of a number of endogenous and exogenous compounds and aids digestion of fat and fat-soluble vitamins
What are the parts in enterohepatic recycling? (3)
- bile facilitates digestion of fat
- some drugs are eliminated in part by biliary secretion
- drugs eliminated into SI, may be absorbed again and reach systemic circulation
What if F?
Fraction of parent drug reaching systemin circulation after oral administration
F=1 all drug absorbed
F=0 no drug absorbed
What does the amount of drug absorbed depend on? (3)
- its release from dosage form
- stomach, intestinal and hepatic (first pass) metabolism
- its permeation through GI mebrane
What are the ways of transportation of drug across the GI membranes? (4)
- paracellular transport
- diffusion
- facilitated diffusion
- drug transporters
What is the removal rate of drug from inside cell far more efficient than sometimes?
Rate of entry
= good protective mechanism for cells
- prevents toxic compounds from accumulating intracellularly
Why are some tumor cells resistant to anticancer drugs?
Drugs transported into cell are removed so efficiently that conc never gets high enough to be effective
What does specific transport protein equal?
Specific transport protein = multidrug resistance protein
What are efflux pumps?
Celullar proteins that can prevent intracellular acuumulation of drugs by pumping drug that enters cell right back out
What are examples of efflux pump?
P-Glycoprotein (PGP)
- present in dif tissues (intestine, placental membrane, blood-brain barrier)
What is PGP responsible for? (3)
- Poor bioavailability
- Low CNS concentration of numerous drugs
- Prevent oral delivery of many anti-cancer drugs
What do PGP inhibitors do?
Prevent drug efflux from endothelial cells and increase oral bioavailability
What do 1st and 2nd gen PGP inhibitors also inhibit?
CYP3A4 = reduced drug clearance
What are 3rd gen PGP inhibitors specific for?
Transporter
- clinically effective
E.g/ administration of topotecan with PGP inhibitor elacridar
= inc oral bioavailability from 40 to 97%
What is the role of dosage form? (5)
- accurate dosing
- Protect the drug (storage and after administration)
- Conceal bad taste/odour
- Easy delivery for certain routes/specific patient groups (suspensions, liquids, syrups, suppositories)
- Optimize delivery and release - fast release, controlled (extended) release
What are the categories of oral dosage forms? (4)
- rapid release (solutions, effervescent tablets)
- delayed release (enteric-coated)
- slow release (0 order kinetics)
- slow release (1st order kinetics)
What may 2 pharmaceutical dosage forms have… but…?
- same rate os absorption
- identical Cmax calues at dif Tmax
(Due to signficant lagtime
What is an examples if delayed absorption? (2)
Gastro-resistant/enteric-coated tablets
- time bomb
- retard used to describe these dosage forms
What may some disage forms have different? Eg/
1st order absorption rates
- most drugs taken orally, the rate of absorption is greater than the rate of elimination
What is 1st order like in terms of absorption? (2)
- amount absorbed per unit time depends on quantity of drug at site of absorption
- greater amoubnt to be absorbed = faster rate
What is 0 order like in absorption?
Amount released per unit time is constant over period of absorption
How does food influence drug absorption? (2)
- GI absorption sometimes modified by food
- eating habits vary in different cultures
What is an example of drug modified by presence of food? (2)
Lapatinib - breast cancer drug
- food = inc bioavailability by 167%
- fatty meal = inc bioavailability by 325%
Why should tetracyclines be paid attention to? (3)
- taken under fasting conditions to maximise bioavailability
- GI absorption dec by presence of Al, Ca, Mg and Fe
- milk products are contra-indicted
How taking of sodium fluoride pose a problem?
Treats osteoporosis
- if Ca supplement also prescribes
What should be avoided when taking antacids?
Milk products
What may delayed/slowed release dosage form be sensitive to?
Presence of food in digestive system
- change of GI transit time
What may the amount of drug reaching systemin circulation be in presence of food? (3)
- increased
- decreased
- unaffected
