Pharmacokinetics 1: Drug Absorption Flashcards
What is pharmacokinetics?
Branch of pharmacology that deals with what the body does to the drug
What are the 4 big questions of pharmacokinetics?
How easily does the drug get into the body?
Where does the drug go once it’s in the body?
Does the drug’s structure change in the body?
How does the drug leave the body?
What are the 3 stages of the pharmaceutical phase?
Ingestion
Disintegration and dissolution
Formation of individual drug molecules.
What are the steps of the pharmacokinetic phase?
Absorption of the drug -> Metabolism + distribution -> excretion
What does ADME stand for?
Absorption Distribution Metabolism and Excretion
What are the key routes of drug administration?
Enteral route (most common (80% of medicine) and covers buccal and sublingual routes)
Parenteral route (Drug administration via route other than intestines which bypasses protective effect of liver and GIT)
What barriers does the enteral route provide for drugs?
Intestinal wall
Blood vessel walls
Liver
What are the 4 methods of parenteral drug administration?
Intramuscular
Subcutaneous
Intravenous
Intradermal
Where must parenteral route be used for drug administration?
In clinical environment
Where does drug absorption of oral drugs take place?
In theory it should be absorbed along full length of GI tract. However in reality the duodenum is the primary route of absorption. (due to high degree of folding in duodenum and high vascularity)
How can drug formulation and absorption be controlled?
The timing and speed of drug release within GI-tract can be controlled through use of bicarbonate, enteric coatings, and delayed release coatings (for release in large intestines).
What does starch and bicarbonate do to drug absorption?
It speeds up gas dissolution in gastric contents.
What does enteric coating do to drugs?
Preserves them from interacting with the stomach contents.
How do drugs get absorbed from the gut?
Transcellular route: influenced by drug size, solubility, and ionisation status. (Through cells)
Paracellular route for small hydrophilic drugs. (between cells)
Newer view has established several classes of membrane drug transporters:
SLC (solute carriers) - they assist passive drug transport.
ABC class transporters use ATP-mediated transport. Some transporters are important for influx and efflux of drugs from the body.
What features are common among influx transporters?
Most are bidirectional SLC class members.
What features are common among efflux transporters?
Most are unidirectional ABC proteins
What efflux transporter is commonly investigated?
P-glycoprotein, this transporter is clinically significant because it returns hundreds of absorbed drugs to the gut lumen.
Where is P-glycoprotein commonly expressed besides gut?
Liver canuliculi (important for liver excretion)
Blood-brain barrier (removes drugs from brain)
Proximal tubule
Testes
What are the most important rules regarding optimal oral absorption? (Lipinski’s “rule of five”)
1) Molecular mass < 500g/mol
2) Calculated log octanol/water partition coefficient of 5 or less
3) Less than 5 hydrogen bond donors (sum of OH and NH)
4) <10 H-bond acceptors (sum of O and N atoms)
4 rules but each one is a multiple of 5
What is the log octanol/water partition coefficient?
A measure of solubility in water vs octanol
What constitutes the polar surface area?
Surfaces of drug molecules contain polarised atoms (O or N) and these are counted through computational predictions to estimate predicted intestinal absorption and toxicity/protein + receptor binding
What are the measures of drug lipophilicity?
LogP
Polar Surface Area (PSA)
What is Egan’s egg?
A graph representation of the limits that a drug’s LogP and PSA can be for optimal absorption and functionality.
How does pH affect drug absorption?
Acidic environment favours absorption at the stomach whereas basic pH favours absorption at the duodenum. This is due to ionisation of the drugs. (although most drugs are absorbed at the duodenum regardless)
