Pharmacokinetics Flashcards
Define absorption
Process of transfer from the site of administration into the general or systemic circulation
Name the routes of medicinal administration
- Oral
- IV
- Intra Arterial
- Intramuscular
- Subcutaneous
- Inhalational
- Topical
- Sublingual
- Rectal
- Intrathecal
What must all drugs do when delivered into the body
Cross at least one membrane in its passage from site of administration to the general circulation (including intracellular sites)
Exception of IV or IA
Four different ways substances can move across the plasma membrane
- Passive diffusion
- Diffusion through pores or ion channels
- Carrier mediated processes
- Pinocytosis
What property do drugs need to have in order to move passively across the plasma membrane
Lipid solubility to cross phospholipid bilayer
Rate of diffusion is proportional to concentration gradient, area and permeability of membrane and inversely proportional to thickness
What property do drugs need to have to move down ion channels
Be very small water-soluble molecules
What substance do carrier proteins need to move substances into a cell and why
ATP
Substances moved against their concentration gradient
What are carrier proteins also called
ATP-binding cassette
How many carrier proteins (ABCs) do we have
49
What is so special about P-gp
An ABC that removes a wide range of drugs from cytoplasm to extracellular side
What drug inhibits P-gp
Verapamil to increase conc. of anti-cancer drugs in the cytoplasm,
How do substances move down carrier proteins passively
facilitated diffusion
or co-transport to move it against a conc. gradient
How many SLCs (solute carriers) are there
300
Where is OAT1 found
Kidney
Role of OAT1
Secretes Penicillin and Uric acid
What drug blocks the action of OAT 1
Probenecid so uric acid is excreted
What drugs tend to be taken up by cells via pinocytosis
Amphotericin into the liposome
What is the basic property for most drugs
Ionisation as they can be either weak acids or bases
What property do ionised drugs have
Water-soluble
What property do non-ionised drugs have
Lipid soluble
What is the PKa of a drug
pH at which half of the substance is ionised and half is unionised
Where are weak acids best absorbed
Stomach
Where are weak bases best absorbed
Intestines
pH in urine vs plasma and what is the consequence of an aspirin overdose because of this
Lower in urine than plasma
Aspirin overdose is a weak acid so will be largely un-ionised and reabsorbed into plasma
How do we prevent aspirin overdose
Alkalinise urine with IV bicarbonate to reduce reabsorption of aspirin + elimination
Easiest delivery of drugs
Oral route
Why is the oral route efficient
Large SA and high blood flow of small intestines gives rapid and complete absorption of oral drugs
What is the major determinant of drug absorption
Drug structure
What properties do drugs need to have to maximise absorption
- Drugs need to be lipid-soluble to be absorbed from gut
What is the problem with highly polarised drugs
Only partially absorbed and most passes into faeces (Olsalazine)
Drug must disintegrate and dissolve to be absorbed rapidly
When is Olsalazine given
Colonic IBD
Problem with drugs that are faced with low pH of the stomach
They may be unstable
How do we overcome drugs that may become unstable at low pH levels
They are formulated to dissolve slowly or have a coating resistant to the acidity of the stomach (enteric coating)
How can gastric emptying be delayed
Food, drugs or trauma
How can gastric emptying be faster
Gastric surgery
What four major barriers do drugs have to pass to reach circulation
Intestinal Lumen
Intestinal Wall
Liver
Lungs
What three bonds can be spilt in the stomach
Peptide
Ester
Glycosidic Bonds
Role of colonic bacteria in drug metabolism
Hydrolysis and reduction of drugs
What is a special property of the upper intestinal walls
Rich in cellular enzymes
Name a cellular enzyme in the upper intestinal wall
MAO (Mono Amine Oxidases)