How does a drug need to be presented to achieve its effect?
Suitable formulation at appropriate site of administration where it is then absorbed and distributed throughout the body
What is ADME?
The journey of the drug throughout the body: Administration, Absorption, Distribution, Metabolism, Excretion, Removal
What are the routes drug takes during administration?
Why is administration important?
Depending on where it is administered, determines the functionality of the drug - e.g. If taken down GI and not absorbed then it is just excreted
Is inhalation effective and how?
Quite effective as it is directly absorbed into the bloodstream but some (specifically very volatile drugs) are exhaled back out
What is local administration?
Restricted to one area of the organism
What is systemic administration?
Affects the entire organism
Are the following local or systemic administration: Salbutamol, Cannabis, Aspirin, Antacid, nicotine
Salbutamol (L&s), Cannabis (S), Aspirin (S), nicotine (S), Antacid (L)
What is enteral administration?
G-I administration, where it can be absorbed orally, buccal, sub-lingual. Easiest way to admin a drug
What is parenteral administration?
Outside of GI tract
How do drugs enter the systemic circulation?
NB: intraperitoneal vs intravenous are nearly as good as each other.
What is the slowest administration method?
What is the fastest administration method?
How do drugs move around the body?
Bulk flow transfer (bloodstream) OR diffusional transfer (molecule by molecule across short distance). Drugs traverse both aqueous and lipid environments
What is the difference between compartments and barriers in drug transport?
Compartments are aqueous and barriers are lipid
How do drugs cross barriers?
Diffuse through lipids and use carrier molecules
Why do drugs have the ability to be charged?
They are mostly either weak acids or weak bases - so exist in ionised or non-ionised forms depending on surrounding pH
What is the pH partition hypothesis? (Using aspirin as example)
Predominantly in stomach is uncharged (L) so is predominantly absorbed here (rapid). In the intestine it is predominantly in the ionised form (R) which can diffuse across the cell membrane (slow).
What is an enteric coating?
It is a sugar coating around the drug to prevent dissolving/absorption in the stomach
What is ion trapping?
Blood pH causes drug to become ionised which causes it to be trapped in the blood but due to dynamic equilibrium a slow amount of non-ionised is being formed steadily so it becomes a slow release drug
Which factors affect drug distribution?
Regional blood flow (perfusion of tissue dictates how quickly the drug will flow through it). Extracellular binding (once drug is bound by protein it is slowly released and that dictates how quickly the drug acts -DE) Capillary permeability (tissue alterations - renal, hepatic) Localisation in tissues (prefer lipid)
How can strenuous exercise affect drug distribution?
Strenuous exercise changes blood flow/perfusion to certain tissues thus how quickly the drug acts on certain tissues
How does extracellular binding affect drug distribution?
If it is bound too tightly then dose must be thought out
How does capillary permeability affect distribution?
Ionised drugs have the ability to move through the pores in the capillary. Dependent on organ we're looking at
Where do drugs localise when drug reaches equilibrium in system?
75% in fatty tissue
What are the two major routes of drug excretion in humans?
Kidneys (eliminates most drugs) and liver (concentrated in bile forming large molecular weight conjugates - excreting through faeces)
How do kidneys excrete drugs?
Not filtered in the glomerulus so are actively secreted in proximal tubule (acids and bases) and proximal/distal tubules (lipid soluble drugs reabsorbed)
Why might treatment with IV Na bicarbonate increase aspirin excretion?
Increased urine pH ionizes the aspirin making it less lipid soluble and less reabsorbed from the tubule, increasing its rate of excretion
How are drugs excreted via the liver?
Large drugs are excreted through bike due to kidney/liver not being able to handle it. Active transport systems move drugs into bile (with bile acids and glucuronides)
What are some other routes of drug excretion?
Lungs (breathe out volatile molecules), skin, GI secretions, saliva, sweat, milk, genital secretions