Flashcards in ADME Deck (51):
Absorption, distribution, metabolism and excretion
The science of drug action.
Define the term drug?
A chemical of know structure, other than a dietary or nutrient supplement, which causes a biological effect on a living organism.
Define the term medicine?
A preparation of one or more drug alongside other substances which is used therapeutically; to treat, diagnose, prevent or cure disease.
Define the term toxicology?
The study of adverse effects of chemicals on living organisms.
Define the term pharmacy?
The patient orientated health care profession, licensed dissension of medicine, patient monitoring and medicine composition.
What are the two branches of pharmacology?
Pharmacodynamics- what the drug does to the body.
Pharmacokinetics- what the body does to the drug.
Give the three eternal routes of absorption?
Sublingual, oral and rectal.
Give the 6 parenteral routes of absorption?
IV, IM, SC, transdermal, topical and inhalation.
What is the most common route of absorption?
Oral. As it has rapid onset, easy dosage and cost effective.
What do orally absorbed drugs have to overcome?
Gastric acid, digestive enzymes, co-exist or avoid food and gut bacteria.
Drugs are ........ of ...........?
Weak acids, weak bases.
What does p-glycoprotein do?
Pumps some drug back across the membrane using ATP.
During first pass effect where does venous drainage from the GI tract go?
Into the hepatic portal vein then to the liver and finally the vena cava.
What is sublingual absorption?
When the drug is placed under the tongue and sucked till dissolved. Rapid, no first pass effect and drugs must be lipophillic.
Eg. Glyceryl trinitrate
What is rectal absorption?
Where the drug is placed into the rectum via the anus. The drug must be lipophillic and it is useful when the oral route is compromised. Minor first pass effect.
What is IV absorption?
Intravenous, the drug is 100% bio available however there is a higher dish and care may be required.
What is IM absorption?
Intramuscular. Inserted at a 90 degree angle, no first pass effect, costly and may require care.
What is subcutaneous absorption?
45 degree angle, no first pass effect, costly and may require care.
What are the benefits of inhalation absorption?
Large surface area of lungs and good blood supply to parenchyma allows a large amount to be absorbed and quickly.
What are the pros of inhalation absorption?
There is no first pass effect, may allow for a route to cross the BBB, easy to take.
What is topical absorption?
Direct application to eye, vagina or skin.
What is transdermal absorption?
The use of patches to create a drug depot.
Define the term distribution?
The reversible movement of a drug from the systemic circulation to the cells and insterstitium of tissues.
What can hydrophilic and large drugs not do?
Cross the plasma membrane.
Eg. Insulin and neostigmine
What targets to lipophillic drugs target?
What order, from highest to lowest permeability, do:
B, A, C.
What are the membrane barriers?
BBB, blood-testes and placenta.
Explain how L-DOPA is taken to avoid problems with the BBB?
Cardidopa is taken alongside to block the DOPA decarboxylase in the periphery so dopamine is only made in the brain.
What is a sequestered drug?
One that has accumulated to a concentration higher than the concentration of blood or plasma.
The chemical modification of drugs and other foreign compounds (xenobiotics). Also known as biotransformation.
What is the purpose of metabolism?
To create a more excretable and less pharmacologically active/toxic drug.
What is the first phase of metabolism?
To modify the drug by oxidation, reduction or hydrolysis.
What is the second phase of metabolism?
Addition of a new chemical group.
What catalyses phase 1 reactions?
What is the most important conjugation reaction?
And give two less important examples?
N-acetylation and sulphonation.
What can exposure to certain drugs do to the enzymes?
Induce (eg. Rifampicin) or inhibit (eg. Cimetidine).
Define the term excretion?
The removal of drugs and their metabolises from the body.
Give the seven methods of excretion?
Saliva, tears, milk, sweat, faeces, lungs and renal.
Give the equation for renal excretion?
Renal excretion= (filtration + secretion) - reabsorption
What are and are not filtered?
Small molecules are filtered but bound molecules are not.
Describe secretion via the kidney?
Diffusion and active transport from the capillaries across the interstitial space into the lumen of the tubules.
What two protein families carry out carrier-mediated transport?
OATs and OCTs.
What are substrates for OATs?
Phase two metabolises and drugs (eg. Benzylpenicilin and ibuprofen).
How is the rapid excretion of benzylpenicilin overcome?
Probenecid is taken alongside to block the actin of OATs and increase it's half life.
Where does reabsorption occur?
In the kidney.
What can be used to treat overdoses?
What sort of urine increases secretion of a weak acid?
Alkaline urine (pH above 7)
Give an example of treating an overdose with pH?
Amphetamine OD use absorbic acid or ammonium chloride. Aspirin OD use bicarbonate.
What is enterohepatic circulation?
The prolonging of a drug but the removal of the glucoronide group by glucoronidase.