Pharmacokinetics Flashcards
What does Pharmacokinetics involve?
Pharmacokinetics involves getting drugs to and from their site of action whereas pharmacodynamics is the effects of drugs after they have reached their site of action.
There are four main steps involved:
1) Give the drug - administration
2) Drug enters circulation - absorption (from outside body into circulation)
3) Drug spreads through body - distribution
4) Drug is removed from the body - elimination
- Chemical changes - metabolism
- Physical expulsion - excretion
What are some methods for drug administration?
There are many factors that influence the choice of the route of administration.
- Patient Convenience (oral vs. rectal)
- Cost (need for sterility for injectable drugs)
- Bioavailability (how much active drug gets to the site of action)
- Local versus systemic effect
Compare the local and systemic effects of drug administration.
Local:
- drug exerts effect at or near site of administration (drug is designed to be administered close to the site of action for optimal administration)
- access to limited tissues (limited by absorption)
- Limited access to tissues
(use poorly absorbed drug & choose concentration so that if drug is absorbed, concentration will be too low for systemic effect) -> Leads to reduced side effects
Systemic: - drug enters the bloodstream (so that the drug is able to access many different sites within the body dependant upon the type of drug/receptors) - will access many tissues (determined by distribution) Examples: - oral (tablets & capsules) - skin (nicotine patches) - lungs (gaseous general anaesthetics) - nose (cocaine) - rectum (antibiotics) - injectable - Subcutaneous (insulin) - Intramuscular (penicillin G) - Intravenous (diazepam for status epilepticus)
All of the above, except intravenous injection require the drug to be absorbed.
Explain factors of drug distribution?
- molecular size (low molecular weight/small to cross vascular endothelium)
- ability to bind to plasma proteins (unbound to cross vascular endothelium)
- lipid solubility (some lipid solubility to cross cell membranes; high solubility will lead to sequestration in lipid)
What is the significance of the BBB in drug distribution?
BBB= Blood Brain Barrier
- endothelial cells of brain capillaries from tight junctions have few pores and acts as a protective mechanism
- thus, only lipid soluble drugs able to cross and enter CNS
- highly polar compounds are excluded (proteins). Proteins fold naturally so that all the polar elements are on the outside of the protein.
What are drug reserviors?
Sites in the body where drug accumulates:
- can prolong action by releasing drug from the stores as concentration falls
- can quickly terminate action if the stored drug has a high capacity
- can lead to slow distribution if the capacity of the store is great
What are some examples of drug reservoirs?
Plasma proteins
- only unbound drug gets from plasma to tissues
- may get displacement from similar drugs
- Aspirin can displace Warfarin
Cells
- accumulation due to active transport or specific binding
- antimalarial quinacrine highly concentrated in liver
Fat
- highly lipid-soluble drugs
- blood supply is poor and capacity large so may lead to slow distribution
What is volume of distribution?
“Volume of body water in which a drug appears to be dissolved in after it has distributed throughout the body” - an apparent volume
It is determined by whether a drug binds to plasma proteins (Vd is small) or is taken up by cells (Vd is large)
This is important so that we know what dose/[] is desired for a give drug effect.
How does Drug Elimination occur?
Drugs are eliminated by either excretion (primarily by the kidney) or metabolism (primarily by the liver) but is usually a combination of both.
Explain the elements of renal excretion.
Glomerular Filtration:
- this is where the first filtration takes place.
- takes drugs out of the blood
- passive filtration through leaky glomerulous
- limited by GFR (=120ml/min)
- not for drugs bound to plasma protein
- drugs that are not excreted will move to the efferent arteriole
Tubular Secretion:
- takes drugs out of blood
- uses active carrier for drugs
- can remove protein-bound drug too
- can be competitively inhibited (probenecid: reduces excretion of acidic drugs; banned in sport as it masks appearance of other banned substances in urine)
Tubular Reabsorption:
- puts drugs back into blood
- passive movement across cell membranes of the tubule and peritubular capillary
- pH dependent
- can be manipulated clinically in overdose (aspirin overdose: can administer NaHCO3 to make the urine basic and increase the amount of ionized aspirin to lead to increased excretion and reduced reabsorption)
What is renal clearance?
amount of blood from which drug is removed by the kidneys per time. It is a reference to how well the kidneys are removing the drug from the blood.
What is involved in drug metabolism?
- biotransformation
- involves a chemical change to a drug
- enzyme-catalyzed reactions
- occurs in most tissues, but mainly in the liver
- increases water solubility to facilitate excretion
What form can metabolites take on?
They can be inactive, active, have new activity or be toxic
What is the difference between Phase 1 and Phase 2 metabolism?
Phase I Metabolism:
- creates chemical functional group (-Oh, -NH2, -SH, -COOH) on drug
Phase II Metabolism:
- conjugation of water soluble molecule to functional group on drug
- molecules transferred include glucoronyl, acetyl, methyl, sulphate, glutathione
- phase II products are nearly always pharmacologically inactive and more water soluble.
