Chapter 4 - Pharmacokinetics Flashcards
Define Pharmacokinetics
Study of drug movement thoroughout the body
What are the 4 phases of pharmacokinetics?
Absorption, Distribution, metabolism and excretion.
Absorption
Movement of a drug from its site of administration into the blood(circulation)
The most common mechanism for drug absorption is
PASSIVE DIFFUSION
Distribution
Drug movement form the blood to the interstitial space of tissues and from there into cells
Metabolism
enzymatically mediated alteration of drug structure.
Excretion
movement of the drugs and their metabolites out of the body
The combination of metabolism and excretion is known as_____?
elimination.
The intensity of the response of a drug is directly related to the ________ of the drug at its site of action.
concentration
What is the major barrier to passage through a cell?
the cytoplasmic membrane (Membrane that surrounds the cell)
What are phospholipids?
fats that contain an atom of phosphate
What are the three ways for a drug to cross the cell membrane?
- Passage through channels or pores
- Passage with the aid of a transport system
- direct penetration of the membrane.
The most common way a drug crosses the membrane is by _______.
direct penetration
Which compounds are likely to cross membranes via channels.
small ions such as potassium and sodium.
What are transport systems?
carriers that can move drugs from one side of the cell membrane to the other.
what is P-gylcoprotein?
transmembrane protein that transports a wide variety of drugs OUT of the cell
P-gylcoprotein transports drugs into the ________ for elimination.
Bile
In the placenta p-gylcprotein transports drugs back into the _________, therby _____ fetal drug exposure
maternal blood; reducing
What is a polar molecule?
molecules with an uneven distribution of electrical charge.
What drug is an example of a polar drug?
Gentimicin
What is an ion?
molecules that bear a net charge
They are unable to cross membranes
What is a quanternary ammonium compound?
molecules containing at least one atom of nitrogen and carry a positive charge at all times
What is an Acid?
a compound that can give up a hydrogen ion (proton donor)
What is a base?
a compound that can take up a hydrogen ion (Proton acceptor)
explain ion trapping
ph partitoning
process whereby a drug accumulates on teh side of a membrane where the pH most favors its ionization.
What factors affect drug absorption?
Rate of dissolution Lipid solubility Surface Area Blood Flow Ph partitioning
The larger the surface are the ______ the absorption will be.
faster
for this reason, a lot of drugs are usually absorbed in the small intestines
What type of insulin is safe for IV infusion
Regular insulin. It is a clear liquid
What type of insulin can only be given SQ
NPH. Fatal if given IV
What would happen if concentrated EPI was given IV
overstimulate the heart and blood vessels, causing severe hypertension, cerebral hemorrhage, stroke and death
When a drug is administered IM _____ is the only barrier to absorption
capillary wall
What is the major barrier to absorption in the GI tract?
The GI epithelium (drugs must pass through these cells rather than between them).
Enteric- coated preparations are covered wit a material designed to dissolve in the ____.
Intestine (not in the stomach)
Define distribution
movement of drugs throughout the body
Drug distribution is determent by what three factors?
- blood flow to tissues
- ability of drug to exit vasuclar system
- ability of a drug to enter cells
Why cant abscess be effectively treated with ABX if they are not drained?
because abscesses have no blood supply. Infection bust be drained before ABX will work
What drugs are able to pass through the blood brain barrier?
Lipid soluble drugs and drugs with a transport system.
Most drug metabolism takes place in the _____
Liver
Drugs metabolised in the liver do so by what system?
P450 system ( hepatic microsomal enzyme system)
What does cytochrome P450 consist of?
12 closely related enzyme families — Three important ones are CYP 1,2 and 3
What does CYP 1, CYP2, and CYP3 do?
They metabolize drugs - The other 9 metabolize endogenous compounds (steroids, fatty acids)
What is a prodrug?
a compound that is inactive at administration and the undergoes conversion its active form via metabolism.
At what age does the liver develop to its full capacity?
1 year of age. Therefore of the drug is , the metabolizing capacity is decreased. This also happens in the elder - may need to REDUCE drug doses
What is a substrate?
drugs that are metabolzied by P450 enzyme
What is an inducer?
Drugs that act on the liver to increase rates of drug metabolism.
What is induction?
Process of stimulating enzyme synthesis
What happens when a drug is an inducer and a substrate?
The drug can increase the rate of its own metolism, thereby necessitating an increase its own dosage to maintain therapeutic effects.
What is an inhibitor?
Drugs that act on the liver to decrease rates of drug metabolism. Process is known as inhibition.
How do inhibitors provide therapeutic consequences?
bc slower metabolism can cause an increase in active drug accumulation. This can lead to an increase in adverse effects and toxicity.
What is first pass effect?
rapid hepatic inactivation of certain oral drugs. The capacity of the liver to metabolize a drug is extremely high and that drug can be completely inactivated on its first pass through the liver. As a result no therapeutic effects can occur.
Name a drug that undergoes first pass effect
nitrocylcerin — so it is given SL
What is enerohepatic recirculation?
repeating cycle in which a drug is transported from the liver into the duodenum/intestine (via the bile duct) then undergoes reabsorption back to the liver(portal blood). — this can prolong a drugs sojourn in the body.
What is glucuronidation?
is the addition of glucuronic acid to a substrate —– example: process in which a hydrophilic glucose (glucuronic acid) derivative is attached to phenytonin. As a result phenytoin is rendered much more water soluble and can be rapidly excreted by the kidneys.
What drugs are most affected by enterohepatic re-circulation?
Drugs that have undergone glucuronidation.
Urinary excretion is the net result of what three processes?
- Glomerular filtration
- passive tubular reabsorption
- Active tubular secretion
Passive tubular renal absorption is limited to_______
Lipid soluble compounds
Competition for transport has been employed clinically to _______ the effects of drugs that normally undergo rapid renal excretion
Prolong
What is an example of competition for transport
Penicillin —– when administered some, penicillin is rapidly cleared from the body by active tubular transport — excretion of Penicillin can be delayed by concurrent ministration of probenecid an agent that is removed from the blood by the same tubular transport system that pumps penicillin
Penicillin can be delayed by concurrent administration of ______
Probenecid
Drug levels ________ as the medication undergoes absorption.
Rise
Drug levels ______ during metabolism and excretion
Decline
The duration of effects on a drug is determined largely by the combination of _______ and ________
Metabolism and excretion
Define half life
The time required for the amount of drug in the body to decreased by 50%
What is the half-life of morphine?
Three hours
The _______ determines the dosing interval of a drug
Half-life
How many half lives does it take to reach a plateau?
About 4.
