Pharmacokinetics, Pharmacodynamics, and Drug Interactions Flashcards
What is pharmacokinetics?
the study of drug movement throughout the body
What is drug absorption?
the drugs movement from its site of administration into the blood
What is drug distribution?
the drugs movement from the blood to its interstitial space and into the cells
What is drug metabolism?
enzymatically mediated alteration of drug structure (happens in liver/kidneys)
What is drug excretion?
the movement of the drug and their metabolites out of the body
metabolism+excretion=
elimination
What are the three ways to cross a cell membrane?
1) Channels and pores: very few cross channels or pores- only small compounds like potassium/sodium…
2) Transport system: carriers that move drugs from one side of cell membrane to another. They are selective. Example: certain oral drugs can’t be absorbed unless there is a transport system to move them across the intestine > blood stream.
3) Direct penetration of a membrane: movement throughout the body is dependent on the ability to penetrate membranes directly because MOST drugs are too large to pass through channels/pores and MOST drugs lack transport systems to help them cross all the membranes *remember “like dissolves like: which means membranes are made up of lipids so to directly penetrate a membrane, a drug much be lipid soluble
Are ions able to cross membranes?
No. They must become non-ionized to cross from one side to the other
Many drugs are weak organic acids or weak organic bases. What significance does this play?
This means they can be “charged or uncharged” and the electrical charge is determine by the pH of the surrounding medium
What are polar molecules?
They have an uneven distribution of electrical charge. polar molecules dissolve in polar solvents
Rate of absorption determines what? Amount of absorption determines what?
RATE determines how soon effects will begin.
AMOUT determines how intense it’s effects will be.
What is the rate of dissolution?
Before a drug can be absorbed it must dissolve. Drugs with slower dissolution have slower onset.
How does surface area affect absorption?
The surface area available for absorption is a major determinant of the rate of absorption. For THIS reason, orally administered drugs are greater in the small intestine than the stomach due to the large surface area of the microvilli
How does blood flow affect absorption?
drugs are absorbed most rapidly from sites where blood flow is high. the greater the concentration gradient the more rapid absorption
How does lipid solubility affect absorption?
lipid soluble drugs are absorbed more rapidly than those who lipid solubility is low
How does pH partitioning affect absorption?
Absorption is enhanced when the difference between the pH of plasma and pH at the site of admin is such that drug molecules have a greater chance to be ionized in plasma
How can abscesses and tumors affect distribution?
Abscesses lack blood supply so abx cannot reach bacteria within. Solid tumors also have limited blood supply so they are often resistant to any type of drug therapy
How do drugs exit the vascular system?
They leave the blood BETWEEN not through capillary beds
How can drugs pass the BBB?
There are tight junctions between the cells of the capillaries in the CNS which prevent drug passage. Only lipid soluble drugs can cross the BBB. This is not fully developed in a newborn so that’s part of why they re more sensitive to drugs.
How does placental drug transfer work?
membranes of the placenta separate the maternal circulation from fetal but it is not an absolute barrier for passage of drugs. Most drugs cross the placenta via simple diffusion… lipid soluble and nonionized compounds readily pass from maternal bloodstream > fetus
How does protein binding affect drug distribution?
drugs can form reversible bonds with various proteins in the body. Plasma albumin is most important because it is too large to leave the blood steam. Important consequence is restriction of drug is restriction of drug distribution bc albumin is too large to leave the bloodstream so drug molecules that are bound to albumin cannot leave either.
What is biotransformation?
the enzymatic alternation of drug structure
What is half-life?
time required for the amount of drug in the body to decrease by 50%
Why is half-life important?
it determines dosing interval
What are special considerations in drug metabolism?
Age
Induction and inhibition of drug-metabolizing enzymes
First-pass effect (some drugs may be completely inactivated in the liver; may need to give IV)
Nutritional status
Competition between drugs
Difference between inducers and inhibitors?
P450 inducers: increase rate of drug metabolism; amount of active drug decreased
Inhibitors: decrease rate of drug metabolism; amount of drug increased
Consequences of inducers and inhibitors
inDuce: Decreased drug level because it induces (speeds up) metabolism of the drug (AKA drug may not reach therapeutic levels)
Inhibit= Increased drug level because it inhibits (slows down) metabolism of the drug (AKA can lead to toxicity)
Renal drug excretion- 3 methods of excretion:
1) glomerular filtration: filters drugs out of blood stream, and into urine (drugs bound to albumin remain in the blood)
2) passive tubular reabsorption: distal to the glomerulus, greater concentration in the renal table will cause drug to diffuse back across the membrane and into bloodstream (particularly lipid soluble drugs)
3) active tubular secretion: active transport systems pump drugs from the blood to the urine
factors that modify renal drug excretion
-pH dependent
-competition for active tubular transport: only so many transport molecules so only some drugs will get to move back over and some will remain in bloodstream
age- newborns are underdeveloped, so they have less excretion. older adults renal fxn declines with smaller kidneys and fewer nephrons
What are non-renal routes of excretion:
breast milk, bile, lungs, sweat, saliva
what is the minimum effective concentration (MEC)?
smallest amount at which therapeutic effects occur
what is the toxic concentration?
level at which toxic effects begin
what is the therapeutic range?
range of drug level between MEC and toxic.
What does the therapeutic WIDTH range mean?
determines safety. smaller width= not as safe. wider width= more safe
What is the single-dose time course?
There is a latent period between administration and MEC which is the ONSET
- extent of this delay is determined by rate of absorption
- duration of effects is determined by metabolism and excretion
Does half-life apply to all drugs?
No. a few agents leave the body at a constant rate regardless of how much is present
Is a percentage or a specific amount of the drug lost during one-half life?
A percentage ONLY.
50 mg morphine, 1/2 gone in 3 hours
What is plateau drug level?
repeated doses will cause drug to build up until plateau is reached
-drug will accumulate until a state has been achieved in which the amount of drug eliminated between doses= amount given with each dose
What is the time to plateau?
as long as dosage remains constant, the time required to each plateaus is independent of dosage size
Loading dose vs maintenance dose
loading dose helps achieve plateau in one dose in certain meds
decline from plateau
will be eliminated over an interval period equal to time to plateau
What is pharmacodynamics?
biochemical and physiologic effects of drugs on the body
maximal efficacy
largest effect a drug can produce; height of the dose-response curve
-some drugs for pain can reach a higher maximal efficacy than others
relative potency
amount of drug we must give to elicit effect; morphine is more potent than meperidine (therefore give less morphine to elicit a reduction in pain)
selectivity
ability to elicit only the response for which drug is given
single occupancy theory:
the intensity of the response to a drug is proportional to the number of receptors occupied by that drug and a maximal response will occur when all available receptors have been occupied
modified occupancy theory:
ascribes two qualities to drugs (affinity and and intrinsic activity)
affinity
strength of the attraction between a drug and its receptor
-drugs with high affinity are very potent
intrinsic activity
ability of a drug to activate a receptor upon binding
-drugs with high intrinsic activity have high maximal efficacy
when drugs bind to receptors which of two things happen?
they either mimic the action of endogenous regulatory molecules or the BLOCK the action of them
Drugs that MIMIC the body’s regulatory molecules are what?
AGONISTS/activate receptors
Drugs that BLOCK the action of regulatory molecules are what?
ANTAGONISTS/prevent receptor activation
example: antihistamines
What’s ED50?
average effective dose
-the dose required to produced a defined therapeutic response in 50% of the population
What’s LD50
lethal dose
-the dose required to be lethal in 50% of the population
large therapeutic index means the drug is:
safe
narrow therapeutic index means the drug is:
relatively unsafe
