Pharmacokinetics Flashcards
ADME acronym
Absorption
Distribution
Metabolism
Elimination
Dose-effect relationship for pharmacokinetics
Pharmacokinetics: dose - concentration part
Pharmacodynamics: concentration - effect part
The time it takes for a drug to be _____ and
______ mainly accounts for the appearance of its effects: onset of action
absorbed and distributed
The time it takes for _____ and _____ accounts for the disappearance of a drug’s effect
metabolism; elimination
_____: involves the movement of a drug from the site of application into the bloodstream
Absorption
Rate and amount of drug absorbed depend on these factors
- route of administration
- local blood flow
- pH, drug ionization
- water solubility
- lipid solubility
- dose
____- the fraction of unchanged drug reaching the systemic circulation by any route
Bioavailability
What is the first pass effect?
the fraction of drug lost during the process of absorption
____ is a major site of drug metabolism
Liver
Pathway of oral drug to reach systemic circulation
oral-> gut-> portal circ. -> liver -> IVC -> heart-> lungs-> heart-> systemic circulation
Most drugs are weak _____
acids or weak bases
A drug is more readily absorbed and passes through cell membrane if it is uncharged- _____
non-ionized
Due to greater blood flow, _____ is often the major site of entry into the bloodstream, rather than stomach (oral route)
duodenum
______ - important enzyme for metabolizing endogenous compounds and drug biotransformation in the liver
Cytochrome P450
Usually described as the ______; a measure of the apparent space in the body available to\ contain the drug
volume of distribution
4 main compartments for drug distribution:
-blood (plasma)
-fat
-extracellular fluid
-intracellular fluid
The balance between distribution compartments determined by
-permeability of barriers
-pH within the compartment
-binding capacity
-fat solubility of the drug
A protein bound drug cannot do these things:
-diffuse through membranes
-be metabolized
-be excreted
-cause effects
What is Vd?
Volume of distribution
the property of the drug which shows how much drug needs to be within the body to get a certain concentration in the plasma
Plasma protein binding greatly _____ the amount of drug free in the plasma
reduces
Vd formula
Vd = total amount of drug in the body /
concentration of drug in plasma
T/F - Drugs with very high volumes of distribution have much higher concentrations in extravascular tissue than in the vascular compartment
T
______: the set of chemical reactions and pathways by which living organisms transform chemical substances
Metabolism
This process begins as soon as the drug reaches systemic circulation
Biotransformation
* One purpose is to eliminate
metabolic wastes
* Drug converted into a metabolite
Most common form of drug inactivation
Active Drug –> inactive metabolites
-typically metabolite is more water soluble
-enhancing elimination
Biotransformation that results in partial loss of activity
Active drug –> active metabolites (heroin–> morphine)
Biotransformation that promotes absorption and maybe to bypass first pass elimination
Inactive drug → active metabolite (aspirin)
What is a drug example of this type of biotransformation?
Active drug → toxic metabolite
Acetaminophen
Metabolism phases
- Phase 1: involves formation of a new or modified
function group or cleavage
– Hydroxylation: most common Phase 1 reaction - Phase 2: involves conjunction with an
endogenous substance
– Glucuronidation: most common Phase 2
reaction
Drugs can act as:
– substrates- material upon which the enzyme acts
– inhibitors- results in decreased metabolism of
drugs; selective or non-selective inhibition
– inducers- results in increased synthesis of P450 enzymes and increased metabolism of drugs
How does the GI tract play a role in metabolism?
enzymes in mucosal cells of intestinal wall
bacteria in large bowel
How does plasma play a role in metabolism?
not a major site; enzymes that degrade
drugs such as succinylcholine and procaine
T/F with elimination drugs removed unchanged or as one or more metabolites
T
the most important organs for drug removal
Kidneys
T/F Reduced renal excretion accounts for more adverse drug effects in the elderly than any other pharmacokinetic factor
T
Clearance equation
Cu x Vu / Cp
Cu- concentration of drug in the urine
Vu- rate of urine production
Cp- concentration of drug in the plasma
Half life of a drug
the amount of time it takes for the blood level (or concentration) of a drug to fall to exactly half of what it was at some previous time
Time to reach steady state is____ half lives
4 ½ to 5
The higher the Cp, the ____ excretion
Faster
When the Elimination rate is proportional to drug concentration, these drugs are following what
first order kinetics
When the Elimination rate becomes independent of drug in system, these drugs are following what
zero-order kinetics
Which drugs are more easily overdosed
Zero-order kinetics
Elimination of constant amount of drug per unit time with
zero-order kinetics
Elimination is a constant percentage of drug/unit time with ___
First order kinetics
