pharmacokinetics / pharmacodynamics Flashcards
ADME
Absorption
Distribution
Metabolism
Elimination
ADME = bioavailability
pharmacokinetics studies…
how does a drug get to its target?
pharmacodynamics studies…
when a drug binds to its target, what is the effect?
absorption includes…
how does a drug get into the bloodstream?
ROA
enteral ROA
(through the GI tract)
oral
rectal
parenteral ROA
(non GI)
injection
inhalation
topical (skin)
mucousal / sublingual
requirements for oral ROA
water soluable
stable / resistant to stomach acids & enzymes and liver enzymes
partially lipid soluable
first pass metabolism
prodrug
advantages / disadvantages of oral ROA
+: easy / non invasive
-: stomach upset / nausea ; actual concentration in blood stream less accurate compared to parenteral; many drugs cannot withstand GI tract
common drug abbreviations
ac – before meals
pc – after meals
hs – at bedtime
NTE – not to exceed
prn – as needed (also qs)
qXh – every X hours
qd – once daily
bid – twice a day
tid – 3 times a day
qid – 4 times a day
XR – extended release
rectal ROA advantages / disadvantages
parenteral ROA advantages / disadvantages
IV ROA advantages / disadvantages
IM ROA advantages / disadvantages
subcutaneous ROA advantages / disadvantages
Advantages:
-fairly rapid
Disadvantages:
-Large volumes not recommended
-Skin irritation
inhalation ROA advantages / disadvantages
Advantages:
Extremely rapid – can be even faster than i.v.!
Rapid accumulation in brain
Disadvantages:
Extremely rapid
lung irritation, possible
lung disease with
repeated administration
mucosal ROA advantages / disadvantages
sublingual / buccal ROA advantages / disadvantages
Advantages: non-invasive, relatively easy, does not go through GI system (more drug gets into system)
Disadvantages: may be unpleasant, have to be able to hold substance in mouth and not swallow
topical ROA advantages / disadvantages
Cmax
highest level of concentration in blood
bioavailability
% of drug in system (compared to IV administration)
volume of distribution (define)
a higher Vd is associated with________
The volume necessary to contain the total amount of administered drug at the same concentration observed in plasma.
In general, higher Vd is associated with:
longer excretion time
more drug needed to get into brain
longer time to get into brain
BBB
metabolism is…
how are drugs broken down
most common route of elimination
kidney
drug half life
**drug accumulation
If a second dose of drug is given before the first dose is eliminated, the overall concentration in the blood will be greater than that of the first dose alone.
With repeated administrations, concentrations are additive.
If 100 mg of a drug with a half-life of 4 hrs is given at noon, at 4:00pm there will be 50 mg in the blood.
If another 100 mg of drug is given at 4:00pm, how much drug will be in the blood at 8:00pm?
75 mg = 25mg (1st dose; 2nd half-life) + 50mg (2nd dose; 1st half-life)
**steady state concentration
Consistent level of drug in body achieved by repeated, regular-interval dosing
~4-6 half-lives
1st = 50%
2nd = 75%
3rd = 87.5%
4th = 93.75%
5th = 96.875%
6th = 98.44%
At steady state the amount of drug eliminated per unit time is equal to the amount of drug absorbed per unit time
theraputic drug monitoring
drug tolerance
A progressive decline in response with repeated usage of a drug.
types of drug tolerance
1: Metabolic tolerance
Usually due to upregulation of enzymes
2: Pharmacodynamic tolerance
Down-regulation of receptors or sensitivity
3: Behavioral conditioning (learning)
Homeostatic theory
Physiological processes can be conditioned to specific stimuli or environments
dependence
Administration of drug is required to avoid withdrawal symptoms
special populations? considerations?
1: pregnant people
2: children
3: elderly
3 reasons drugs may differ in their effectiveness
1: different mechanisms
2: lipid soluability
3: affinity for site of action
bonds formed between drug and receptor are typically ______
ionic (weak, reversible)
3 types of drug names
1: chemical
2: generic
3: trade
how do ionotropic receptors work?
Ionotropic receptors have recognition sites located on the ion channel.
Activation of receptor change shape of channel
fast / brief / rapid open and close / affect membrane voltage
metabotrophic receptors
A recognition site extends into the extracellular fluid, and a special protein called a G protein is located on the receptor’s intracellular side.
G proteins can open nearby ion channels or activate second messengers.
slower / longer / varied effects
actions can be direct or indirect
competitive vs noncompetitive binding
Competitive Binding: Drug occupies the same binding site on the receptor that the NT occupies
-drug with higher affinity / concentration wins
Noncompetitive Binding: Drug occupies a different binding site on the receptor than the NT
isomers
Molecules that have the same molecular formula, but a different shape:
Same “ingredients” - put together in diff ways
Isomers bx diff
optical isomers
Isomers that are mirror images of each other
Enantiomers
The distinction is important, as often only one form will be biologically active, or the different forms will produce different effects
racemic mixture / racemate
Most substances contain both isomers in equal proportions (50% L and 50% D)
Only ½ the molecules are biologically active
why purify a racemate?
By purifying a racemic mixture so that the drug only contains the biologically active isomer, a drug’s potency can be increased.
why do side effects happen
Same receptors responsible for multiple bx , or sometimes other receptors / systems activated other than target
what do dose response curves tell us?
Potency: Amount of drug required to elicit response
Efficacy: Maximum effect obtainable
Slope: The difference in concentration required between a minimal and maximal effect
Variability: individual differences in response
ED50 is….
the dose at which a 50% response is achieved
LD50 is….
the dose at which 50% of subjects die
the larger the TI ….
the safer the drug
TI formula
TI = LD50/ED50
drug interactions
placebo effects
Which route of administration is characterized as “enteral”?
oral and rectal
Drugs administered “sublingually” (under the tongue) and drugs administered orally are absorbed mostly in the ____________ and ____________, respectively.
mouth; small intestine
What are the two main differences between capillaries in the periphery and capillaries in the brain?
Capillaries in the brain have tighter junctions and are surrounded by membranes of astrocyte cells
which is the most dangerous mode of drug administration?
IV
The degradation of drugs by enzymes present in the gastrointestinal tract and liver is known as:
first pass metabolism
most drugs are excreted via …
the kidneys
The time for the plasma level of a drug to fall by 50% is called the
elimination half life
The “steady-state” concentration of a drug (the stable level achieved in blood with repeated, regular dosing) is
achieved when the amount of drug administered per until time equals the amount eliminated per unit time
The ability of liver enzymes to degrade a drug more efficiently in the continued presence of the drug is termed
Metabolic tolerance
“Pharmacodynamic” tolerance occurs in the _______________; “metabolic” tolerance occurs in the ____________________.
Synapse/neuron; liver
The study of the effects a drug has when it binds to it’s target/receptor is termed
pharmacodynamics
A drug that is more efficacious than another drug has
a larger maximum effect
most side effects are…
predictable and mild
The observation that caffeine cannot exert as much central nervous system stimulation as amphetamine indicates that caffeine
is less efficacious than amphetamine
during pregnancy, intestinal motility…..
intestinal motility decreases
a drug that is more potent than another drug has ….
a smaller ED50
According to the DEA the most dangerous drugs are typically scheduled as
schedule 1
affinity refers to…
the strength of attraction between a molecule (ligand) and it’s target (receptor)
A drug that blocks the effect of the naturally occurring (endogenous) compound is called:
antagonist
