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Transcript

all drugs not in gaseous state need to use
fluid routes of excretion
◦ fluid routes include -sweat, tears, saliva, mucous,
urine, bile, human milk
◦ amount of drug excreted in each of these fluids is
in direct proportion to amount of fluid excreted
SO…….

numerous functions –
◦ filters out metabolic products


numerous functions –
main function – maintain correct balance
between water and salt in body fluids
◦ filters out metabolic products
◦ blood continuously flowing through kidneys
 factors that influence a substance not being
resorbed
 not lipid soluble
 ionized

dialysis –
absorption, distribution and excretion do
not occur independently
first pass metabolism
blood
brain
1.
Body weight - smaller size
•
concentration of drug based on body fluid
2.
Sex differences
3.
Age
4.
Interspecies differences
rabbits – belladonna (deadly nightshade)
5.
Intraspieces differences
6.
Disease states
7.
Nutrition
8.
Biorhythm


half-life - time takes for the blood
concentration to fall to half its initial value
after a single dose
½ life tells us critical information about how
long the action of a drug will last
How long would it take for a
drug to reach 12.5% remaining
in blood if its ½ life is 2 hours?
How long would it take for a
drug
to reach 12.5% remaining in
blood if its ½ life is 100 hours?

Provides a good indication of the time
necessary to reach steady state after a dosage
regime has been initiated (6X)


drug elimination = drug availability
usually try and maintain steady state
concentration in therapeutic window

So if a drug had a 3 hour ½ life – how long
would it take to reach steady state?

Therapeutic drug monitoring - branch of
clinical chemistry that specializes in the
measurement of medication levels in blood.
Its main focus is on drugs with a narrow
therapeutic range,

- need to reach threshold plasma
concentration at the receptor site to initiate
and maintain a pharmacological response.
◦ assume that plasma represents good indicator of
local site

TDM is actually indirect

How is TDM determined?

What happens if?
◦ Plasma levels are too high –
◦ Plasma levels are too low –

Focus on levels rather than dose



info on a range of doses of drug
dose usually presented on horizontal axis
(log concentration)
size of effect or percentage affected usually
on vertical axis


the intensity or magnitude of the response
in a single person
the % of people who exhibit a characteristic
effect at a given dosage


potency - amount of drug required to elicit
a response
slope of the line tells you about how much
difference in drug is needed for small
effects relative to larger effect

Efficacy - maximum effect obtainable
- peak of the DRC indicates the maximum effect

Variability and slope –
individual differences in drug response
Different DRC depending upon measure of
interest



ED 50 - The dose of a drug that produces
the desired effect in 50% of the population
LD 50 –
TI = Therapeutic Index – measure of safety
LD 50/ED 50
hypothetical drug that can be used as a sedative –
this is tested in mice –
** dose cannot guarantee 100% sleeping and no deaths
Caution in interpreting DRC
Often see a bell-shaped curve in response to drug


antagonist - one drug diminishes the effect
of another
agonist – one drug is additive to the effect of
another

Pharmacodynamics
◦ drugs produce their effects by binding to and
interacting with receptors

What is a receptor?
◦ usually a protein on the surface or in the cell

each NT binds to its own receptors
◦ there can be multiple receptor subtypes

each NT binds to its own receptors
◦ there can be multiple receptor subtypes

useful for understanding drugs that work on
the specific neurotransmitters


1. ionotropic postsynaptic receptors
quick action and over quickly
Ion channel - close
7111232
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Ion channel - open
7111231
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Ligand-gated channels
Neurotransmitter
receptor
Ca2+ -activated
K+ channel
Cyclic nucleotide
gated channel
Na+
Na+
Glu
cAMP
Ca2+
K+
7111158
cAMP
K+
cGMP
K+
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motifolio.com

2. G-protein coupled receptors
◦ (metabotropic)
◦ 2nd messenger systems
◦ more than 50 G protein coupled receptors have
been identified
◦ control many cellular processes

3. carrier proteins (transporter)
◦ presynaptic transporters – transport NT back into
presyn ending

4. enzymes –
◦ what is an enzyme?
◦ breakdown NT -

1. the drug binds to the same location that
the endogenous NT occupies
 results in similar effects as NT – agonist

2. binds to a site near the binding site for
the NT
◦ facilitates NT binding
◦ allosteric effect
◦ modulatory effects

3. binding to a receptor site normally
occupied by the NT but not activating
receptor and blocking NT
◦ antagonist

certain drugs may be more potent than the nt

expected results – due to the principal
actions of the drugs

less expected –

no drug is completely selective


definition?
types of tolerance
◦ metabolic tolerance – enzyme induction
◦ pharmacodynamic tolerance –
chemical see-saw
drug
brain response
The brain wants to rebalance the activity


definition?
types of tolerance
◦ metabolic tolerance – enzyme induction
◦ pharmacodynamic tolerance –
◦ behavioral tolerance