Transcript Routes of Excretion

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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…….
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numerous functions –
◦ filters out metabolic products
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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
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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
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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?
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Provides a good indication of the time
necessary to reach steady state after a dosage
regime has been initiated (6X)
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drug elimination = drug availability
usually try and maintain steady state
concentration in therapeutic window
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So if a drug had a 3 hour ½ life – how long
would it take to reach steady state?
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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,
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- 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
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TDM is actually indirect
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How is TDM determined?
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What happens if?
◦ Plasma levels are too high –
◦ Plasma levels are too low –
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Focus on levels rather than dose
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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
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the intensity or magnitude of the response
in a single person
the % of people who exhibit a characteristic
effect at a given dosage
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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
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Efficacy - maximum effect obtainable
- peak of the DRC indicates the maximum effect
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Variability and slope –
individual differences in drug response
Different DRC depending upon measure of
interest
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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
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antagonist - one drug diminishes the effect
of another
agonist – one drug is additive to the effect of
another
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Pharmacodynamics
◦ drugs produce their effects by binding to and
interacting with receptors
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What is a receptor?
◦ usually a protein on the surface or in the cell
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each NT binds to its own receptors
◦ there can be multiple receptor subtypes
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each NT binds to its own receptors
◦ there can be multiple receptor subtypes
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useful for understanding drugs that work on
the specific neurotransmitters
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1. ionotropic postsynaptic receptors
quick action and over quickly
Ion channel - close
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Ion channel - open
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Ligand-gated channels
Neurotransmitter
receptor
Ca2+ -activated
K+ channel
Cyclic nucleotide
gated channel
Na+
Na+
Glu
cAMP
Ca2+
K+
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cAMP
K+
cGMP
K+
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2. G-protein coupled receptors
◦ (metabotropic)
◦ 2nd messenger systems
◦ more than 50 G protein coupled receptors have
been identified
◦ control many cellular processes
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3. carrier proteins (transporter)
◦ presynaptic transporters – transport NT back into
presyn ending
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4. enzymes –
◦ what is an enzyme?
◦ breakdown NT -
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1. the drug binds to the same location that
the endogenous NT occupies
 results in similar effects as NT – agonist
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2. binds to a site near the binding site for
the NT
◦ facilitates NT binding
◦ allosteric effect
◦ modulatory effects
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3. binding to a receptor site normally
occupied by the NT but not activating
receptor and blocking NT
◦ antagonist
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certain drugs may be more potent than the nt
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expected results – due to the principal
actions of the drugs
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less expected –
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no drug is completely selective
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definition?
types of tolerance
◦ metabolic tolerance – enzyme induction
◦ pharmacodynamic tolerance –
chemical see-saw
drug
brain response
The brain wants to rebalance the activity
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definition?
types of tolerance
◦ metabolic tolerance – enzyme induction
◦ pharmacodynamic tolerance –
◦ behavioral tolerance