 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

brain blood first pass metabolism

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 Copyright © motifolio.com

Ion channel - open Copyright © motifolio.com

Copyright © motifolio.com Ligand-gated channels Neurotransmitter receptor Ca 2+ -activated K + channel Cyclic nucleotide gated channel Na + K+K+ Glu K+K+ Ca 2+ Na + K+K+ cAMP cGMP

 2. G-protein coupled receptors ◦ (metabotropic) ◦ 2 nd 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 drugbrain response

The brain wants to rebalance the activity

 definition?  types of tolerance ◦ metabolic tolerance – enzyme induction ◦ pharmacodynamic tolerance – ◦ behavioral tolerance