Therapeutic Drug Levels

Front 1

Therapeutic Level

Back 1

Important for drugs with a narrow window of therapeutic index (low margin of safety)

Front 2

Measure blood levels when

Back 2

You want to evaluate efficacy
Drug has low margin of safety (narrow therapeutic index)
Monitor compliance
Drug interactions
Poor absorbtion
Onset of pathological changes

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Most useful information gained

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Whena steady-state has been acheived (5 half-lives)
Immeduately prioir to a scheduled dose ("bottom" point)
Take samples of both blood & saliva

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What biological fluid should be test to determine therapeutic drug levels?

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Blood: Yes
Saliva: Yes
Urine: No b/c no equilibrium, only tests to see if a drug has been taken at some time

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Time Action Pattern
Phase 1

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Time to onset of action (latent period)
Factors: absorbtion, distribution, complexation, activation of latent drug

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Time Action Pattern
Phase 2

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Time to peak effect
Factors: nature of responding tissue and trpe of drug action i.e. direct or indirect acting

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Time Action Pattern
Phase 3

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Duration of action: From onset to time when no longer effect
Factors:Stabiity of drug in body, biotransformation, elimination

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Time Action Pattern
Phase 4

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Only Some Drugs
Residual (carryover) effect

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Determination of recent drug or alcohol use

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Urine test is scientifically acceptable but many limitations

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False Positives

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Molecule being tested is similar to another molecule
If test is positive then a Mass Spec GC test is done

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Nonspecificity

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Some tests are to general and a legal drug may look like an illegal substance
i.e. pseudophendrine (sudafed) can sometimes test positive for amphetamine

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False accusation of drug use

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Marijuana can be tested as postive from second hand smoke
Narcotics: codeine from a legitimate Rx can be biotransformed into morphine

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Prolonged Elimination

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Drugs with a high lipid solubility haveing along half life will be found in the urine for may days after use
Would NOT indicate recnt use
May have to do a Quantitative Analysis on a weekly basis
A Qualitative will just say if it is at a threshold

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Constitutional Restriction

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The FOURTH amendment protects citizens from being test w/o a probable cause
Private company's do not have to abide by this

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Determination of impairment

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Only a blood test is valid
Or a breath test in the case of alcohol

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Membrane Phenomena

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Permeability of cell membranes may be altered (decreased or increased)
Affect transport of ions
Local anesthetics prevent Na+ entrance, cell can't fire if Na+ transport blocked

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Enyzme Inhibition

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Know what enzyme you are talking about
Anabolic Enzymes
Catabolic Enzymes

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Anabolic Enzyme Inhibtion

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Drugs that block this enzyme:
Decrease synthesis
Decrease effect of ENDOgenous substances

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Catabolic Enzyme Inhibition

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Drugs that block this enzyme:
Increase the activity of an ENDOgenous substance
Increase production of a substance

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Enzyme Stimulation

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Adenylate Cyclase

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Interactions with a Neurotransmitter

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Best way to control a cell
Block a membrane and knock out the whole cell
Block a specific function of a cell much better

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Mimic NT

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Direct interaction with - and activation of - receptor site of a NT
Something about Dopamine?

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Block NT

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Drug combines with receptor site for a specific NT but does NOT activate the receptor