TDM & Toxicology Flashcards
Serum concentration is not equivalent to the concentration of ___________
Receptors
[could be correlated with physiological responses in certain cases]
Why do we monitor TDM?***
-to guard against overdoes or underdoses
-check for compliance
Study of the rate of process of absorption, distribution, and biotransformation (metabolism, and excretion)
pharmacokinetics
Study of biochemical physiological effects of drugs and their mechanisms of action
pharmacodynamics
A discipline concerned with the study of adverse effects of agents on living systems.
toxicology
What is the pharmacokinetics order of biotransformation?
LADME**
-liberation
-absorption
-distribution
-metabolization
-excretion
Absorption: Rate and extent of drug absorption vary from different ________& _______
sites, drugs
What is the first-pass effect?
***after ORAL administration, drug is absorbed by small intestine and carried via portal vein to liver where the drug is extensively metabolized.
Mechanisms of pharmacokinetics?
-passive diffusion (95% of drugs)
-active diffusion (needs carrier protein, against conc. gradient)
-facilitated transport
-convective (pore) transport
-pinocytosis (fat soluble cells)
The drug must be in true ________ solution at the site of absorption.
aqueous
weak acid pKa: ______in H2O
Strong acid pKa:_____ in H2O
-2 ~12
< -2
upon entering the circulatory system, most drugs will quickly equilibrate between
a ______ and _______ state
free, bound
Only ______ drug is available for distribution beyond the vascular compartment.
free
physiological response of drugs is dependent only the _____ form of the drug (active)
free
Bound drug distribution is dependent on kinetic binding and physiological ________ parameters.
filtration
major sites for biotransformation and drug metabolism?
major: liver
minor: kidneys, brain, lungs, skin, and GI tract
metabolism may affect the drug in what three ways?
-Increase activity (prodrug)
-decrease activity (inactivation or detoxication)
-no effect on activity
metabolites are generally more…
soluble
-some metabolites may still be pharmacologically active* (needs to be factored into the half-life) *****on test, trick question
biotransformation changes the _______ of the drug
shape
what happens after a prodrug is metabolized?
activity increases
What are the two major metabolic pathways of drugs?
-phase 1- inactivation- reactions metabolize lipophilic drugs to more polar forms to facilitate renal excretion
-phase 2- Excration
-accomplished by oxidative or deductive processes
-Cytochrome P-450 enzymes on microsomal membranes oxidize to inactive drugs
-metabolites can be metabolically active compounds
Phase 1- Innactivation
what enzyme metabolises most drugs?
Cytochrome P-450 (polar drugs)
-redactions involve conjugation of drugs with compounds such as glutathione, glucuronic acid, sulfate, and phosphate
-conjugates produced are water-soluble and can be excreted by the kidneys
Phase 2-Exreation
lipid-soluble drugs are excreated primarily through ________.
bille
The lowest drug concentration in circulation
most reliable indicator of appropriateness of dosage
trough blood concentration
When is trough blood concentration measured?
30 min before the next dose is given
the highest drug concentration achieved within the dosing cycle
when is it typically measured?
peak blood concentration
0.5-2 hours after the dose
MTC =
minimum toxic concentration
MEC =
minimum effective concentration
How is therapeutic drug monitoring done?
-immunoassay***
-fluorescent polarization immunoassay
-immunonephlometry
-gas-liquid chromatography
-HPLC
specimen for TDM should be serum without a serum separator. why?
certain drugs have a tendency to be absorbed in the gel of the separator
______________ plasma is suitable for most drug analyses.
what is not usually acceptable?
heparinized plasma
EDTA, citrate, or oxalate
___________ is utilized for immunosuppressive drugs**
whole
what are the ANTICONVULSANTS?
Phenobarbital / phenytoin / Valproate
What are the cardioactive drugs?
Digoxin, Lidocaine, Procainamide, Quinidine, Propranol ***
Bronchodilator drug?
Theophylline (works on beta receptor) also increases HR
antibiotics?
Aminoglycosides, Vancomycin, Chloramphenicol
psychotropic drugs?
Lithium, Tricyclic antidepressants; doxepin, imipramine, protriphylline, Neuroleptic;
Haloperidol, Phenothiazine
antineoplastic drugs?
Methotrexate (for tumors) , cf. leucovorin (minimizes toxic effects of chemo)
immunosuppressant drugs?
Cyclosporine, Tacrolimus
how do anticonvulsive drugs work?
decrease voltage-gated Na+ channels and increase GABA
What are the drugs used to treat epilepsy and seizures?
Phenobarbital / phenytoin / Valproate
what is grand mal?
abnormal electrical brain activity
what drugs are used for grand mal seizers?
Phenobarbital and Phenytoin (dilantin)
involves temp disturbances of the brain and small muscle twitching
what drug is used?
petit mal
Valproate
another anticonvulsive:
inactive prodrug of phenobarbital
primidone
another anticonvulsive:
treatment of seizures and neuralgia
Tegretol
another anticonvulsive:
also used to treat petit mal seizures
Ethosuximide
CO =
HR x SV
improves cardiac contractility by altering force of contraction through its effect on sodium potasium-ATPase pump in heart muscles that effects sodium, potassium, and calcium transport in the heart.
Digoxin
-treats CHF patients
-tistrubution rate is slow: peaks in 6 to 10 hours
Digoxin
causes more sodium to go into cell and less calcium to go out of cell (gets stored in SR)
Digoxin
Local anesthetic drug: stabilize neuronal membrane potential by inhibiting ionic fluxes
Lidocaine
