CHEM 210 - LO4

What is therapeutic drug monitoring

science of analyzing tissue or body fluids to determine the concentration of a prescribed drug present at a particular time and correlating to the concentration of drug in that compartment with its patient affect

what is the purpose of therapeutic drug monitoring

all the patient to attain the desired clinical effect while reducing the risk of toxicity - ensures drug dosage produces the maximum therapeutic benefit and minimal toxic or adverse effects

What are the main organs for standard dose? What causes the amount to be altered from a normal individual?

main organs are the kidney and liver - disease state may produce altered physiologic conditions in which the standard dose does not produce the predicted concentration

WHat is a drug

a chemical that will selectively act upon certain tissues or organ functions

What are the criteria to determine if a chemical is a drug

selective to a specific target, reversible in its action, produces a beneficial or positive outcomeWha

What is monitoring

implies a constant process of determining the quality of drug required to produce the desired effect without being toxic

When is TDM indicated

consequences of overdosing and underdosing are serious - small difference between a therapeutic and toxic range - poor relationship between the dose of the drug and the circulating concentrations but a good correlation between circulating concentration and therapeutic or toxic effect - change in patient physiology - drug interactions - monitor patient compliance

What is Pharmacokinetics

the study of drug absorption, metabolism, and secretion

What are the 6 types of route of administration to the body

Intravenous, Intramuscular, Subcutaneous, Inhaled, Absorbed (transcutaneous), or rectal (suppository)

Which route of administrations have 100% bioavailability

intravenous and inhalation

Which administration method requires a lower dose

rectal (suppository)

What is bioavailability

amount of drug that reached the intended site

how are most drugs absorbed? How are drugs carried? What does the metabolizing?

passive diffusion in stomach and intestine - carried through hepatic portal vein to the liver - liver metabolized drug before it enters circulation

What changes can affet absorption

intestinal (motility, pH) - Other drugs (alcohol) - pregnancy - food interactions (grapefruit) - inflammation (GI infections) - Age - Pathology

How is the distribution of drugs determined?

chemical structure

Where are hydrophobic drugs stored

adipose tissue

What happens to highly ionized drugs

bind to protein and are less likely to diffuse into cells

What can drug distribution affect

amount of free drug available to have the appropriate affect at the site of action

How do we measure the amount of free drug in serum

amount of drug that is active at the site intended

What is inactive drug?

the % that is bound to protein

What can changes in albumin do to drugs?

can affect the amount of inactive drugs - nothing for them to bind to - some drugs bind more than others

What can affect the amount of free drug present in serum

inflammation, pregnancy, nephrotic syndrome, malnutrition, hepatic disease, acid-base balance disturbances

What happens in drug metabolism

liver metabolizes (activates) and distributes drugs - some drugs are inactivated decreasing the amount of active drug in circulation- some drufs are not active until metabolized by liver

What happens to drug metabolism when there is a liver problem

lowers because the liver is not functioning properly

What 2 things work together for drug elimination

hepatic metabolism and renal filtration or a combon

What way is water soluble drugs excreted

kidney

What way is lipid soluble drugs excreted

bile duct of liver

how long does it take for elimination to happen

half life the time needed for serum concentration of a drug to decrease by half

When do serum drug concentrations rise

rise when the rate of absorption exceeds the rate of distribution and ellimination

How long does it take to eliminate 50% of the active drug in the bloodstream

half life of drug

What is the peak level

highest concentration of drug measured in the blood

When are peak levels drawn

immediately upon reaching steady state levels

What is the trough level

lowest concentration of drug measured in the blood

When are the trough levels drawn

within one hour or just before the administration of the next dose

How can age affect drug concentrations

reduced liver and kidney function - longer to clear drugs - lower concentrations may produce the same affect - reduced absorption of GI tract - decreased body fluids

How does pregnancy affect drug concentrations

higher blood volume - renal flow increased = increased secretion - nausea may interfere with absorption

What other physiologic factors can affect drug concentrations

genetic heterogeneity - prescence of disease (liver or kidney) - other drug interactions - inactivity - body temperature - body size and composition - gender

What is pharmacodynamics

relationship between drug’s concentration at its site of action and its pharmacological response

What is the therapeutic index

indicates how safe a drug is - helps determine if a drug needs TDM - varies drug to drug - varies from patient to patient

On the Dose Response Curve, what happens when the ratio is above 100

drug is fairly stable and no TDM is required

On the Dose Response Curve, what does it mean if it is under 10

drug is highly toxic and requires TDM - Digoxin, Warfarin, insulin, phenylioin

What is the most important factor with TDM

time of sample collection

When are peak levels most commonly drawn

1 hour after oral administration

What can happen if levels are drawn to early

They may be falsely high indications - adjustments don’t need to happen

For Digoxin collection, when does the peak level occur? Why is the level drawn at this time? Is there a trough level drawn?

Peak level is drawn 8-10 hours after administration - digoxin has slow uptake in cells - there is no trough level drawn

What specimen is preferred for TDM

Serum without gel - separator gel may absorb some drugs with prolonged contact especially if underfilled

If a doctor or pharmacist phone, what information may they need?

dose administration - time of collection - time of next dose - physiological changes - helping to determine peak and trough - clues to why drug level may have changed - other drugs the patient is taking

What are the types of cardioactive drugs? (3) Which one is tested in hospital? Which ones are tested in reference labs?

Digoxin (hospital), Quinidine and Procainamide (reference lab)

What are the 2 other names for digoxin? What is digoxin used to treat?

Digitalis and foxglove - used to treat congestive heart failure - improves cardiac contractility by inhibiting membrane Na, K ATPase - causes decrease in intracellular potassium which increases intracellular calcium in cardiac myocytes - some is excreted in urine and some is protein bound

What are antibiotics

high therapeutic index - no therapeutic monitoring is used

What is aminoglycosides?

antibiotic - antimicrobial agents - treatment of gram negative bacterial infections - Gentamicin, tobramycin, amikacin - can cause nephrotoxicity and ototoxicity (disruption of the inner ear) - effects are irreversible

What is vancomycin

antibiotic - glycopeptide - treatment of gram positive bacterial infections

What are the types of antiepileptic drugs are tested in hospital

phenobarbital, phenytoin, valporic acid, and carbamazepine

What are the types of antiepileptic drugs are tested in reference labs

ethosuximide, gabapentin, primidone, lamotrigine, levetiracetam, and topiramate

What is phenobarbitol

common antiephileptic drug - slow reacting barbiturate - sedative - primary hepatic excretion (hard on liver) - trough levels are usually elevated unless toxicity is suspected

What os phenytoin? What is the other name for it

Dilantin - common antiepileptic drug - treats seizure disorders - no sedative properties - hepatic elimination - albumin is monitored

What is valproic acid?

antiepileptic drug - used in treatment of petit-mal and absence seizures - hepatic elimination

What is carbazepine? What is the other name for it?

Tegretol - antiepileptic drug - used to treat seizure disorders - serious toxic effects (can cause agranulocytosis and aplastic anemia - CBC must be monitored as causes leukopenia - used in patients who don’t respond to other AEDs) - excreted by liver and can cause liver dysfunction - liver enzymes are monitored

What are the types of psychoactive drugs?

Lithium and Tricyclic Antidepressants

What are the 3 types of tricyclic Antidepressants (psychoactive drugs) that are tested in reference labs

Amitriptyline - Nortiptyline (metabolic product)
Imipramine - Desipramine (metabolic product)
Clozapine

What is the lithium drug

psychoactive drug tested in hospital - treatment of bipolar disorder, recurrent depression , and aggressice self-mutilating behaviour - cationic metal - does not bind to protein - Tested by ISE or colorimetric techniques - renal function also monitored

What are bronchodialators

theophyllone (highly toxic) - treatment of asthma - given IV in acute attack

What are the types of immunosuppressive drugs

Cyclosporine, tacrolimus, and sirolimus (tested in hospital)
Mycophenolic acid is tested in reference labW

What is cyclosporine

immunosuppressive drug - treats transplant rejection, rheumatoid arthritis, and severe psoriasis - whole blood specimen (drug is bound to protein) - manual pretreatment to release drug from RBCs must be performed before testing

What is tracolimus

immunosuppressive drug - more potent than cyclo (100x) - whole blood specimen - pretreatment

What is sirolimus

immunosuppressive drug - approved for kidney transplant - extremely potent and toxic - adverse effects (thrombocytopenia, anemia, infections) - whole blood specimens - pretreatment - commonly used in conjunction with cyclo and tacro

What are antineoplastic drugs

Types: Methotrexate - no established correlation between plasma concentration and therapeutic levels (no use for monitoring) - therapeutic rance for many of these drugs include concentrations associated with toxic effectsWhat

What is methotrexate

antineoplastic drug - inhibits DNA synthesis in all cells 0 leucovorin reverses the action (rescue) - serum concentration is used to determine how much leucovorin is needed to counteract the toxic effects of methotrexate