Therapeutic Drug Monitoring (TDM) Flashcards
What is the general drug class for methotrexate?
Antineoplastic
What is the general drug class for phenobarbital?
Anticonvulsant
What is the general drug class for vancomycin?
Antibiotic (antimicrobial)
What is the general drug class for ethosuximide?
Anticonvulsant
What is the general drug class for digoxin?
Cardioactive
What is the general drug class for theophyline
Bronchodilator
What is the general drug class for tricyclic antidepressants?
Anti-psychotic
What is the general drug class for chloramphenicol?
Antibiotic (antimicrobial)
What is the general drug class for quinidine?
Cardioactive
What is the general drug class for primidone?
Anticonvulsant
What is the general drug class for mycophenolic acid (MPA)?
Immunosuppressant
What is the general drug class for aminoglycosides (gentamicin, tobramycin, amikacin, neomycin)?
Antibiotic (antimicrobial)
What is the general drug class for alkylating agents?
Antineoplastic
What is the general drug class for lithium?
Anti-pyschotic
What is the general drug class for valproic acid?
Anticonvulsant
What is the general drug class for sirolimus (rapamycin)?
Immunosuppressant
What is the general drug class for serotonin-release inhibitors?
Anti-psychotic
What is the general drug class for lidocaine?
Cardioactive
What is the general drug class for caffeine?
Bronchodilator
What is the general drug class for phenytoin?
Anticonvulsant
What is the general drug class for tacrolimus (Prograf or FK-506)?
Immunosuppressant
What is the general drug class for serotonin-selective reuptake inhibitors (SSRI’s)?
Anti-psychotic
What is the general drug class for procainamide?
Cardioactive
What is the general drug class for carbamazepine?
Anticonvulsant
What is the general drug class for cyclosporine?
Immunosuppressant
A chemical used to selectively perturb specific tissues or a specific function of these tissues?
Drug
A drug given to produce a DESIRABLE effect
Theraapeutic drug
The minimum concentration that one can take to have a desired effectiveness
Minimum effective concentration (MEC)
Minimum concentration that one can take to have a toxic effect
Minimum toxic concentration
The fraction of a drug taht is absorbed into circulation
Bioavailability
When the rate of drug input is equal to the rate of drug elimination
Stead-state concentration
Time required for drug concentration to decrease by one-half
Half-life
The highest concentration reached after a dose
Peak drug level
Lowest drug concentration acheived, usually sampled shortly before teh next scheduled dose
Trough drug level
Three purposes of therapeutic drug monitoring
- Check for compliance or non-compliance
- Initiation and maintenance of the most appropriate dosing regimen for a particular patient
- Interpreting toxic symptoms of patients to whom a drug is prescribed
Three general tyeps of candidates for therapeutic drug monitoring (TDM)
- Pediatric or geriatric patients
- Patients w/ other underlying ocnditions
- Patients on multiple drug therapies
Two general reasons why certain drugs may require monitoring
- ?
- ?
Represents the range of drug concentrations w/in which the probability of the desired clinical response is relatively high and the probability of unacceptable toxicity is relatively low
Therapeutic range
Represents the range of values for a physiologic measurement in healthy persons
Reference range
List three goals of dosing
- Trough should be reached before giving the next dose
- Trough should not fall below the MEC
- Peak should not be above the MTC
What are the three general factors that affect drug deposition?
- Biological
- Physiological
- Pathological
List the condition associated w/ biological factors that affect drug deposition?
Genetics (enzyme deficiencies)
List at least one of the conditions associated w/ physiological factors that affect drug deposition?
- Body weight and composition
- Age
- Temperature (hyper- or hypothermia)
- Gastric emptying time and gastrointestinal motility
- Blood flow rates (resting or exercise)
- Environment (high altitude → ↓ O2 → ↑ RBCs → ↑ “drug carriers”)
- Nutrition
- Pregnancy
- Circadian rhythm
List at least one of the conditions associated w/ physiological factors that affect drug deposition?
- Renal impairment
- Hepatic impairment
- Cardiac disease and/or congestive heart failure
- Gastrointestinal disease
- Burns
- Shock
- Trauma
Response to a drug that is greater than expected if the drug were administered alone
Synergistic drug interaction
Response to a drug that is less than expected than if the drug were adminstered alone
Antagonistic drug interaction
Field of pharmacy which quantitatively studies drug disposition in the body, measuring LADME system for an individual patient, to set a specific dosage regimen for each patient
Pharmocokinetics
Field of pharmacy which studies the interaction of pharmacologically-active substances w/ target sites and the biochemical and phsyiological consequences leading to therapeutic or adverse effects at the site of action
Pharmacodynamics
What do the letters in the acronym LADME stand for?
L → liberation A → absorption D → distribution M → metabolism E → elimination
Define liberation and the organ system involved
Process of a drug passing into solution
- Mouth
Explain how liberation works in the LADME system
- Saliva in the mouth causes the disintegration agent to swell, creating channels for the saliva
- Fast-dissolving granules dissolve and the tablet disintegrates
Define absorption and the organ system involved
Process of takin ghte drug into the body’s circulation
- GI tract, skin, intramuscular injection, or intrathecal injection
Define distribution and the organ system involved
How drugs are delivered throughout the bloodstream after being absorbed
- Blood space → enter extravascular fluids → migrate into tissues or organs
Define metabolism and the organ system involved
Process of biotransformation of the parent drug to one or more metabolites
- Liver and kidney, but also in plasma and muscle tissue
Define elimination and the organ system involved
Final excretion of drug from the body
- Kidney (urine) and liver (bile and feces)
Four sites of drug absorption
- GI tract
- Small intestine
- Skin
- Intramuscular/intrathecal injection
When drugs are absorbed from the intestine they are transported by portal circulation to liver where they are substantially metabolized before reaching systemic circulation. This lowers the concentration of active parent drug.
First-pass metabolism
7 general factors which affect drug distribution
- Binding of drug to circulating blood components
- Binding of drug to fixed receptors
- Passage through membrane barriers
- Ability to dissolve in structural or storage lipids
- Molecular weight of drug
- pKa of drug (acidic vs. basic)
- Condition of patient
Drug metabolism
- Two primary and two secondary sites of metabolism
Primary: liver and kidney
Secondary: plasma and muscle tissue
Drug metabolism – Phase I
- Types of processes
- Oxidation
- Hydroxylation
- Reduction
Drug metabolism – Phase I
- Usual products
Active metabolites
Drug metabolism – Phase I
- Change w/ age
Greater
Drug metabolism –Phase II
- Types of processes
Conjugation
Drug metabolism – Phase II
- Usual products
Inactive metabolites
Drug metabolism – Phase II
- Change w/ age
Less
Drug metabolism
- Differentiation of hepatic enzyme induction and inhibition
Inhibition: concentration of drug stays higher
Induction: ?
How do zero order kinetics affect drug metabolism?
- Constant AMOUNT per unit of time is metabolized
- Rate doesn’t increase as drug concentration increases
How do first order kinetics affect drug metabolism?
- Constant FRACTION per unti of time is metabolized
- Rate increases as drug concentration increases
Two major routes of drug elimination
Kidney or liver
Four minor routes of drug elimination
- Skin (sweat)
- Lungs (expired air)
- Mammary glands (milk)
- Salivary glands
Why is protein binding of a drug important for distribution and elimination of a drug?
Alteration in protein concentration will alter the free and bound portions of drug in the blood stream.
- Only FREE drug is available for distribution and elimination
- Only FREE drug may cross cell membranes or may interact with cellular receptors
Three general conditions which may cause altered protein binding of a drug
- Uremia
- Conditions of acute stress
- Aging patients
How does cardiac disease affect the LADME system?
Affects distribution and elimination of the drug
How does liver disease affect the LADME?
Affects metabolism and elimination of a drug
How does renal disease affect the LADME system?
Affects metabolism and elimination of a drug
?
?
Steady-state drug levels
- Number of half-lives before steady-state is achieved
4-5 half lives
Steady-state drug levels
- Importance of monitoring peak and trough drug levels in setting dosing regimens
To avoid toxicity
Active metabolites of procainamide
n-acetyl procainamide (NAPA)
Active metabolite of primidone
Phenobarbital
Active metabolite of theophylline
Caffeine
Which microorganisms are susceptible to aminoglycosides?
Gram-negative
What microorganisms are susceptible to chloramphenicol?
Gram-negative
What microorganisms are susuceptible to vancomycin?
Some Gram-positive and some Gram-negative
What is the specific disorder treated by lithium therapy?
Manic-depressive disorders (bipolar disorders)
Organ transplant associated w/ cyclosporine
- Inhibits cytokines that control lymphocyte proliferation
- Reduces cellular response to Ags
- Used after BM transplant
Organ transplant associated w/ mycophenolic acid (MPA)
- Inhibits transcription in T-lymphocytes
- Used after kidney transplants in combination w/ cyclosproine
Organ transplant associated w/ sirolimus (Rapamycin)
- Blocks lymphocyte proliferation due to inhibition of interleukin production
- Used after kidney transplants
Organ transplant associated w/ tacrolimus (Prograf or FK-506)
- Blocks lymphocyte proliferation due to inhibition of interleukin production
- Used after liver transplantation
Why do certain drugs require monitoring?
- Consequences of overdosing and underdosing are serious
- Small difference b/w a therapeutic and toxic dose
- Change in patient’s physiologic state that may unpredictably affect drug concentrations
- Poor relationship b/w dose and circulating concentration but good correlation b/w circulating concentrations adn therapeutic/toxic effects
- A drug interaction may be or is occurring
- Monitor of patient compliance
What happens when therapeutic drug monitoring is not indicated?
If dose and clinical response of patient have a good correlation, therapeutic drug monitoring is not indicated
