Therapeutic Drug Monitoring Flashcards
Methotrexatate
Antineoplastic
Phenobarbital
Anticonvulsant
Vancomycin
Antibiotic (antimicrobial)
Cyclosporine
Immunosuppressant
Ethosuximide
Anticonvulsant
Digoxin
Cardioactive
Theophyline
Bronchodilator
Tricyclic antidepressants
Anti-Psychotic
Chloramphenicol
Antibiotic (antimicrobial)
Quinidine
Cardioactive
Primidone
Anticonvulsant
Mycophenolic acid
Immunosuppressant
Aminoglycosides (Tobramycin and Gentamicin)
Antibiotic (Antimicrobial)
Alkylating agents
Antineoplastic
Lithium
Anti-Psychotic
Valproic acid
Anticonvulsant
Sirolimus (Rapamycin)
Immunosuppressant
Serotonin-release inhibitors
Anti-Psychotic
Lidocaine
Cardioactive
Caffeine
Bronchodilator
Phenytoin
Anticonvulsant
Tacrolimus (Prograf or FK-506)
Immunosuppressant
Serotonin-selective reuptake Inhibitors (SSRI’s)
Anti-Psychotic
Procainamide
Cardioactive
Carbamazepine
Anticonvulsant
A chemical used to selectively perturb specific tissues or a specific function of these tissues
Drug
A drug given to produce a DESIRABLE effect
Therapeutic drug
The minimum concentration that one can take to have a desired effectiveness
Minimum effective concentration
Minimum concentration that one can take to have a toxic effect
Minimum toxic concentration
The fraction of drug that is absorbed into circulation
Bioavaliability
Three general types of candidates for therapeutic drug monitoring (TDM)
- Pediatric or geriatric patients
- Patients with other underlying conditions
- Patients on multiple dug therapies
List 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
Two general reasons why certain drugs may require monitoring
*
Represents the range of drug concentrations within which the probability of the desired clinical response is relatively high and the probability of unacceptable toxicity is relatively low
Therapeutic Range
*
Reference Range
Define Liberation
- organ system involved
Process of a drug passing into a solution
Define Absorption
- organ system involved
Process of taking the drug into the body’s circulation
- GI tract, skin, intramuscular injection, or intrathecal injection
Define Distribution
- organ system involved
How drugs are delivered throuhout the bloodstream after being absorbed
- blood space, enter extravascular fluids, migrate to tissues or organs
Define Metabolism
- 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
- 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”
seven 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, 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
- Differentiation of hepatic enzyme induction and inhibition
Inhibition: concentration of drug stays higher
Induction:?
two major routs of drug elimination
Kidney or Liver
four minor routes of drug elimination
Skin (sweat), lungs (expired air), mammary glands (milk), salivary glands
Protein binding of a drug
- why it is 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
Protein binding of a drug
- 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 system?
Affects metabolism and elimination of a drug
How does Renal disease affect the LADME system?
Affects metabolism and elimination of a drug
Three general factors that affect drug disposition and an example of one condition associated with each factor
Biological - Genetics
Physiological - Age
Pathological - Burns
(*many more examples on page D)
Define synergistic dug interaction and give its general mechanism
Definition: a response to a drug that is greater than expected than if the drug were administered alone
Mechanism: ?
Define antagonistic drug interactions and give its general mechanism
Definition: A response to a drug that is less than expected than if the drug were administered alone
Mechanism: It blocks cellular activity
Steady-state drug levels:
- how dosing regimens are set according to the drug’s half-life
Measure LADME
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
Three goals goals of dosing
- Through should be reached before giving next dose
- Trough should not fall below MEC
- Peak should not be above the MTC
Active metabolites of procainamide
n-acetyl procainamide or NAPA
Active metabolite of primidone
Phenobarbital
Active metabolite of theophylline
Caffeine
What microorganisms are susceptible to aminoglycosides?
Gram negative
What microorganisms are susceptible to chloramphenicol?
Gram negative
What microorganisms are susceptible to vancomycin?
Some gram positive and some gram negative
List specific disorder treated by lithium therapy
Manic-depressive disorders (bipolar disorders)
