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Clinical Chemistry 2 (Lecture) > Therapeutic Drug Monitoring (Bishop | F) > Flashcards

Therapeutic Drug Monitoring (Bishop | F) Flashcards

1
Q

What is TDM?

A

It is the analysis, assessment, and evaluation of circulating concs. of drugs in serum, plasma, / whole blood (WB)

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2
Q

What is the purpose of TDM?

A

To ensure that a given drug dosage produces maximal therapeutic benefit and min. toxic adverse effects

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3
Q

When is TDM used?

A

It is used when safe dosage regimens have not been established and a trial and error approach is not appropriate

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4
Q

In TDM, where is std dosage derived?

A

It is derived from observations in healthy population

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5
Q

TDM involves what?

A

It involves quantitative evaluation of circulating drug conc.

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6
Q

What are the key factors of TDM?

A

1) Route of administration
2) Rate of absorption
3) Distribution of drug within body
4) Rate of elimination

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7
Q

What are the different routes of administration?

A

1) Intravenous (IV)
2) Intramuscular (IM)
3) Subcutaneous (SC)
4) Transcutaneous
5) Suppository
6) Oral administration

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8
Q

What is the principle of IV (w/c is 1 of the routes of administration)?

A

Injected directly into circulation

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9
Q

What is the principle of IM (w/c is 1 of the routes of administration)?

A

Injected into muscle

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10
Q

What is the principle of SC (w/c is 1 of the routes of administration)?

A

Injected just under skin

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11
Q

What is the principle of transcutaneous (w/c is 1 of the routes of administration)?

A

Inhaled or absorbed through skin

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12
Q

What is the principle of suppository (w/c is 1 of the routes of administration)?

A

Rectal delivery

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13
Q

What is the principle of oral administration (w/c is 1 of the routes of administration)?

A

By mouth

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14
Q

For orally administered drugs, efficiency of absorption from GIT depends on what factors?

A

1) Formulation of drug
a. Tablets
b. Capsules
c. Liquid solutions
2) Uptake by transport mechanisms intended for dietary constituents vs. passive diffusion
3) Changes in :
a. Intestinal motility
b. pH
c. inflammation
d. food
e. other drugs
4) Variation among population
5) Age
6) Pregnancy
7) Pathologic conditions

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15
Q

What are the types of drugs?

A

1) Free (unbound)

2) Bound

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16
Q

What is the characteristic of free fraction of drug?

A

It can interact w/ site of action and cause biologic response

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17
Q

The percentage of free fraction of drug depends on what?

A

1) Physiologic parameters

2) Biochemical parameters

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18
Q

The physiologic and biochemical parameters where the percentage of free fraction of the drug depends on are what?

A

1) Inflammation
2) Malignancies
3) Pregnancy
4) Hepatic disease
5) Nephrotic syndrome
6) Malnutrition
7) Acid-base disturbances

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19
Q

The percentage of free fraction of drug also depends on what?

A

Conc. of other substances competing for binding sites

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20
Q

What is the principle of drug distribution?

A

1) Ability of drug to diffuse out of circulation

2) Depends on lipid solubility of drug

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21
Q

What is the principle of drug elimination?

A

Rate of change of drug conc. over time varies continuously in relation to conc. of drug

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22
Q

What is the elimination equation?

A

ΔC/ΔT = -kC

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23
Q

What are the cmpts related to drug elimination?

A

1) Metabolic clearance

2) Renal clearance

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24
Q

What is the system of metabolic clearance?

A

Hepatic mixed function oxidase (MFO) system

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25
What are the events that occur in hepatic MFO system?
1) Converts hydrophobic substances into H2O-soluble ones | 2) Transports them into bile or circulation, eliminates them by filtration
26
What is pharmacokinetics?
It is the mathematic modeling of drug conc. in circulation
27
Pharmacokinetics assists in what?
It assists in establishing or modifying a dosage regimen
28
Pharmacokinetics takes into account what?
It takes into account all factors that determine conc. of a serum drug and its rate of change (absorption, distribution, and elimination)
29
What is the timing for sx collection?
It is critical
30
When does trough concs. occur (in sx collection)?
Right before next dose
31
When does peak concs. occur (in sx collection)?
1 hr after oral dose
32
What is the sx of choice for TDM?
1) Serum | 2) Or plasma
33
What are the cmpts of pharmacogenomics?
1) Responders | 2) Non-responders
34
Who are responders (in pharmacogenomics)?
Pts benefitting from therapeutic and desired effects of drug
35
Who are non-responders (in pharmacogenomics)?
Pts not benefitting from therapeutic and desired effects of drug
36
What is pharmacogenomics?
Therapeutic effectiveness of drugs has been attributed to inter-individual variation in genetic polymorphisms of drug metabolism pathways
37
What is cytochrome P450?
It is the gene grp family that affects drug metabolism
38
What are the cardioactive drugs requiring TDM?
1) Cardiac glycosides a. Digoxin 2) Antiarrhythmics a. Quinidine b. Procainamide c. Disopyramide
39
What is the purpose of digoxin?
It is used in treatment of congestive heart failure (CHF)
40
What is the fxn of digoxin?
It inhibits membrane Na-K-ATPase
41
What are the characteristics of absorption (in digoxin)?
1) It is variable 2) It is influenced by dietary factors 3) It is influenced by GI motility 4) It is influenced by formulation of drug
42
How is digoxin eliminated?
Via renal filtration of plasma free form
43
What is the half-life (plasma; in connection to digoxin)?
38 hrs in ave adult
44
What is the method (and what is its purpose) done for measurement of digoxin?
Immunoassay (to determine total conc. in serum)
45
What are the most common formulations of quinidine?
1) Quinidine sulfate | 2) Quinidine gluconate
46
What is the action of disopyramide?
It is used as a quinidine substitute when quinidine's adverse effects are excessive
47
What are the exs of antibiotics?
``` 1) Aminoglycosides Most common: a. Gentamicin b. Tobramycin c. Amikacin d. Kanamycin 2) Vancomycin ```
48
What are aminoglycosides?
A grp of chemically related antibiotics used for treatment of infections w/ gram-(-) bacteria that are resistant to less toxic antibiotics
49
What is vancomycin and what is its action?
It is a glycopeptide antibiotic that is effective against gram-(+) cocci and bacilli
50
What are the different antiepileptic drugs?
1) First generation a. Phenobarbital b. Phenytoin c. Valproic acid d. Carbamazepine e. Ethosuximide 2) Second generation a. Felbamate b. Gabapentin c. Lamotrigine d. Levetiracetam e. Oxcarbazepine f. Tiagabine g. Topiramate h. Zonisamide
51
What is phenobarbital and what is its action?
It is a slow-acting barbiturate that effectively controls several types of seizures
52
What are the uses of phenytoin?
1) A commonly used treatment for seizure disorders | 2) It is used as a short-term prophylactic agent in brain injury to prevent loss of fxnal tissue
53
What is the use of valproic acid?
It is used as a monotherapy for treatment of petit mal and absence seizures
54
What are the characteristics of carbamazepine?
1) It is an effective treatment in various seizure disorders | 2) It has serious toxic adverse effects
55
What is the result of the characteristic of carbamazepine due to its serious toxic adverse effects?
It is less frequently used
56
What is the use of ethosuximide?
It is used for control of petit mal seizure
57
How is felbamate administered?
Orally
58
What is the characteristic of felbamate (in connection for it as being orally administered)?
It is nearly completely absorbed by the GIT
59
What is the characteristic of felbamate?
It is toxic (/ it is known for its toxicity)
60
What is the primary indication of felbamate?
It is primarily indicated in severe epilepsies (such as Lennox-Gastaut syndrome [children]) and refractory epilepsy (adults)
61
What may be the indication of gabapentin?
It may be indicated as monotherapy or in conjunction w/ other antiepileptic drugs in pts suffering from complex partial seizures w/ or w/out generalized seizures
62
What is the indication of levetiracetam?
It is indicated in partial and generalized seizures
63
What is oxcarbazepine and what is its characteristic?
It is a pro-drug that is almost immediately metabolized to licarbazepine
64
What is the indication of oxcarbazepine?
1) It is indicated for monotherapy of partial seizures | 2) In generalized tonic-clonic seizures
65
What is the indication of tiagabine?
It is indicated in partial seizures
66
What are the indications of topiramate?
It is indicated in partial and generalized seizures
67
What are the indications of zonisamide?
It is indicated in partial and generalized seizures
68
What are the exs of psychoactive drugs?
1) Lithium 2) Tricyclic antidepressants 3) Clozapine 4) Olanzapine
69
How is lithium administered?
Orally
70
What is the use of lithium?
It is used to treat manic depression
71
What are the uses of tricyclic antidepressants?
It is a class of drugs used to treat: 1) Depression 2) Insomnia 3) Extreme apathy 4) Loss of libido
72
What is clozapine?
It is an atypical antipsychotic
73
What is the use of clozapine?
It is used to treat otherwise treatment-refractory schizophrenia
74
What is olanzapine?
It is a thienobenzodiazepine derivative
75
Olanzapine effectively treats what conditions?
1) Schizophrenia 2) Acute manic episodes 3) Recurrence of bipolar disorders
76
What are the exs of immunosuppressive drugs?
1) Cyclosporine 2) Tacrolimus 3) Sirolimus 4) Mycophenolic acid
77
What is the primary clinical use of cyclosporine?
Its primary clinical use is suppression of host-versus-graft rejection of heterotropic transplanted organs
78
What is the characteristic of tacrolimus?
It is 100 times more potent > cyclosporine
79
What is sirolimus?
It is an antifungal agent
80
What is the activity present / capable of doing of sirolimus?
Immunosuppressive activity
81
FDA approved sirolimus can be administered to whom?
To / for pts receiving kidney transplants
82
What is mycophenolic acid?
It is a lymphocyte proliferation inhibitor
83
Mycophenolic acid is most commonly used as what?
As supplemental therapy (w/ cyclosporine and tacrolimus) in renal transplant pts
84
Provide an ex of antineoplastics
Methotrexate
85
What is 1 of the few antineoplastic drugs in w/c TDM offers benefits to a therapeutic regimen?
Methotrexate
86
High-dose methotrexate followed by leucovorin rescue has been shown to be what?
To be an effective therapy for various neoplastic conditions
87
Basis of the therapy (for various neoplastic conditions w/c is shown by high-dose methotrexate followed by leucovorin rescue) involves what?
Involves relative rate of mitosis of normal vs. neoplastic cells
88
What are the characteristics of neoplastic cells (in connection w/ the effective therapy w/c is shown by high-dose methotrexate followed by leucovorin rescue)?
1) These divide more rapidly > normal cells 2) These have higher requirement for DNA 3) These are susceptible to deprivation of this essential constituent before normal cells
89
The efficacy of methotrexate depends on what?
Controlled period of inhibition
90
How is the efficacy of methotrexate accomplished?
It is accomplished by leucovorin

Clinical Chemistry 2 (Lecture) (17 decks)

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