THERAPEUTIC DRUG MONITORING AND CLINICAL TOXICOLOGY Flashcards

1
Q

Clinical chemistry laboratory

– Provides information concerning the diagnosis and management of patients suspected to _______________

– Provides information in patients __________________

– Assessment of individuals _____________

A

have taken drug overdose

taking drugs for treatment of disease conditions

screened for drugs of abuse

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2
Q

Therapeutic Drug Monitoring

Involves the analysis, assessment and evaluation of ___________ in serum, plasma, or whole blood.

Purpose is to ensure the medication dose is __________ and not _____

A

circulating concentrations of drugs

at therapeutic range and not toxic.

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3
Q

TDM enables the assessment of the ______ and ______ of a particular medication in a variety of clinical settings.

A

efficacy and safety

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4
Q

The goal of TDM is to _______ therapeutic regimens for optimal patient benefit

A

individualize

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5
Q

Key points of therapeutic drug monitoring

Goal
-Ensure that a given drug dosage produces maximal ______ and Minimal ________

-Must have _______ at site of action that produces benefits

A

therapeutic benefit ; toxic adverse effects

an appropriate concentration

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6
Q

Key points of therapeutic drug monitoring

Standard dosages are derived from _______

Only the ______ fraction of drugs can interact with site of action, resulting in a biologic response

A

healthy population

free

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7
Q

THERAPEUTIC RANGE/ THERAPEUTIC WINDOW

The therapeutic range is the _____ of drug in plasma where the drug has been shown to be _____ without ________

A

concentration range

efficacious; causing toxic effects in most people.

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8
Q

TARGET CONCENTRATION AND THERAPEUTIC RANGE -Range introduces uncertainty into ___________ the desired dose

A

exactly how to prescribe

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9
Q

INDICATIONS FOR TDM

Drugs for which relationship between dose and plasma concentration is unpredictable, e.g _________

Drugs with a narrow therapeutic window:- will allow dosage alterations to produce optimal therapeutic effect or to avoid toxic effects. Ex: ____,_____ and _____

Drugs for which there is difficulty in measuring or interpreting the clinical evidence of therapeutic or toxic effects,e.g, Nausea & vomiting occur in both ______ toxicity & ______

Drug with poorly defined end point or difficult to clinically predict the response. Example: _______ drugs

A

Phenytoin

Lithium, phenytoin, and digoxin

digitalis; congestive heart failure

immunosuppressant

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10
Q

INDICATIONS FOR TDM

Drug interactions: When another drug alters the relationship between dose & plasma concentration e.g. plasma concentration of lithium is increased by _______

For diagnosis of suspected toxicity & determining drug abuse
To evaluate compliance of patient
Guiding withdrawal of therapy: _____,_____

A

thiazide

Antiepileptics, Cyclosporine.

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11
Q

DRUGS THAT ARE NOT SUITABLE FOR TDM

Drugs having (narrow or wide?) therapeutic index

Toxicity is not a realistic concern ( ____ )

Effects can be measured using laboratory tests (______)

Plasma concentration not predictably related to effects ( ______ )

Effect of the relationship remains undefined (________)

A

Wide; Penicillin

Anticoagulants

Anticoagulants

Antidepressants

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12
Q

The following are important considerations to ensure an optimum TDM service in any setting

-Measurement of ___________ taken at appropriate time after drug administration
-Knowledge of _______________________

-Knowledge of _________ like demographic data, clinical status, laboratory and other clinical investigations

-__________ after taking into consideration all of the above information and individualizing drug regimen according to the clinical needs of the patient.

A

patient’s serum or plasma drug concentration

pharmacological and pharmacokinetic profiles of the administered drugs

relevant patient’s profile

Interpretation of SDC

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13
Q

Pharmacokinetics’ Process assists in establishing or modifying a dosage regimen

T/F

A

T

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14
Q

Most drugs given as a single bolus or mass

T/F

A

F

Most drugs given on a scheduled basis not as a single bolus or mass

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15
Q

Goal of dosage regimens

Achieve troughs in _______ and peaks that _____

A

therapeutic range

are non-toxic

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16
Q

_______, which gives a measure of the unbound drug concentration, may be a useful alternative when blood samples are difficult to collect.

A

Saliva

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17
Q

Avoid serum-separator tubes because these may _______ due to the ________

A

lower drug concentrations

adsorption of drug into the matrix.

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18
Q

Storage of samples: __________ type tubes are acceptable for most assays

A

Plastic cryovial

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19
Q

GUIDELINES TO SPECIMEN COLLECTION

1) Blood specimens for drug monitoring can be taken at ______ times - during the _________ therapeutic concentration (‘peak’ level), or its _____ (‘trough’ level).

Occasionally called _____ levels, trough levels show _______ levels; whereas peak levels show ____

A

two different

drug ́s highest ; lowest

residual; sufficient therapeutic

toxicity

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20
Q

Peak and trough levels should fall within the therapeutic range.

T/F

A

T

21
Q

For chronically administered oral medications the peak levels usually occur _____ after the dose and the trough serum concentration ________.

______ is one exception.

A

1-2 hours

shortly after the dose is administered

Digoxin

22
Q

The serum level to determine peak activity should be drawn after the serum digoxin __________ i.e., ______ after the oral dose.

Drawing the trough level at _______ is usually sufficiently accurate.

A

has had time to equilibrate with the tissue

6-10 hours

the time the dose is given

23
Q

Intravenous medications should be given time to equilibrate before the peak level is drawn.

T/F

A

T

24
Q

Intravenous medications should be sampled _____ after administration.

For example, the peak serum level of Gentamicin should be drawn _________ after infusion of the drug ends and not ______________

A

1⁄2-1 hour

thirty minutes

immediately after the infusion.

25
Q

Intramuscularly administered medications if injected in an area with good blood flow will achieve peak levels within a similar time frame as intravenous.

T/F

A

T

26
Q

CLINICAL SIGNIFICANCE OF TDM

Maximizes _____
Avoids ______
Identifies ______
Facilitates the therapeutic effect of drug by achieving ———-
Identify poisoning, drug toxicity and drug abuse

A

efficacy; toxicity

therapeutic failure

target drug concentration

27
Q

Digoxin is measured in serum using immunoassay.

T/F

A

T

28
Q

Lidocaine
Used to correct _________ and prevent _________

Completely eliminated by the ____ if ____ given as monoethylglycinexylidide (MEGX).

Toxic effects include _____

A

ventricular arrhythmias

ventricular fibrillation.

liver; orally

CNS depression

29
Q

Drug Groups: Cardioactive

Quinidine

-Used to treat _______ problems

-Inhibits _______ channels

-Prevents arrhythmias, atrial flutter and fibrillation

A

cardiac arrhythmic

sodium and potassium

30
Q

Procainamide

-Used to treat _______ situations

-Blocks ______ channels

-Affects cardiac muscle contraction

-Often measured with _______

A

cardiac arrhythmic

sodium

NAPA(N-Acetyl procainamide)

31
Q

Drug Groups: Antibiotics

Aminoglycosides

Used to treat infections with gram- ______ bacteria that are resistant to less toxic antibiotics

Inhibits protein synthesis of the micro-organism
Examples include: gentamycin, tobramycin, amikacin and kanamycin
Associated with nephro and ototoxicity

A

Negative

32
Q

Vancomycin

Used to treat infections with more-resistant gram- _____ cocci and bacilli Inhibits cell wall synthesis

A

positive

33
Q

Drug Groups: Psychotherapeutic

Used to treat manic depression (bipolar disorder)
–______
–__________
–_____

A

Lithium

Tricyclic Antidepressants “TCAs”

Clozapine

34
Q

Drug Group: Antiasthmatic
Used to treat neonatal breathing disorders or respiratory disoders of adults or children, like asthma
Examples include _______ and ______

A

theophylline and theobromine

35
Q

Drug Group: Immunosuppressive

Monitoring of this group of drugs important to prevent ________ (host-versus-graft)
Used to treat _______ disease

A

organ rejection

autoimmune

36
Q

Drug Group: Immunosuppressive

Examples
– Cyclosporine
Whole blood is the specimen of choice, since it _______
– Tacrolimus (Prograf)
Prevents ________ and ___________

A

sequesters in the RBC

rejection of liver and kidney transplants

37
Q

Methotrexate is an anti_______

A

Neoplastic

38
Q

Methotrexate:
– The efficacy of therapy is dependent on _______, one that is ___________

– This is accomplished by the administration of _______, which ____________ at a specific time after methotrexate infusion.
– This is referred to as __________

A

a controlled period of inhibition

selectively detrimental to neoplastic cells.

leucovorin; reverses the actions of methotrexate

leucovorin rescue.

39
Q

Methotrexate:
– Failure to stop methotrexate actions results in _____ effects to most cells.
– Evaluation of _______ concentration, after the ______ period has passed, is used to:
determine how much _____ is needed to counteract many of the toxic effects of methotrexate.

A

cytotoxic

serum methotrexate

inhibitory time

leucovorin

40
Q

TECHNIQUES FOR MEASUREMENT IN TDM
1. HPLC: ___________: The separation of a substance depends on the relative distribution of mixture constituents between two phases, a ____ phase ( _______ ) and a ______ phase.
.

A

High Pressure Liquid Chromatography

mobile

carrying the mixture

stationary

41
Q

TECHNIQUES FOR MEASUREMENT IN TDM

  1. LC/MS: _____________: All chromatography-based techniques work on the principle that different substances are absorbed differently in solution. Two “phases” or materials are used to separate the components of a solution. The mobile phase ___________________________________, which separates out the components in the sample.
A

Liquid Chromatography Mass Spectrometry

carries the sample along the stationary or solid phase

42
Q

GC/MS:_________ is a separation method using _____ temperatures to cause sample vaporization.

In mass spectrophotometry the vaporized fractions are _________. The molecules can be separated on the basis of ______. The pattern of separation is unique to each drug and therefore establishes a “ _____ ” for identification.

A

Gas chromatography

very high

passed through an electrical field

molecular weight

fingerprint

43
Q

TECHNIQUES FOR MEASUREMENT IN TDM

_________ is the gold standard method for the identification of drugs of abuse.

A

GC/MS

44
Q

Management of poisoning include use of specific antidotes like _____ for paracetamol poisoning

A

N-acetylcystein

45
Q

Paracetamol poisoning

Metabolites following poisoning are mostly soluble and excreted in urine as ______ and ______

However, ________ formed through the action of cytochrome p450 accumulates following exhaution of ______ and causes hepatotoxicity

A

glucoronides and sulphate

n-acetyl-p-benzoquinoneimine (NAPQI)

glutathione

46
Q

Clinical features of paracetamol poisoning

Insidious onset with _______ in first 24 hr

_______ is maintained unless associated sedative
Then ________, abnormal ______, elevated _____ and _____
Encephalopathy, liver and renal failure may follow depending on severity

A

nausea and vomiting

Consciousness

abdominal pain; prothrombin time

liver enzymes and bilirubin

47
Q

Treatment of paracetamol poisoning

Regular ______

__________ management

Acid base homeostasis, renal status

Use of specific antidote _____ given by ___

Oral ______ assist in ______ regeneration

A

blood level monitoring

Fluid and electrolyte

N-acetylcystein; IV

methionine; glutathione

48
Q

Screening for drugs

________ may just suffice for screening and diagnosis especially for drugs of abuse

This may be key for patient brought into the emergency unit in _____ state

In suspected case of _____, identification of poison is vital and be carried out by qualified personnel in special labs using urine or blood

A

Qualitative

unconscious; homicide

49
Q

_________ is the antidote for alcohol or methanol

_______ is the antidote for beta blockers

______ is the antidote for heparin

______ is the antidote for warfarin

_______ is the antidote for methotrexate

A

Fomepizol

Glucagon

Protamine sulphate

Vitamin K

Leucovorin