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Analytical and Clinical > Week 7 - Clinical Biochemistry > Flashcards

Week 7 - Clinical Biochemistry Flashcards

1
Q

What is TDM?

A
  • Drug measurements in body fluids – aid to patient management
  • Optimise treatment
  • Routine in labs since 1970s
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2
Q

MTD

A

max. tolerated dose

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3
Q

MED

A

min. effective dose

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4
Q

MED

A

min. effective dose

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5
Q

bioavalability

A

how much of drug that is available when body gets intravenous and where

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6
Q

Therapeutic window

A

in-between MTD and MED

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7
Q

What are the 3 things to consider when choosing drug dosage?

A
  • dosing regimen
  • drug at site of action or compartment
  • clinical effects
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8
Q

Things to consider - Pharmokinetics

A

compliance

dosing

physiological differences- body mass

drug interactions

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9
Q

Things to consider - Pharmacodynamics

A

drug receptor status

genetics

drug interactions

tolerance

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10
Q

PHARMACOKINETICS

A

Bioavailability

First pass metabolism

Distribution – solubility – lipid or water

Volume of distribution – theoretical value

Metabolism/excretion

Clearance – body weight, renal/hepatic function

Elimination rate

Plasma protein binding – bound - inert

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11
Q

PHARMACODYNAMICS

A

Relationship between drug concentration and effect

Receptors – pathological condition, other drugs

Most drugs have a linear relationship between dose and plasma conc.
Some exceptions – phenytoin – rate of mettabolism close to max capacity of enzymes involved (zero order kinetics)

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12
Q

What is quality control?

A

Procedures to confirm validity of biochemical results

Monitoring analytical performance

Internal QC – controls, reproducibility (drift)

External QC – EQA e.g. UKNEQA

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13
Q

QC - Levey-Jennings chart

A

Results expected to be =/- 2SD from mean

Trend – 6 or more showing consecutive move in same direction (up or down)

Shift – 6 or more results on one side of the mean

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14
Q

QC PARAMETERS

A
  • All laboratory trimmed means (ALTM) – remove top & bottom 5% of results – target value
  • Bias - % deviation from target value
  • Rolling bias – mean of current and previous 5 results
  • Rolling variability – mean of current and previous 5 results (ignoring direction)
  • Bias index score (BIS) – comparison of deviation from target
  • Overall lab performance – mean of BIS for all analytes
  • Method bias – mean from ALTM for each method
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15
Q

INDICATIONS FOR TDM

A

Suspected toxicity due to drug or metabolite – overdose

A sub therapeutic response of a drug – dosage, dialysis, nonadherence,
disease state

Assessment of potential drug interactions

Assessment of therapy when the patient is clinically unstable or has organ
damage

Assessment of therapy following initiation or change of regimen

Evaluation of patient compliance

Narrow therapeutic index

A high incidence of adverse effects

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16
Q

SUSPECTED TOXICITY DUE TO DRUG OR METABOLITE

A

Too much of a drug – intentional or not

Dose too high

Liver/kidney damage – metabolism/excretion

Drugs with lower therapeutic index

Examples
Levothyroxine
Carbamazepine
Digoxin
Lithium carbonate
Warfarin

17
Q

POTENTIAL DRUG INTERACTIONS
Example – digoxin

A

Unexpectedly high [digoxin] – interaction with amiodarone, quinidine, verapamil

Serum concentrations of hepatically cleared drugs affected by drugs which include or inhibit cyt P450

18
Q

THE ASSESSMENT OF THERAPY WHERE THE PATIENT IS CLINICALLY UNSTABLE

A

Cancer treatment – cancer drugs represent a challenge – toxicity/lack of
specificity – optimal dose narrow range

19
Q

TDM NOT REQUIRED

A
  • Drugs with broad therapeutic index
  • Toxicity is not a realistic concern (Penicillin)
  • Effects can be measured using functional laboratory tests (Anticoagulants)
  • Plasma concentration not predictably related to effects(anticoagulants)
  • “Hit and run drugs”: Omeprazole, MAO inhibitors.
20
Q

DRUGS THAT REQUIRE TDM - GENERAL

A

Cardioactive drugs

Antibiotics- aminoglycosides

Anti-epileptic drugs

Psychoactive drugs

Immunosuppressive drugs e.g. cyclosporin

Anti-neoplastics e.g. methotrexate

21
Q

Cardioactive drugs

A
  • Digoxin
    –> cardiac glycoside - CHF – affected by serum electrolytes, hyperthyroidism – immunoassay
  • Quinidine
    –> trough level monitoring – immunoassay
  • Procainamide
    –> cardiac arrhythmia – altered renal/hepatic function affects conc.
22
Q

Anti-epileptic drugs

A

Phenobarbital
– hepatic metabolism – administered as pro-drug primidone

Phenytoin
– seizures

23
Q

Psychoactive drugs

A
  • Lithium
  • TCAS
24
Q

DRUGS REQUIRING TDM – EXAMPLE - AMINOGLYCOSIDE - WHAT DOES IT TREAT?

A

Aminoglycoside antibiotics are
used to treat bacterial infections e.g. streptomycin

25
Q

DRUGS OF ABUSE

A

Misuse of therapeutic drugs

Performance enhancement – athletic

Professional, industrial settings

Medicolegal

26
Q

How do aminoglycoside antibiotic kill bacteria?

A

specifically target aerobic gram-negative bacteria - inhibit protein synthesis

27
Q

Aminoglycoside absorbtion

A

very poor oral absorption
- wide distribution occurs

28
Q

How much does aminoglycoside bind to plasma?

A

little or no binding to plasma protein

29
Q

Is aminoglycoside metabolised?

A

no
- its excreted almost entirely into urine by GF

30
Q

Aminoglycoside Half-Life

A

elimination half-life of 2-3 hours approx

31
Q

Aminoglycoside Distribution

A

Distributed by active transport to renal transport cells
- accumulates in the
kidney causing nephrotoxicity

  • Main toxic effect within the tubular cell by altering phospholipid
    metabolism
  • Also cause renal vasoconstriction
32
Q

AMINOGLYCOSIDE- Ototoxicity

A

– generate free radicals in inner ear – damage to sensory cells and
neurones
– mild reversible hearing loss

33
Q

Amphetamines - Drug Abuse

A
  • used clinically for narcolepsy, ADHD
  • Initial well-being, followed by restlessness and possible psychosis
  • Measurement – liquid chromatography, GC
34
Q

Anabolic Steroids - Drug Abuse

A
  • clinical application male hypogonadism
  • Increase muscle mass, improved athletic performance
35
Q

Cannabinoids – marijuana - Drugs of Abuse

A
  • THC most abundant
  • Metabolite in urine 3-5 days after single use
  • GC/MS
36
Q

Cocaine - Drugs of Abuse

A
  • high conc. CNS stimulation – excitement and euphoria
  • GC/MS
37
Q

Opiates - Drugs of Abuse

A
  • analgesia, sedation, anaesthesia
  • GC/MS
38
Q

How do liver enzymes play a role in terms of liver damage?

A

When your liver gets damaged or a part of the liver gets damaged, it’ll release enzymes into the bloodstream.

39
Q

What enzyme is used as a biomarker of prostate cancer?

A

acid phophotase

Analytical and Clinical (11 decks)

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