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clinical chem year 2 > TDM > Flashcards

TDM Flashcards

(64 cards)

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1
Q

Receptor Interactions

A

drugs binding to receptors on cell surface or inside

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2
Q

Surface receptors

A

drugs that act on receptors on the surface of cells - GPCRs

Betablockers that bind to receptors on cardiac cell surface to block adrenaline reducing heart rate and pressure

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3
Q

intracellular receptors

A

steroid hormones cross cell membrane and bind to intracellular receptors to directly influence gene expression

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4
Q

agonist

A

drugs that mimic action of natural substance by binding = biological response

morphine opioid agonist binds to receptors = analgesia = pain relief

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5
Q

antogonist

A

drug that binds to receptor without activating it and prevents the natural substance from bidning

Naloxone blocks opioid receptor to reverse OD

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6
Q

pharmacodynamics

A

how drugs interact with target and what biological effects are produced

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7
Q

enzyme inhibition

A

drugs inhibit enzymes to prevent molecule breakdown alters a physiological pathway = controls bp, reduces inflammation

ACE inhibitors like enalapril inhibit ACE causing decrease in angiotensin 2 helping BP to go down

Statins like atorvastatin inhibits HMG-CoA reductase , rate limiting enzyme = lowers cholesterol

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8
Q

Enzyme activation

A

Fibrates like gemfibrozil activates PPARs to increase lipid breakdown which lowers TRIG level

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8
Q

Pharmacokinetics (PK):

A

metabolism of drugs by liver enzymes and influence drug levels in blood stream

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9
Q

Prodrugs

A

some drugs are inactive in their original form so they need to be converted with enzyme to become active

Enalapril = ACE inhibitor

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10
Q

Half-life (t₁/₂)

A

time it takes for the drug concentration to decrease by half in the bloodstream. It helps determine dosing intervals.

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11
Q

Volume of Distribution (Vd):

A

the extent to which a drug spreads into tissues.

drug size, solubility, and protein
binding.

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12
Q

Clearance (Cl):

A

volume of plasma from which the drug is completely removed per unit time

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13
Q

five main stages of drug movement in the body outlined by

A

ladme

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14
Q

L in ladme

A

Liberation
-when drug is released from dosage form (pill) into a solution to be absorbed into the blood

essential for drugs that need to dissolve in gastric fluids

Drug Dissolution:- solid drugs that need to dissolve in your stomach to be absorbed

Poor dissolution can delay the
onset of action or reduce the therapeutic efficacy of a drug

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15
Q

A in ladme

A

Absorption
-when drug passes from site of administration into the blood stream

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16
Q

What are key factors that affect absorption

A

Route of administration
Oral - needs to go through GI tract using dissolution, diffusion, and transport

IV= right into bloodstream (no absorption phase)

IM - absorption depends of blood flow to muscle and drug solubility

Rectal - partial absorption

GI motility - how fast it gets through Gi depends on how fast its absorbed

Presence of food - some need it for increasing or decreasing absorption

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17
Q

First pass effect

A

initial metabolism of drug by liver before systemic circulation

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18
Q

D in ladme

A

Distribution
how the drug is transported through blood stream to target tissues

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19
Q

Free drug fraction

A

only unbound (free) drug is active
-drug bound to plasma proteins like albumin is not biologically active

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20
Q

BBB

A

only lipophilic drugs can cross the BBB and affect the CNS whereas hydrophilic drugs cannot

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20
Q

M in ladme

A

metabolism
the process the body uses to transform the drug in the liver forms active metabolites

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21
Q

Phase I Metabolism:

A

oxidation, reduction, or hydrolysis reactions mediated by cytochrome P450

polymorphisms in CyP450 can cause differences in how different ppl process different drugs

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22
Q
  • Phase II Metabolism:
A

conjugation with substances such as glucuronic acid, sulfate, or
glutathione, making the drug more water-soluble and easier to excrete.

measured i plasma (e.g., µg/mL)

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23
E in ladme
Elimination -removal of drug from the body mostly through renal via urine
24
What helps minimize risk of toxicity
precise monitoring of drugs with narrow therapeutic windows lithium to avoid toxicity
25
how to distinguish between Non compliance and OD symptoms
Using TDM low warfarin - non compliance too much = OD
26
Trough samples
Should be collected just BEFORE next dose
27
Peak levels
collected one hour after oral dose to measure highest concentration
28
Preferred sample
serum HEP PLASMA can be used depending on the test
29
Cardio active drug Digoxin for CHF
inhibits NA/K pump increasing Ca and cardiac contractility narrow therapeutic range - needs monitoring to avoid toxicity. Ppl wil renal impairment or lyte imbalance - hypokalemia are greatest at risk symptoms: nausea, arrhythmias >3.2 nmol/L measure with Immunoassay immunoenzymatic or immunochemiluminescent with serum or plasma
30
Aminoglycosides (Gentamicin, Tobramycin) and Glycopeptides (Vancomycin)
ABtics with narrow therapeutic range -can cause nephrotoxicity or ototoxicity especially when given for a long time or in too high doses Aminoglycosides (-treats GN bacterial infections Glycopeptides like vancs treat GP infection like MRSA
31
How to measure ABtics
Trough - just before next dose Peak - 30 minutes after infusion to assess efficacy and ensuring adequate levels for bactericidal activity Monitoring for ppts with renal impairment, because kidney issues can lead to drug buildup and toxicity Use immunoassays - ELISA
32
Anticonvulsants/Anti-Epileptics (AEDs): phenytoin, carbamazepine, and valproic acid
for epilepsy and seizures -have variable metabolism in pts due to age, preggo, or comorbin conditions liek liver disease preg increases clearance of the drug so shell need higher doses to maintain therapeutic levels test with HPLC - GOLD standard - accuracy Immunoassay - phenytoin
33
Imuunosuppresive drugs examples
FK506 - POST TRANSPLANT -prevents organ rejection in transplant pts -cacineurin inhibitor that supresses immune response lowering the risk of rejection -Goal to maintain blood levels that prevent graft rejection while avoiding renal toxicity which can happen from an elevated drug concn
34
how to measure the Immunosuppressive drugs
HPLC - accurate levels in plasma Mass spec - precise drug levels and analyzes pharmacokinetic variations in individual patient monitor regularly for efficacy and preventing toxic side effects like nephrotoxicity
35
Antineoplastics: example
MTX -high dose chemo drug for cancer and low dose for autoimmune like RA -causes toxicity if too high , renal toxicity and myelosuppression given with rescue therapy to mitigate toxicity. measure with Immunoassay
36
Acute toxicity
effects that occur immediately after single high dose exposure
37
chronic toxicity
repeat low dose exposure for long period of time asbestos leads to mesothelioma
38
What does a dose response curve help with
determines therapeutic range and toxic and lethal doses
39
ED50
Effective dose - beneficial in 50% of the population
39
TD50
Toxic dose - produces a toxic effect in 50% of the population
39
LD50
lethal dose fatal in 50% of the population
39
What are limitations to immunoassays
cross reactivity - false pos or false negs especially when compounds are similar needs confirmation of positive results like GC, HPLC or mass spec
40
GC
Gas chromatography -seperates compounds based on volatility and how they interact with a stationary phase in a column ETOH, CO, acetone , coke, meth very sensitive specific limitation needs a high tech instrument and trained ppl
41
HPLC
separates based on polarity and how they interact in a liquid column with the stationary phase -good for non volatiles and thermally labile compounds -ID of prescription drugs - DIG , phenytoin , SALCS and AMET in OD cases Advantage -accurate concentration Limitation time consuming compared to enzyme assays
42
Headspace Gas chromatography HS GC
measures ethanol concentrations in biological fluids like blood, urine, or breath headspace is the gas phase above liquid detects ETOH ad- non invasive - breath analyzer testing High accuracy and sensitivity Limitations needs calibration and standardization to ensure accuracy
43
Ethyl Glucuronide (EtG) Testing:
ethanol metabolite used in forensic and clinical settings for detection of alcohol consumption -EtG is detected in urine 80 hours after alcohol intake - good for monitoring abstinence or IDing alcohol use where regular testing is inconclusive
44
Carbon Monoxide Mechanism of toxicity Testing Method
Mechanism -CO competes with O2 for hgb binding in blood to form COhb , reducing O2 capacity of the blood impairing O2 release to tissues Causes tissue to become hypoxic - confusion, dizzy
45
how to test for CO
Co-Oximetry -measures COhb in blood , done in ER GC can also measure but more time consuming
46
Salicylates (Aspirin and related compounds uses Signs of toxicity
analgesic pain relieving antipyretic - fever reducing treat fever and cardiovascular diseases (break clot) Tinnitus nausea confusion
47
Metabolic acidosis occurs when
as poisoning progresses , SALCS interfer with cellular metabolism to cause lactic acidosis and metabolic acidosis (pH decrease)
47
Respiratory alkalosis occurs when
early stage of SALCs poisoning , decrease of blood CO2
48
How to measure SALC concn
Trinder assay - colorimeteric method measues SALCS concn serum - violet color product color change is measured spectrophotometrically Enzymatic method
49
How does ODing on ACET paracetamol work
- ACET is metabolized by the liver and conjugated to non toxic metabolites but when you take too much normal pathways become saturated and the extra ACET is metabolized into Salicylates (Aspirin and related compounds - NAPQI depletes glutathione causing oxidative stress and hepatoxicity leading to acute liver failure
50
how to test ODing on ACET
Immunoassay - quick and easy HPLC - precise helps to confirm OD cases
51
What is the treatment for ACET OD
NAC N-acetylcysteine helps to replenish glutathione stores helping to detoxify NAPQI and helps to prevent liver damage
52
how to test coke , heroin and what is the confirmatory testing
do immunoassays confirm with GCMS - high specificity and sensitivity to confirm what it is and its concentration
53
In which scenario is TDM MOST useful for assessing a patient's adherence to a prescribed medication regimen
Detecting non-compliance with the prescribed treatment
54
Which of the following drugs is most likely to require dose adjustment in an elderly patient due to altered pharmacokinetics?
Morphine because drug metabolism and clearance can be altered as ppl age and there are changes in liver and kidney Morph is metabolized in the liver but can accumulate in the liver
55
What is the function of an internal standard in Gas Chromatography-Mass Spectrometry (GC-MS)?
To calibrate the instrument for accurate quantification
56
When methanol is ingested, what toxic metabolites are formed in the liver
Formaldehyde and formic acid
57
What method is commonly used to measure blood ethanol levels?
Enzymatic Assay (Alcohol Dehydrogenase) which helps to To metabolize ethanol into acetaldehyde
58
Which testing method is commonly used for initial screening of drugs of abuse?
Immunoassays for drugs of abuse

clinical chem year 2 (4 decks)

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