TOXICOLOGY Flashcards
is the study of the adverse effects of chemical agents on biological systems.
TOXICOLOGY
Involved in the recognition,
identification, and quantitation of hazard
Develops standards and regulations to
protect health and environment
Involved in the safety assessment and
use of data as basis for regulatory
control of hazards
Determines risk associated with the use
of chemicals
TOXICOLOGISTS
Risk Assessment
Hazard Identification
Dose Response Assessment
Exposure Assessment
Risk Characterization
Risk Assessment:
Whether Physical, Chemical, Biological
Hazard Identification
Risk Assessment:
Biological System
Dose Response Assessment
Risk Assessment:
Effect or Response
Exposure Assessment
Risk Assessment:
Exposure situation
Risk Characterization
Major Factors that influence toxicity
Route of administration
Duration and Frequency of Exposure
Dose or concentration
Rapidly of Response with respect to
route of exposure:
Intravenous
Inhalation
Intraperitoneally
Subcutaneous
Intramuscular
Intradermal
Topical
Some xenobiotics cause toxicity by
disrupting _______
normal cell functions
xenobiotics disrupt normal cell functions by:
Bind and damage proteins (structural
enzymes)
Bind and damage DNA (mutations)
Bind and damage lipids
React in the cell with oxygen to form
“free radicals” which damage lipid,
protein, and DNA.
Types of Toxic Effects:
Death
Arsenic, Cyanide
Types of Toxic Effects
Organ Damage
Ozone, Lead
Types of Toxic Effects
Mutagenesis
UV Light
Types of Toxic Effects
Carcinogenesis
Benzene, Asbestos
Types of Toxic Effects
Tetratogenesis
Thalidomide
Target Organ Toxicity: Central Nervous System
Lead
Target Organ Toxicity: Immune System
Isocyanates
Target Organ Toxicity: Liver
Ethanol, Acetaminophen
Target Organ Toxicity: Respiratory Tract
Tobacco Smoke, Asbestos, Ozone
Target Organ Toxicity: Eye
UV Light (sunlight)
Target Organ Toxicity: Kidney
Metals
Target Organ Toxicity: Skin
UV Light, Gold, Nickel
Target Organ Toxicity: Reproductive System
dibromochloropropane
Spectrum of Undersided Effects
Allergic reactions
Chemical allergies
Idiosyncratic reactions
Immediate vs. delayed toxicity
Reversible vs. irreversible toxicity
Local vs. systemic toxicity
Is the use of drug concentration
measurements in body fluids as an aid
to the management of drug therapy for
the cure, alleviation or prevention of
disease.
TDM
The monitoring of therapeutic drugs involves measuring drug concentrations in ______, ______ or ______. This information is used to individualize dosage so that drug concentrations can
be maintained within a target range.
plasma, serum or blood
Therapeutic drug monitoring is useful only for drugs that have a poor correlation between ______ and ________ (high pharmacokinetic variability).
dose and clinical effect
TDM is not generally helpful in the ________ of patients. Examples of this are the measurement of blood pressure during antihypertensive therapy; glucose in patients treated with heparin or warfarin, and cholesterol in patients treated with cholesterollowering drugs.
routine monitoring
The main reasons for measuring drugs
To ensure that sufficient drug is reaching the drug receptor to produce the desired response (the onset of which may be delayed)
To ensure that drug (or metabolite) concentrations are not so high as to produce symptoms or signs of toxicity
To guide dosage adjustment in clinical situations in which the pharmacokinetics are changing rapidly (e.g., in neonates, children or patients in whom hepatic or renal function in changing)
To define the pharmacokinetic parameters and concentration effect relationships of new drugs.
Indicators for therapeutic drug
monitoring include:
Toxicity
Dosing
Monitoring
diagnosing toxicity when the clinical syndrome is _______ (unexplained nausea in a patient taking digoxin)
(toxicity) ; undifferentiated
Avoiding toxicity (_________, __________)
(toxicity) ; aminoglycoside, cyclosporine
- After dose adjustment (usually after reaching a steady state)
- Assessment of adequate loading dose (after starting ______ treatment)
- Dose forecasting to help predict a patient‟s
dose requirements (__________)
(dosing) ; phenytoin ; aminoglycosides
In monitoring, the information required to allow
interpretation of the result should include the ____________, _____________, __________ and _____________.
time of the sample collection, the time of the last dose, the dosage regimen, and the indication for drug monitoring.
Assessing compliance (anticonvulsant concentrations in patients having frequent seizures)
Diagnosing under treatment (particularly important for prophylactic drugs such as anticonvulsants, immunosuppressants)
Diagnosing failed therapy (therapeutic drug monitoring can help distinguish between ineffective drug treatment, noncompliance and adverse effects that mimic the underlying disease)
Monitoring
may be defined as what that body does to drugs (the processes of absorption, distribution, metabolism and excretion)
Pharmacokinetics
as what the drugs do to the body (mechanisms of drug
action and biochemical/pathophysiological effects
such as tissue responsiveness, presence of other drugs and disease states).
Pharmacodynamics
is the fraction of the dose that reaches the blood
Bioavailable fraction
the time required to reduce a drug level to half of its initial value
Half-life
the ratio between the minimum toxic and maximum
therapeutic serum concentration
Therapeutic index
the difference between highest and lowest effective dosage
Therapeutic range
the lowest concentration of a drug obtained in the
dosing interval
Trough concentration
Commonly Monitored Drugs - Cardioactive drugs
(normalize heart rhythm)
digoxin, procainamide
Commonly Monitored Drugs - Antiepileptic
(treatment of seizures)
valproic acid,
phenobarbital,
phenytoin,
carbamazepine
Commonly Monitored Drugs - Antibiotics
amikacin, gentamicin, vancomycin, tobramycin
Commonly Monitored Drugs - Immunosuppressants:
(prevent or minimize the risk of organ transplantation)
cyclosporine, tacrolimus, sirolimus
Commonly Monitored Drugs - Antidepressants
(increases the effect of neurotransmitters)
nortriptyline, desipramine, lithium
Commonly Monitored Drugs - Bronchdilators
(CNS and cardiac stimulant, causes smooth muscle relaxation and diuresis)
theophylline
Commonly Monitored Drugs - Antineoplastic
Methotrexate
Commonly Monitored Drugs - Antipsychotic
(produce emotional calmness and mental
relaxation)
promethazine
Requirements when making a request for
TDM
Accurate information about the patient (name, identification number, age, gender and pathology)
The drug therapy (dose, formulation and route of administration, length of therapy, date and time of last dose)
The date and time of the sample are essential for proper interpretation
Additional information such as the patient‟s weight, renal and hepatic function and other prescribed medication may also be required in many circumstances.
SAMPLES..
_____ or _______ is commonly used for
drug assays.
Plasma or Serum
SAMPLES..
_________: for Cyclosporine, tacrolimus, sirolimus, as there are large shifts of drug between red cells and
plasma with storage and temperature change.
Whole blood
SAMPLES…
_______, which gives a measure of the unbound drug concentration, may be a useful alternative when blood samples are difficult to collect. Ex: Phenytoin, Lithium, Amitriptyline, Marijuana, Cocaine, Alcohol
Saliva
SAMPLES..
OTHER. BODY FLUIDS:
______: Benzodiazepines
______: Cocaine & Heroin
______: Alcohol
Urine
Sweat
Breath
____________ is also important. Ensure complete absorption and distribution
Timing of sample-taking
For TDM to be meaningful, the patient Should be in _______ on the present dose of the drug. However, when suspected toxicity is being investigated, waiting to attain steady state is clearly contraindicated. The time taken to reach steady state is determined by the elimination half-like of the drug. In practice, samples are taken after drug dosing has continued for at least _______.
steady state ; four half-lives
