Midterm Flashcards
Study of exogenous clinical compounds that profoundly influence bodily functions, either in a deleterious way or for therapeutic benefits
TOXICOLOGY
enables physicians to adjust and optimize the dosage on an individual basis
Therapeutic drug monitoring (TDM)
identify the offending drug/s (what function)
Identification of drugs in acute intoxication
establish diagnosis, assess level of intoxication, suggest course of therapy (what function)
Identification of drugs in acute intoxication
pre-employment and medico-legal cases (what function)
Urine testing for drugs of abuse
4 areas : CLINICAL TOXICOLOGY LABORATORY
- drugs of abuse
- therapeutic drugs
- environmental carcinogens
- toxins
Test animals are used
-Direct administration: ingestion, application to the skin, inhalation, gavage, etc.
-Indirect: test animal is exposed to the substance in its environment (H20 or air)
Toxicity is measured as clinical “endpoints”:
- Mortality (death)
-Teratogenicity (cause birth defects)
-Carcinogenicity (cause cancer)
-Mutagenicity (cause changes in the DNA)
-Received regular maintenance doses of the drug for about five half-lives of the drug (OPTIMAL TIME FOR BLOOD SPECIMENS)
Steady state concentration
For most orally taken drugs (OPTIMAL TIME FOR BLOOD SPECIMENS)
Just before the next dose
-Shortly after receiving the drug
- For patients who exhibit toxic symptoms
(OPTIMAL TIME FOR BLOOD SPECIMENS)
Peak or post-dose level
TECHNIQUES FOR DRUG ANALYSIS
•Immunologic
- Enzyme immunoassay systems
- Fluorescence immunoassay
- radioimmunoassay
TECHNIQUES FOR DRUG ANALYSIS
•Chromatographic
-HPLC
-GLC
-TLC
TECHNIQUES FOR DRUG ANALYSIS
•Spectrophotometry
-Visible spectrum, ultraviolet spectrum and fluorescence
–Serum + antibody + enzyme- labelled drug + substrate
ENZYME MULTIPLIED IMMUNOASSAY TECHNIQUE (EMIT)
Measured enzyme activity of EMIT
drug concentration
More rapid than RIA
ENZYME MULTIPLIED IMMUNOASSAY TECHNIQUE (EMIT)
1st homogenous Enzyme Immunoassay
ENZYME MULTIPLIED IMMUNOASSAY TECHNIQUE (EMIT)
most useful; less likely to be affected by serum constituents (in EMIT)
MDH (Malate dehydrogenase) & G-6-PD (glucose-6-phosphate dehydrogenase)
Measures drugs (mg/L) & drug metabolites in biological fluids
EMIT
Some drugs detected in EMIT
Cocaine & metabolites, cannabinoides, opiates & barbiturates
Drug to be measured is the hapten
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)
Specific antibodies bound to a solid state carrier
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)
Separation of the bound drug from the unbound
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)
Digoxin and digitoxin tests
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)
Rodenticides, weed killers, insecticides
Arsenic
Interacts w/ enzyme SH (sulfhydryl) groups > disrupts multiple metabolic systems
Arsenic
Acute fatal dose of arsenic
120 mg
Toxicity manifested w/in the first hour : GI symptoms (diarrhea)
Arsenic
Analysis of urine, hair and nails: Ion Emission Spectroscopy
Arsenic
Treatment for Arsenic
- Gastric lavage or emesis
- Dimercaprol or BAL
- Hemodialysis
Acute poisoning common in young children
Iron
Toxic amount of Iron
> 30mg/kg
Once absorbed, removal is difficult
Iron
Hepatic cell damage, shock, lactic acidosis
Iron
initial manifestation of Iron
Vomiting
others: Severe gastroenteritis, melena, abdominal pain and hematemesis
Diagnosis of Iron
• Serum iron concentration
• TIBC (Total Iron Binding Capacity)
Treatment of Iron
- Supportive treatment
- Emesis or gastric lavage
- Chelation therapy: deferoxamine
Forms of Mercury
- Elemental or metallic: toxic when inhaled
- Mercurous/ Mercuric: salt form
- Alkyl mercury: environmental pollutants
Acute toxicity of Mercury
24 hr. urine levels
Chronic toxicity of mercury
hair analysis
Treatment of mercury
• Treatment: gastric lavage or emesis
- Dimercaprol and succimer
Organic and inorganic _____: highly toxic
lead
Interacts with -SH, -COOH & PO4 in proteins (e.g. enzymes)
lead
effect CNS (Central Nervous System) and PNS (Peripheral Nervous System)
lead
introduce in the body by Inhalation or ingestion
lead
Fatal dose of lead
0.5mg absorbed/day - chronic toxicity
0.5 g absorbed - acute toxicity
Acute toxicity: Signs and symptoms of lead
—CNS symptoms:
Encephalopathy (enlargement of brain), convulsions, stupor
—GI symptoms: colic
Chronic toxicity of lead
Accumulation in blood, soft tissues and bone
Low-level exposure of lead
ADHD & decrease in I.Q
Characteristic of lead
“wrist drop or foot drop” manifestation
LEAD TOXICITY
•Bone - 96% of burden
- Half-life of lead in bone is 32 years mas madami
- Reservoir for endogenous intoxication
•Lab. Diagnosis of lead
•basophilic stippling in RBCs
• gama ALA in urine
Diagnosis of lead
• AAS
•Anode stripping voltametry.
Treatment of lead
•Supportive
• Gastric lavage
• Dilute MgSO4 or Na2SO4
•Chelating agents: dimercaprol, calcium disodium acetate & succimer
esters of H3PO4 or thiophosphoric acid
•Organophosphates
synthetic derivatives of carbamic acid
•Carbamates
• Widely used as pesticides
•Interfere with neurotransmission
•Carbamates
•Inhibit acetylcholinesterase: ORGANOPHOSPHATE AND CARBAMATES
hydrolyzes acetylcholine after it has effected an action potential
excitatory neurotransmitter of ORGANOPHOSPHATE AND CARBAMATES
•Acetyl choline
Signs and Symptoms of ORGANOPHOSPHATE AND CARBAMATES
- Parasympathetic manifestations: salivation, lacrimation, urination and defecation
Autonomic manifestations of ORGANOPHOSPHATE AND CARBAMATES
-Muscular weakness, tachycardia, hypertension
CNS manifestations of ORGANOPHOSPHATE AND CARBAMATES
-Confusion, slurred speech, ataxia, convulsions
Diagnosis of ORGANOPHOSPHATE AND CARBAMATES
• Assay of cholinesterase activity
Treatment of ORGANOPHOSPHATE AND CARBAMATES
- Respiratory support
-Gastric lavage or emesis
-Atropine
-Pralidoxime (organophosphate)