Toxicology (part 2) Flashcards
therapeutic drugs that undergo toxicology
Salicylates
Acetaminophen
aka Salicylates
Acetylsalicylic acid or Aspirin
Common analgesic (relieves pain), antipyretic (anti-fever), anti-inflammatory and anticoagulant
Salicylates
Mechanism of salicylates as anticoagulant
blocks cyclooxygenase reducing thromboxane and prostaglandins
Adverse effects of Salicylates
Platelet aggregation inhibition
GI function interference
Rye Syndrome (in children)
Viral infection
Treatment for Salicylates toxicity
Neutralization and elimination
Maintain electrolyte imbalance
Salicylates intoxication value
Serum lvl: >90 mg/dL 6 hrs after ingestion
Effects of acute ingestion of Salicylates (high doses)
Metabolic acidosis (salicylates are acid)
Respiratory alkalosis (direct stimulation of the respiratory center, causing hyperventilation)
Inhibits Kreb’s cycle (increases lactate
and pyruvate formation → muscle cramps)
Ketone formation
Death
Methods for Salicylate measurement
Gas Chromatography
Liquid Chromatography
Chromogenic Assay (Trinder Reaction)
Has the highest analytical sensitivity for salicylates
Liquid Chromatography
A method for salicylate measurement that uses ferric nitrate to form a colored complex measured using spectro
Chromogenic Assay (Trinder Reaction)
aka Acetaminophen
Paracetamol
a common analgesic
Acetaminophen
Common brand (US) of Acetaminophen
TYLENOL
predicts acetaminophen-induced hepatic damage based on serum conc. of acetaminophen at a known time after ingestion (graphical representation)
Rumack-Matthew Nomogram
Rumack-Matthew Nomogram must not be used in these individuals
px. with ethanol abuse
(metabolizes acetaminophen at rapid rate)
Rumack-Matthew Nomogram is used for predicting?
acetaminophen-induced hepatic damage
Effect of Acetaminophen overdose
severe hepatotoxicity
Acetaminophen overdose value
300 ug/mL 2 hours after ingestion
Acetaminophen measurement methods
Immunoassay – commonly used
HPLC – reference method
DRUGS OF ABUSE assessed in toxicology
Amphetamines
Ecstasy
Anabolic Steroid
Cannabinoids
Cocaine (crack)
Opiates
Phencyclidine
Sedatives-Hypnotics
OTHERS:
Lysergic Acid Diethylamide (LSD)
Piperazines
Methaqualone (Quaalude)
Tryptamines
can cross the placenta
arsenic
cocaine
Most common Amphetamines
SHABU
drug of abuse with ↓ therapeutic dose; very close to toxic dose
Amphetamines
drugs that develops tolerance (HIGH POTENTIAL ABUSE)
Amphetamines
Cannabinoids
Opiates
Amphetamines is a tx for
narcolepsy (uncontrolled sleeping)
attention deficit disorder
Drug for reducing weight (induces anorexia nervosa)
Amphetamines
Blocks dopamine receptors in the brain causing initial effects
Amphetamines
Examples of Amphetamines
Amphetamines
Methamphetamines (Shabu/Ice, Poor Man’s Ecstasy)
Methylphenidate (Tx: hyperactive children)
Benzphenidate
Diethylpropion
Amphetamine-like compounds
Ephedrine
Pseudoephedrine
Phenylpropanolamine
content of Chinese drug said to be effective against COVID-19 (Lianhua Qingwen); may induce hypertension
Ephedrine
INITIAL EFFECTS of Amphetamines
Increased mental and physical capacity
ADVERSE/TOXIC EFFECTS of Amphetamines
Restlessness
Irritability
Psychosis
An amphetamine derivative
Ecstasy
Ecstasy is a derivative of
3,4-methylenedioxymethamphetamine
A designer drug (modified form of the available drug of abuse)
Ecstasy
INITIAL EFFECTS of Ecstasy
Hallucinations
Euphoria
Emphatic and emotional response
Increased visual and tactile sensitivity
ADVERSE EFFECTS of Ecstasy
- Headaches
- Nausea
- Vomiting
- Anxiety
- Agitation
- Impaired memory
- Violent behavior
- Tachycardia
- Hypertension
- Respiratory depression
- Seizure
- Hyperthermia
- Multiple organ toxicity
Testosterone derivatives
Anabolic Steroid
Anabolic Steroid is initially a tx for
male hypogonadism
↑ muscle mass (used by athletes)
Anabolic Steroid
Chronic use of Anabolic Steroid causes
- Toxic hepatitis
- Accelerated atherosclerosis
- Abnormal plt aggregation
- Cardiomegaly
- Testicular atrophy
- Sterility
- Impotence
Group of psychoactive compounds found in marijuana
Cannabinoids
Cannabinoids is naturally derived from
Cannabis sativa leaves
drugs of abuse that are CNS stimulants
Cannabinoids
Cocaine (crack)
most potent and abundant compound of marijuana
Tetrahydrocannabinoid (THC)
A hallucinogen; a lipophilic substance; Rapidly distributed to hydrophobic compartments (brain, fats); Reaches brain w/n 30 sec upon exposure
Tetrahydrocannabinoid (THC)
MAJOR URINARY METABOLITE of Cannabinoids
11-nor-deltatetrahydrocannabinol-9-carboxylic acid (THC-COOH)
11-nor-deltatetrahydrocannabinol-9-carboxylic acid (THC-COOH) is detected in urine with SINGLE THC use for
3-5 days
11-nor-deltatetrahydrocannabinol-9-carboxylic acid (THC-COOH) is detected in urine with CHRONIC use for
4 weeks (or 45 days)
T/F
Cannabinoids accumulates in adipose tissue; not readily excreted in urine (slow elimination) – only eliminated when fats are metabolized
T
INITIAL EFFECTS of Cannabinoids
Sense of well-being
Euphoria
THC Adverse effects
memory and intellectual impairment
Toxic Effects of Cannabinoids
- Paranoia
- Disorientation
- Altered physical senses
- Bronchopulmonary dse
Methods for Cannabinoids
IA (screening)
GC-MS (confirmatory)
An alkaloid salt (in the form of ecgonine)
Cocaine (crack)
Cocaine (crack) is naturally derived from
Coca-plant (Erythroxylon coca)
Effective local anesthetic for nasopharyngeal surgery
Cocaine
NOT a TRUE ADDICTIVE DRUG (fails to develop dependence)
Cocaine
Potent CNS stimulator
Cocaine
METABOLITE of Cocaine
Benzoylecgonine
single use of cocaine can be detected for
3 days
chronic use of cocaine can be detected for
20 days
INITIAL EFFECTS of cocaine
Excitement
Euphoria
Cocaine overdose causes
violent behavior
Adverse/toxic effects of cocaine
- Hypertension, arrythmias, seizure, MI
- Uterine malformation
- Mental retardation, slow mental development and drug dependence (newborns)
- Sudden death (due to direct toxicity to myocardium
drug of abuse that can cause sudden death (due to direct toxicity to myocardium)
cocaine
Capable of analgesia, sedation and anesthesia
Opiates
Opiates is derived from
opium poppy plant
Types of opiates
Naturally occurring
Chemically modified
Synthetic
Naturally occurring opiates
Opium
Morphine
Codeine
powerful analgesic; relieves excruciating pain (burn, cancer); a heroin metabolite
Morphine
Mild analgesic and antitussive (relieves cough)
Codeine
Chemically modified opiates
Heroin
Hydromorphone (Dialudin)
Oxycodone (Percodan)
Synthetic opiates
Meperidine (Demerol)
Methadone (Dolophine)
Proxyphene (Darvon)
Pentazocine (Talwin)
Fentanyl (Sublimaze)
major drug of abuse (1960’s -70’s)
HEROIN
Forms of Heroin
No. 4 (China white)
No. 3 (Brown sugar) –
No. 2 and 1
purest form of heroin
No. 4 (China white)
heroin form used for smoking
No. 3 (Brown sugar)
unprocessed heroin
No. 2 and 1
MAJOR METABOLITES of HEROIN
N-acetylmorphine
Morphine
ADVERSE/TOXIC EFFECTS of Opiates
Respiratory acidosis
Myoglobinuria
Cardiopulmonary failure
Pupillary constriction (pinpoint pupils)
Antidote for opiate toxicity
Naloxone (Narcan) – opiate inhibitor
methods for opiate
IA (screening)
GC-MS (confirmatory)
used to detect morphine and codeine; can cross react with other opiates (nonspecific)
IA (screening)
aka Phencyclidine
angel dust
angel hair
peace dust
Illicit drug with stimulant, depressant, anesthetic, and hallucinogenic properties
Phencyclidine
Lipophilic drugs
Phencyclidine
Tetrahydrocannabinoid (THC)
10-15% of this administered drug is eliminated and unchanged
Phencyclidine
Initial effect of Phencyclidine
Hallucinations
Adverse effects of Phencyclidine
- Agitation
- Hostility
- Paranoia
OVERDOSE effects of Phencyclidine
Stupor
Coma
T/F
Methods for PCD det. detects the metabolite
F
detects parent drug – PCD itself
PCD Chronic user can detect the drug for
30 days after abstinence
methods for PCD
IA (screening)
GC-MS (confirmatory)
Tranquilizers
Sedatives-Hypnotics
drugs that are CNS depressant
Sedatives-Hypnotics
COMMON TYPES of Sedatives-Hypnotics
Barbiturates
Benzodiazepines
condensation products of urea and malonic acid
Barbiturates
has higher abuse potential than benzodiazepines
Barbiturates
Examples of Barbiturates
Phenobarbital (long acting)
Amobarbital (intermediate acting)
Secobarbital, Pentobarbital (short acting)
treatment for cocaine addiction
Benzodiazepines
most commonly found in abused and overdose situations due to wide availability
Benzodiazepines
Examples of Benzodiazepines
Diazepam (Valium)
Chlordiazepoxide (Librium)
Lorazepam (Ativan)
a minor tranquilizers; rapid control of acute seizure
Diazepam (Valium)
Overdose effects of Sedatives-Hypnotics
Lethargy
Slurred speech
Coma
Respiratory depression (most serious toxicity; may
result to death)
most serious toxicity of sedatives
Respiratory depression
methods for sedatives det.
IA (screening)
GC-MS (confirmatory)
a hallucinogen; one of the most potent pharmacologic material
Lysergic Acid Diethylamide (LSD), Lysergide
Shows the same pleasant feeling as amphetamines
Piperazines
Major derivatives of Piperazines
N-benzylpiperazines (BZP)
Phenylpiperazines
Minor derivatives of Piperazines
1-(3,4-methylene-dioxybenzyl) piperazine (MDMP)
1-(3- trifluoromethylphenyl) piperazine (TFMPP/Molly)
Most popular Piperazines
BZP
TFMPP/Molly
2,3-disubstituted quinazoline with anesthetic, antihistamine, antitussive, and hallucinogenic properties
Methaqualone (Quaalude)
a drug that is a serotonin derivative
Tryptamines
Examples of Tryptamines
N,N-dimethyltryptamine (DMT)/Businessman’s lunch
Psilocin
Ayahuasca
N,N-dimethyltryptamine (DMT) (a tryptamine) is aka
Businessman’s lunch
a short-term hallucinogen
N,N-dimethyltryptamine (DMT)/Businessman’s lunch
hallucinogen; component of magic mushrooms (Psilocybe)
Psilocin
tea with tryptamines
Ayahuasca
R.A. 9165 is aka
COMPREHENSIVE DANGEROUS DRUGS ACT OF 2002
COMPREHENSIVE DANGEROUS DRUGS ACT OF 2002 is aka
R.A. 9165
Head of the Laboratory
Pathologist
Doctor who undergone training under DOH for lab management
Analyst of the laboratory
Medical technologist
Pharmacist
Chemist
Nurses
Requirement when conducting drug testing in Remote Collection Site
permit from Bureau of Health Facilities and Services – Center for Health Development (BHFS-CHD/DOH) 10 days prior
Accepted Specimens for drug testing
Urine (most commonly used)
Saliva
Blood
Hair
Sweat
Tissue
Nail Clippings
type of collection that requires validity test
Unobserved Collection
urine creatinine value indicating adulterated spx
<20 mg/dL
SG indicating that the specimen is no longer urine
<1.003
Agents used for Specimen Tampering
Water (most common)
Salt (2nd most common)
Others: Liquid soap, Bleach, Vinegar, Ammonia, Baking soda, Glutaraldehyde,
Potassium Nitrate, Lemon Juice, Cologne
Documents required for drug testing
Consent form
Custody and Control Form
Memorandum for Record
Screening methods for drug testing
Thin-layer Chromatography
Gas-liquid Chromatography
Colorimetric “spot” test
May be used as confirmatory test for drugs detected by TLC
Gas-liquid Chromatography
Confirmatory tests for drug testing
Enzyme Multiplied Immunoassay technique [EMIT]
Gas-Chromatography/Mass Spectrometry
Utilizes antibodies to detect drugs
Enzyme Multiplied Immunoassay technique [EMIT]
first line confirmatory and reference method; can detect low drug levels
Gas-Chromatography/Mass Spectrometry
detect presence of specific compound (separation technique)
GC
quantitate the compound detected by GC
MS
T/F
any method is valid in the absence of GC/MS provided that it is completely different from the 1st method
T
Amphetamine cut-off level (ng/mL) in URINE using EMIT
500
Amphetamine cut-off level (ng/mL) in URINE using GC-MS
250
Marijuana cut-off level (ng/mL) in URINE using EMIT
50
Marijuana cut-off level (ng/mL) in URINE using GC-MS
25
Cocaine cut-off level (ng/mL) in URINE using EMIT
150
Cocaine cut-off level (ng/mL) in URINE using GC-MS
100
Opiates cut-off level (ng/mL) in URINE using EMIT
2000
Opiates cut-off level (ng/mL) in URINE using GC-MS
2000
PCD cut-off level (ng/mL) in URINE using EMIT
25
PCD cut-off level (ng/mL) in URINE using GC-MS
25
Drugs with the same cut-off levels (ng/mL) in urine using EMIT and GC-MS
Opiates
PCD