TOXICOLOGY Flashcards by Patricia Baltazar

TDM concepts

-highest point; amount of drug absorbed and distributed is greater than the
amount metabolized and excreted

-must not be above the MTC (Minimum Toxic Concentration)

-1 hour after oral administration

PEAK

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TDM concepts

o lowest concentration achieved just before the next dose
o most not be below the MEC (Minimum Effective Concentration)

TROUGH

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TDM concepts

o time required for the concentration of the drug to decrease by half
o affected by protein binding and renal and hepatic functions
o considered when determining the appropriate time of subsequent dose
administration and blood collection
o has bearing in the attainment of a steady state

HALF-LIFE

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TDM concepts

amount of drug absorbed and distributed equals amount metabolized and
excreted

usually reached after 5-7 half-lives

Steady state

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TDM concepts

lowest concentration of drug in the blood that will produce adverse
response

MTC (Minimum Toxic Concentration)

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TDM concepts

lowest concentration of drug in the blood that will produce desired effect

MEC (Minimum Effective Concentration)

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TDM concepts

range of values between the MTC and MEC that produce therapeutic effect

Therapeutic range

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TDM concepts

drug dose that produces adverse effect in 50% of the population

TD50

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TDM concepts

drug dose that produces beneficial effect in 50% of the population

ED50

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TDM concepts

drug dose that produces death in 50% of individuals

LD50

“AT-BE-DL”
Adverse - TD50
Beneficial - ED50
Death - LD50

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TDM concepts

-ratio between TD50 and ED50
o The wider the safer
o TDM is only recommended for drugs with narrow TI

Therapeutic index

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TDM - Analytical techniques

used as a semi-quantitative screening test; interpretation of results uses Rf values of solutes in comparison to aqueous standards

Thin-layer Chromatography

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TDM - Analytical techniques (TLC)

distance migrated by a sample component divided by the distance migrated by the solvent

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TDM - Analytical techniques

For insufficiently volatile and thermolabile compounds.

Liquid Chromatography

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TDM - Analytical techniques

type of Liquid chromatography wher ethe mobile phase is a liquid that is pass over the stationary phase of the column

HPLC (ex. HBA1C)

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TDM - Analytical techniques

useful for compounds that are naturally volatile or can easily be converted into a volatile form (various organic molecules including many drugs)

Gas Chromatography (GC)

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TDM - Analytical techniques

Gold standard for drug analysis

GC/MS

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TDM - Analytical techniques

common detector system in GC or HPLC (for insufficiently volatile and thermolabile compounds)

produces a signal for ID and quantification of the solutes

Mass spectro

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what the body does to the drugs

Pharmacokinetics (ADME)

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drug activity or fate of drugs in the body as influenced by:

(ADME)

-Absorption
-Distribution
-Metabolism
-Excretion

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Pharmacokinetics

through the GI tract for orally administered drugs
dependent on many factors and is related to the drug’s bioavailability
100% bioavailability if the route is parenteral administration/intravenous
affected by first pass metabolism, which reflects the activity of metabolic enzymes in the liver and intestines

Absorption

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Pharmacokinetics

diffusion out of the vasculature into interstitial and intracellular spaces; dependent on the lipid solubility of the drug

Distribution

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Pharmacokinetics

hepatic uptake and enzymatic biotransformation during passage through the liver (first-pass metabolism)

Metabolism

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Pharmacokinetics

elimination through hepatic or renal clearance or a combination of the two

Excretion

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-What the drug does to the body - - -Biochemical and physiological effects of drugs and the mechanisms of their actions - Involves receptor binding, post-receptor effects, and chemical interactions

Pharmacodynamics

Specimen Considerations when toxicity is suspected, what sampling is required?

STAT sampling

Specimen Considerations collected before the next dose is administered

trough specimen

Specimen Considerations Peak spx - Oral: - IV: - IM:

- Oral: collected 1 hour after administration (Half-life: >2 hours) - IV: collected 15-30 minutes after administration - IM: collected 30-60 minutes after administration

Specimen Considerations Tube AC that can cause falsely ↓ antiarrhythmics and tricyclic antidepressants due to drug absorption by the gel

Gel separator tube: SST & PST

Specimen Considerations preferred for most drug assays

Serum (plain tube)

Specimen Considerations suitable for most drugs; except lithium or free drug assays (may affect protein binding)

Heparinized plasma

Specimen Considerations AC that is appropriate for immunosuppressants

EDTA whole blood

Specimen Considerations recommended for the impedance method of aspirin determination

Hirudin

DRUGS THAT REQUIRE TDM what classification of drugs are the ff: Digoxin Antiarrhythmics

Cardioactive drugs

DRUGS THAT REQUIRE TDM used to treat Atrial fibrillation and Congestive heart failure -- CHF (acts by inhibiting the sodium-potassium ATPase pump)

Cardiac glycosides (Digoxin)

DRUGS THAT REQUIRE TDM used to treat tachyarrythmias or ventricular tachycardias (action depends on the blockage of one of the channels or receptors involved in the generation of action potential)

Antiarrhythmics

DRUGS THAT REQUIRE TDM Antiepileptics/anticonvulsants/anti-seizure used to treat grand mal seizures (tonic-clonic seizures), generalized, and simple seizures

Phenobarbital Benzodiazepines

DRUGS THAT REQUIRE TDM Antiepileptics/anticonvulsants/anti-seizure slow-acting barbiturate; inactive form = primidone which is quickly converted to a phenobarbital and must be monitored also

Phenobarbital

DRUGS THAT REQUIRE TDM Antiepileptics/anticonvulsants/anti-seizure used to treat petit mal / absence seizures

Ethosuximide Valproic acid

DRUGS THAT REQUIRE TDM Tiagabine, Vigbatrin, Gabapentin, Topiramate, Felbamate

New generation anticonvulsants (has wider therapeutic index; safer; do not usually need TDM)

DRUGS THAT REQUIRE TDM Bronchodilators?

Theophylline Caffeine

DRUGS THAT REQUIRE TDM a bronchodilator that used to treat asthma and other Chronic-Obstructive Pulmonary Disorders (COPDs) ?

Theophylline

DRUGS THAT REQUIRE TDM a bronchodilator that is minor metabolite of theophylline, tx for neonatal apnea

caffeine

DRUGS THAT REQUIRE TDM Psychoactive drugs/Anti-depressants antimanic agent; used to treat bipolar/Manic-depressive disorders; overdose can lead to hypercalcemia

Lithium

DRUGS THAT REQUIRE TDM Psychoactive drugs/Anti-depressants -(used to treat schizophrenia)

Neuroleptics/Antipsychotics

DRUGS THAT REQUIRE TDM used to treat clinical depression

antidepressants

DRUGS THAT REQUIRE TDM TC(Tricyclic)As -- TCAs -(amitriptyline [nortriptyline], imipramine [desipramine], doxepin), what are these?

antidepressants

DRUGS THAT REQUIRE TDM Antibiotics used to treat gram negative infections via disruption of protein synthesis o toxic effects include autotoxicity and nephrotoxicity o both peak and trough measurement are done

Aminoglycosides (Tobramycin, Amikacin, Gentamicin, Kanamycin)

DRUGS THAT REQUIRE TDM - Aminoglycosides, Glycopeptides what classification?

Antibiotics

DRUGS THAT REQUIRE TDM Antibiotics - Vancomycin - Used to treat gram positive infections via inhibition of cell wall synthesis - May cause autotoxicity, nephrotoxicity, and RED MAN SYNDROME (erythemic flushing of the extremities)

Glycopeptides

DRUGS THAT REQUIRE TDM immunosuppressants used to prevent Graft rejection & GVHD; fat soluble cyclical peptide isolated from Trichoderma

Cyclosporine

DRUGS THAT REQUIRE TDM immunosuppressants -macrolide lactone isolated from Streptomyces - 100x more potent than cyclosporine -assoc w/ thrombus formation in px w. toxic levels

Tacrolimus

DRUGS THAT REQUIRE TDM ex of immunosuppressants?

Cyclosporine Tacrolimus

DRUGS THAT REQUIRE TDM ex of antineoplastics?

Methotrexate (antimetabolite) Busulfan (alkylating agent)

DRUGS THAT REQUIRE TDM Antineoplastics - inhibits DNA synthesis - requires administration of leucovorin to rescue host cells from methotrexate inhibition - tx for CML and HL

Methotrexate (antimetabolite)

DRUGS THAT REQUIRE TDM Antineoplastics alkylating agent used to treat CML, Lymphoma before B.M transpalntation and used for myeloablation

Busulfan (alkylating agent)

TOXICOLOGY - TD commonly abused Aspirin (acetylsalicylate) Tylenol (Acetaminophen) what are these?

Analgesic

TOXICOLOGY - TD commonly abused used as an analgesic, antipyretic, and anti-inflammatory; exhibits antiplatelet activity through inhibition of CYCLOOXYGENASE; toxic effects include MIXED ACID-BASE DISORDER & REYE'S SYNDROME

Aspirin (acetylsalicylate)

TOXICOLOGY - TD commonly abused preferred over aspirin in patients with a bleeding disorder, toxic effect HEPATOTOXICITY/LIVER DAMAGE

Acetaminophen (Tylenol)

TOXICOLOGY - ILLICIT DRUGS used to treat NARCOLEPSY (severe daytime sleepiness) and attention-deficit disorder

Amphetamines (MDMA – methylenedioxymethamphetamine or ecstasy, methamphetamine or shabu)

TOXICOLOGY - ILLICIT DRUGS examples of Amphetamines?

(MDMA – methylenedioxymethamphetamine or ECSTACY, methamphetamine or shabu)

TOXICOLOGY - ILLICIT DRUGS - therapeutically used as local anesthetic; primary metabolite is BENZOYLECGONINE and has a short half-life of 1-2 hours (0.5-2 hours) -

Cocaine

TOXICOLOGY - ILLICIT DRUGS examples of STIMULANTS "UPPERS" (dopaminergic pathway stimulant)

Cocaine Amphetamines

TOXICOLOGY - ILLICIT DRUGS STIMULANTS euphoria producing synthetic phenylethylamines

designer drugs

TOXICOLOGY - ILLICIT DRUGS what are those depressants (Sedative/hypnotics)?

"BBM" Barbiturates Benzodiazepines Methaqualone

TOXICOLOGY - ILLICIT DRUGS Depressants (Sedative/hypnotics) o Intermediate-acting: Amobarbital o Short-acting: Secobarbital, Pentobarbital o Long-acting: Phenobarbital

Barbiturates

TOXICOLOGY - ILLICIT DRUGS Depressants (Sedative/hypnotics) Diazepam (Valium) Chlordiazepoxide Lorazepam

Benzodiazepines

TOXICOLOGY - ILLICIT DRUGS Depressants (Sedative/hypnotics) -has similar properties with barbiturates

Methaqualone

TOXICOLOGY - ILLICIT DRUGS used for sedation, analgesia, anesthesia

Opiates/Narcotics

TOXICOLOGY - ILLICIT DRUGS Codeine (antitussive) Opium Morphine

NATURALLY OCCURING Opiates/Narcotics

TOXICOLOGY - ILLICIT DRUGS Heroin Oxycodone Hydromorphone

CHEMICALLY MODIFIED Opiates/Narcotics

TOXICOLOGY - ILLICIT DRUGS Meperidine (Demerol) Methadone (Dolophine) Propoxyphene (Darvon) Pentazocine (Talwin) Fentanyl (Sublimaze) -- is 80x more potent than morphine

FULLY SYNTHETIC Opiates/Narcotics

TOXICOLOGY - ILLICIT DRUGS Cannabis sativa; primary cannabinoid component is THC (Tetrahydrocannabinol) which is detected in urine (THC-COOH)

Marijuana

TOXICOLOGY - ILLICIT DRUGS - also called as angel hair or angel dust - has tricyclic compounds w/ varied actions and paradoxical symptoms - lipophilic or rapidly distributes into fatty tissues and the brain which makes elimination slow; effects: auditory and visual hallucinations

Phencyclidine

TOXICOLOGY - ILLICIT DRUGS -MOST POTENT hallucinogen; - acts as SEROTONIN agonist -causes undulating/blurred visions and panic reactions/bad trip; just 20 ug can cause potent effects -

Lysergic acid diethylamide

TOXICOLOGY - ILLICIT DRUGS commonly used as an anesthetic for short surgical procedure in pediatric medicine

ketamine

TOXICOLOGY - ILLICIT DRUGS what are those HALLUCINOGENS/ psychedelics?

"PKML" P - Phencyclidine K - ketamine M - Marijuana L - Lysergic acid diethylamide

TOXICOLOGY - Other toxic substances most commonly abused substances in the world, chronic exposure is associated with toxic hepatitis and cirrhosis

ethanol

TOXICOLOGY - Other toxic substances Stages of impairment: SUBCLINICAL - No obvious impairment

0.01-0.05 BAC (% w/v)

TOXICOLOGY - Other toxic substances Stages of impairment: Mild euphoria: some impairment of motor skills

0.03-0.12 BAC (% w/v)

TOXICOLOGY - Other toxic substances Stages of impairment: CUT OFF FOR LEGAL INTOXICATION

>0.1%w/v

TOXICOLOGY - Other toxic substances Stages of impairment: EXCITEMENT - Loss of critical judgment, memory impairment

0.09-0.25 BAC (% w/v)

TOXICOLOGY - Other toxic substances Stages of impairment: CONFUSION - Mental confusion, strongly impaired motor skills

0.18-0.30 BAC (% w/v)

TOXICOLOGY - Other toxic substances Stages of impairment: STUPOR - Impaired consciousness

0.27-0.40 BAC (% w/v)

TOXICOLOGY - Other toxic substances Stages of impairment: COMA - Complete unconsciousness; deep, possibly fatal, coma

0.35-0.50 BAC (% w/v)

TOXICOLOGY - Other toxic substances Stages of impairment: DEATH - Respiratory arrest

>0.45 BAC (% w/v)

TOXICOLOGY - Other toxic substances methods: Ethanol + NAD acetaldehyde +NADH

Enzymatic mtd for Ethanol

TOXICOLOGY - Other toxic substances methods: reference mtd for ETHANOL

Gas-liquid chromatography (GLC)

TOXICOLOGY - Other toxic substances methods: screening for intoxicating substances like ethanol

Osmometry/OSMOLAL GAP

TOXICOLOGY - Other toxic substances causes acidosis, blindness, and death due to formation of FORMALDEHYDE & FORMIC ACID

Methanol

TOXICOLOGY - Other toxic substances produces severe, acute ethanol-like symptoms that persist for a long period of time

Isopropanol

TOXICOLOGY - Other toxic substances ingestion produces severe metabolic acidosis and renal tubular damage

Ethylene glycol

TOXICOLOGY - Other toxic substances 245x greater affinity for Hb compared to oxygen; shifts the oxyhemoglobin dissociation curve to the LEFT (Hypoxia)

Carbon monoxide

TOXICOLOGY - Other toxic substances -commonly used as rodenticide/insecticide -characteristic odor of BITTER ALMONDS - binds to heme iron and mitochondrial cytochrome oxidase inhibiting oxidative phosphorylation and causing cellular hypoxia

Cyanide

TOXICOLOGY - Other toxic substances -Aspiration is associated with pulmonary edema and shock, which can rapidly progress to death. --Ingestion causes metabolic acidosis or alkalosis and may produce lesions or perforations in the esophagus and Gl tract resulting in hematernesis, abdominal pain, and possibly shock.

Caustic agents

TOXICOLOGY - Other toxic substances Heavy metals examples?

"CALM" Cadmium Arsenic Lead Mercury

TOXICOLOGY - Other toxic substances Heavy metal -component of insecticides, pesticides, and herbicides: high affinity for KERATIN -binds to sulfhydryl groups of proteins; characterized by (GARLIC BREATH) odor and metallic taste -associated with transverse white striations in the nail beds called Mees lines

Arsenic

TOXICOLOGY - Other toxic substances Heavy metal metal food containers or industrial exposure; may cause RENAL TUBULAR DAMAGE (ATN)

Cadmium

TOXICOLOGY - Other toxic substances - inhibits many enzymes and affects vitamin D metabolism and heme synthesis pathway -- ALA DEHYDRATASE/PBG SYNTHASE, FERROCHELATASE/ HEME SYNTHASE

Lead

TOXICOLOGY - Other toxic substances Routes of exposure to LEAD

- INGESTION, INHALATION, & DERMAL CONTACT

TOXICOLOGY - Other toxic substances acquired through inhalation and ingestion; may also cause renal tubular damage

Mercury

TOXICOLOGY - Other toxic substances Most toxic form of Mercury?

Alkyl - organic mercury

TOXICOLOGY - Other toxic substances Forms of Mercury compounds -metallic form (Hg°); liquid at room temperature: -mercurous (Hg") and mercuric (Hg²*) forms: -alkyl aryl, a and alkoxyalkyl forms:

-Elemental - Cationic/ingrganic -Organic

TOXICOLOGY - Other toxic substances Methods for Heavy metals screening test for heavy metals; arsenic = black, mercury = silvery gray

Reinsch test:

TOXICOLOGY - Other toxic substances Methods for Heavy metals most commonly used method; gold standard for divalent cations and trace metals

AAS

TOXICOLOGY - Other toxic substances Methods for Heavy metals Anodic stripping voltammetry:

polarography; lead determination