TUMOR MARKERS, TDM, & TOXICOLOGY Flashcards
Tumor type : liver
Tumor marker : ?
AFP
Also increased in germ cell tumors
AFP
Tumor type : Colorectal
Tumor marker : ?
CEA
Tumor type : Ovarian
Tumor marker : ?
CA-125
Tumor type : GASTRIC
Tumor marker : ?
CA 72-4
Also increased in colorectal cancer
CA 72-4
Tumor type : pancreatic
Tumor marker : ?
CA 19-9
Also related to Lewis blood group antigens ; also increased in gastric and colorectal cancers
CA 19-9 pancreatic
Tumor type : breast
Tumor marker : ?
CA 15-3, 27.29
ER, PR, HER-2 / neu
Used to monitor therapy and detect recurrence
CA 15-3, 27.29
Prognostic and hormonal therapy indicator ; detected in biopsy specimens using immunohistochemistry
ER, PR, HER-2/neu
Tumor type : prostate
Tumor marker : ?
PSA
Used for prostate cancer screening in combination with DRE
PSA
Tumor type : NEUROENDOCRINE TUMORS
Tumor marker : ?
NEURON-SPECIFIC ENOLASE
Prognostic indicator and monitoring progression
NEURON-SPECIFIC ENOLASE
Tumor type : Lung
Tumor marker : ?
CYFRA 21-1
Subunit of cytokeratin fragment expressed in simple epithelia
CYFRA 21-1
Tumor type : URINARY BLADDER
Tumor marker : ?
NUCLEAR MATRIX PROTEIN
Oncogene -encoded protein
Nuclear matrix protein
Tumor type : thyroid
Tumor marker : ?
Thyroglobulin
Increased in other thyroid diseases
Thyroglobulin
Major source of thyroglobulin assay interference
Anti-thyroglobulin antibody
Tumor type : medullary thyroid
Tumor marker : ?
calcitonin
Screening, response to therapy, and monitoring recurrence
Calcitonin
Tumor type : ovarian, testicular
Tumor marker : ?
B-hCG
Also increased in gestational trophoblastic diseases e.g. choriocarcinoma, hydatidiform mole, GI neoplasia
B-hCG
Tumor type : NEUROBLASTOMA
Tumor marker : ?
Homovanillic acid (HVA) , vanillylmandelic acid (VMA)
Determined on 24 hr urine using HPLC
HVA, VMA
Tumor type : PHAEOCHROMOCYTOMA
Tumor marker : ?
Metanephrine, normetanephrine
Determined on 24 hr urine or plasma using HPLC
Metanephrine , normetanephrine
Highest point ; amount of drug absorbed and distributed is greater than the amount metabolized and excreted
Peak
Lowest concentration achieved just before the next dose
Trough
Time required for the concentration of the drug to decrease by half
Half-life
Amount of drug absorbed and distributed equals amount metabolized and excreted ; usually reached after 5-7 half-lives
Steady state
Lowest concentration of drug in the blood that will produce adverse response
MINIMUM TOXIC CONCENTRATION (MTC)
Lowest concentration of drug in the blood that will produce desired effect
Minimum effective concentration
Range of values between the MEC and MTC that produce therapeutic effect
Therapeutic range
Drug dose that produces beneficial effect in 50% of the population
ED50 (EFFECTIVE)
Drug dose tat produces adverse effects in 50% of the population
TD50 (TOXIC)
Drug dose that produces death in 50% of the population
LD50 (LETHAL)
THERAPEUTIC INDEX
RATIO OF ED50 TO TD50
Used as a semi-quantitative screening test ; interpretation of results utilizes Rf values of solutes in complains to aqueous standards
Thin-layer chromatography
Distance migrated by a sample component / distance migrated by the solvent
Rf
For insufficiently volatile and thermolabile compounds
Liquid chromatography
Type of liquid chromatography where the mobile phase is a liquid that is passed over the stationary phase of the column
HPLC
Polar stationary phase and nonpolar mobile phase
Normal-phase LC
Nonpolar stationary phase and polar mobile phase
Reverse-phase LC
Useful for compounds that are naturally volatile or can easily be converted into a volatile form (various organic molecules including many drugs)
Gas chromatography
Time it takes for a compound to elude l used as basis for identification of a solute
Retention time (tr)
Proportional to the amount of solute present ; see for quantification
Peak area/height
Common detector system in GC or HPLC ; produces a signal for identification and quantification of the solutes
Mass spectrometry
Uses microparticles as solid phase, an enzyme label, and fluorogenic substrate
Micro particle enzyme immunoassay (MEIA)
A homogenous assay in which the activity of an enzyme as a label is inhibited by the binding of antibody to antigen conjugated with enzyme
Enzyme-multiplied immunoassay technique (EMIT)
Uses polarized light to excite a fluorescent label ; rat of rotation is inversely proportional to the degree of polarization and analyte concentration
Fluorescence polarization immunoassay (FPIA)
Drug activity or fate of drugs in the body
PHARMACOKINETICS
PHARMACOKINETICS is influence by the
Absorption
Distribution
Metabolism
Through the GI tract for orally administered drugs ; dependent on many factors and is related to the drug’s bioavailability
Absorption
Amount of drug absorbed relative to the quantity given ; affected by firs-pass metabolism, which reflects the activity of metabolic enzymes, in the intestine and liver
Bioavailability
Diffusion out of the vasculature into interstitial ad intracellular spaces ; dependent on the lipid solubility of the drug
Distribution
Hepatic uptake and enzymatic bio transformation in the hepatic microsomes via the cytochrome P450 enzyme system
METABOLISM
Elimination through hepatic or renal clearance or a combination of the two
Excretion
Biochemical and physiological effects of drugs and the mechanisms of their actions ; involves receptor binding, post receptor effects and chemical interactions
Pharmacodynamics
TDM SPECIMEN CONSIDERATIONS
_____ must be established before sampling
Steady sate
TDM SPECIMEN CONSIDERATIONS
______ when toxicity is suspected
STAT Sampling
TDM SPECIMEN CONSIDERATIONS
_______ before the next dose is administered
Trough specimen
TDM SPECIMEN CONSIDERATIONS
1 hour after oral administration ; 0.5 hour after completion of IV administration
Peak specimen
Specimen preferred for most drug assays
Serum
Suitable for most drugs lithium and free drug assays
Heparinized plasma
May falsely decreased TCAs and anti-arrythmics
SST/PST
Appropriate for immunosuppressants
EDTA WB
Recommended for the impedance method of aspirin determination
Hirudin
A cardiac glycoside used to treat congestive heart failure ; inhibits sodium, potassium ATPase, causing decrease in intracellular potassium and increase in intracellular calcium resulting in improved contraction of cardiac muscle
DIGOXIN
Used to treat tachyarrhthymias
Antiarrhythmics
Cardioadictive drugs classes I-IV
Sodium channel blockers
Beta blockers
Potassium channel blockers
Calcium channel blockers
“So Be It Pota Ca”
Cardioadictive drug class I
Lidocaine, quinidine, disopyramide, procainamide
Cardioadictive drug class II
Propanolol
Cardioadictive drug class III
Amiodarone
Cardioadictive drug class IV
Verapamil
Metabolized to monoethylglycinexylidide (MEGX), which enhances toxicity
LIDOCAINE
Metabolized to N-acetylprocainamide (NAPA) which exhibits the same physiologic effect as the parent drug
Procainamide
First generation (classical) anticonvulsants
Phenobarbital
Benzodiazepines
Phenytoin (Dilantin)
Carbamazepine (tegretol)
Ethosuximide
Valproic acid (Depakote)
First generation anticonvulsants used to treat granola or tonic-clonic seizure
Phenobarbital
Benzodiazepines
Phenytoin
Carbamazepine
Inactive form of phenobarbital
Primidone
New generation anticonvulsants
Tiagabine, vigbatrin, gabapentin, topiramate, felbamate
BRONCHODILATOR (B-andrenergic agonists) : used to treat asthma and COPDs
Theophylline
BRONCHODILATOR (B-andrenergic agonists) :
Minor metabolite of theophylline ; treatment of neonatal apnea
Caffeine
PSYCHOACTIVE DRUG : Major tranquilizers used to treat schizophrenia
Neuroleptics
Neuroleptics:
Phenothiazines — chlorpromazine
Butyrophenones — haloperidol (Haldol)
PSYCHOACTIVE DRUG : antimanic drug ; used to treat bipolar disorder/ manic depressive disorder
Lithium
PSYCHOACTIVE DRUG : used to treat clinical depression (major depressive disorder)
ANTIDEPRESSANT
ANTIBIOTICS : used to treat gram negative infection by inhibiting protein synthesis ; toxic effects include nephrotoxicity and ototoxicity (Deafness)
Aminoglycosides
Antibiotic used to treat gram positive infection ; may cause erythemic flushing of extremities called REDMAN SYNDROME
VANCOMYCIN
Used to prevent graft-versus-host disease
Immunosuppressant
Immunosuppressant : block T lymphocyte function
Calcineurin inhibitors
Immunosuppressant (Calcineurin inhibitors) : fat-soluble cyclical peptide isolated from Trichoderma
Cyclosporine
Immunosuppressant (Calcineurin inhibitors) : macrolide lactone isolated from Streptomyces ; 100x more potent than cyclosporine (administered in much lower doses) ; associated with thrombus formation in patients with toxic levels
Tacrolimus
Immunosuppressant : sirolimus (rapamycin), everolimus, mycophenolate, leflunomide
Proliferation signal inhibitors
ANTINEOPLASTIC : Inhibits DNA synthesis ; requires administration of LEUCOVORIN
Methotrexate
To rescue host cells from methotrexate inhibition
Leucovorin
ANTINEOPLASTIC : alkylating agent used to treat leukemias and lymphomas before bone marrow transplantation
Busulfan
Associated with a single, short-term exposure to a substance, the dose oof which is sufficient to cause immediate toxic effects
Acute toxicity
Results from repeated frequent exposure for extended periods at doses insufficient to cause an immediate response l may affect different systems
Chronic toxicity
Used as an analgesic, antipyretic, and anti-inflammatory ; exhibits antiplatelet activity through inhibition of clyclooxgenase ; toxic effects include mixed acid base disorders, Reye syndrome
Acetylsalicylate (Aspirin)
Preferred over aspirin inhibitors patients with a bleeding disorder ; toxic effect hepatotoxicity
Acetaminophen (Tylenol)
Domapinergic pathway stimulants : local anesthetic ; primary metabolite ______ ; short half life of _______
Cocaine ; benzoylecgonine ; 1-2 hours (05.-1 hr)
Domapinergic pathway stimulants : used to treat narcolepsy
Amphetamines (methamphetamine)
Domapinergic pathway stimulants : euphoria-producing synthetic phenylethylamines
Designer drugs
Domapinergic pathway stimulants : MDMA
ECSTASY
DEPRESSANTS :
SEDATIVE/HYPNOTICS
OPIATES/NARCOTICS
SEDATIVE / HYPNOTICS
BARBITURATES
BENZODIAZEPINES
METHAQUALONE (QUAALUDE)
Not structurally similar to but has many of the properties of barbiturates
METHAQUALONE
Depressant used for sedation, analgesia, and anesthesia
Opiates/narcotics
Opium, morphine, and codeine
Naturally occurring narcotics
Heroin, hydyromorphone (Dilaudid), and oxycodone (percodan)
Chemically modified narcotics
Hallucinogens/psychedelics : primary cannabinoid component
tetrahydrocannabinol
Hallucinogens/psychedelics :
Major urinary metabolite of cannabis saliva
tetrahydrocannabinol carboxylic acid
Hallucinogens/psychedelics : structurally similar to serotonin l acts as serotonin agonist l produces panic reactions and undulating vision
Lysergic acid diethylamide
Hallucinogens/psychedelics : structurally similar to serotonin l acts as serotonin agonist l produces panic reactions and undulating vision
Lysergic acid diethylamide
Hallucinogens/psychedelics : angel dust or angel hair
Phencyclidine
Hallucinogens/psychedelics : a tricyclic compound with varied actions and paradoxical symptoms in pediatric medicine
Phencyclidine
Hallucinogens/psychedelics : commonly used as an anesthetic for short surgical procedures
Ketamine
Miscellaneous classes : derivatives of serotonin with hallucinogenic properties e.g. dimethyltryptamine and psilocin/psilocybin
Tryptamines
Miscellaneous classes : produce effects similar to to hose of the amphetamines
Piperazines
Miscellaneous classes : psychoactive designer drugs that produce amphetamine-or cocaine-like effects ; causes false positive methamphetamine screening result
Synthetic cathinones (bath salts)
Miscellaneous classes : non-benzodiazepine agents
Sleep aids
Miscellaneous classes : CNS depressant used in pain management
Muscle relaxants
Most commonly abused substance in the world l chronic exposure is associated with toxic hepatitis and cirrhosis
Ethanol
Blood alcohol legal intoxication (% w/v)
> 0.1
BAC (w/v%) : 0.01-0.05
Level of impairment : no obvious impairment
Influence : ?
Subclinical
BAC (w/v%) : 0.03-0.12
Level of impairment : mild euphoria ; some impairment of motor skills
Influence : ?
Euphoria
BAC (w/v%) : 0.09-0.25
Level of impairment : loss of critical judgment ; memory impairment
Influence : ?
Excitement
BAC (w/v%) : 0.18-0.30
Level of impairment : mental confusion ; strongly impaired motor skills
Influence : ?
Confusion
BAC (w/v%) : 0.27-0.40
Level of impairment : impaired consciousness
Influence : ?
Stupor
BAC (w/v%) : 0.35-0.50
Level of impairment : complete unconsciousness ; deep, possibly fatal, coma
Influence : ?
Coma
BAC (w/v%) : >0.45
Level of impairment : respiratory arrest
Influence : ?
Death
Reference method for ethanol
Gas-liquid chromatography
Most commonly used / effective screening test for ethanol
Osmometry / osmolal gap
Causes acidosis, blindness, and death due to formation of formaldehyde and formic acid
Methanol
Produces severe acute ethanol-like symptoms that persist for a long period of time
Isopropanol
Ingestion produces severe metabolic acidosis and renal tubular damage
Ethylene glycol
245x greater affinity for Hb compared to oxygen ; shifts the oxyhemoglobin dissociation curve to the left (hypoxia)
Carbon monoxide
Commonly used as rodenticide/insecticided ; characteristic odor of BITTER ALMONDS ; binds to heme iron and mitochondrial cytochrome oxidase inhibiting oxidative phosphorylation and causing cellular hypoxia
Cyanide
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 GI tract resulting in hematemesis abdominal pain and possibly shock
Caustic agent
Component of insecticides, pesticides, herbicides ; high affinity for KERATIN, binds to sulfhydril groups of proteins ; characterized by GARLIC BREATH odor and metallic taste ; associated with transverse WHIITE STRIATIONS in the nail beds called MEES LINE S
ARSENIC
Metal food container or industrial exposure ; may cause RENAL TUBULAR DAMAGE
Cadmium
Inhibits many enzymes and affects vitamin D metabolism and heme synthesis pathway
Lead
Enzymes inhibited in the heme synthesis pathway
ALA dehydrates / PBG synthase
Ferrochelatase / heme synthase
Inhibition of ALA dehydrates / PBG synthase causes high ____
Delta-aminolevulinic acid in urine
Inhibition of Ferrochelatase / heme synthase causes high ____
Free erythrocyte protoprophyrin
Acquired through inhalation, ingestion ; may also cause renal tubular damage
Mercury
Metallic form of mercury ; liquid at room temperature ; nontoxic
Elemental
Mercurous and mercuric forms ; moderately toxic
Cationic / inorganic
Alkyl, Aryl, and alkoxyalkyl forms ; environmental pollutants ; extremely toxic
Organic
Most toxic organic mercury because of their lipophilic nature that can easily cross membranes
Alkyl (methyl mercury)
Condition associated with methyl mercury
Minamata disease
Condition associated with methyl mercury
Minamata disease
