Term
|
Definition
| the study of the harmful effects of chemicals on biological systems |
|
|
Term
|
Definition
| any substance that can cause death, disease, or injury |
|
|
Term
| What are the 4 routes of poison entry to the body? |
|
Definition
1) oral
2) inhalation
3) parenteral
4) dermal |
|
|
Term
| How are poisons classified? |
|
Definition
Under borad headings s.a.
irriants
systemics
corrosives
gases
or by chemical structure s.a.
acids
bases
organic solvents
heavy metals
etc. |
|
|
Term
|
Definition
| any substance in the environment as a consequence of human activity |
|
|
Term
|
Definition
| locally, systemically, or both |
|
|
Term
| What determines time before posion effect is noticed/duration & intensity? |
|
Definition
1) dose
2) age
3) personal habits
4) genetics
5) route of administrationWhe |
|
|
Term
| What is the leading cause of all poisons in the U.S.? |
|
Definition
|
|
Term
|
Definition
| ADME of toxins, toxic doeses of therapeutic agents, and their metabolites |
|
|
Term
|
Definition
| the injurious effects of these substances on vital functions |
|
|
Term
| When will a chemical produce a toxic effect on a biological system? |
|
Definition
| when it reaches a critical concentration in traget tissue |
|
|
Term
|
Definition
| dose of a chemical required to produce death in 50% of organisms exposed to it |
|
|
Term
|
Definition
| dose producing desired parmacological effect in 50% of individuals |
|
|
Term
Equation
Therapeutic index |
|
Definition
|
|
Term
| In general, what route of exposure leads to the most rapid & greatest effect? |
|
Definition
|
|
Term
|
Definition
| single exposure or multiple exposures over a 24 hr period |
|
|
Term
|
Definition
| multiple exposures over 24 hr to 3 month period |
|
|
Term
|
Definition
| muliple exposures over period of 3 months or more |
|
|
Term
def
non-cumulative poisons |
|
Definition
readily cleared by the body & doesn't cause permanent irreversible damage at low doses
(total dose not important, so long as individual doses are small) |
|
|
Term
|
Definition
| accumulate in the body or cause irreversible damage where total exposure is critical |
|
|
Term
|
Definition
| rate of drug elimination is independent of of drug concentration |
|
|
Term
| How are drugs usually eliminated, first or zero order kinetics? |
|
Definition
|
|
Term
| When do drugs become zero order? |
|
Definition
|
|
Term
| What causes the change from first order to zero order kinetics in overdose situations? |
|
Definition
|
|
Term
| What happens at saturation? |
|
Definition
| processes are functioning at maximum & therefore limits rate of drug removal |
|
|
Term
| Equation
ke (zero order rate constant) |
|
Definition
| ke = (A0-A)/t
A0 = amount of drug at time 0
A = amount of drug at any other given time |
|
|
Term
| When will zero order kinetics yield a straight line? |
|
Definition
|
|
Term
| When will we see zero order kinetics with toxic agents? |
|
Definition
higher doses
(first order at low doses & mixture in between) |
|
|
Term
| What everyday substances (as examples) observe first order kinetics below saturation & zero order kinetics above? |
|
Definition
|
|
Term
| What are some examples of heavy metals? |
|
Definition
lead
murcury
arsenic
cadmium
chelators |
|
|
Term
|
Definition
| metals that are not metabolized & so pose a significant threat since they stay in the body for long periods of time |
|
|
Term
| What do heavy metals combine with in the body to exert their toxic effect? |
|
Definition
| essential aa residues of enzymes => inhibition of catalytic activity |
|
|
Term
| What are the sources of lead exposure? |
|
Definition
Environmental (water, air, soil, food)
Household (crayons, toys, paint, etc)
Occupational (miners, spray painters, etc) |
|
|
Term
Sx
Acute Inorganic Pb poisoning |
|
Definition
Severe GI
Progresses to: CNS (stupor/convulsions to coma/death) |
|
|
Term
| Why is Dx of acute inorganic Pb poisoning difficult? |
|
Definition
| Sx ~ appendicitis, peptic ulcer, pancreatitis |
|
|
Term
Sx
Chronic inorganic Pb poisoning |
|
Definition
Weakness, anorexia, nervousness, tremor, wt. loss, headache, GI
(recurrent abdominal pain & extensor muscle weakness w/o sensory disturbances => Pb poisoning possibility) |
|
|
Term
| What is the most characteristic finding in chronic inorganic Pb poisoning? |
|
Definition
|
|
Term
| How do you confirm Dx of inorganic Pb poisoning? |
|
Definition
1) measure blood level
2) ID abnormalities of porphyrin metabolism |
|
|
Term
| What usually causes organic Pb poisoning? |
|
Definition
| tetraethyl or tetramethyl Pb in gasoline |
|
|
Term
| Why is organic Pb readily absorbed thru skin & RT? |
|
Definition
| highly volatile & lipid soluble |
|
|
Term
| What has diminished organic Pb in environment? |
|
Definition
| phase-out of leaded gasoline |
|
|
Term
|
Definition
acute CNS disorders
few hetatological abnormalities
rapidly progressing => hallucinations, insomnia, headache, & irritability |
|
|
Term
| Where in the body does inorganic Pb distribute to after absorption? |
|
Definition
| soft tissues (primarily kidney & liver) => redistribution to bone, teeth, & hair => eventually 95% found in bone |
|
|
Term
| What is most circulating inorganic Pb associated with? |
|
Definition
|
|
Term
What is the half life of Pb in blood?
in bone? |
|
Definition
blood: 1-2 mo.
bone: 20 yr. |
|
|
Term
| What are tetraethyl & tetramethyl lead metabolized to by the liver? |
|
Definition
| trialkyl Pb & inorganic Pb |
|
|
Term
| What is trialkyl Pb responsible for? |
|
Definition
|
|
Term
| Where are trialkyl & inorganic Pb excreted? |
|
Definition
|
|
Term
| What is the primary screening procedure for Pb poisoning? |
|
Definition
| FEP test (RBC protoporphyrin will be increased due to inhibitionof ferrochelatase by Pb) |
|
|
Term
| What happens due to Pb inhibition of several enzymes in heme biosynthesis? |
|
Definition
| elevated urinary prophyrin |
|
|
Term
| How does Pb cause anemia? |
|
Definition
| inhibiting hemoglobin synthesis in bone marrow & increasing fragility of RBC |
|
|
Term
Heme metabolism
Succinyl CoA + Glycine -> ?
What enzyme is used? |
|
Definition
| δ-Aminolevulinate synthase is used to produce δ-Aminolevulinate |
|
|
Term
Heme metabolism
δ-Aminolevulinate -> ?
What enzyme is used? |
|
Definition
| δ-Aminolevulinate dehydratase is used to produce Prophobiliongen |
|
|
Term
Heme metabolism
Prophobilinogen -> ?
Which enzymes are used? |
|
Definition
| Porphobilinogen deaminase & uroporphyrinogen III cosynthase are used to produce Uroporphyrinogen III |
|
|
Term
Heme metabolism
Uroporphyrinogen III -> ?
What enzyme is used? |
|
Definition
| Uroporphyrinogen decarboxylase is used to produce Coproporphyrinogen III |
|
|
Term
Heme metabolism
Coproporphyrinogen III -> ?
What enzyme is used? |
|
Definition
| Coproporphyrinogen oxidase is used to produce Protoporphyrun IX |
|
|
Term
Heme metabolism
Protoporphyrin IX -> ?
What enzyme is used? |
|
Definition
| Ferrochelatase + Fe2+ are used to produce heme |
|
|
Term
| What 2 enzymes in heme metabolism does Pb have an effect on for sure? |
|
Definition
| δ-Aminolevulinate dehydratase & Ferrochelatase |
|
|
Term
| What 2 enzymes in heme synthesis does Pb probably have an effect on? |
|
Definition
| δ-Aminolevulinate synthase & Coproporphyrinogen oxidase |
|
|
Term
| What happens to δ-Aminolevulinate as a consequence of Pb? |
|
Definition
| it's excreted in the urine |
|
|
Term
| What happens to coproporphyrinogen as a result of Pb? |
|
Definition
|
|
Term
| What happens to protoporphyrin IX as a consequence of Pb? |
|
Definition
|
|
Term
|
Definition
1) orevent further exposure & provide supportive measures
2) Tx of seizures with diazepam
3) Tx of cerebral edema w/ mannitol & dexamethasone
4) Maintain fluid & electrolyte balance
5) initiate chelation therapy asap |
|
|
Term
| What are the 3 forms of Hg? |
|
Definition
elemental
inorgangic
organic |
|
|
Term
| Which form of Hg is more completely absorbed through GI? |
|
Definition
|
|
Term
| Which Hg form is poorly absorbed thru GI, but is quite volatile & can be absorbed thru the lungs? |
|
Definition
|
|
Term
Which organic Hg is most dangerous?
Why? |
|
Definition
| methylmercury - more completely absorbed thru GI |
|
|
Term
| Where, after distribution, is Hg concentration the highest? |
|
Definition
|
|
Term
| What does Hg bind to in the body? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Which Hg is more predominant in CNS? |
|
Definition
|
|
Term
| How are patients with acture Hg intoxication being exposed? |
|
Definition
| inhalation of Hg vapor (occupational exposure) |
|
|
Term
|
Definition
chest pain
SOB
metallic taste
N/V
=> acute kidney damage
if survives, severe gingivitis & gastroenteritis occur
Severe cases: muscle tremor & psychopathology develop |
|
|
Term
Sx
Chronic Hg intoxication |
|
Definition
mouth/GI disorders w/ Sx of renal insufficency
gingivitis, discolored gums, loose teeth
enlarged salivary glands
Tremor of digits, arms, & legs
altered handwriting
ocular changes (Hg deposition in lens)
personality change |
|
|
Term
| Where are organ toxicity most present in Hg poisoning? |
|
Definition
|
|
Term
| Why is Hg very corrosive? |
|
Definition
| ability to precipitate protein on contact |
|
|
Term
|
Definition
| removal from exposure & chelation with dimercaprol |
|
|
Term
|
Definition
| Oral penicillamine or N-acetylpenicillamine (chelation) |
|
|
Term
| How is Hg chelation success monitored? |
|
Definition
|
|
Term
| What are 4 the chemical forms of arsenic? |
|
Definition
elemental
inorganic
organic
asine gas |
|
|
Term
| When is arsenic used medically? |
|
Definition
| only in certain tropical diseases |
|
|
Term
| What are the 2 inorganic arsenic forms that cause major toxiological effects? |
|
Definition
primary: trivalent
pentavalent |
|
|
Term
| Why does pentavalent also have toxicologic effects? |
|
Definition
| uncoupler of oxidative phosphorylation |
|
|
Term
| How do trivalent arsenics produce toxological effects? |
|
Definition
| act as sufhydryl reagents => inhibition of SH-sensitive enzymes |
|
|
Term
|
Definition
| closes sulfhydryl ring by connecting to both S in the enzyme complex |
|
|
Term
|
Definition
stabilization of patient & prevention of further absorption.
chelation with dimercaprol followed bby penicillamine |
|
|
Term
| What contributes to cadmium (Cd) exposure? |
|
Definition
cigarette smoking
<5% of Cd is recycled in environment => pollution |
|
|
Term
| What is the half life of Cd? |
|
Definition
|
|
Term
| Why are smokers at an increased risk to Cd posioning? |
|
Definition
| build up sm. amounts of Cd/year due to cigarettes + Cd has an extremely long half life (prone to accumulation) |
|
|
Term
|
Definition
no effective Tx established
stabilization & prevention of further absorption
Chelation with calcium disoodium (never with dimercaprol => mobilizaes Cd causes it to concentrate in kidney & dissociates from chelator) |
|
|
Term
def
heavy metal antagonists |
|
Definition
|
|
Term
|
Definition
| desined to bind to heavy metals & prevent or reverse binding of metals to cellular molecules |
|
|
Term
| How are chelators flexible? |
|
Definition
| 2+ electronegative groups that for stable covalent bonds with cationic metal |
|
|
Term
| How is binding b/w chelator & metal ion accomplished? |
|
Definition
|
|
Term
| What are the common donor atoms for electron supply on the chelator? |
|
Definition
|
|
Term
| What 4 things does chelating effectiveness depend on? |
|
Definition
1) affinity for heavy metal
2) affinity for essential metals in body
3) distribution of metal & chelator in body
4) ability of chelator to mobilize metal |
|
|
Term
| What are the desirable propertirs of a good chelating agent? |
|
Definition
| 1) water solubility
2) resistance to metabolism
3) ability to distribute to same sites as metal
4) ready excretion of chelation complexes
5) can function at physiological pH
6) complexes are less toxic than free metal
7) low affinity for Ca2+ & Zn2+
8) high affinity for metal
9) minimal inherant toxicity
10) absorbed orally |
|
|
Term
| What are the 4 chelators used? |
|
Definition
1) Dimercaprol
2) EDTA
3) penicillamine
4) desferoxamine mesylate |
|
|
Term
| What are the propterties of dimercaprol? |
|
Definition
colorless oily liquid with offensive odor
readily absorved IM |
|
|
Term
| When is dimercaprol contraindicated? |
|
Definition
| liver disease or severe renal disease |
|
|
Term
|
Definition
Cardiovascular (HTN, tachycardia)
headache
fever in children
etc.
N/V |
|
|
Term
| Why do congeners of dimercaprol have less SE? |
|
Definition
| more water soluble & therefore confined to extracellular space |
|
|
Term
| When is EDTA an efficient chelator? |
|
Definition
|
|
Term
| What limits the clinical usefulness of EDTA? |
|
Definition
| chelation of essential calcium |
|
|
Term
| When in EDTA contraindicated? |
|
Definition
Hg poisoning
renal disease |
|
|
Term
| How is invivo calcium binding circumvented with EDTA? |
|
Definition
| addition of calcium-disodium |
|
|
Term
| How is penicillamine formed? |
|
Definition
| degradation of penicillin |
|
|
Term
| Why is the D isomer of penicillamine preferred over the L isomer? |
|
Definition
|
|
Term
| What is penicillamine most used to Tx? |
|
Definition
| Pb, Hg, & Cu poisoning (Wilson's disease since Cu chelation) |
|
|
Term
| When are SE seen in penicillamine |
|
Definition
only in chronic use
(allergic rxn, leukopenia, eosinophilia, nephrotoxicity) |
|
|
Term
| What is deferoxamine mesylate isolated from? |
|
Definition
|
|
Term
| When is deferoxamine mesylate used? |
|
Definition
iron toxicity (possibly aluminium toxicity as well)
only use when severity of poisoning justifies it, since it's toxic as well |
|
|
Term
| When is deferoxamine mesylate contraindicated? |
|
Definition
|
|
Term
|
Definition
diarrhea
HTN
cataract formation |
|
|
Term
10 yo boy living near pigment manufacturing plant presents with burning snesation in glove and stocking distribution with sever bilateral arm & leg weakness. He presents with hyperpigmentation & thickening of skin over pamls & soles. He is in the habit of eating paint.
Neurological exam reveals decreased senation, decreased motor stregeth, absent tendon reflexes, & wasting in arms & legs.
Arsenic levels elevated in blood, urine, & hair.
What should be used for Tx? |
|
Definition
| penicillamine or oral DMSA |
|
|
Term
| When do neurological Sx predominate over GI Sx in arsenic poisoning? |
|
Definition
|
|
Term
5 yo boy brought to medical clinic b/c of sudden, vigorous vomiting with no previous nausea. Mother states he's been behaving stragely & been irritable. Child complains of weakness in hands & feet. Boy lives in an old house recently renovated. He's had episodes of abdominal pain in the past.
PW shows pallor, lethary, foot drop, retinal strippling, lines in gum, wasting of muscles of hands with motor weakness.
Labs show hyperchromatic, microcytic anemia with casophilic strippling, hyperuricemia, increased urinary coproporphyrin & aminolevulinic acid, elevated blood Pb.
X-rays show increased density at metaphysis
Edema of the brain & peripheral nerve segmental demyelination present
Acid fast intranuclear bodies in renal tubluar cells, hepatocytes, & osteoclasts.
What Tx is indicated? |
|
Definition
sepatation from source of exposure
IM chelation with CaEDTA or DMSA orally, dimercaprol |
|
|
Term
28 yo male, professor of chemistry, come to ER complaining of acute retosternal & epigastric pain & frequent vomiting of blood-tinged material. He admits to a suicide attempt thru ingestion of several teaspoons of mercurium bichloride. On arrival he had a bloody, diarrhetic bowel movement.
PE shows hypotenstion, tachycardia, pallor, cold & clammy skin, whitish tongue, & confused demeanor. Patient was oliguric & dyspneic, exhibited moderate abdominal tenderness & grayish discoloration of buccal mucosa.
Lab showed elevate serum creatinine & BUN. tubular casts in urine analysis. Markedly increased fractional excretion of sodium & elevated serum hemoglobin levels
He has acute tubular necrosis, acute irritative colitis with mucosal necrosis with sloughing & hemorrhage.
What Tx is indicated? |
|
Definition
Specific chelation therapy with dimercaprol & siccomer.
Supportive management of acute tubular necrosis |
|
|
Term
| What are the properties of carbon monoxide (CO)? |
|
Definition
| colorless, tasteless, odorless, non-irritating |
|
|
Term
| What are the major sources of CO? |
|
Definition
| automobile exhause, charcoal fires, gas furnaces, methylene chloride |
|
|
Term
|
Definition
| It combines with Hb at O2 binding sites to form carboxyhemoglobin (unable to transport O2 from lungs to tissue)
Hb affinity for CO is >200x that of Hb for O2
therefore CO is dangerous at LOW levels |
|
|
Term
| What tissues are most affected by CO poisoning? |
|
Definition
|
|
Term
| How do Sx of CO poisoning vary? |
|
Definition
|
|
Term
|
Definition
| headache, weakness, N/V => loss of muscular control, collapse, unconsciousness & death |
|
|
Term
| Why are the cardiac & resp. systems affected by CO? |
|
Definition
|
|
Term
|
Definition
| 1) remove from source of exposure
2) maintain respiration
3) may need to administer O2 |
|
|
Term
| Why is it important to remove indivudual from exposure & maintain respiration (besides the obvious) in CO poisoning? |
|
Definition
| Once removed from exposure, CO readily dissociated from COHb via expiration |
|
|
Term
| What are the cources of cyanide (CN)? |
|
Definition
occupational chemicals (fumigants, cleaners, rubber, etc)
produced in fired involving N-containing plastics
Home environment (silver polish, insecticides, fruit seeds) |
|
|
Term
| How soon after inhalation of toxic doses of CN as Sx seen? |
|
Definition
|
|
Term
|
Definition
Sm dose: giddiness, headache, palpitations, N/V => increased dose: ataxia, convulsions, soma, death
very lg dose: collapse & death almost immediately |
|
|
Term
|
Definition
Abruptness of Sx onset
Odor of bitter almonds on breath |
|
|
Term
|
Definition
| CN bings to ferric iron in cytochrome oxidase of mitochondra => inhibits cellular respiration => cytotoxic hypoxia |
|
|
Term
|
Definition
| Administer amyl nitrite or sodium nitrite to produce methemeoglobin from hemoglobin [Fe(II) to Fe(III)].
This provides a large pool of Fe(III) for CN to bind to
Tx of induced hypoxia via O2 inhalation |
|
|
Term
| What are the sources of methanol? |
|
Definition
| industrial chemical (anitfreeze, paint remover) |
|
|
Term
| How does MeOH removal compare to EtOH? |
|
Definition
| MeOH is more slowly oxidized |
|
|
Term
| What are the 2 MeOH products responsible for MeOH toxicity? |
|
Definition
| MeOH -> fomaldehyde -> formic acid |
|
|
Term
|
Definition
~ to those with EtOH
Severe GI cramps, vomiting, acidosis, cardiac depression
early: vision disturbances (blurred, dilated pupils)
resp. & circulatory failure => coma, delirium, death
(protracted blondness can be premanent, even if recovery occurs) |
|
|
Term
| What causes blindness in MeOH toxicity? |
|
Definition
| formaldehyde by damaging retinal cells |
|
|
Term
| What causes cadiac Sx & is a systemic acidifier in MeOH toxicity? |
|
Definition
|
|
Term
| What is the key to survaval of MeOH poisoning? |
|
Definition
|
|
Term
|
Definition
keep patient warm
protect patient eyes from light
correct acidosis by administration of sodium bicarbonate
continuously monitor blood pH & gases
may administer EtOH since both are metabolized by EtOH dehydrogenase, but with a higher affinity for EtOH |
|
|
Term
| Where is the major source of ethylene glycol? |
|
Definition
| antifreeze (major component) |
|
|
Term
| What metabolizes ethylene glycol? |
|
Definition
|
|
Term
| What does EtOH dehydrogenase metabolize Ethylene glycol to? |
|
Definition
|
|
Term
| Why does oxalate cause severe renal injury & failure? |
|
Definition
|
|
Term
| What causes acidosis in ethylene glycol intoxication? |
|
Definition
| formic acid production (just like MeOH) |
|
|
Term
Tx
Ethylene glycol intoxication |
|
Definition
gastric lavage
correct acidosis with sodium bicarbonate
administration of EtOH to compete for EtOH dehydrogenase & slow metabolism of ethylene glycol
hemodialysis |
|
|
Term
| How much of acetaminophen (APAP) is absorbed from GI? |
|
Definition
| 100% absorbed (& rapidly) |
|
|
Term
| How soon after APAP administration is plasma concentration peak seen? |
|
Definition
|
|
Term
| What is the half life of APAP? |
|
Definition
|
|
Term
| What is APAP metabolized to? |
|
Definition
primarily: glucuronide
sulfate conjugates |
|
|
Term
|
Definition
24-48 hr: pallor, N/V
2-4 d: heptaic damage observed |
|
|
Term
| Why is early diagnosis of APAP toxicity critical? |
|
Definition
| it's metabolized during 1st pass metabolism (must monitor LFT) |
|
|
Term
|
Definition
majority: gluronidated
sm amount: hydroxylated by CYP450 => conjugation to GSH & excreted |
|
|
Term
| What happens to GSH levels in massave APAP doses? |
|
Definition
| depletion => hydroxylated metabolite binding to tissue => necrosis |
|
|
Term
|
Definition
| N-Acetylcysteine (asministration of sulfhydryl compound to maintain hepatic GSH or act as an alternative target for hydroxylated APAP metabolite) |
|
|
Term
| What is one of the major causes of accidental poisoning in children under 5? |
|
Definition
|
|
Term
| What is the source of most vitamin toxicities? |
|
Definition
| chronic use of vitamins over many years |
|
|
Term
|
Definition
|
|
Term
| Which vitamins are most likely to cause overdose? |
|
Definition
| fat soluble (A & D more prominent, E & K rarely seen) |
|
|
Term
| What is the main source of "multivitamin" toxicity? |
|
Definition
|
|
Term
A 29 yo mechanic brought to ER after complaining of persistent headache, nausea & dizziness. He has been working indoors all day bc of the cold weather & felt tired, dizzy, & nauseated. He has otherwise been in good health.
PE reveals tachycardia & patient is lethargic & disoriented.
Labs reveal carboxyhemaglobin concentraion of 38%
What Tx should be administered? |
|
Definition
| 100% oxygen until carboxyhemoglobin concentration <5%. |
|
|
Term
6 yo boy is brought to ER b/c of severe vomiting. Patient was with his father in the garage when he drank some antifreeze. On arrival, the boy started having tonic-clonic seizures.
PE reveals tachycardia, no fever, hypotension, & the patient was hyperventilating & experiencing convulsions.
Labs reveal leukocytosis, ethylene glycol in blood, metabolic acidosis w/ elevated osmolar & anion gap, hyponatremia & hyperkalemia. BUN & creatinine were normal. ECG showed premature ventricular beats.
Chest x ray showed no evidence of bronchoaspiration of ethylene glycol.
What Tx should be administered? |
|
Definition
administration of EtOH to saturate EtOH dehydrogenase.
administer pyridoxine, folate, & thiamine to counteract effecs of toxic metabolites
Treat convulsions with diazepam & monitor vital signs.
hemodialysis if necessary |
|
|
