Tox Flashcards
Reasons to use and dont use flumazenil in benzo od
Only when no benzo dependence and patient hasn’t taken any other substance in addition to benzo.
Risk of withdrawal sx and seizures
Flumazenil is especially contraindicated in
P w increased intracreamical pressure, closed head injury, taking TCA, epilepsy (inc risk of seizures)
AEs of benzos in therapeutic doses
Slurred speech
Ataxia
Sedation
Benzo withdrawal sx
HT, tachy, tremoulosnes, seizures, low grade fever, delirium
What benzos are not detected in blood tests
midazolam, chlordiazepoxide, and flunitrazepam
GHB moa
Neuroinhibitory + inc gaba b and dopa
Mild GHB intoxication
Slurred speech
Disinhibition
Euphoria
Mild lethargy
Moderate GHB intoxication
CNS and mild respiratory depression
Agitation when stimulated
Myoclonus
Severe GHB intoxication
Unresponsive coma Miosis Bradycardia Mild hypotension Seizures Respiratory depression and apnea
Short acting iv barbs
methohexital, thiopental, hexobarbital, pentobarbital
Short acting oral barbs
secobarbital and butabarbital oral
Patient has nystagmus, a bit slurred speech, a bit ataxia, seems somnolent and confused (dec GCS?), what drug might he have been taking
Mild to moderate overdose of barbs
Barb severe overdose, what will be seen on: Echo: BT machine: Counting RR: Thermometer: Glucosometer: When talking to p:
Echo: Dec contractility BT machine: HoT Counting RR: Dec Thermometer: Dec Glucosometer: Dec! In many p! When talking to p: Coma or close to coma
What may enchange elimination of phenobarbital?
urinary alkalization
Administer 1 to 2 mEq/kg (2 to 3 ampules in an adult) of bicarbonate IV initially followed by an infusion of 3 ampules of sodium bicarbonate mixed in 1 liter of D5W given at 1.5 to 2 times maintenance fluid rates.
Goal urine pH is 7.5 to 8. Do not allow serum pH to exceed 7.55.
Follow urine pH, serum pH and serum potassium carefully. Add potassium chloride to IV bicarbonate if the serum potassium is low.
Observation criteria phenobarbital
Over 8 mg/kg
An iminostilbene derivative with a tricyclic structure
Carbamazepine
Carbamazepine effect on cyp 450
Enhances it
Some medications that decrease elimination of carbamazepine
Erythromycin, isoniazid, propoxyphene
Sx of od carbamazepine
Hallucinations Blurred vision Drowsiness Slurred speech Ataxia Nausea, vomiting Tremors Seizures Oliguria Bullous skin formations
Ocular
Mydriasis
Nystagmus
Ophthalmoplegia
Cardiovascular
Tachycardia
Hypotension
Neurologic
Ataxia
Slurred speech
Dystonia, myoclonic activity
Varying degrees of CNS agitation to depression progressing to coma
Seizures, headache, confusion, and athetosis
Increased or decreased deep tendon reflexes
Respiratory depression, apnea
Delayed gastric emptying, abdominal pain
Oliguria, urinary retention
Therapeutic level of carbamazepine
4-12 mg/L,
Carbamazepine effect on heart
May give AV-block due to interference with purkinjae and HIS
DDx of carbamazepine overdose
- alcohol and other psychoaktive substance abuse
- anticholinergic toxidrome
- antidepressant toxicity
- lithium
-
other antiepileptic drugs toxicity (VPA, Phenytoin) - Neuroleptic Malignant Syndrome
-
encephalitis - sintus bradycardia
What to do when QRS is wider than 100ms in carbamazepine poisoning
Administer Sodium Bicarbonate
Valproate effect on cyp450
Slows it down
Cimentidine and ranitidine effect of valproic acid
Increase function by inhibitiong hepatic metabolism
Drugs that may slow down the gi absorption of valproate
Opiates and antihistaminsae
Valproate od sx
Unspecific, N/V, CNS, confusion and dec GCS
Important dangerous ae of valproate od that may occur after 72 h
Cerebral edema (due to hyperammonemia)
Aliphatic HCs
Linear hydrocarbons (alkanes, eses, ines)
Aromatic HC like benzene is used for
Solvents such as glue and paint
Most commonly ingested hydrocarbons
gasoline, chlorofluorocarbon propellants, motor oils, lighter fluid/naphtha, lamp oil, and mineral spirits
Acute systemic effects of hydrocarbons
Arrythmia CNS depression Seizures Hepatic necrosis Acute renal tubular necrosis
Pulmonary effects of HCs
- Causes aspiration
- Causes pneumonia by direct toxic effect of parenchyma, and injury t type II cells causing collapse,
- As a concequense, hemorrhagic alveoli’s
- Inflammation, hemorrhage, edema, brachial necrosis, vascular necrosis
CNS effects of HCs
- Direct
- Hypoxia
- Hypercarbia (sniffing from bag)
Long term: - White matter atrophy
- Peripheral neuropahty
- Blurred vision
- Sensory impairment
- Muscle atrophy
- Parkinsonism
Hepatotox of HCs
Cl is the worst
Carbon tetrachloride!
Make free radicals -> bind metabolites -> both bind liver enzymes and nucleic acids -> lipid per oxidation (electrons stolen and cell membranes destroyed) -> necrosis
Typically cbentrilobular
Problem with methylene chloride
Its metabolized by cup 450 to CO
HC effect on heart
Makes it more sensible for catecholamines -more risk for tachyarryhtmias and sudden cardiac death
HC effect on GI
Vomiting 1/3 and diarrhea
What HC is the worst for kidney
Aromatic toluene from chronic occupational -> distal renal tubular acidosis (collecting duct can’t excrete acid) -> anion gap acidosis
Hx of HC
What agent Route Amount Time Any other substances Vomiting or coughing before hospital Attemts of treatment before hospital?
kerosene and other aliphatic hydrocarbons smell like
petroleum distillate odor
halogenated hydrocarbons smell
halogenated hydrocarbons
Vitals after HC
Fever and dec O2
HC effect on CBC
Initial leukocytosis
Eventualu aplastic anemia, risk of AML
Blood tests to take for HC
Metabolic BUN Cr CK (rhabdo?) Glu Ele Hepatic Anion gap
What may be found in CXR after HC
Multiple small patchy densities with ill defined margins indicating aspiration pneumonia
May appear before sx, take XR at once
5 Ws
Who, What, When, Where, Why
Coma cocktail
O2, glucose, naloxone, dextrose, thiamine
Why observe
May have serious effects that are not apparent ant once
Important rule outs
ATOMIC
Alcohol
Trauma (CT)
Overdose
Metabolic distrurbance (electrolytes, glycose, thyroid, creatinine)
Infection (pneumonia, aspiration pneumonia sepsis, meningitis)
CO
PE
Undress p completely
Check for objects and substances
- Mental status
- Vital signs
- Pupils
- Bowel sounds (stimulation in alcoholic withdrawal, mushrooms, phosphor organic)
- Muscle, activity and coordination, tone, lead pipe,
- Skin
- Lungs
- Cardiovascular
When to be cautious about naloxone
Opioid addiction, multi-drug poisoning
Naloxone dose adutls
2 mg, repeat every 2 minutes until 10 mg
Naloxone infants and children under 5 years
0,1 per kg initially
Acetaminophen anti-dote
N-acetulcysteine
Beta blockers antidote
Glucagon
Ca channel blockers antidote
Iv Ca, insuline and glucose
Carbamates antidote
Atropine, pralidoxime
What is the effect of ipecac
It can induce emesis
MOA: Irritation of stomach and chemotrigger zone in brain
When not to induce emesis
Generally never in hospital but also Not in - Dec mental status or seizures - vomiting - corrosive poisons - volatile poisons - Heart disease p - Pregnant - Hyrdrocarbons and other that are worse for lungs than gi
When to perform gastric leakage from HCs
Benzene, toluene, camphor, halogenated hydrocarbons, pesticides, heavy metals if more than 5ml/kg, eg 500 ml in 100 kg man
Charcoal indication
In general poor evidence but
- Multiple sunstances
- life threatening amount
Drugs that may benefit from multi dose charcoal
Phenobarbital
Carbamazepine
Aspirin
Theophylline
Charcoal is not effective for
cyanide mineral acids caustic organic solvents, hydrocarbons metals (iron, lithium, mercury, lead) ethanol, methanol, ethylen glicol, isopropranol
Poisins that mainly cause death by airways
Carbamate, pesticides, hydrocarbons, solvents, petrol
Contraindication for alkaline diuresis
Renal failure
Is acidification of urine done?
No, the risk of rhabdo makes it not worth it
LIpid rescue is used for
Good for lipophilic substances
- TCA
- CCBs
- BBs
- Cocaine
- Anti-convulsants
- Anti-depressants
- Organic solvents
- Bio-weaponds
- Bupivacaine
Toxins that may require hemodialysis
Ethylene glycol Lithium Methanol Salicylates Theophylline VPA Phenobarbital
Whats in common?
Ethylene glycol Lithium Methanol Salicylates Theophylline VPA Phenobarbital
May require hemodialysis
Major groups of new psychoactive substances
Depressant
Stimulant
Hallucinogenic
Synhtethic cannabinoids
Other name of ephedrone
Scientific: Methcathinone
(made from oxidation of ephedrine)
MCat
Methcathinone effect
Similar to amphetamine Psychoactive stimulant Dopamine rey-take inhibitor Confusion to psychosis Euphoria Lack of appetite Forgetting to drink Locomotor activity Hypertension
Methyldioxyprovalerone (MDPV) MOA
NDRI (norepie and dopa reuptake inhibitor)
Similar to ritalin but 4 times more potent
Short term effects of MDPV
Basically SNS activation
Alterness and awareness
High doses of MDPV cause
Psychosis and panic
Lack of sleep
Addiction
Sexual desire
Long term effects of MDPV
Comedown syndrome
Postural hypotension, depression, lethargy
“Spice” moa
Cannabonoid agonist
Treatment in spice
Usually monitoring and hydration is enough, maybe benzos
What can be given to counteract on psychotic effects on the heart, to reduce risk of arrhythmia
Benzos
Pestisides include
Active biological substance and something to carry it, often a HC
Major deadly pesticides
Organophosphorius (endosulphan)
Aluminium phosphide
Paraquat
Some examples of organophosphates
Chlorpyrifos, parathion, dimethoate, fenthoin
Sx of organophosphate poisoning
1 Acute cholinergic crisis
2 Intermediate syndrome
3 Delayed polyneuropathy
Organophosphates MOA
Inhibit AChH, (by binding in a way thats hard to reverse)
Dimethyl vs diethyl
Dimethyl is fast, diethyl is fast (Bort act on reactivation of ACHE
Organophosphates cause __ syndrome
Muscarinic syndrome (and also nicotinic)
Sx nicotinic syndrome
Fasciculations, muscle cramps, fatigue, paralysis, tachycardia, HT
ECG changes after organophosphates
Small vintage (peak to peak QRS under 5 in limb or 10 in precordial)
ST-T changes
Prolonged QT
VES ++
Possible reasons for intermediate syndrome of organophosphate poisoning
toxin-induced myonecrosis
combined pre- and postsynaptic impairment of
neuromuscular transmission
downregulation or desensitization of postsynaptic ACh receptors after prolonged ACh stimulation
What is intermediate syndrome of organophosphate poisoning
Occurs a couple of days after
initial weakness of neck flexion
respiratory muscle weakness and respiratory failure
cranial nerve palsies (typically III, IV, VI, VII and X)
proximal muscle weakness of extremities
Ginger paralysis syndrome
= delayed effects of organophosphate poisoning
- neuropathy
- waekness
- Peronality changes
- Pancreatitis
When use atropine in OP poisoning
HR under 80, HoT under 80 systolic ++
high HR not contraindication
Pralidoxime and obidoxime are
ACHE reactivates
Advantage of glycopyrrolate for reversal of OP poising
No CNS effect
aldicarb, benomyl, carbaryl, carbendazim, carbofuran, propuxur, triallate are
carbamates
Carbamates differences from OPs
Also affect pseudocholinesterase BChE
Reversible
Less CNS effect
What are OCs
Organochloride pesticides
Chloridated cyclic hydrocarbons
DDT, BHC (benzene) and lindane are
OCs
Lindane effect on heart
Histologic alteration of LV wall
OC moa
- Depolarize nerves
- Dicoordinate GABA
- Predispose to arrythmias
OC sx
Many, CNS and seizures are most important
Cholestyramine may be useful in
Biliary-fecal excretion of OC
Pyrethins and pyrethroids use
Mosquito and scabies
Pyrethins and pyrethroids moa
Na channels
Pyrethins and pyrethroids sx and tx
Not supersevere, usually supportive
Paraquat is __ and may be mistaken for __
Bypyridyl herbicide
Cola
Bipryidyl herbicides MOA
Free radicals destroy cell membrane, worst for liver, kidney and lung
Paraquat typical sx
Hemorragic pumonary edama, ARDS, fibrosis
Diquat typical
To cns, like like parkinson or brain stem infarction
Paraquat oral ingestion sx
Just think that cells are dying everywhere
Liver failure Hepatic failure Ventricarular arrhythmia and arrest CNS depression or seizures Pulmonary hemorrhage Prorgressive pulmonary firbosis Rhabdo
Diquat is same, but generally more CNS and less other
Dx of paraquat and diquat
Add salt and look for color in urine
Tx in bipyridayl herbicides
All the normal stuff and immunosupression
Careful with O2 (free radicals)
2,4-D (2,4-dichlorophenoxyacetic acid), dichloroprop, mecoprop, are
Chlorophenoxyacetic herbicides
Chlorophenoxyacetic herbicides moa
Damage cell membranes and ruins oxidative phosphorylation by disrupting of acetylcoenzyme A
Sx of Chlorophenoxyacetic herbicides
- Intravascular volume loss -> hypovolemia
- Hypertonia and reflex
- CNS depression and respiratory depression
Alkaline diuresis effect on herbicide?
Yes
Dinitrophenols mechanism
Shuttling of protons
Dinitrophenols sx
Marked increase in metabolism:
Everything goes up
Severe:
All the normal organ problems, cns, lints, heart, kidney, liver
Methemeglobinemia anemia
Yellow skin, stool and urine
Yellow skin, stool and urine is seen in
Dinitrophenols
Glyphosate moa
Not sure, combination with other active ingredients
Glyphosphate sx
GI burns,
hyperthermia
Metabolic acidosis ++
Tx Glyphosphate
All the normal
ENdoscopy to look for burns
Correct acidosis and hydrate well
Symptoms of metallobisdithiocarbamates poisoning:
irritation and alcohol dehydrogenase inhibition
Antidote for ethanol glycol and methanol
Fomepizol (and ethanol)
Heavy metal antidote
Chealating drugs
Iron antidote
Deferoxiamine
Isoniazid antidote
Pyridoxime
TCA antidote
NaHCO3, alkanization to open fast sodium channels, dec cardiac effects
Cyanide antidote
Hydroxycobalamin
Methyl mercury in concentrated in
NS, and RBCs
Organomercurials legal?
Banned in many countries because of toxicity
Organomercurials sx
Acrodynia
Slurred speech, hearing, vision, balance etc
Essential part of organomercurail management
Chealation (DMSA etc)
Dialysis in organomercurials
May be necessary in addition to chelation, even low doses are life threatening
-tyltin are
Organotins
Organothins moa
Seveal mitochonrihal enzymes, problems w oxidative phosphorylation
Organothins sx
Hepatomegaly and liver ennymes
Hyperexitability, LOC and other CNS
Thallum fast
No, CNS effects can take a week;
Lethargy, paresthesia, ataxia ++
Alopecia takes 2 w
Thallum on gi
Bloody diarrhea, salivation
Aphemtaimine and cocain time to reach urine
3 days indicate decreasing dose elimination phase, not increasing (roughly)
Chronic weed user will have evidence in urine
1 months after
What can be given to increase fecal excretion of thallum
potassium ferric ferrocyanide (Prussian blue)
Warfarins moa
Inhibit 2,7,9,10
Direct capillary damage
CT
Take in cocaine, brain hemorrhage
Antidote for warfarin
Vit K1, not K3 and K4
Superwarfarins onset and duration
48 h - several months
Contraindication for gastric levage
No agreement from patient, even if uncoucious and life life threatening
Aluminium phosphide MOA
Taken up in mucos membrane, PH3 gas made -> Inhibits cyt c -> ROS -> cell damage
Metabolism of AP
In liver to phosphine which is also toxic
Gastric leakage size
36 french, very large, not normal size, 45 com long
Contraindication of gastric leavage
Uncorporative
Non-toxic dose (few pills)
Hydrocarbons only if intubates!
AP severe dose sx
ARDS, cardiac arrhythmias, liver and
renal failure, convulsions, coma and death
AP sx
symptoms usually develop within 30 min of ingestion
GI – severe epigastric pain, repeated vomiting, diarrhoea
circulation – hypotension, tachycardia, toxic myocarditis, arrhythmias, ST-T changes, subendocardial infarction
respiration – cough, dyspnoea, cyanosis, pulmonary oedema, ARDS
metabolic acidosis, intravascular haemolysis
typically, patients remain conscious till the late stages
AP tx
gastric lavage with potassium permanganate (
Zink phosphide smell
Rotten fish
CCBs bradycardia
Atropine
Clinical features of zinc phosphide poisoning:
similar to those of AP but slower in onset (slower release of
phosphine)
early symptoms – nausea, vomiting, thirst, tightness in the chest, excitement, agitation
pulmonary oedema, ECG changes, shock, oliguria
convulsions, coma
hepatotoxicity
metabolic acidosis, hypocalcaemia, thrombocytopenia
Barium conpouncds MOA
Interfere w sodium-potassium pump -> changes in cell membrane permeability -> paralysis of muscle s
Barium conpouncds sx
Interfere w muscle cell membrane!
repeated vomiting, abdominal pain
tightness of the muscles of the face and neck, muscle tremors
loose motions, anxiety, convulsions, perioral paraesthesia that spreads to other parts of the body, ascending quadriparesis with respiratory muscle involvement, difficulty in breathing
cardiac arrhythmias – wide-complex tachyarrhythmias, ectopics, ventricular tachycardia, ventricular fibrillation, prolonged QTc interval, prominent U waves
hypokalaemia (obs! )
What not to give in barium compounds
Mg sulphate
Mulluscicides kill
Snails
Low Vd and low protein binding its good for
Hemodyalysis
Quetiapine goode for hemodialysis?
No, high protein binding and liver rather than kidney elimination
Hemodialysis pro
Very small particles compared to the other
Hemoperfusion moa
Use charcoal or cuisine, should be larger particles, but can take larger amount then hemodialus
Can take larger size like plasma proteins
Hemofiltration
Particle size in between hemodialysis and hemoperfusion, can not take plasma proteins and things bound to them
Hemodialysis mechanism
Diffusjon
Hemofilter w semipermeable membrane, dialysite
Inducation for hemodialysis
Absolute:
Must have taken drug and drug must fit for hemorrhages (small partible low vd low protein binding)
Clinically necessary
Hemodialysis used for
Alchohols Lithium Salisylates Theophylline Valproate
Benefits of hemodialysis
Correct acidosis and other metabolic problems
Can treat kidney failure with hypervolemia
Methaldehyde moa
The mechanism of metaldehyde toxicity is not well understood:
harmful effects are mediated by a mechanism similar to its sister compound acetaldehyde (?)
decrease of the inhibitory GABA activity in the brain convulsions
Metaldehyde sx
Symptoms of acute metaldehyde poisoning:
onset after acute ingestion is generally within 1-3 h
traces amounts – salivation, facial flushing, fever, abdominal cramps, nausea, vomiting
up to 50 mg/kg – drowsiness, tachycardia, spasms, irritability
50-100 mg/kg – ataxia, increased muscle tone
100-150 mg/kg – convulsions, tremor, hyperreflexia
150-200 mg/kg – muscle twitching
about 400 mg/kg – coma, death (generally secondary to CNS depression and consequent respiratory failure)
Methaldehyde tx
- Gastic leavage and charcoal
- Supportive
- N-acetylcystein may help liver and kidney
Albumin dialysis
Idea is to eliminate protein bound, very expensive, main indication is liver failure, eg APAP toxicity, alcoholic liver,
DEET is
Diethyltoluamide
DEET acute poisoning
hypotension, respiratory depression
CNS toxicity:
behavioural disorders, restlessness, irritability
headache, ataxia
rapid loss of consciousness, seizures
sometimes flaccid paralysis and areflexia
Symptoms of cutaneous exposure to EDB (ethylene dibromide)
ulcerations
conjunctivitis
gastrointestinal and mucosal irritation
CNS irritation and depression
Symptoms of oral ingestion of EDB:
vomiting, diarrhoea, burning in the throat soon
after ingestion (features may last for 1-3 days)
ulceration of the mouth and throat
tremors, CNS depression, altered consciousness hypotension
oliguria
jaundice
uncommon features – pulmonary oedema, muscle necrosis, hyperthermia
tropane alkaloids
atropine, scopolamine, and hyoscyamine
Plants that contain alkaloids
Datura species (jimson weed, angel’s trumpet, thorn apple)
Hyoscyamus niger (henbane)
Atropa belladonna (deadly nightshade)
Mandragora officinarum (mandrake)
Benzos safe
Not really when alone, but synergic w alcohol and not good in combinations
Datura use
Resuse pain, dilate bronchioles
Tropane alkaloids moa
Anticholinergic
Important to remember about tropane alkaloids
Gastric emptying is slowed and dose in blood may continiue to increase for up to 48 days
Remember about flumazenil
Last short, may only gain consciousness for some minutes, but good to ask what they took
Has some diagnostic purpose
Rather intubate than give continilous doses of flumazenil
Careful if there might be dependence!! (Strong withrawl syndrome, and seizures)
Benzos elimination
Nothing can be done to enhance it
Barbituates vs benzos (or thiopental?)
Barbituates cause deeper coma, more respiratory depression and more cardiotox
Carbamazepine is structurally similar to
TCAs
Kinetics of carbamazepine
Large Vd
Unpredictable absorption
Needs to be monitored
Pathyphyys of carbamazepine
Opening of sodium channels
Carbamazepine metabolite
Metabolized by CYP450
Very active metabolite
Cause autoincudtion after long use, need to increase the doses eventually
Clinical course of carbamazepine
Therapeutic window is very narrow 4-11 mg/L!
Theoretically conscious but nystagmus, tremors, vomiting etc
Large doses give cholinolytic delirium (like in alcohol)
Cardiac depression and HoT, many CNS, alcohol like
Next stage will give Resp dec
Cholinergic properties, urinary retention (needs to have urinary catheter)
Skin changes that may give TEN syndrome
DRESS
Bind nucleic acids
Ddx of carbamazepine
Other cholinergic
Antihistaminic
TCA
Alcohol withdrawal
Electrolytes in carbamazepine
Hyponatremia (connected w effect on ADH)
Charchoal in carbamazepine
Yes, but exclutde ileus first!!
What to do if widening of QRS in carbamazepine
Give saline
Less toxic HC
Solid
Aspiration hazard HCs
Turprentine, gasoiline, keraosene, minral seed oil
Tropane alkaloids sx
Dry mucous membranes and skin Dysphagia and dysarthria Photophobia Blurred vision Tachycardia Urinary retention initial signs and symptoms may be followed by hyperthermia, confusion, agitation, combativeness, seizures, coma, and death. amnesia regarding events following ingestion of tropane alkaloids is common.
Tropane alkaloids mnemonic
The mnemonic “red as a beet, dry as a bone, blind as a bat, mad as a hatter, and hot as a hare” is useful to remember the anticholinergic toxidrome.
Can atropine etc be tested in blood?
No, but in urine
Lab tests for ethanol
ABG
AG & OG
60 year old patient with asthma, ER, severe N/V, abdominal pain, seizures, mild agitation, tremors? severe tachycardia with hypotension, tachypnea. Lab: hypokalemia with hyperglycemia?. You expect
Theophylline gives
- Hyperglycemia
- Hypokalemia
- (Hypercalcemia)
- (Hypophosphatemia)
- N/V pain, diarrhea
- Tremors, restlessness, agitation
- Seizures
- Tachycardia
- Hypotension
- Tachypnea
Amphetamine overdose sx
- Exitation
- Tachycardia w hypotension and tachypnea is possible
Not really any GI sx
Physostigmine prehospital?
No
What is metabolized to acetone?
Isopropanol, reason why it cause keto acidosis
When is physostigmine used?
Only in the most severe cases of atropine poisoning
Physostigmine contraindications
TCA Disopyramide Quinidine Procainamine Cocaine or other making cardiac conduction abnormalities
Airway disease, intestinal obstruction, depolarization agents
Most toxic mushroom
Cyclopeptides
Orellanine
Nephrotoxic mushroom
Ibotenic acid and muscimol (A muscaria, A pantherina), also termed isoxazoles
Intoxication and jerking movements
Gyromitryn or monomethylhydrazine (Gyromitra mushrooms)
Hemolytic
Muscarine (Inocybe and Clitocybe mushrooms)
Cholinergic
Coprine (Coprinus atramentarius, inky cap)
Disulfiramlike reaction
Psilocybin (Psilocybe and Paneolus mushrooms, magic mushrooms)
Hallucinogenic
Allenic norleucine (Amanita smithiana)
Nephrotoxic
Amantia time for sx
6-12 hours after ingestion, may not realize the mushroom was the reason
Amantia phalloides moa
primarily alpha-amanitin, are responsible for the hepatic, renal, and encephalopathic effects.
interrupts the actin polymerization-depolymerization cycle and impairs cell membrane function.
Give very uncomfortable diarrhea
Amatoxin
nhibitsRNA polymerase II, therefore interfering with DNA and RNA transcription. The toxin mainly affects tissues with high rates of protein synthesis, including the liver, kidneys, brain, pancreas, and testes.
May take days
Amanita important indicator for prognosis
PT
Amatnina gastric levage
Can be done up to 12 h after (delayed gastric poisoning)
Amanita charcoal
GIve multiple dose
Must be given many times because it has hepatic circulation (absorbed in liver, excreted in bile, taken up again, back into liver etc, cycle needs to be stopped)
Neurologix sx of atropine
Agitation, confusion, hallusiationas
Seizures, respiratory depression, coma
Bp after atropine
Incosistent high and low
Physostigmine dose
2mg repeated within hour
Contrainidation to physostigmine
(remeber will give PNS effects)
Astma HT DM Gangrene Obstruction Reciving depolarizing drugs
Precations when giving physostigmine
Monitor heart
Have atropine ready in case of hypoxia from bronchoreha and bronchosmams
Uwaga fasiculations and muscle weakness (have patient lying down)
When give physostigmine
Only severe problems that can’t be fixed in other way
- Seizure, hemodynamic or psychosis
Contraindicated drug when atropin intox
phenothiaziedes (antipsychotic that has anticholinergic properties)
How long sx free before set atropine p free(home from hospital)
6h
What mushrooms give cholinergic toxidrome?
ClitoCYBE
InoCYBE
some AMANTIIA
some BOLetus
Mnemonic cholinergic toxidrome
SLUDGE Salivation Lacromation Urination Diarrhea GI distress Emesis
What mushrooms give GABAergic syndrome
Anything containing muscimol
Amanita gemmata
Amanita muscaria (rød fluesopp)
Amanita pantherina (panter-fluesopp)
A kokeri
Ibotenic acid in mushrooms cause
Glumaminergic syndrome
Typical sx of mushrooms containing both isotonic acid and muscimol
Will result from increase in glutaminergic effects (NMDA, major excitatory) and in GABA effects (inhibitory)
HALLUSINATIONS
- Dysarthria
- Ataxia
- Muscle craps
- Everything from agitation to coma
What toxins are found in amanita mascara (rød fluesopp)
Muscarine (causing sludge but not very important)
Ibotenic acid and muscimpol (causing GABA and glumatminergic stimulation, hallusinctaions ++)
Does NOT!! contain cyclopeptide amatoxin with life threatening hapatotox!!!
-CYBE have
muscarine
Muscarine does not act on
Nicotonic, only M1 and M2, no muscle effect
Not on CNS!!
Act on POSTganglionec sm and glands
Muscarine vs Ach
Similar effects but longer half life because cholinesterase can’t break it down
- euphoria, visual and religious hallucinations and feeling closer to nature have been reported.
- Visual hallucinations may include perceived motion of stationary objects or surfaces.
- psychosis
- sympathomimetic activity such as mydriasis and tachycardia.
Psilocybin-containing mushrooms
Inoles
Similar to LSD, act on serotonin recepotors
Do not treat fever its because of agitation
Toxins in A phalloides (grønn fluesopp)
Phalloidin (cyclopeptide toxin) and amatoxin
Phalloiding effect
Interrups actin polymerization-depolymerization cycle
Amatoxin effect
Inbibit RNA somtehing, high rate of prog sync means more effective
LIver, kidney, brian, pancreas, testes
Amantine absorbtion
In bile
Lethal dose of alfa amantidin
Under 0.1 mg / kg
Phalloidins if found in
Phalloides
verna
virosa
bisporigera
Amatinas stages
Stage I:
sudden onset of nausea, vomiting, watery diarrhea, and cramping abdominal pain occurs 6-12 hours after ingestion
Stage II:
clinical improvement occurs with supportive care
despite the resolution of symptoms, hepatic and renal damage is ongoing, which is evident by rising laboratory test values.
Stage III:
if discharged, patients may return to the hospital 2-6 days later with severe coagulopathy, renal failure, and encephalopathy.
Amantita sx
Related to hepatic failure and bleeding
Tachy and HoT
Amanita tx
Alkanization of unit first hours!
silymarin/sylinibib
Indcuationf for new liver after amanita
Two-fold prolongation in PT, despite fresh-frozen plasma
Persistent hypoglycemia
Serum bilirubin levels of more than 25 mg/dL
Hiperammonemia
Grade III or grade IV hepatic encephalopathy
Coprinus atramentarius give what effect
disulfiram-like (the drug used for alcoholics to feel worse when then drink)
Disulfiram reaction
Hangover like
Flushing or blotching red rash (face, neck, thorax)(ASIAN FLUSH) Sense of face and hand swelling Diaphoresis (=sweathing) Palpitations/chest pain Dyspnea/hyperventilation Nausea/vomiting METALLIC TASTE Headache Vertigo/dizziness Tingling PARESTHEISAS (perhaps due to hyperventilation) Apprehension/sense of impending doom Weakness
HT or HoT
Fomepizole
blocking alcohol dehydrogenase and formation of acetaldehyde.
MMH comes from
Gyromitra
Important to remember about MMh
It is also volatile
MMH neurotox MOA
pyridoxomine, importnatn enzymes, GAD
-> GABA DEFICIENCY
Gyromitra sz
GI Hematopoetic JAUNDICE (hemolusus) CYANOSIS (methemoglobinesiA) HoT P+ HEMOFEC HEMOLYSIS
Tx seizures after gyromitra
Pyridoxine B6 (not benzo!)
Toxin in cortinarius species
Orellanine, NEPROTOXIC
proximal tubule!
and almost only there! (FA)
+ GI
APAP metabolism
90 percent of acetaminophen is metabolized in the liver to sulfate and glucuronide conjugates via sulfotransferase (SULT) and UDP-glucuronosyl transferases (UGT)
The remaining acetaminophen is metabolized via oxidation by the hepatic cytochrome P450 (CYP2E1, CYP1A2, CYP3A4 subfamilies) mixed function oxidase pathway into a toxic, highly reactive, electrophilic intermediate, N-acetyl-p-benzoquinoneimine (NAPQI)
Metabolism og NAQUI (the toxic metabolite of APAP)
By GSH to cysteine conjugates
the Rumack–Matthew nomogram,
was developed to estimate the likelihood of hepatic injury due to acetaminophen toxicity for patients with a single ingestion at a known time.
EtOH effect of APAP
Less toxicity w acute, more w chronic etOH
Factors increasing APAP toxicity
- Dose and acuity
- Age
- Chronic alcohol
- other drugs or herbs
- malnutrishion
APAP stage I
Unspecific, maybe maybe AST ALT
APAP stage II
After over 24 h, less sx, worse liver
APAP stage III
72 h, liver damage and lactic acidosis
Mech of lactic acidosis in APAP III
- Mitochondrial damage from NAPQI, and dysfunctional liver bad at clearance
BAd prognostic factor in APAP III
Lactate
Tx APAP
50 g charcoal first 4 h
N-acetulcysteine
