Toxic Flashcards
reward circuit
VTA, nucleus accumbens, caudate
a compact DOPE vent - DA- accumbens, pars compacta, VTA
Opioids
endogenous - dynorphins, enkephalins, endorphins, endomorphins
Opioid Rs:
-delta - analgesia, antidepressant, dependence
-kappa - spinal anesthesia (agonists prevent KAPPA KRUNCHy SPINE) , sedation, miosis, inhibit ADH
-mu: supraspinal analgesia, dependence (mu1); resp depression, miosis, euphoria, decrease GI motility, dependence (mu2)
-ORL/orphanin (nociceptin R) - anxiety, depression, appetite, tolerate to mu agonists
overdose - Tx IV naloxone
Opioid withdrawal - normal DTRs
amphetamine MOA
amphetamine - increase DA+NE and prevent reuptake DA+NE
cocaine - prevents presynaptic DA uptake - inhibits NET and DAT - NE and DA transporter (hot cocoa in left corner = presyn)
Reserpine, tetrabenazine - inhibit VMAT
EtOH
Intoxication-Confusion, somnolence, hypotension, tachycardia -> Tx Thiamine
-glucose may increase high metabolic demand and precipitate Wernicke’s (ophthalmoplegia, nystagmus)
-hemorrhagic mammillary bodies
Chronic Wernicke’s = Korsakoff - anterograde amnesia
petechial hemorrhages - mamillary, hypothalamus, medial thalami, periacqueductal gray (not caudate)
EtOH-inhibits glutamate excitation->addictive CNS depressant
Seizures: 6-48 hrs
delirium tremens - 48-96 hrs
EtOH, benzo withdrawal - increased DTRs
nicotine
caffeine
nicotine: agonist at nicotinic ACh R
caffeine: adenosine antagonist (prevents lying down in A DEN)
hallucinogens
5-HT, agonist and antagonist
B12 deficiency+ mimics
B12 deficiency - no cofactor to convert homocysteine to methionine ->no methylation myeline basic protein-> abnormal myelin structure ->neuronal dysfxn
-MMA + homocysteine elevated
-subacute combined b/c peripheral neuropathy + myelopathy
Copper deficiency - overdose of Zinc - subacute combined degeneration - spastic paraplegia, large fiber neuropathy, pancytopenia
-Zinc increases metallothionein ->binds copper, impairs absorption
Vitamin E deficiency - spinocerebellar ataxia~Friedrich’s, dysarthria, areflexia, extensor toes
-abetalipoproteinemia (Bassen-Kornweig) - mutation TG transfer protein->no apolipo B
-acanthocytosis
thiamine deficiency
dry beriberi-peripheral neuropathy-axonal sensorimotor
-no extensor plantar responses
-causes Leigh syndrome subacute necrotizing encephalomyelopathy
-decreased erythrocyte transketolase-> measure before+after thiamine pyrophosphate ; if increase 25% = thiamine deficiency
Poisoning
-Arsenic - garlic breath; AIDP; chronic ~GBS - distal to proximal sense loss + weak; rash palms/soles; MEEs lines on nails
-source: distilling moonshine, mining, well water, decorative glass
-KUB - GI radiopaque material
-acute Tx: chelation
(dimercaprol, DMSA/meso2,3 dimercaptosuccinic); charcoal, cardiac monitor
-test hair + nails for chronic
-Cyanide - almonds; cherry red skin (high venous oxyhemoglobin); abnormal taste; pulmonary edema
-competes with O2 to bind ferric ion- no electron transport chain ; increases glutamate
-industrial fires, seeds/pits of fruits; from sodium nitroprusside (NO+cyanide)
Tx: sodium thiosulfate, hydroxycobalamin (binds cyanide)
-Mercury - inflamed gums; ataxia, tremor; anxiety, irritable, depression, fatigue
Tx: chelation therapy-
-CO - cherry red skin - globus pallidus necrosis
-forms carboxyhemoglobin; high venous oxyhemoglobin; O2 can’t be released
Tx: 100% O2
-Lead - ankle+foot drop + encephalopathy (extensors weaker than flexors); anorexia; bluish gums
-increases protoporphyrins in RBC
-basophilic stippling/microcytic anemia
Tx: remove source +/- chelation
-Manganese - parkinsonian ; psychosis (manganese madness)
-high T1 in globus pallidus
Tx: chelation
-Thallium - (Thaler hair loss, pain) -alopecia, painful neuropathy (+ANS); 2-4 wks after ingestion
-Methanol - blindness, optic nerve+putamen necrosis
-forms formate -> retinal injury
-Ethylene glycol (calcium stones)
Tx: FOMEpizole—inhibits alcohol dehydrogenase and is an antidote For Overdoses of Methanol or Ethylene glycol.
-Hexacarbon - glue sniffer - hallucinogens, peripheral neuropathy
organophosphate poisoning
AChE inhibitors-> increase ACh
Tx: atropine - competes with Ach at muscarinic R
-does not bind nicotinic R- does not treat neuromuscular dysfxn
pralidoxime - cholinesterase reactivating - activates muscarinic + nicotinic R
NO gastric lavage b/c increase secretions
Botulism
binds synaptotagmin II R on presynaptic cholinergic synapses -> heavy chain binds, light chain translocates into cell ->cleaves SNAP 25 (Botox A, E, C)-> no ACh released
Sx: multiple cranial neuropathies, pupillary dilation, descending weakness, constipation
Chemo side effects
Peripheral neuropathy most common
Cytarabine - cerebellar Sx; aspetic meningitis
(liposomal cytarabine)
Methotrexate - aseptic meningitis (intrathecal), leukoencephalopathy (high dose) - confusion, spastic quadriparesis
Vincristine, cisplatin - peripheral neuropathy
5-FU-pancerebllar syndrome
Rituximab - PML; JC virus
