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Isoniazid (INH) Aṣeju ati Iro Morel (Gyromitra) Awọn Imulu olu: Vitamin B6 Antidote

Awọn nọmba pajawiri yato nipasẹ orilẹ-ede. Oju-iwe yii nlo 911, nọmba fun Amẹrika ati Kanada. Ọpọlọpọ awọn orilẹ-ede miiran lo 112, 999, tabi nọmba miiran. Wa nọmba fun orilẹ-ede rẹ.

Gbigbe iwọn apọju ti isoniazid (INH), oogun ikọ-igun igun kan ti a rii ni awọn miliọnu awọn idile ni agbaye, tabi jijẹ ti a ko pese sile ** eke morel olu (Gyromitra esculenta, Gyromitra gigas, tabi Gyromitra ambigua)** ti nfa ọkan ninu awọn oogun ipaniyan ipanilara pupọ julọ ati ni iyara. Laarin ** 30 si 90 iṣẹju *** ti iwọn apọju isoniazid nla (tabi ** 5 si wakati 12 *** lẹhin jijẹ ounjẹ olu eke morel eke ti o jẹ hydrolyzes ninu ikun sinu ** monomethylhydrazine [MMH]), alaisan naa ndagba tingling lojiji lojiji, rudurudu, eebi, ọrọ sisọ, ati ipo ibẹjadi ti ko ni agbara. epilepticus *** ti o tẹle pẹlu ** lactic acidosis giga-anion-gap giga (pH ẹjẹ nigbagbogbo n lọ silẹ ni isalẹ 6.8)** ati hyperthermic coma. Ko dabi warapa lasan, awọn ikọlu wọnyi jẹ idi nipasẹ isunmi biokemika nla ti ** gamma-aminobutyric acid (GABA), neurotransmitter inhibitory akọkọ ti ọpọlọ, nitori awọn hydrazines run ati aiṣiṣẹ pyridoxal-5'-phosphate (PLP, fọọmu ti nṣiṣe lọwọ ti Vitamin B6). Nitoripe awọn anticonvulsants laini akọkọ boṣewa bi lorazepam, diazepam, tabi midazolam ṣiṣẹ nikan nipa mimu GABA ti o wa tẹlẹ pọ si ni GABA-A olugba, ati ** phenytoin (Dilantin) jẹ ailagbara patapata ati agbara cardiotoxic ** ni awọn ikọlu majele ti o fa majele, alaisan ti o ni isoniazid ti o lagbara tabi majele gyromitrin yoo tẹsiwaju mimu si iku ayafi ti awọn oludahun pajawiri fi sii ** Pyridoxine inu iṣan (Vitamin B6) lori * giramu-for-gram ni ẹgbẹ 5 gr[kẹsẹkẹsẹ] benzodiazepines.

Ti ẹnikan ba ti mu awọn oogun ikọ-ọpọlọ pupọ, ti farahan si ile-iṣẹ tabi aaye afẹfẹ hydrazine (N2H4) rocket propellant, tabi idagbasoke eebi, dizziness, tabi isan twitching lẹhin foraging orisun omi morel-bi olu, pe agbegbe rẹ nọmba pajawiri (911 ni United States ati Canada, 112 kọja awọn European Union, 999 ni United Kingdom) nipasẹ wa pajawiri awọn nọmba liana lẹsẹkẹsẹ, ki o si alagbawo ipo warapa ati awọn ijagba pipẹ, igbo olu foraging ati loro ọgbin jijẹ, ati majele akọkọ iranlowo.

Ṣe eyi ni bayi

  1. ** Pe 911/112/999 ati Iṣakoso majele lẹsẹkẹsẹ ki o kede “Isoniazid / Hydrazine Overdose: Nilo IV Pyridoxine (Vitamin B6)”**: Maṣe duro fun awọn aami aisan lati bẹrẹ. Sọ fun olupin pajawiri ati Iṣakoso majele (1-800-222-1222 ni AMẸRIKA) orukọ gangan ti oogun naa (Isoniazid, INH, Rifamate, tabi Rifater) tabi olu (False Morel / * Gyromitra ) ati isunmọ nọmba ti awọn tabulẹti gbe. Pupọ awọn ambulances ko gbe iwọn-giga iṣan ẹjẹ Pyridoxine (5 grams, ati ọpọlọpọ awọn apa pajawiri ile-iwosan ti o kere ju 1 si 2 giramu ninu awọn ọkọ ayọkẹlẹ jamba wọn, nitorinaa titaniji ile-iwosan gbigba ni kutukutu gba ile elegbogi lati fa gbogbo vial ti IV Pyridoxine (tabi mura slurry tẹẹrẹ-tabulẹti titẹ sii) ṣaaju ki alaisan to de.
  2. Ma ṣe gbe alaisan lọ si ile-iwosan funrarẹ ***: Aṣeyọri isoniazid nla kọja sinu ọpọlọ ni iyara ati nfa airotẹlẹ, awọn ijagba tonic-clonic gbogbogbo iwa-ipa laarin ** 30 si 60 iṣẹju ** ti jijẹ laisi ikilọ. Ti alaisan ba bẹrẹ gbigba ni ijoko ero ti ọkọ ayọkẹlẹ aladani, o ko le daabobo ọna atẹgun wọn tabi tu wọn si. Nigbagbogbo lo ohun To ti ni ilọsiwaju Life Support (ALS) ọkọ alaisan.
  3. ** MAA ṢE fa eebi tabi fun ounjẹ, omi, tabi awọn afikun lori-counter-counter si alaisan alaisan kan ***: Nitori ipadanu airotẹlẹ ti imọ-jinlẹ ati awọn ijagba lemọlemọ le kọlu ni eyikeyi akoko, ohunkohun ninu ikun ṣẹda eewu ajalu ti ** ifojusọna ẹdọforo ** lakoko ijagba.
  4. **Ti ijagba ba bẹrẹ, daabo bo ori, yi alaisan pada si ẹgbẹ wọn, ki o si fi akoko gbigbọn naa kuro ***: Ko awọn nkan ti o ni lile tabi ti o mu kuro, gbe ori rẹ pẹlu jaketi ti a ṣe pọ, tu aṣọ kola ti o nipọn, ki o si yi eniyan lọ si ipo imularada ti ita ** ni kete ti ẹrẹkẹ ati lile ẹsẹ gba laaye lati jẹ itọ, ẹjẹ, tabi eebi ti ẹnu. Maṣe fi awọn ika ọwọ, awọn ṣibi, awọn apamọwọ, tabi awọn tabulẹti Vitamin B6 ti a fọ ​​si ẹnu ẹni ti o mu tabi ti o sun.
  5. ** Fipamọ gbogbo awọn igo egbogi, awọn idii roro, tabi aise / jinna awọn iyokuro olu ninu apo iwe kan ***: Ka iye awọn tabulẹti ti o padanu lati igo oogun (awọn tabulẹti INH agbalagba ti o jẹ deede jẹ ** 300 mg *** tabi ** 100 mg ***) nitorina awọn oniwosan pajawiri le ṣe iṣiro gangan **gram-for-gram Pyridoxine doses antidote.1 gram of IV Pyridoxine for every 1 gram of Isoniazid ingested, titi di 5 grams ni ibẹrẹ). Ti wọn ba jẹ awọn olu, gbe eyikeyi awọn eso igi ti ko tii, awọn fila, tabi awọn ayẹwo eebi sinu apo iwe ti o lemi (kii ṣe ṣiṣu ti a fi edidi, eyiti o jẹ olu rots) fun idanimọ mycological.
  6. **Kilọ fun ẹgbẹ yara pajawiri lati yago fun Phonytoin (Dilantin) ati lati darapo Benzodiazepines pẹlu Pyridoxine *: Awọn oogun warapa deede bii ** phenytoin tabi fosphenytoin ** ṣiṣẹ lori awọn ikanni iṣuu soda foliteji-gated ati kuna patapata ni awọn ijagba GABA-idinku lakoko ti o buru si awọn idaduro idari ọkan ọkan. Apapọ fifipamọ igbesi aye pataki jẹ ** Pyridoxine inu iṣọn (Vitamin B6) (lati mu pada sipo GABA) pẹlu ** Benzodiazepines inu iṣọn-ẹjẹ (Lorazepam, Diazepam, tabi Midazolam) *** tabi ** Phenobarbital / Propofol *** (eyiti o ṣe taara lori GABA-A ikanni kiloraidi olugba).

Kini idi ti Awọn oogun Imudaniloju Didara kuna Laisi Pyridoxine inu iṣan (Vitamin B6)

Ninu ọpọlọ eniyan, neurotransmitter calming ** GABA (gamma-aminobutyric acid)** jẹ iṣelọpọ lati excitatory glutamate nipasẹ enzymu ** Glutamic Acid Decarboxylase (GAD)**, eyiti o nilo lọwọ **Vitamin B6 (Pyridoxal-5'-Phosphate, tabi PLP) agbofinro. - ** Isoniazid (INH) *, ** Monomethylhydrazine (MMH lati * Gyromitra * eke morels), ati Hydrazine ile-iṣẹ ** pakute ati run PLP ati dojuti ** pyridoxine phosphokinase **, tiipa iṣelọpọ GABA tuntun laarin awọn iṣẹju 30 lakoko ti o nlọ glutamate excitory lai ṣe abojuto. - Nitori benzodiazepines (lorazepam, midazolam, diazepam)** nikan pọ si igbohunsafẹfẹ ti ṣiṣi ikanni chloride nigbati GABA endogenous ti wa tẹlẹ ninu synapse *, awọn benzodiazepines nikan padanu imunadoko ni kete ti awọn ile itaja GABA synaptic ti rẹwẹsi. - Pyridoxine inu iṣọn-ẹjẹ1 gram IV per 1 gram of INH ingested, tabi 5 grams IV empirically ti iwọn lilo naa ko ba jẹ aimọ) tun bẹrẹ iṣelọpọ GABA laarin awọn iṣẹju ati ṣiṣe ni irẹpọ pẹlu awọn benzodiazepines lati fopin si bibẹẹkọ ipo warapa apaniyan ati yiyipada lactic acidosis.

Igi ipinnu: Triaging isoniazid, hydrazine, ati eke morel (Gyromitra) majele

flowchart TD
    Start["Ifihan Hydrazine-kilasi ti a fura si: Isoniazid (INH) Awọn oogun TB, Eke Morel (Gyromitra) Olu, tabi Rocket/Hydrazine ile-iṣẹ"] --> AssessSource{"Ṣe idanimọ Orisun Majele Kan pato ati Ago"}

    AssessSource -->|1. Acute Isoniazid (INH) Overdose (> 15-20 mg/kg or >= 1.5-3 Grams in Adult)| INH_Acute["Ibẹrẹ iyara (30 si awọn iṣẹju 90): ríru, Ọrọ sisọ, Ataxia, Tachycardia -> Ipo Refractory Explosive Epilepticus, Lactic Acidosis ti o lagbara (pH <6.8), Hyperthermia, Coma"]
    AssessSource -->|2. False Morel Mushroom (Gyromitra esculenta / gigas) Ingestion or Cooking Fume Inhalation| Gyromitra["Idaduro Ibẹrẹ (Awọn wakati 5 si 12): Gyromitrin Hydrolyzes ni Ìyọnu sinu Monomethylhydrazine (MMH) -> Olomi / Ẹjẹ gbuuru, Vomiting, Vertigo -> Awọn ikọlu, Methemoglobinemia, Negirosisi Hepatic & Hemolysis (Awọn ọjọ 2-5)"]
    AssessSource -->|3. Industrial / Aerospace Hydrazine or Hydrazide Exposure (Dermal, Inhalation, Oral)| HydrazineInd["Caustic Mucosal/Irun Awọ, Edema Ẹdọforo, Pelu Irẹwẹsi PLP Systemic, Awọn ikọlu, Methemoglobinemia, ati Ikuna Hepatorenal"]

    INH_Acute --> SeizureCheck{"Njẹ Alaisan naa Ngba lọwọlọwọ, Comatose, tabi Hemodynamically Aiduro?"}
    Gyromitra --> SeizureCheck
    HydrazineInd --> SeizureCheck

    SeizureCheck -->|YES: Active Status Epilepticus or Coma| ImmediateRescue["1. Airway / Oxygen / Intubation + IV Benzodiazepine (Lorazepam 4 mg IV tabi Midazolam 10 mg IM / IV) 2. IMMEDIATE IV PYRIDOXINE (VITAMIN B6): Iwọn INH ti a mọ: 1 Gram IV fun 1 Gram INH Ingested (Ti o to 5-1 g0 min); Iwọn aimọ: 5 Grams IV Empirically (Paediatric: 70 mg / kg IV, Max 5 g); Olu Gyromitra: 25 mg/kg IV Pyridoxine lori awọn iṣẹju 15-30 (Tun soke si 15-20 g fun ọjọ kan)"]

    SeizureCheck -->|NO: Awake, Asymptomatic, Early Presentation (< 1 Hour Post-INH Ingestion)| EarlyPreemptive["1. Ṣeto Wiwọle nla-Bore IV ati Abojuto Ilọsiwaju 2. Ṣakoso eedu ti a mu ṣiṣẹ (1 g/kg) NIKAN ti Ji, Itaniji, ati <Ijẹji lẹhin-wakati 1 (Pẹlu Ṣetan Ọkọ ofurufu) 3. Prophylactic Gram-for-Gram IV Pyridoxine (tabi NG Crushed Ibẹrẹ ti o ba bẹrẹ)"]

    ImmediateRescue --> RefractoryCheck{"Njẹ Awọn ikọlu duro ni iṣẹju 15-20 Lẹhin iwọn lilo Pyridoxine akọkọ + Benzodiazepine bi?"}

    RefractoryCheck -->|YES: Ongoing Seizures| EscalateICU["1. Tun ṣe IV Pyridoxine (Miran 5 Grams IV ni Awọn agbalagba / 70 mg / kg ni Awọn ọmọde) 2. Ilọsiwaju si Tari awọn olutọpa ikanni GABA-A: IV Phenobarbital (15-20 mg / kg) tabi Propofol Infusion (AVOID Phenytoin) 1 g INH)"]
    RefractoryCheck -->|NO: Seizures Terminated| PostIctalCare["Atẹle ni ICU: Lactic Acidosis Ṣe ipinnu ni kiakia ni kete ti Awọn ikọlu Duro (Yẹra fun iṣuu soda bicarbonate ti o pọju ayafi pH <7.1); Tọpinpin CPK/Rhabdomyolysis, AST/ALT Hepatotoxicity, ati Methemoglobin (Fun Methylene Blue ti MetHb> 20-30% ni Gyromitra)"]

Pathophysiology: Bawo ni Hydrazines Ṣe Pa Vitamin B6 run ati Idilọwọ Ọpọlọ Paralyze

1. Iwontunws.funfun Glutamate-to-GABA ati Hydrazine Double Hit

Iduroṣinṣin itanna deede ni kotesi cerebral eniyan da lori lilọsiwaju, millisecond-by-millisecond tug-of-ogun laarin ** L-glutamate ** (aifọkanbalẹ excitatory akọkọ ti o yọkuro awọn neurons si awọn agbara iṣe ina) ati ** GABA (gamma-aminobutyric acid) (gamma-aminobutyric acid) GABA-A awọn ikanni kiloraidi lati hyperpolarize ati awọn neuronu idakẹjẹ).

  1. *Bawo ni Ọpọlọ Ṣe Ṣepọ GABA : Awọn Neurons ko le fa GABA lati inu ẹjẹ; wọn gbọdọ ṣelọpọ taara ni inu awọn ebute nafu ara lati L-glutamate nipa lilo enzymu-diwọn oṣuwọn ** L-glutamic acid decarboxylase (GAD). GAD jẹ aiṣiṣẹ patapata funrararẹ - o nilo ** Pyridoxal-5'-Phosphate (PLP), fọọmu tnṣiṣe lọwọ phosphorylateti **Vitamin B6 (pyridoxine) **, ni wiwọ ni wiwọ si aaye ti nṣiṣe lọwọ bi cofactorNibayi, enzymu ti fọ GABA ( GABA transaminase) ko ni itara pupọ si awọn silẹ PLP nla.
  2. ** Hydrazine naa “Ikọlu Meji” lori Vitamin B6 ti nṣiṣe lọwọ **: Mejeeji ** isoniazid *** (isonicotinic acid hydrazide, eyiti o ṣe idasilẹ awọn metabolites hydrazine ọfẹ) ati ** monomethylhydrazine (MMH) ** (ti a tu silẹ nigbati ikun acid hydrolyzes ** gyromitrin ** lati awọn olu morel eke) ni ifaseyin pupọ ** hydrazine (-NH-NH2) ẹgbẹ iṣẹ *** ti o parẹ PLP neuronal ti nṣiṣe lọwọ nipasẹ awọn ọna igbakana meji:
  3. ** Itọpa Kemikali Taara (Idasile Hydrazone) *: Isoniazid ati MMH sopọ taara si ẹgbẹ aldehyde ti nṣiṣe lọwọ ** pyridoxal-5'-phosphate (PLP) ati pyridoxal ninu ẹjẹ ati ọpọlọ lati ṣe aiṣiṣẹ **isonicotinyl-hydrazone *** tabi ** awọn ile-iṣẹ methylhydrazone ni iyara.
  4. ** Idilọwọ ti o lagbara ti Pyridoxine Phosphokinase ***: Paapaa diẹ sii ni itara, awọn ile-iṣẹ hydrazone tuntun ti a ṣẹda ni idije dojuti ** pyridoxine phosphokinase **, enzymu ti o nilo lati fosphorylate pyridoxine ti ijẹunjẹ ti nṣiṣe lọwọ **PLP *** - pẹlu isunmọ ** 1000 si awọn akoko adayeba ti Vitamin 1.
  5. ** Kini idi ti Ikun-omi ara pẹlu Awọn iwọn Giramu ti Awọn iṣẹ Pyridoxine ***: Nitori idinamọ hydrazone ti pyridoxine phosphokinase jẹ ** ifigagbaga , ṣiṣe abojuto nla, supraphysiological ** awọn iwọn ipele giramu ti Pyridoxine iṣan inu iṣan (ẹgbẹẹgbẹrun awọn akoko ti o ga ju ounjẹ ojoojumọ lọ) 1.3 to 2 mg/day) bori blockade enzymatic nipasẹ iṣẹ ti o pọju, ti n ṣe atunṣe ni kiakia **PLP ***, tun bẹrẹ iṣẹ ṣiṣe enzyme **GAD **, atunṣe synapti GABA laarin awọn iṣẹju, ati didaduro ipo idapada warapa.

2. Kini idi ti Isoniazid Fa Ọkan ninu Awọn Acidos Lactic Lactic Pupọ julọ ni Oogun

Awọn alaisan ti o de ile-iṣẹ pajawiri lẹhin iwọn apọju isoniazid nigbagbogbo ṣafihan pH ẹjẹ iṣọn laarin 6.70 ati 7.05, omi ara bicarbonate kan (HCO3-) ni isalẹ 5 mEq/L, ati omi ara ** lactate loke 15 to 25 mmol/L** - ṣiṣe nipasẹ awọn ọna ṣiṣe amuṣiṣẹpọ meji:

  • ** Ibalẹ iṣan Anaerobic ti o tobi ***: Itẹsiwaju tonic-clonic ipo warapa n ṣe awọn iwọn nla ti lactic acid lati hypoxia isan iṣan.
  • ** Idilọwọ taara ti Iyipada Lactate Hepatic (NAD+ Blockade): Isoniazid ṣe idiwọ taara ** nicotinamide adenine dinucleotide (NAD+* -igbẹkẹle ** lactate dehydrogenase (LDH)** ati awọn ipa ọna mitochondrial Complex I, idilọwọ ẹdọ lati yi iyipada lactate pada si pyruvate (iwọn Cori) titi ti awọn ijagba yoo fi duro pẹlu Pyridoxine.

Ifiwera Titunto: Isoniazid (INH) Aṣeju iwọn la. Morel eke (* Gyromitra *) Olu la.

isẹgun & Biokemika Ẹya Isoniazid nla (INH) Oogun Aṣeju Morel eke (* Gyromitra esculenta / gigas / ambigua *) Majele Morel Njẹ otitọ (* Morchella esculenta / elata *)
Majele & Kemika idanimọ Isoniazid (Isonicotinic Acid Hydrazide); wàláà ti 100 mg tabi 300 mg, omi ṣuga oyinbo (50 mg/5 mL), tabi awọn oogun ikọ-fèé apapọ (Rifamate [INH + Rifampin], Rifater [INH + Rifampin + Pyrazinamide]). Gyromitrin (acetaldehyde N-methyl-N-formylhydrazone), eyi ti hydrolyzes ni inu acid (tabi nya nigba farabale) sinu iyipada, neurotoxic ** Monomethylhydrazine (MMH)** (CH3-NH-NH2). Ko si nigba ti jinna daradara (ni awọn hemolysins ti ooru-labile kekere ninu / GI irritants ti o fa eebi ti o ba jẹ aise, ** rara *** gyromitrin/MMH).
** Awọn iloro iwọn lilo majele *** - > 15 to 20 mg/kg (-1 to 1.5 g ninu agbalagba): ataxia, dizziness, paresthesias.
- >= 30 to 40 mg/kg (>= 2 to 3 g ninu agbalagba; diẹ bi awọn tabulẹti 7 si 10 ti 300 mg **): ** eewu giga ti awọn ijagba gbogbogbo ***.
- >= 80 to 150 mg/kg (>= 6 to 10 g): ** ipo iku ni iyara warapa, coma, ati imuni ọkan ọkan *** laisi Pyridoxine.		 Jije aise, ti ko jinna, tabi paapaa parboi * Gyromitra esculenta * (nibiti a ti jẹ omi farabale tabi ti a ti fa simi); Iwọn majele ti gyromitrin jẹ **10 to 30 mg/kg ninu awọn ọmọde *** ati 20 to 50 mg/kg ninu awon agba(-0.2 to 0.6 kg ti olu tuntun). Njẹ nikan nigbati o ba jinna daradara; ma je aise.
** Idanimọ ti ara / Awọn itọka Ẹkọ-ara** White gba wọle wàláà ontẹ pẹlu INH 300 tabi 100, tabi awọn capsules pupa/osan didan nigba ti a ba ni idapo pẹlu Rifampin (eyiti o yi ito, lagun, ati omije didan ** pupa-osan**). ** Fila ***: Alaiṣedeede, bii ọpọlọ, riru, lobed, apẹrẹ gàárì, pupa-pupa si chestnut-brown.
Inu inu nigbati a ba ge wẹwẹ ni inaro ***: **Iyẹwu, ti a fi pẹlu pith funfun ti owu funfun / awọn agbo (KO ṣofo) ***; fila so ni ayika tabi pẹlú awọn stalk kuku ju laisiyonu ni mimọ.		 ** Fila *: Iyatọ ** hihan afara oyin pẹlu awọn ọfin deede ati awọn oke.
 Inu inu nigba ti ge wẹwẹ ni inaro lati sample si ipilẹ ***: ** 100% ṣofo patapata lati oke ti fila si isalẹ ti yio ***, pẹlu eti isalẹ ti fila ti a so taara si igi.
** Ferese Ibẹrẹ Aisan** ** Iyara (30 si 90 iṣẹju, tente oke 1 si 2 wakati)**: ríru, ìgbagbogbo, ọrọ sisọ, tingling perioral, dizziness, tachycardia, mydriasis, ati idaduro ito -> ** ipo ibẹjadi warapa ***. Biphasic ti o da duro (wakati 5 si 12 lẹhin ounjẹ, tabi wakati 2 si 8 lẹhin fifa simi sise nya simi): ikun ti nbọ, omi nla / gbuuru ẹjẹ, eebi ti ko le fa, orififo ikọlu, vertigo -> **delirium, tremors, ati awọn ijagba gbogbogbo ***; atẹle ni ** Ọjọ 2 si 5 ** nipasẹ ** negirosisi ẹdọ ẹdọ, jaundice, hemolysis, ati methemoglobinemia ***. Ti a ba jẹun ni aise / ti ko jinna: ríru ti ara ẹni, ìgbagbogbo, ati inudidun inu laarin wakati 1 si 5 ** (ko si negirosisi ẹdọ tabi iparun PLP).
**Classic Clinical Triad *** **Iwọn INH Aṣeju iwọn Mẹta *:
1. Benzodiazepine-refractory Ipo Epilepticus
2. ** Àìdá High-Anion-Gap Lactic Acidosis (pH < 6.9)
3. ** Jin Coma ** (pẹlu hyperthermia ati rhabdomyolysis).		 ** Gyromitrin / MMH Triad *:
1. ** Idaduro Gastroenteritis (6-12h)
2. PLP-Iparun Ipasẹ & Ataxia
3. ** Idaduro Hepatotoxicity + Oxidative Hemolysis / Methemoglobinemia **.		 Gastroenteritis kekere ti o ba jẹ abẹ; awọn fifa IV atilẹyin ati awọn antiemetics nikan.
**Aṣogun kan pato & Ilana iwọn lilo *** Pyridoxine inu iṣan (Vitamin B6):
- ** Iwọn ti a mọ **: ** 1 giramu IV Pyridoxine fun gram 1 INH ingested *** (to **5 giramu ** bolus ibẹrẹ).
- ** Iwọn aimọ ***: ** 5 giramu IV *** (Awọn ọmọde: ** 70 mg / kg IV *, max 5 g) ju iṣẹju 5 si 10 lọ; tun ṣe ni iṣẹju 15-20 ti awọn ikọlu ba tẹsiwaju.
Plus ** IV Benzodiazepine (Lorazepam/Midazolam).		 Pyridoxine inu iṣan (Vitamin B6):
- ** 25 mg / kg IV ti a fi sii ju iṣẹju 15 si 30 (le tun fun awọn ami iṣan ti nlọ lọwọ titi di ** 15 si 20 giramu / ọjọ , ibojuwo fun neuropathy ifarako ni awọn abere ikojọpọ nla).
- ** IV Benzodiazepines *** fun ijagba.
- ** Methylene Blue (1-2 mg/kg IV* ti o ba jẹ aami aisan ** Methemoglobinemia (> 20-30%).
- ** N-Acetylcysteine ​​(NAC) nigbagbogbo lo fun hepatotoxicity nla.		 Ko si oogun oogun ti a beere; boṣewa roba tabi IV rehydration.

Ile-iwosan Igbesẹ-Igbese ati Ilana Antidote EMS fun Isoniazid Overdose

1. Iṣiro ati Ṣiṣakoṣo Pyridoxine inu iṣọn-ẹjẹ (Vitamin B6)

Nitori awọn benzodiazepines boṣewa ko le ṣiṣẹ ni kete ti GABA neuronal ti dinku, ** Pyridoxine (Vitamin B6)** jẹ oogun apakokoro igbala-aye ati pe o gbọdọ fun ni ** ni igbakanna pẹlu benzodiazepine iṣọn-ẹjẹ ***:

  1. **Nigbati Iye Gangan ti Isoniazid Ingested jẹ mimọ ***:
  2. Abojuto ** Pyridoxine inu iṣọn-ẹjẹ lori ipilẹ 1:1 giramu-fun-giramu** (1 gram of IV Pyridoxine for every 1 gram of Isoniazid ingested).
  3. Apeere: Ti agbalagba ba gbe ogun mì 300 mg awọn tabulẹti INH (6,000 mg = 6 grams), fun 5 giramu IV Pyridoxine lẹsẹkẹsẹ fun iṣẹju marun si mẹwa, ti o ku ** gram 1 ti o tẹle ni iṣẹju 15 si 30 to nbọ.
  4. **Nigbati Iye Isoniazid Ingested jẹ Aimọ ***:
  5. ** Agbalagba ***: Abojuto 5 giramu (5,000 miligiramu) ti Pyridoxine inu iṣọn-ẹjẹ ti iṣan.
  6. ** Awọn ọmọde ati Awọn ọmọ-ọwọ *: Abojuto ** 70 mg/kg ti Pyridoxine inu iṣọn-ẹjẹ (titi de iwọn lilo ibẹrẹ ti o pọju ti 5 giramu).
  7. ** Oṣuwọn Idapo Da lori Ipo ijagba ***:
  8. ** Ipo ti nṣiṣe lọwọ Epilepticus ***: Fi sii 5 gram (tabi 70 mg/kg) Iwọn Pyridoxine ti fomi po sinu 50 mL ti 5% Dextrose tabi Saline deede ni oṣuwọn iyara ti 0.5 si 1 giramu fun iṣẹju kan (ti o pari bolus 5-gram lori iṣẹju 5 si 10) titi awọn ijagba yoo duro, lẹhinna fun eyikeyi iwọntunwọnsi giramu-for-gram iṣiro to ku lori 30 si 60 iṣẹju.
  9. ** Asymptomatic tabi Pre-Seizure Overdose ***: Fi giramu-fun-gram Pyridoxine iwọn lilo ju **15 si 30 iṣẹju ** lati ṣe idiwọ ikọlu lati bẹrẹ nigbagbogbo.
  10. ** Awọn ijagba ti o tẹsiwaju tabi Loorekoore *: Nitori pe idaji-aye pilasima ti INH awọn sakani lati ** 1 si 4 wakati ** (da lori boya alaisan jẹ jiini kan “acetylator fast” tabi **“ acetylator ti o lọra” ** nipasẹ ẹdọ ẹdọ * N-acetyltransferase-2 [NAT2]*, ati gigun si awọn wakati 5 + ti o ba tẹsiwaju lati ṣe atunṣe **5+ Ni iṣẹju 20 lẹhin iwọn lilo akọkọ, ** tun 5-gram (tabi 70 mg / kg) IV iwọn lilo Pyridoxine ** lẹgbẹẹ igbega **IV Lorazepam (0.1 mg/kg), Midazolam, Phenobarbital (15 to 20 mg/kg IV), tabi Propofol ***.

2. Iṣẹ-iṣẹ pajawiri: Kini Ti Ile-iwosan ba Jade Ninu Pyridoxine inu iṣọn-ẹjẹ?

Nikan kan 5-gram iwọn lilo antidote agba nilo ** aadọta 100 mg/mL lẹgbẹrun ** ti Pyridoxine injectable - diẹ sii ju pupọ julọ awọn yara pajawiri ile-iwosan agbegbe ti o wa lori selifu. Ti IV Pyridoxine ko ba si tabi ko to:

  • ** Oral / Nasogastric Crushed Pyridoxine Tablet Slurry *: Lori-counter tabi ile elegbogi ile iwosan ** ẹnu Vitamin B6 (Pyridoxine Hydrochloride) awọn tabulẹti (50 mg, 100 mg, tabi 250 mg Awọn tabulẹti) ti wa ni gbigba ni kiakia lati inu ati duodenum laarin ** 15 si 30 iṣẹju **.
  • ** Bi o ṣe le Ṣakoso Ni aabo ***: Ninu gbigba tabi alaisan ti o yami, ** ṣe aabo ọna atẹgun pẹlu intubation endotracheal akọkọ **, kọja nasogastric (NG) tabi tube orogastric (OG), fọ iwọn giramu giramu ti a beere fun awọn tabulẹti Pyridoxine (fun apẹẹrẹ, ogun) 250 mg wàláà = 5 grams), tu wọn sinu omi tabi iyọ bi slurry, ki o si gbin taara nipasẹ tube NG / OG lakoko ti o nṣakoso awọn gbigbọn fun igba diẹ pẹlu iwọn-giga ** IV Benzodiazepines, Propofol, tabi Phenobarbital ** titi ti Pyridoxine ti nwọle ti nwọle.

Ewu toje ti Akopọ Pyridoxine Loju iwọn (> 20 si 30+ Giramu)

Lakoko ti 5 si 15 giramu ti IV Pyridoxine jẹ ailewu patapata ati pe o jẹ dandan lati ṣafipamọ igbesi aye kan ni iwọn apọju INH ti o lagbara, awọn abere akojo lọpọlọpọ (** ga ju 1 to 2 grams/kg tabi 20 to 50+ grams lapapọ ***, paapaa nigba ti a ba fun ni lainidi fun awọn ifihan kekere ti kii-INH tabi tun ṣe pupọju ni * Gyromitra * majele olu) le fa aiṣan, ti o le duro ** dorsal root ganglion sensory neuropathy *** - nlọ alaisan pẹlu isonu nla ti proprioception (ailagbara lati lero ibiti awọn ẹsẹ wọn wa ni aaye), ataxia ifarako, ati numbness. Ṣe deede iwọn lilo Pyridoxine nigbagbogbo si iwuwo ile-iwosan ati iwuwo giramu INH ti a mọ ni ijumọsọrọ pẹlu onimọ-jinlẹ iṣoogun kan.

Dive Jin: Morel eke (* Gyromitra esculenta *) Majele olu ati Awọn eewu eefin Sise

Gbogbo orisun omi kọja Ariwa America, Scandinavia, Ila-oorun Yuroopu, ati agbegbe Awọn adagun Nla, awọn onisọpa ti n wa awọn ẹbun otitọ ** morels otitọ (* Morchella * eya)** ikore lairotẹlẹ tabi murasilẹ ni imomose ** morels eke (* Gyromitra esculenta *, * Gyromitra gigas , * Gyromitra fastigiata, tabi *Verpahem.

1. Idi ti Parboiling eke Morels le tun majele ti Cook ati Diner

  1. ** Iyipada Gyromitrin-si-MMH *: Alabapade Gyromitra esculenta ninu to to 0.1% to 0.3% gyromitrin (acetaldehyde N-methyl-N-formylhydrazone). Nigbati o ba jẹ tabi kikan ninu omi, gyromitrin gba ipele meji-igbesẹ hydrolysis - akọkọ yiyọ kuro ni ẹgbẹ formyl lati ṣẹda N-methyl-N-formylhydrazine (MFH), ati lẹhinna hydrolyzing sinu ** Monomethylhydrazine (MMH), gangan kanna iyipada kemikali ti a lo bi hypergolic bipropellant idana ni spacecraft thrugolic.
  2. ** Inhalation ti Sise Nya si ni Ibi idana ***: Nitori Monomethylhydrazine (MMH) ni o ni kan farabale ojuami ti 87.5 degrees Celsius (189.5 degrees Fahrenheit), ibile Northern/European ọna ti ** parboiling eke morels lemeji ati discarding awọn omi ** tu majele ti ** MMH oru taara sinu idana nya ***. Awọn ounjẹ ti o tẹra si ikoko ti awọn olu farabale Gyromitra laisi eefun eefi nigbagbogbo dagbasoke ni kikun ** majele MMH (vertigo, orififo, eebi, ati awọn ijagba) laarin awọn wakati 2 si 8 nikan lati ifasimu ategun ***, lai jẹ jijẹ olu kan ṣoṣo.
  3. ** Yiyọ majele ti ko pe ati Ipa Ipele Alapapọ *: Paapaa lẹhin parboiling leralera tabi gbigbe, gyromitrin iyokù wa ninu ẹran olu. Nitoripe MMH ni imurasilẹ dinku neuronal ati ẹdọ-ẹdọ PLP fun awọn ọjọ diẹ, idile ti o jẹ ounjẹ * Gyromitra * awọn ounjẹ ni Ọjọ 1 ati Ọjọ 2 pẹlu awọn aami aiṣan odo le lojiji sọdá pataki ** “Ilẹ-isunmọ PLP” ni Ọjọ 3 ati jiya awọn ijagba lojiji ati ikuna ẹdọ nla.

2. Iyatọ Hematologic ati Awọn ilolu Hepatic ti Gyromitra (Awọn ọjọ 2 si 5)

Ko dabi isoniazid elegbogi mimọ (nibiti hepatotoxicity ti jẹ ìwọnba si iwọntunwọnsi lẹhin imularada nla), Monomethylhydrazine (MMH) lati * Gyromitra * olu n ṣe ifaseyin ** methyl free radicals ** ati aapọn oxidative kọja awọn sẹẹli ẹjẹ pupa, hepatocytes ẹdọ, ati awọn tubules kidirin:

  • ** Methemoglobinemia ati Hemolysis Intravascular *: MMH oxidizes hemoglobin ferrous (Fe2+sinu ferric ** methemoglobin (Fe3+) (nfa ẹjẹ "chocolate-brown" ati cyanosis ti ko dahun si atẹgun) ati awọn okunfa **Heinz-body hemolytic anemia *, hemoglobinuria, ati ipalara kidinrin nla. Symptomatic methemoglobinemia (> 20% to 30%) ni itọju pẹlu Methylene Blue inu iṣọn-ẹjẹ (1 to 2 mg/kg IV over 5 minutes lẹhin ti o ṣe idajọ aipe G6PD.
  • ** Ẹdọjẹdọ Cytolytic ti o da duro *: Laarin ** 36 ati 96 wakati lẹhin mimu-inu, awọn transaminases ẹdọ-ẹdọ (AST ati ALT) ati bilirubin le lọ soke sinu ikuna ẹdọ fulminant nla, ti iṣakoso pẹlu ** N-Acetylcysteine ​​inu iṣọn-ẹjẹ (NAC)**, idena hypoglycemia, ati abojuto ICU asopo.

Bii o ṣe le Sọ Morel Otitọ kan (Morchella) lati ọdọ Morel Iro Apaniyan kan (* Gyromitra *) ni iṣẹju-aaya 5

Ge gbogbo olu naa ni mimọ ni idaji ni inaro lati ori ipari fila naa si isalẹ ti yio: - Morel tootọ (Morchella)**: Gbogbo olu - mejeeji fila-pitted oyin ati igi - jẹ ** ẹyọkan, iho ti o ṣofo patapata lati oke de isalẹ *, ala isalẹ ti fila naa ni a dapọ taara si igi. - ** Morel eke ( Gyromitra * tabi * Verpa)**: Fila naa dabi ** wrinkled, ti ṣe pọ ọpọlọ eniyan ** (lobes ati convolutions dipo ti awọn pits oyin), ati inu ti yio ati fila ti wa ni ** yara, ṣe pọ, tabi sitofudi pẹlu owu-bi funfun àsopọ *** (tabi, ni *Verpa cap bohemigs loore) nikan ti a so ni awọn hanners ti o wa ni oke bohemica. awọn igi). **Nigbati o ba ni iyemeji, sọ ọ jade.

Awọn nọmba pajawiri agbegbe ati awọn ilana ile-ibẹwẹ

Ekun / Orilẹ-ede Nọmba Ambulansi pajawiri National Poison Iṣakoso Helpline Awọn akọsilẹ Ilana isẹgun osise
Ilu Amẹrika ati Kanada *** 911 ** US : ** 1-800-222-1222 (Awọn ile-iṣẹ Majele ti Amẹrika) / Canada ***: ** 1-84POISON-X (1-844-764-7669) Awọn ile-iṣẹ majele ṣe ipoidojuko ikojọpọ ile elegbogi ile-iwosan lẹsẹkẹsẹ ti ** iwọn-giga IV Pyridoxine (5 grams Empiric tabi 1:1 giramu-fun-giramu)**; awọn nẹtiwọki antidote ile-iwosan agbegbe pin ọja Pyridoxine lakoko awọn iwọn apọju nla.
Apapọ ijọba gẹẹsi 999 (tabi 112) NHS 111 (Gbagba) / NPIS TOXBASE (0344 892 0111 fun awọn alamọdaju) UK Royal College of Emergency Medicine (RCEM) & NPIS designate ** Pyridoxine inu iṣọn-ẹjẹ** gẹgẹbi ** Ẹka A (Wọ Lẹsẹkẹsẹ) *** Antidote Ẹka Pajawiri (1 g per 1 g INH, max 5 g iwọn lilo akọkọ).
Idapọ Yuroopu 112 Kan si ile-iṣẹ majele ti orilẹ-ede nipasẹ ** 112 ** (fun apẹẹrẹ, Finland ** 0800 147 111 , Sweden ** 112 / 010-456 6700, Jẹmánì +49 30 19240) Nordic ati awọn ile-iṣẹ majele ti Ila-oorun Yuroopu ṣetọju awọn ilana pataki fun orisun omi ***Gyromitra esculenta * (Korvasieni / Stenmurkla) *** awọn ifihan25 mg/kg IV Pyridoxine + methemoglobin/abojuto ẹdọ; Titaja ti * Gyromitra * tuntun jẹ idinamọ tabi ofin ni muna kọja ọpọlọpọ awọn orilẹ-ede EU.
** Australia & Ilu Niu silandii *** ** Australia ***: 000 / ** IlNiuilandii ***: 111 Australia: 13 11 26 (Ile-iṣẹ Alaye Oloro) / ** Ilu Niu silandii**: 0800 764 766 (0800 POISON) Awọn Itọsọna Iwosan Toxicology ṣe itọsọna lẹsẹkẹsẹ ** IV Pyridoxine (1 g per 1 g INH, tabi 5 g ti a ko ba mọ; 70 mg/kg ninu awọn ọmọde) *** pẹlu IV benzodiazepines; oral crushed pyridoxine nipasẹ NG tube ti o ba ti IV iṣura ti re.
**India, South Africa & Asia-Pacific *** India: 112/108 / South Africa: 10177/112 / Philippines: 911 India: Ile-iṣẹ Majele AIIMS (1800-116-117) / South Africa: Laini Iranlọwọ Alaye Oloro (0861 555 777) Itankale giga ti idile Isoniazid (INH) ati apapọ iwọn lilo itọju TB (* 4-FDC: Rifampicin + Isoniazid + Pyrazinamide + Ethambutol *); Awọn oniwosan ile-iwosan lo Pyridoxine ẹnu ti o ni iwọn giga ti a fọ ​​nipasẹ tube nasogastric lẹgbẹẹ IV diazepam/phenobarbital nigbati awọn lẹgbẹrun Pyridoxine injectable ko ṣọwọn.

Awọn ibeere ti a beere nigbagbogbo

Kilode ti awọn oogun ijagba pajawiri ti o ṣe deede bii lorazepam (Ativan), midazolam, tabi phenytoin (Dilantin) da idaduro isoniazid (INH) ijagba apọju funrawọn?

Phenytoin ati fosphenytoin ṣiṣẹ nipa didi awọn ikanni iṣuu soda foliteji-gated lati da itankale ijagba duro, eyiti ko ṣe nkankan nigbati gbogbo ọpọlọ ko ni kemikali braking akọkọ rẹ, GABA (gamma-aminobutyric acid), ati pe o le fa awọn idamu riru ọkan ti o lewu ni awọn alaisan ti majele. Awọn Benzodiazepines bii lorazepam ati midazolam ṣiṣẹ nipa ṣiṣe awọn olugba GABA diẹ sii ni itara si GABA ti o wa ninu ọpọlọ. Sibẹsibẹ, nitori isoniazid npa Vitamin B6 ti nṣiṣe lọwọ (pyridoxal-5'-phosphate), ọpọlọ nṣiṣẹ patapata ni GABA laarin ọgbọn si 60 iṣẹju. Ni kete ti GABA synapti ti lọ, awọn benzodiazepines ko ni nkankan ti o ku lati pọ si titi ti Pyridoxine inu iṣọn-ẹjẹ (Vitamin B6) yoo fi kun lati tun iṣelọpọ GABA bẹrẹ.

Kini ti yara pajawiri ko ba ni awọn lẹgbẹrun ti Pyridoxine inu iṣọn-ẹjẹ (Vitamin B6) fun iwọn lilo 5-gram kan?

Nitori iwọn lilo antidote agbalagba 5-gram kan nilo aadọta 100-milligram lẹgbẹrun ti Pyridoxine injectable, ọpọlọpọ awọn ile-iwosan ko ni giramu 5 ni kikun ninu ọkọ ijamba eka pajawiri wọn. Nigbati awọn ipese iṣọn-ẹjẹ ba kuru, awọn dokita wọ inu alaisan naa lati daabobo ọna atẹgun, tẹ awọn ikọlu naa fun igba diẹ pẹlu propofol tabi phenobarbital, fọ awọn tabulẹti oral Vitamin B6 (pyridoxine hydrochloride) sinu omi, ki o si ṣakoso iwọn lilo 5-gram (tabi giramu-fun-gram) bi slurry olomi nipasẹ inu iṣan nasogas 1 lati fa omi inu tube sinu nasogas 5. 30 iṣẹju.

Kini idi ti ito ati omije alaisan ṣe tan-pupa pupa-osan lẹhin ti o gbe awọn oogun iko mì?

Ọpọlọpọ awọn alaisan iko-ara mu awọn tabulẹti apapo (gẹgẹbi Rifamate, Rifater, tabi awọn akojọpọ iwọn lilo 4-oògùn) ti o darapọ Isoniazid (INH) pẹlu Rifampin (rifampicin). Rifampin ni chromophore pupa-osan-pupa naphthohydroquinone ti o yara ni awọ ito, omije, lagun, itọ, ati paapaa awọ oju ti o ni pupa-osan-osan (“Red Man Syndrome”). Lakoko ti awọ pupa-osan wa lati ẹya paati Rifampin, awọn ikọlu eewu ti igbesi aye, coma, ati lactic acidosis wa lati ẹya Isoniazid ni oogun kanna gangan, nilo Pyridoxine inu iṣọn-ẹjẹ lẹsẹkẹsẹ (Vitamin B6).

Ṣe o ailewu lati jẹ eke morel (* Gyromitra esculenta *) olu ti o ba parboil wọn ki o si sọ omi nù?

Asiwaju toxicology ati awọn ile-iṣẹ aabo ounje ni Ariwa America ati Yuroopu ni imọran maṣe jẹ Gyromitra esculenta (eke morels) laibikita bawo ni wọn ṣe jinna. Sise eke morels tu monomethylhydrazine (MMH) - a rocket-propellant neurotoxin - sinu awọn nyara idana nya si, eyi ti o le majele awọn Cook nipa ifasimu nikan. Pẹlupẹlu, parboiling ko yọ 100 ogorun ti majele gyromitrin kuro, ati jijẹ awọn iṣẹ atunṣe ni ọpọlọpọ awọn ọjọ ni ilọsiwaju ti npa Vitamin B6 kuro ninu ọpọlọ ati ẹdọ titi awọn ijagba lojiji, methemoglobinemia, tabi ikuna ẹdọ nla waye.

Ti awọn dokita ba fun ni awọn iwọn lilo nla ti iṣuu soda bicarbonate inu iṣọn-ẹjẹ lati ṣatunṣe lactic acidosis ti o nira (pH < 6.9) ni isoniazid overdose?

Ninu majele isoniazid, lactic acidosis ti o ga julọ ni a mu nipasẹ awọn rudurudu iṣan tonic-clonic ti nlọ lọwọ ati idena INH ti iṣelọpọ lactate ẹdọ. Ni kete ti Pyridoxine inu iṣọn-ẹjẹ (Vitamin B6) ati awọn benzodiazepines da awọn ijagba duro, ara alaisan naa yarayara yọ lactic acid kuro ati ṣe deede pH ẹjẹ funrararẹ laarin awọn wakati 1 si 3. Nitorinaa, awọn onimọ-jinlẹ dojukọ iṣakoso Pyridoxine lẹsẹkẹsẹ dipo awọn infusions iṣuu soda bicarbonate ti ibinu, ni ifipamọ bicarbonate iṣọra ni muna fun acidemia ti o lagbara (pH ni isalẹ 7.0 si 7.1) pẹlu aisedeede hemodynamic.

Jẹmọ awọn itọsọna

Awọn orisun ati osise itoni

  • Ile-ẹkọ giga ti Ilu Amẹrika ti Toxicology (ACMT) & Awọn ile-iṣẹ Majele ti Ilu Amẹrika: * Awọn Itọsọna Iṣeduro Amoye fun Titoju Awọn Antidotes ni Awọn ile-iwosan Ti o pese Itọju Pajawiri: Pyridoxine fun Isoniazid ati Majele Hydrazine *.
  • Ajo Agbaye ti Ilera (WHO): * Iwe Afọwọkọ Alabaṣepọ si Awọn Itọsọna WHO fun Isakoso Eto ti Ikọ-ara-Resistant ti oogun: Isakoso Isoniazid Overdose ati Neurotoxicity *.
  • Royal College of Emergency Medicine (RCEM) & National Poiss Information Service (NPIS, United Kingdom): Itọsọna lori Wiwa Antidote fun Awọn Ẹka pajawiri (Ẹka A: Pyridoxine Hydrochloride).
  • Awọn ile-iṣẹ fun Iṣakoso ati Idena Arun (CDC) & Ile-iṣẹ ti Orilẹ-ede fun Aabo Iṣẹ iṣe ati Ilera (NIOSH): * Awọn Itọsọna Iṣakoso Iṣoogun fun Hydrazine, Methylhydrazine, ati Gyromitrin Olu Majele *.
  • Ẹgbẹ Awuyewuye ti Ariwa Amerika (NAMA): Awọn Aisan Majele ti Olu: Gyromitrin (Monomethylhydrazine) Saa ati Awọn Ilana Igbala Pyridoxine.
  • Itọsọna yii wa fun awọn idi alaye ati pe ko rọpo igbelewọn iṣoogun pajawiri ọjọgbọn, ijumọsọrọ Iṣakoso Majele, tabi iṣakoso itọju aladanla. Nitori ipo warapa ti o fa majele le fa idaduro atẹgun lojiji ati acidosis ti o lagbara, a ṣeduro ni iyanju gbigba gbigba ọwọ-lori iranlọwọ akọkọ ati iṣẹ CPR nipasẹ International Federation of Red Cross and Red Crescent Societies (IFRC), Red Cross ti orilẹ-ede rẹ awujọ, St John Ambulance, tabi olupese agbegbe ti a fọwọsi.