Tata laksana overdosis

dan keracunan
Farmakoterapi kegawatdaruratan
Evaluasi

 Adanya tanda2 keracunan

 Identifikasi senyawa penyebab
 Penilaian keparahan
 Prediksi toksisitas
Tata laksana

 Berikan terapi pendukung

 Pencegahan absorpsi racun
 Peningkatan eliminasi racun
 Pemberian antidotum
Terapi pendukung

 ABC (Airway, breath, circulation)

 Tada vital, status mental, ukuran pupil
 Rekaman pulse, cardiac monitoring, ECG
 Perlindungan jalan nafas
 Akses intravenous
 immobilization jika diduga ada trauma
 Cek hipoglikemia
 Naloxone untuk keracunan opiat
Riwayat

 Kemasan obat
 Alcohol
 Riwayat pengobatan
 Obat2 OTC
 Catatan bunuh diri
Pengujian fisik

 Eksitasi fisiologis–
anticholinergic, sympathomimetic, atau central
hallucinogenic agents, drug withdrawal
 Depresi fisiologis–
cholinergic (parasympathomimetic), sympatholytic,
opiate, atau sedative-hypnotic agents, atau alcohols
 kombinasi–
polydrugs, hypoglycemic agents, tricyclic
antidepressants, salicylates, cyanide
Deteksi obat di urin
Konsentrasi Obat dlm Darah
 Pencegahan absorpsi
Pengosongan lambung
 Tidak boleh untuk pasien tak sadar (resiko aspirasi)
 Pipa fleksibel dimasukkan lewat hidung ke lambung
 Isi lambung disedot via pipa
 Larutan salin disuntikkan via pipa
 Direkomendasikan hingga 2 jam stlh paparan TCA (antidepresan
trisiklik & hingga 4 jam stlh overdosis salisilat

Induksi muntah
 Ipecac – tidak selalu direkomendasikan
 Resiko aspirasi
 Pencegahan absorpsi
Activated charcoal
 Mengadsorpsi senyawa toksik atau iritan, sehingga
menghambat absorpsi saluran cerna
 Penambahan sorbitol → laxative effect
 Oral: 25-100 g single dose
 Dosis berulang berguna untuk meningkatkan eliminasi obat-
obat tertentu (eg, theophylline, phenobarbital,
carbamazepine, aspirin, sustained-release products)
 Tidak efektif untuk cyanide, mineral acids, caustic alkalis,
organic solvents, iron, ethanol, methanol poisoning, lithium
 Eliminasi racun
Renal elimination
 Obat-obat untuk stimulai urinasi atau defekasi dapat diberikan untuk
mengeluarkan kelebihan oba dengan lebih cepat.
Forced alkaline diuresis
 Infus dosis besar NS+NAHCO3
 Digunakan untuk mengeliminasi obat-obat asam yang terutama
diekskresikan di ginjal, eg salicylates
 Gangguan cairan & elektrolit serius bisa terjadi
 Membutuhkan monitoring tim ahli
Hemodialysis or haemoperfusion:
 Dibutuhkan untuk keracunan parah
 Obat harus dialyzable i.e. Terikat protein dengan volume distribusi
rendah
 Bisa juga digunakan bila ginjal rusak akibat overdosis
Antidotum

 Apakah tersedia antidotumnya?

 Apakah bisa diprediksi keparahan
sehingga dibutuhkan antidotum?
 Ratio benefit vs resiko?
 Apakah ada kontraindikasi?
Overdosis spesifik
Opiat
 Antidot – naloxone
 Mode of Action: Antagonis opioid berkompteisis dan
menggantikan narkotik pada sisi reseptor opioid
 I.V. (preferred), I.M., intratracheal, SubQ: 0.4-2 mg
every 2-3 minutes as needed
 Dosis lebih rendah pada pasien ketergantungan
opiat
 T ½ eliminasi naloxone hanya 60-90 menit
 Pemberian ulang/infus kadang diperlukan
 Efek samping: perubahan tekanan darah;
arrhythmias; seizures;
Benzodiazepin
 Antidot – flumazenil
 MOA: Benzodiazepine antagonist
 IV administration 0.2 mg over 15 sec to max 3mg
 Efek samping: N&V; arrhythmias; convulsions
 Kontraindikasi : pemakaian bersama TCAD; status
epilepticus
Antidepresan Trisiklik
 FARMAKOLOGI:
 TCA mempunyai banyak efek seluler penting, termasuk
penghambatan:

Reuptake neurotransmitter prasinaps

Kanal Na jantung
Reseptor muskarinik sentral & perifer

Reseptor Histamine (H1)

Reseptor CNS GABA-A
Overdosis TCAD
Manifestasi klinik
 Aritmia
- widening of PR, QRS, and QT intervals;
heart block; VF/VT
 Hipotensi
 Toksisitas antikolinergik
- hyperthermia, flushing, dilated pupils,
intestinal ileus, urinary retention, sinus tachycardia
 Confusion, delirium, hallucinations
 Seizures
Diagnosis

 History
 Blood/urine toxicology screen
 Levels not clinically useful
TCAD overdose -Treatment

 ABC – many require intubation

 Consider gastric lavage if taken < 2hrs
 Activated charcoal
 Treatment of hypotension with isotonic saline
 Sodium bicarbonate for cardiovascular toxicity
 Alpha adrenergic vasopressors (norepinephrine)
for hypotension refractory to aggressive fluid
resuscitation and bicarbonate infusion
 Benzodiazepines for seizures
Na Bicarbonate untuk overdosis TCA

 Hypertonic sodium bicarbonate (NaHCO3)

- QRS widening >100 msec; ventricular
arrhythmias, and/or refractory hypotension
 ↑ serum pH promotes protein binding and ↓ free drug
concentrations; narrows the QRS complex, ↑ systolic blood
pressure, and controls ventricular arrhythmias
 1 to 2 meq/kg (two to three 100 mL ampules of 8.4 percent
NaHCO3) rapid IV push large bore IV then infusion if working
 reasonable goal pH is 7.50 to 7.55 then taper dose
 S/E Volume overload, hypernatreamia, and metabolic alkalosis
Special Cautions in TCAD overdose

 Class IA and IC antiarrhythmic agents are

contraindicated eg quinidine;disopyramide,
flecainide; propafenone
 Class IB Lignocaine, phenytoin used
 Phenytoin may precipitate arrhythmias
 Magnesium may be useful
 Flumazenil must not be given
Salicylate overdose

 Aspirin (acetylsalicylic acid)

 Methyl salicylate (Oil of Wintergreen)
 5 ml = 7g salicylic acid
 Herbal remedies
 Fatal intoxication can occur after the
ingestion of 10 to 30 g by adults and as
little as 3 g by children
Salicylate levels

 Plasma salicylate concentration

 Rapidly absorbed; peak blood levels usually occur
within one hour but delayed in overdose 6-35 hrs
 Measure @ 4 hrs post ingestion & every 2 hrs until
they are clearly falling
 Most patients show signs of intoxication when the
plasma level exceeds 40 to 50 mg/dL (2.9 to 3.6
mmol/L)
Salicylate overdose
 Inhibition of cyclooxygenase results in decreased synthesis of
prostaglandins, prostacyclin, and thromboxanes
 Stimulation of the chemoreceptor trigger zone in the medulla
causes nausea and vomiting
 Direct toxicity of salicylate species in the CNS, cerebral
edema, and neuroglycopenia
 Activation of the respiratory center of the medulla results in
tachypnea, hyperventilation, respiratory alkalosis
 Uncoupled oxidative phosphorylation in the mitochondria
generates heat and may increase body temperature
 Interference with cellular metabolism leads to metabolic
acidosis
Clinical features

 Early symptoms of aspirin toxicity include tinnitus,

fever, vertigo, nausea, hyperventilation, vomiting,
diarrhoea

 More severe intoxication can cause altered mental

status, coma, non-cardiac pulmonary oedema and
death
Metabolic abnormalities
 Stimulate the respiratory center directly, early fall in the PCO2
and respiratory alkalosis

 An anion-gap metabolic acidosis then follows, due to the

accumulation of organic acids, including lactic acid and ketoacids

 Mixed respiratory alkalosis and metabolic acidosis with ↑ anion

gap

 Arterial Ph variable depending on severity

Metabolic abnormalities

 Metabolic acidosis increases the

plasma concentration of protonated
salicylate

 thus worsening toxicity by allowing

easy diffusion of the drug across cell
membranes
Salicylate overdose - treatment

 directed toward increasing systemic pH by the administration

of sodium bicarbonate

 IV fluids +/- vasopressors

 Avoid intubation if at all possible (↑ acidosis)

 Supplemental glucose (100 mL of 50 percent dextrose in

adults) to patients with altered mental status regardless of
serum glucose concentration to overcome neuroglycopaenia

 Hemodialysis
Alkalinization of plasma and urine

 Alkalemia from a respiratory alkalosis is not a contraindication

to sodium bicarbonate therapy

 A urine pH of 7.5 to 8.0 is desirable

 Blood gas analysis every two hours

 Avoid severe alkalemia (arterial pH >7.60)

Haemodialysis - indications

 Altered mental status

 Pulmonary or cerebral edema

 Renal insufficiency that interferes with salicylate excretion

 Fluid overload that prevents the administration of sodium

bicarbonate

 A plasma salicylate concentration >100 mg/dL (7.2 mmol/L)

 Clinical deterioration despite aggressive and appropriate supportive

care
Paracetamol
 Widely available
 Potential toxicity underestimated
 Toxicity unlikely to result from a single dose of less than 150
mg/kg in child or 7.5 to 10 g for adult
 Toxicity is likely with single ingestions greater than 250 mg/kg
or those greater than 12 g over a 24-hour period
 Virtually all patients who ingest doses in excess of 350 mg/kg
develop severe liver toxicity unless appropriately treated
Factors influencing toxicity
 Dose ingested
 Excessive cytochrome P450 activity due to induction by
chronic alcohol or other drug use eg carbamazepine,
phenytoin, isoniazid, rifampin
 Decreased capacity for glucuronidation or sulfation
 Depletion of glutathione stores due to malnutrition or chronic
alcohol ingestion
 Acute alcohol ingestion is not a risk factor for hepatotoxicity
and may even be protective by competing with
acetaminophen for CYP2E1
Clinical features
 Stage I (0.5 to 24 hours)
No symptoms; N&V Malaise
 Stage II (24 to 72 hours)
Subclinical elevations of hepatic aminotransferases (AST, ALT)
right upper quadrant pain, with liver enlargement and tenderness.
Elevations of prothrombin time (PT), total bilirubin, and oliguria and
renal function abnormalities may become evident
 Stage III (72 to 96 hours)
Jaundice, confusion (hepatic encephalopathy), a marked elevation in
hepatic enzymes, hyperammonemia, and a bleeding diathesis
hypoglycemia, lactic acidosis, renal failure 25%, death
 Stage IV (4 days to 2 weeks)
Recovery phase that usually begins by day 4 and is complete by 7
days after overdose
Paracetamol overdose
 The risk of toxicity is best predicted by relating the time of
ingestion to the serum paracetamol concentration
 The dose history should not be used as studies have found no
correlation
 Peak serum concentrations reached within 4 hrs following
overdose of immediate-release preparations
 May be delayed with extended releases preparations or drugs
that delay gastric emptying (eg, opiates, anticholinergic
agents) are coingested
 Check level at >= 4 hrs
Paracetamol overdose treatment

 Activated charcoal within four hours of

ingestion
 May reduce absorption by 50 to 90 percent
 Single oral dose of one gram per kilogram
 Inhibits absorption of oral methionine
N-acetylcysteine
 Antidote – MOA: a glutathione precursor
 Limits the formation and accumulation of NAPQI
 Powerful anti-inflammatory and antioxidant effects
 IV infusion or oral tablets (also oral methionine)
 150mg/Kg over 15 min; 50mg/Kg over next 4 hrs; 100mg/kg over
next 16 hrs up to 36hrs
 Beyond 8 hours, NAC efficacy progressively decreases
 S/Es nausea, flushing, urticaria, bronchospasm, angioedema,
fever, chills, hypotension, hemolysis and rarely, cardiovascular
collapse
Paracetamol overdose treatment

 At the end of NAC infusion, a blood sample should be taken

for determination of the INR, plasma creatinine and ALT. If
any is abnormal or the patient is symptomatic, further
monitoring is required and advice sought from the NPIS

 Patients with normal INR, plasma creatinine and ALT and who
are asymptomatic may be discharged from medical care. They
should be advised to return to hospital if vomiting or
abdominal pain develop or recur
 Indications for liver transplantation

 Liver transplantation is life-saving for fulminant hepatic necrosis

 The indications for liver transplantation are:
1 - Acidosis (pH < 7.3), or
2 - PT > 100 sec
3 - Creatinine > 300 mcg/l
4 - Grade 3 encephalopathy (or worse)
 It is better to contact the local liver transplant centre earlier than this.
 Grossly abnormal prothrombin times should trigger referral:
 PT > 20 sec at 24 hr
 PT > 40 sec at 48 hr
 Alcohol poisoning

 Clinical features of acute alcohol poisoning include:

 Ataxia and anaesthesia leading to accidental injury
 Dysarthria and nystagmus
 Drowsiness which may progress to coma
 Inhalation of vomit which can be fatal & should be prevented
 Hypoglycaemia in children and some adults
 Check BM stix and give 50% glucose i.v. if required
 o
Coma (alcohol induced)
 In cases of alcohol induced coma exclude:
1. Coincident head injury
2. Hepatic failure
3. Meningitis
4. Wernicke’s encephalopathy
5. Other associated drug ingestion
 A blood test will confirm substantial levels of alcohol
 Rule out alcoholic hypoglycaemia
 The airway and circulation must be maintained
 But glucose- containing fluids may precipitate Wernicke's
encephalopathy
 Thiamine should given to all
 Intravenous naloxone has reversed coma in a proportion of cases