TOKSIKOLOGI KLINIKFokus kajian pada penyakit yang disebabkan atau secara unik berhubungan dengan substansi toksikKeracunan menurut cara terjadi :Self poisoningAttempted poisoningAccidental poisoningHomicidal poisoning

Keracunan menurut mula waktu terjadi :AkutKronis

Keracunan menurut alat tubuh yang terkenaKeracunan menurut jenis bahan kimia

PENYEBAB KERACUNAN Anak balita minyak tanah, obat berlapis gulaDewasa obat hipnotik sedatif, opiat, insektisidaKeracunan makanan Enterotoksin stafilokokusKeracunan logam berat Arsen, Hg, dll

GEJALA DAN DIAGNOSISAnamnesisGejala spesifik sesuai jenis obat atau bahan kimia lihat tabelLaboratorium pemeriksaan spesimen biologik- kualitatif- kuantitatif KLTKromatografi gasHPLC kromatografi cair kinerja tinggi

TERAPI KERACUNAN

Untuk kepentingan klinik, semua agen toksik dibagi 2 klas :Agen toksik yang memerlukan terapi spesifik atau ada antidotnyaAgen toksik yang tidak memerlukan terapi spesifik Tx simtomatik memperbaiki fungsi vital Tx supportivePrinsip penting dalam toksikologi klinik : Treat the patient, not the poison

Terapi keracunan akut :Mempertahankan fungsi vitalMengusahakan konsentrasi racun di jaringan yang penting serendah mungkin dg cara mencegah absorbsi dan meningkatkan eliminasi

Mencegah absorbsi racun selanjutnya dengan :Emesis -merangsang pharynx di bag.posterior-Ipecac-ApomorphineGastric lavageChemical adsorbtion activated charcoal

Inaktivasi bahan kimia-antidote-netralisasi asam atau basaPurgation- Katartik - WBI : whole bowel irrigationBila keracunan melalui inhalasi atau kulit :-pindahkan pasien dari sumber racun-bersihkan kulit yang terkena dg air-pakaian yg terkena racun dilepas

Bila kena mata secepatnya irigasi dg air selama 15 menitMENINGKATKAN ELIMINASI RACUN diuresis paksa dialisis

Assessment and ManagementThe primary goal of physical assessment of poisoned patients is to identify the poisons effects on the three vital organ systems most likely to produce immediate morbidity and mortality:Respiratory systemCardiovascular systemCentral nervous system

Five Signs of Major ToxicityComaCardiac dysrhythmiasGI disturbancesRespiratory depressionHypotension or hypertension

HISTORYWhat was ingested? (obtain samples of substance, vomitus)Route of intoxication?When was the substance ingested?How much of the substance was ingested?Use of alcohol or other possibly potentiating substances?Was an attempt made to induce vomiting?Has an antidote or activated charcoal been administered?Patterns of drug habituation or abuse?Does the patient have a psychiatric history pertinent to suicide attempts or recent episodes of depression?

Physical ExamPay special attention to:Skin condition (cyanosis, pallor, wasting, needle marks, staining)Pupil responses, impaired visionSigns of caustic ingestion, burningAmount of salivation, breath odor, presence of vomitusBreath sounds for evidence of aspiration, atelectasis, pulmonary secretionsCardiac dysrhythmiasAbdominal pain

General Principles of ManagementPrevent aspiration, consider intubationReduce or prevent absorptionDO NOT induce vomiting in most casesUse of gastric lavage and/or activated charcoal may be preferredMaintain airway, breathing and circulationGastric Lavage A method of GI decontamination that may be superior to ipecac-induces emesisAdvantages:Immediate recovery of a portion of the gastric contents (if performed within 1 hour of ingestion)Control of lavage durationDirect access for administration of activated charcoal

Tehnik gastric lavageUse large bore (36-40 French) orogastric tube, smaller 24-28 French NG tube may be too small to remove gastric contentsPlace the patient in left lateral Trendelenburg to minimize chance of aspirationInsert tube through mouth into esophagus and advance until tip is placed in the stomachCheck tube placement by insufflation of air into stomach with syringe while auscultatingInfuse 150-200 mL aliquots of tap water or NS in adults, 50-100 mL >5 yearsDrain stomach contents after each infusion, return volume should be approximately equal to what was infusedContinue until return fluid comes back clearFollow with activated charcoal

Potential complications gastric lavage:Patient agitationInadvertent tracheal intubationEsophageal perforationAspiration pneumonitisFluid and electrolyte imbalances in pediatric patients

Activated charcoal:A medication that works by binding to certain poisons, preventing them from being absorbed into the body.Used only for ingested toxins.

Activated Charcoal Trade Names InstaChar Actidose LiquiChar SuperChar Two Types of Activated Charcoal

Contraindications to Charcoal Altered mental statusIngestion of an acid or alkaliInability to swallowHistory of recent seizures

Administration of Activated CharcoalShake container thoroughly.

Activated Charcoal continuedPour liquid into container.

Activated Charcoal continuedHave patient drink full dose.

CHEMICAL ADSORPTION

Activated charcoal adsorbs drugs and chemicals on the surfaces of the charcoal particles, thereby preventing absorption and toxicity

chemicals are adsorbed by charcoal :theophylline, phenobarbital carbamazepine, dapsone and quinine .

Chemical are not well adsorbed by activated charcoal : alcohols, hydrocarbons, metals, and corrosives

should not be used simultaneously with ipecac because charcoal can adsorb the emetic agent in ipecac and thus reduce the drug's emetic effect.

Charcoal also may adsorb and decrease the effectiveness of specific antidotesan adsorbent (charcoal) in the intestine may interrupt enterohepatic circulation of a toxicant, thus enhancing its excretion tricyclic antidepressants and glutethimide

CHEMICAL INACTIVATION need more time than charcoal and gastric lavage

Antidotes can change the chemical nature of a poison by rendering it less toxic or preventing its absorption

Exp :Formaldehyde + ammonia hexamethylenetetramine Sodium formaldehyde sulfoxylate can convert mercuric ion to the less soluble metallic mercury

Sodium bicarbonate converts ferrous iron to ferrous carbonate, which is poorly absorbed

PURGATIONto minimize absorption by hastening the passage of the toxicant through the gastrointestinal tract cathartic indicated after the ingestion of enteric-coated tablets when the time after ingestion is greater than 1 hour Exp. Sorbitol sodium sulfate avoided in patients with congestive heart failure. magnesium sulfate should be used cautiously in patients with renal failure

Whole-bowel irrigation (WBI) polyethylene glycol

is a technique that not only promotes defecation but also eliminates the entire contents of the intestines

WBI may be considered in cases of acute poisoning by sustained-release or enteric-coated drugs and possibly toxic ingestions of iron, lead, zinc.

INHALATION AND DERMAL EXPOSURE TO POISONS

When a poison has been inhaled remove the patient from the source of exposure Skin has had contact with a poison washed thoroughly with water Contaminated clothing should be removed chemical injuries to the eye thorough irrigation of the eye with water for 15 minutes should be performed immediately.

Carbon monoxide poisoning... can be a serious possibility with fire victims.

Common toxins that can be absorbed.

Enhanced Elimination of the Poison

BIOTRANSFORMATION

Many chemicals are toxic because they are biotransformed into more toxic chemicals

Exp : methanol formic acid (highly toxic metabolite), by alcohol dehydrogenase ethanol is used to inhibit the conversion

Acetaminophen is converted by the CYP system to an electrophilic metabolite that is detoxified by glutathione, a cellular nucleophile Acetaminophen does not cause hepatotoxicity until glutathione is depleted, whereupon the reactive metabolite binds to essential macromolecular constituents of the hepatocyte, resulting in cell death. The liver can be protected by maintenance of the concentration of glutathione, and this can be accomplished by the administration of N-acetylcysteine

Renal excretion of basic drugs such as amphetamine theoretically can be enhanced by acidification of the urine

Acidification can be accomplished by the administration of ammonium chloride or ascorbic acid. Urinary excretion of an acidic compound is particularly sensitive to changes in urinary pH if its pKa is within the range of 3.0 to 7.5; for bases, the corresponding range is 7.5 to 10.5.

DIALYSISHemodialysis and peritoneal dialysis Hemodialysis is much more effective than peritoneal dialysis and may be essential in a few life-threatening intoxications, such as with methanol, ethylene glycol, and salicylates

ANTAGONISM OR CHEMICAL INACTIVATION OF AN ABSORBED POISONSpecific chemical antagonists of a toxicant, such as opioid antagonists Atropine as an antagonist of pesticide-induced acetylcholine excess fomepizole, an inhibitor of alcohol dehydrogenase, approved for treatment for poisoning by ethylene glycol and methanol Chelating agents with high selectivity for certain metal ions are used more commonly Antibodies offer the potential for the production of specific antidotes for a host of common poisons and for drugs that frequently are abused or misused Exp purified digoxin-specific Fab fragments of antibodies in the treatment of potentially fatal cases of poisoning with digoxin

Organophosphate PoisoningMUSCARINICD-efacationU-rinationM-iosisB-bronchorreaE-xcitation (muscular)L-acrimation, salivationNICOTINICM-uscle weaknessT-achycardiaW-weaknessH-hypertensionF-fasiculations

TreatmentAnticholinergicatropinewhat physiologic effects would you expect to see from atropine?pralidoxime (2-PAM)regenerates acetylcholinesterasewhat is the function of acetylcholinesterase?What physiologic response would you expect to see?

The development of human monoclonal antibodies directed against specific toxins has significant potential therapeutic value snake bite, marine animal bite

Rattlesnake

Marine AnimalsStingray

Venom can destroy proteins, other tissue components, red blood cells, and affect clotting factorInfarction and necrosis may develop at the bite siteSevere bite can be fatal in 6-30 hours (rarely in

Snake bite

The development of human monoclonal antibodies directed against specific toxins has significant potential therapeutic value

snake bite

In Malang SABU = SERUM ANTI BISA ULAR

Injection

Ingestion

Inhalation

Absorption

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