poisoning (farmakologi)

7/30/2019 Poisoning (Farmakologi)

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Prof.dr.H.Aznan Lelo PhD.SpFKdr.Datten Bangun MSc,SpFK

Dept.Farmakologi & Terapeutik

Fak.Kedokteran U S U

M E D A N


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"All substances are poisons; there isnone which is not a poison. The rightdose differentiates a poison and a

remedy.

Paracelsus (1493-1541)


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Try and get as much history as possibleincluding witnesses

People truly wanting to commit suicide often

lie Remember the ABCs:

Airway Clear mouth & throat, gagreflex

Breathing O2 saturation, ABGs Circulation Venous access, IV fluids if shocked

Assess GCS

Examination


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When, what, how much ?

Why?

Circumstances PMHx, Drug history

Psychiatric history

Assess mental status and capacity


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Analgesic agents

Cosmetics/ personal care products

Household cleaning products

Sedative hypnotics/ antipsychotics

Foreign bodies/ toys

Cough/ cold OTC preparations

Topical preparations

Pesticides

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All chemicals have potential to be poisons ifgiven a large enough dose

Poisoning occurs when exposure to asubstance adversely affects function of any

organ systemGeneral Approach to the Poisoned Patient

SystematicTreatment and Diagnostic Actions in Parallel

Goal is rapid stabilization, categorization of

poison class, initiation of general treatment

then specific treatment when available


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1. Stabilization

2. Rapid Patient Evaluation (Physical, Lab)

3. Prevention of further toxin absorption

4. Enhancement of toxin elimination

5. Specific antidote

6. Supportive therapy

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History is often absent or unreliable

Information from any source usually helpful

Physical exam is very important

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Largely supportive !

oxygen, iv access & fluids

Decrease drug absorption

activated charcoal within 1 hour

( whole bowel irrigation )

( gastric lavage )

Increase drug eliminationurinary alkalisation

haemodialysis/perfusion /plasmaexchange


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A (Airway)

B (Breathing)

C (Circulation)

D (Disability-AVPU/ Glasgow Coma Scale)

DEFG ( Dont ever forget the Glucose)

GET A SET OF BASIC OBSERVATIONS

General Management -2

Use all your senses, search for the clues

LOOK -Track Marks

- Pupil Size

FEEL - Temperature, Sweating

SMELL - Alcohol


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Physiologically based abnormalities that areknown to occur with specific classes ofsubstances and typically are helpful in

diagnosis Patterns of signs and symptoms

Useful to help in diagnosis and treatment ofunknown poisons

Patterns of signs and symptoms

Useful to help in diagnosis and treatment

of unknown poisons


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Odor Poison

Bitter almonds cyanide

Eggs hydrogen sulfide,

mercaptans

Mothballs naphthalene, camphor

Wintergreen methylsalicylate

Garlic As, org- phosphates,DMSO, Thallium

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Supportive Correct hypoxia, hypotension, dehydration,

hypo- hyperthermia, and acidosis

Control seizures

Monitor

TPR, BP, ECG, Oxygenation, GCS

General

Absorption Elimination

Specific antidotes


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Sympathomimetic

Anticholinergic

Cholinergic (muscarinic)

Narcotic

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Vital signs: Tachycardia, hypertension,hyperpyrexia.

Clinical appearance: diaphoresis (sweating),piloerection, mydriasis and hyperreflexia. Insevere cases, seizures, hypotension (later effect)and dysrhythmias may occur.

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Vital signs: Bradycardia, increased respiratory rate(initially)

Clinical appearance: SLUDGE

Salivation

LacrimationUrination

Defecation Diaphoresis

Gastrointestinal distress

Edema (Pulmonary)

Also see: miosis (pinpoint pupils), muscle fasciculations,CNS depression

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1.Initial management:

(2) Stabilization:

a.ABCs: airway protection mostcommonly needed

b.Orogastric lavage or NG tube: if liquid

ingestion and pt has not vomited yetc.IV access for antidotes and fluids


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2.Antidotes

(1) Atropine:a.effect:

competitive inhibition of Ach at

muscarinic receptors in smooth muscles

and CNS

No effect on nicotinic receptor

(N-M junction):cant reverse muscle

weakness

b.bronchorrheahypoxiatachycardia

more atropin


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(2) Pralidoxime (2-PAM,Protopam)

a.effect: form a complex of PAM-OP-AchE

PAM-OP released fromcomplex AchE reactivation

metabolize Achb.decreases atropine effect

c.treatment as early as possibledecreased effect after 36-48 hrs

exposure

aging effect


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Vital signs: Tachycardia, hypertension,hyperpyrexia

Clinical appearance: Hot, dry skin, mydriasis, diminishedor absent bowel sounds, urinary retention, confusionand delirium. Sinus tachycardia is most common butother cardiac conduction abnormalities may occur.

Seizures may occur with agents that enter the CNS.

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Most common drug taken in overdose

Few symptoms or early signs

As little as 12 gr can be fatal

Hepatic and renal toxin

Centrolobular necrosis

More toxic if liver enzymes induced or

reduced ability to conjugate toxin


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General measures including U&Es, LFTs, glucose, clotting ABG, bicarbonate,

paracetamol and salicylate levels

Activated charcoal


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>8 hours Urgent action required because the

efficacy of NAC declines progressively

from 8 hours after the overdose Therefore, if > 150mg/kg or > 12g

(whichever is the smaller) has beeningested, start NAC immediately,

without waiting for the result of theplasma paracetamol concentration

>24 hours

Still benefit from starting NAC


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Precursors of glutathione Dosage for NAC infusion - ADULT

(1) 150mg/kg IV infusion in 200ml 5%dextrose over 15 minutes, then

(2) 50mg/kg IV infusion in 500ml 5%dextrose over 4 hours, then (3) 100mg/kg IV infusion in 1000ml 5%

dextrose over 16 hours Side-effects

Flushing, hypotension, wheezing,anaphylactoid reaction Alternative is methionine PO (


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Aspirin (acetylsalicylic acid)

Methyl salicylate (Oil of Wintergreen)

5 ml = 7g salicylic acid

Herbal remedies

Fatal intoxication can occur after the ingestionof 10 to 30 g by adults and as little as 3 g by

children


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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)


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Inhibition of cyclooxygenase results in decreasedsynthesis of prostaglandins, prostacyclin, andthromboxanes

Stimulation of the chemoreceptor trigger zone in themedulla causes nausea and vomiting

Direct toxicity of salicylate species in the CNS,cerebral edema, and neuroglycopenia

Activation of the respiratory center of the medullaresults in tachypnea, hyperventilation, respiratory

alkalosis Uncoupled oxidative phosphorylation in the

mitochondria generates heat and may increase bodytemperature

Interference with cellular metabolism leads tometabolic acidosis


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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


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directed toward increasing systemic pH by theadministration of sodium bicarbonate

IV fluids +/- vasopressors

Avoid intubation if at all possible ( acidosis)

Supplemental glucose (100 mL of 50 percent dextrosein adults) to patients with altered mental status

regardless of serum glucose concentration toovercome neuroglycopaenia

Hemodialysis


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Antidote naloxone

MOA: Pure opioid antagonist competes and

displaces narcotics at opioid receptor sites

I.V. (preferred), I.M., intratracheal, SubQ: 0.4-2 mg

every 2-3 minutes as needed

Lower doses in opiate dependence

Elimination half-life of naloxone is only 60 to 90

minutes Repeated administration/infusion may be necessary

S/E BP changes; arrhythmias; seizures; withdrawal


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Antidote flumazenil

MOA: Benzodiazepine antagonist

IV administration 0.2 mg over 15 sec to max

3mg S/E N&V; arrhythmias; convulsions

C/I concomitant TCAD; status epilepticus

Should not be used for making the diagnosis Benzodiazepines may be masking/protecting

against other drug effects


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Deaths from poisoning with benzodiazepines alone arerare, but may be lethal in combination with other CNSdepressants

Treatment is supportive and aimed at maintaining

adequate ventilation whilst supporting cardiovasculardepression

Flumazenil (specific benzodiazepine antidote) is notlicensed (in the UK) for routine use in benzodiazepineoverdoses

Flumazenil may induce seizures; particularly dangerouswhere tricyclic antidepressants have been taken

Flumazenil, may however, be used in the differentialdiagnosis of unclear cases of multiple overdoses but expertadvice is ESSENTIAL.


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PHARMACOLOGY

TCAs have several important cellular effects,

including inhibition of:- Presynaptic neurotransmitter reuptake

- Cardiac fast sodium channels

- Central and peripheral muscarinic acetylcholinereceptors

- Peripheral alpha-1 adrenergic receptors- Histamine (H1) receptors

- CNS GABA-A receptors


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Arrhythmias

- widening of PR, QRS, and QT intervals;

heart block; VF/VT

Hypotension

Anticholinergic toxicity

- hyperthermia, flushing, dilated pupils,

intestinal ileus, urinary retention, sinustachycardia

Confusion, delirium, hallucinations

Seizures


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History

Blood/urine toxicology screen

Levels not clinically useful


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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 fluidresuscitation and bicarbonate infusion

Benzodiazepines for seizures


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Carbon monoxide (CO) intoxication is one of the most

common causes of accidental and intentional poisoning Atmospheric composition


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Pathophysiology


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CO is colourless, odourless, nonirritant toxicgas

CO toxicity due to

Cellular hypoxia

Direct cellular injury

Cellular hypoxia

CO competes with O2 for binding to Hb

Affinity of Hb for CO x 200-250 > affinity for O2 O2-Hb dissociation curve shift to the left

Impaired tissue release of O2 and cellular hypoxia


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High level of clinical suspicion

Serum COHb level

Exhaled breath COHb level

Measured by spectrophotometry

Pulse oximetry cannot distinguish betweenHbO2 and COHb

Comprehensive neurological andneuropsychological assessment

CO Neuropsychological Screening Battery CT brain to exclude other conditions


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High-flow, FiO2 ~100%, normobaric O2

O2 shortens the half life of COHb 21% O2 = 4-6 hours 100% O2 = 40-80 minutes 100% O2 2.5atm = 15-30 minutes

Continue O2 until COHb normal Beware concomitant smoke inhalation and burn

injury Normobaric v Hyperbaric O2 therapy

HBO hastens resolution of acute symptoms

Unclear evidence for effect of HBO on latecomplications and mortality


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Irritant Poisons

Definition:

Those agents that set up an inflammatory process at the site ofapplication or contact. They do not destroy body tissues

The most common signs and symptoms of irritant and poisons are

due to their local action on the mucosa of the GIT, causing

inflammatory changes and partial desquamation of the intestinal

mucosa

This leads to burning pain, vomiting and diarrhea with bloody

stools

After absorption, the main symptoms of toxicity include rapid irregular

pulse, fall in blood pressure, convulsions and coma

Examples: mercuric chloride, silver nitrate, iodine, bromine, hydrogen

peroxide

Poisoning by Silver


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Poisoning by Silver

Silver nitrate is used as local styptic (astringent) and

antiseptic Ingestion of a silver salt solution causes burning sensation

of GIT, abdominal pain, vomiting with black vomitus,

diarrhea, severe shock and convulsions

Repeated use of silver preparations may result indeposition of greyish-blue metallic silver in the pigment

layer of the skin

Treatment:

1. Gastric lavage with NaCl to precipitate silver2. Administration of demulcents, e.g., milk and egg

white which combines with sliver as proteinate

3. Administration of cathartics and cleansing enemas

Poisoning by Iodine


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Poisoning by Iodine

Iodine is used in medicine as antiseptic and disinfectant

Ingestion of iodine causes gastric pain, vomiting (brown-stained vomitus), diarrhea (bloody stool), collapse and

nephritis.

Inhalation of iodine causes inflammation of respiratory

tract, cough, and pulmonary edema.

Iodine produces inflammation, desquamation and

corros ion of mucous membranes

Treatment:1. Gastric lavage with water or 1-1.5% solution of sodium

thiosulphate

2. Administration of starch solution and demulcents,

e.g., milk and egg white

Poisoning by Bromine


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Poisoning by Bromine

Exposure to bromine vapor causes lacrimation,

pharyngitis, salivation, cough, pulmonary edema and

ulceration of eyelids and cornea pain, vomiting (brown-

stained vomitus), diarrhea (bloody stool)

Bromine produces yellow brown discoloration of the skin,

feeling of heat and ulcer

Treatment:

1. Transferring the patient to fresh air

2. Administration of oxygen

3. Treat bronchospasms and pulmonary edema byaminophylline I.V.

Poisoning by Hydrogen Peroxide


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Poisoning by Hydrogen Peroxide

Hydrogen peroxide is used in medicine as antiseptic and disinfectant

Hydrogen peroxide has two mechanisms of toxicity; local tissue injury

and gas formation. The extent of local tissue injury is determined bythe strength of the hydrogen peroxide solution:

Dilute hydrogen peroxide (usually 3%) is an irritant

Concentrated hydrogen peroxide (10-30%) is a caustic

Gas formation results when hydrogen peroxide interacts with tissuecatalase, liberating molecular oxygen and water.

The main symptoms of toxicity are vomiting, abdominal pain and

gastric mucosal erosions

Treatment:

1. Give water or milk to dilute

2. Use gastric tube to prevent increased pressure

Poisoning by Sulphuric Acid


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Poisoning by Sulphuric Acid

Treatment:

Skin Contact

a. Remove acid by flooding with water for at least 15 minutesb.Do not use chemical antidotes

c. Treat damaged areas as for thermal burns

Ingestion

1. Do not use gastric lavage or emesis because of the danger of

perforation

2. Ingested acid may be diluted by drinking large quantities of water or

milk

3. Treat shock by administration of 5% dextrose in saline

4. Give morphine sulphate to relieve pain

5. Treat asphyxia by maintaining an adequate airway6. If perforation of the stomach or esophagus is suspected

Inhalation

a. Give artificial respiration

b.Treat bacterial pneumonia with organism specific chemotherapy


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Common chemical

Rapidly acting

Blood Agents is a misnomer

No direct effect in blood

Where is cyanide found?Occurs naturally in foods (some fruits, lima beans)Cyanide salts used in industry

(e.g. ore extraction)Produced in smoke of burning plastics/syntheticsElectroplatingMetal polishingSmells like bitter almonds


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Inhibits cellular respiration Cytochrome a-a3

Tissues cannot utilize oxygen

Arterialization of venous blood


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Pulmonary Dyspnea

Tachypnea Pulmonary edema Apnea

Gastrointestinal Nausea, vomiting Caustic effects


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Clinical picture

Lactic acidosis

ABG:

metabolic acidosis

ABG sample

Parameter Finding

PO2 Normal

Calc O2 Sat Normal

Venous O2 Sat Increased


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Remove from source

Oxygen

Cyanide antidote kit

Cyanide kit causes methemoglobinemia


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Amyl nitrite perle until IVestablished

Sodium Nitrite (300mg IV) Peds: 0.33 ml/kg of 10% solution)

Sodium Thiosulfate (12.5gm IV)

Peds: 1.65 ml/kg of 25% solution)

Cyanide antidote kit


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A systematic approach has proven to be themost efficacious way to treat critically illpoisoned patients.

Categorization of the poisoned patientsclinical appearance into a toxic syndromeallows the clinician to initiate effectivetreatment without knowing the specific

poison involved. More research is needed to develop new and

more effective treatments for poisoning.

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poisoning (farmakologi)

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