Pharmacology therapy in acute poisoningocw.usu.ac.id/course/download/1110000130-emergency... ·...
Transcript of Pharmacology therapy in acute poisoningocw.usu.ac.id/course/download/1110000130-emergency... ·...
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Pharmacology therapy inacute poisoning
Prof.Dr.Aznan Lelo,PhD,SpFK
Dr.Datten Bangun MSc,SpFK1
Dept.Farmakologi & Therapeutika
Fak. Kedokteran
U S U
1
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"All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.“
Paracelsus (1493-1541)
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General Management History:
• Applies to ANY episode of Poisoning
= WHAT
= HOW MUCH (Ideally mg/Kg)
= WHEN
= ELSE (Including Alcohol)
= WHY
= Use Paramedics, friends, relatives, anyone!!
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General Management -1
• A (Airway)
• B (Breathing)
• C (Circulation)
• D (Disability-AVPU/ Glasgow Coma Scale)
• DEFG ( Don’t ever forget the Glucose)
• GET A SET OF BASIC OBSERVATIONS
General Management -2
Use all your senses, search for the cluesLOOK -Track Marks
- Pupil SizeFEEL - Temperature, SweatingSMELL - Alcohol
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Specific Management Options-1
. DECREASING DRUG ABSORPTION
– Gastric Lavage
– Absorbants
Specific Management Options -2INCREASING DRUG ELIMINATIONINCREASING DRUG ELIMINATION
- Alkaline Diuresis (Aspirin)- Haemodialysis (Aspirin)
Specific Management Options - 3
ANTAGONISING THE EFFECTS OF THE POISON:- Desferrioxamine ----- (Iron)- Naloxone ---------------- (Opioid)- N- Acetylcysteine------ (Paracetamol)
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TREATMENT OF ACUTE POISONING
• Treat the patient, not the poison", promptly
• Supportive therapy essential
• Maintain respiration and circulation –• Maintain respiration and circulation –primary
• Judge progress of intoxication by: Measuring and charting vital signs and
reflexes
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PREVENTION OF ABSORPTION OF POISON
• Decontamination from skin surface
• Emesis: indicated after oral ingestion of most chemicals; – must consider time since chemical ingested
• Contraindications:• Contraindications:• ingestion of corrosives such as strong acid or
alkali;
• if patient is comatose or delirious;
• if patient has ingested a CNS stimulant or is convulsing;
• if patient has ingested a petroleum distillate
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PREVENTION OF ABSORPTION OF
POISON
Induce emesis in the following ways: • mechanically by stroking posterior pharynx;
• use of syrup of ipecac, 1 oz followed by one glass of water;
• use of apomorphine parenterally• use of apomorphine parenterally
Gastric lavage: insert tube into stomach and wash
stomach with water or ½ normal saline to remove unabsorbed poison
Contraindications:= should not be attempted with young children,
= are the same as for emesis except that the procedure
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PREVENTION OF ABSORPTION OF
POISON
• Chemical Adsorption1 activated charcoal will adsorb many poisons thus
preventing their absorption
2 do not use simultaneously with ipecac if poison is excreted into bile in active formexcreted into bile in active form
adsorbent in intestines may interrupt enterohepatic circulation
PurgationUsed for ingestion of enteric coated tablets when time after ingestion is longer than one hour Use saline cathartics such as sodium or magnesium sulfate
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PREVENTION OF ABSORPTION OF POISON
Chemical Inactivation
• Not generally done, particularly for acids or bases or inhalation exposure
• For ocular and dermal exposure as well as burns on skin; treat with copious watercopious water
Decreasing passive resorption:= from nephron lumen------Diuresis= Cathartics= Peritoneal dialysis = Hemodialysis = Hemoperfusion
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Antagonism of the absorbed poison
• If poisoning is due to agonist acting at receptors for which specific antagonist is available; antagonist may be available
• Drugs that stimulate antagonistic
• If poisoning is due to agonist acting at receptors for which specific antagonist is available; antagonist may be available
• Drugs that stimulate antagonistic • Drugs that stimulate antagonistic
physiologic mechanisms may of little
clinical value; titration difficult
• Use of antibodies
• Drugs that stimulate antagonistic
physiologic mechanisms may of little
clinical value; titration difficult
• Use of antibodies
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Acute poisoning,a dynamic process
possible death
Worsening
possible sequelae
Timet 0
recoveryfree interval
24 to 72 h
exposureexposure
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Prehospital emergency care
• Decreasing the ‘free medical interval’
– Diagnosis or approximation of diagnosis
– Evaluation of severity, recognition of risk
factorsfactors
– Supportive treatment
– Specific treatment? antidotes?
– Prevention of early complications
– Orientation (Hospital, ICU)
• As early as possible
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Antidotes drugs• Atropine
• Beta-blockers
• Calcium gluconate
• Dicobalt edetate
• Digoxin antibodies
• Ethanol
• Glucagon
Methylene blueNaloxoneOxygenPhentolaminePhysostigminePrenalterolProtamin sulphate• Glucagon
• Glucose
• Hydroxocobalamin
• Isoprenaline
• 4-methylpyrazole
Protamin sulphateSodium nitriteSodium nitroprussideSodium thiosulfate
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Questions?
• Is the antidote effective?
• Is the antidote needed within one hour?
• How many patients should a facility prepare for …?
• What amount of the antidote is needed to • What amount of the antidote is needed to treat a 70-Kg patient?
Dinegara kita:=antidotum apa yang tersedia?= di RS kita,antidotum apa yg harus ada?
Dinegara lain bagaimana?
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Toxidromes
• Patterns of signs and symptoms
• Useful to help in diagnosis and • Useful to help in diagnosis and treatment of unknown poisons
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• Opium– Fluid obtained
from the poppy plant
• Opiate– a substance
derived from opium
DEFINITIONS
OPIOID
Papaver Somniferum“Poppy Plant”
opium• Opioid
– substance with morphine-like actions, but not derived directly from the poppy plant
Opiate or opioid tend to be used interchangeably.
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In the class of opioid/opiate substances, all of the following can be prescribed legally
except for heroin.
• Heroin*
• Morphine
• Oxycodone– OxyContin– Percodan– Percocet• Codeine
• Methadone
– Percocet
• Hydrocodone– Vicodin
• Fentanyl• Hydromorphone
– Dilaudid
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OPIATE INTOXICATION�MOST COMMON
� Miosis (small pupils; except with Demerol use which causes paralysis of the ciliary body and pupils dilate)
� Nodding
� Hypotension (low blood pressure)� Hypotension (low blood pressure)
� Depressed respiration
� Bradycardia (slow heart rhythm)
� Euphoria
� Floating feeling
Classic triad seen in opioid OD:=Miosis,respiratory depression,coma
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Rescue breathing
Many agencies teach mouth to mouth
Treatment in opioid OD:
How about Oxygen?
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Naloxone (Narcan)
• Opioid antagonist which reverses opioid related sedation and respiratory depression and may cause withdrawal
• Displaces opioids from the receptors, then • Displaces opioids from the receptors, then occupies the receptor for 30-90 minutes
• No psychoactive effects
• Over the counter in Italy
• Routinely used by EMS
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Administration of naloxone:
• Inject into muscle but subcutaneous and intravenous are also effective
• Acts in 2-8 minutes
• If no response in 2-5 minutes repeat
• Lasts 30-90 minutes
Injectable Inexpensive- $0.25- 1.00 / dose
Well-documented effectiveness Requires injection
Naloxone preparations
IntranasalMore expensive $6-9.00 per doseLess well-documentedEasier to use
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Sympathomimetics / Stimulants
• Agitation/delusions/paranoia
• Fight/Flight response
• Tachycardia
• Hypertension
Toxidromes
• Hypertension
• Arrhythmias
• Dilated pupils
• Seizures
• Hyperpyrexia
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Common causes• Cocaine
• Amphetamines
• Decongestants
• Ecstasy
Treatment:until now:- benzodiazepine,or hypothermia
How about β-adrenergic blockers?---���� it opposes only β-,not α-adrenergic
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Anticholinergic• Tachycardia
• Arrhythmias
• Pupils: mid-point or dilated / divergent
• Confusion / drowsiness / coma
• Seizures
• Dry flushed skin
Toxidromes
• Dry flushed skin
• Urine retention
• Hypertonia, Hyper-reflexia, Myotonic jerks
Anticholinergic signs -Hot as a hare-Blind as a bat-Dry as a bone-Red as a beet -Mad as a hatter
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Common causes
• Antidepressants-Tricyclics
• Antihistamines
• Atropine
• Antipsychotics
• Antispasmodics• Antispasmodics
Treatment for atropin intoxication:= physostigmine
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Serotonin Syndrome
• Similar to anticholinergic syndrome
– loss of consciousness: uncommon
– sweating and tremor: common
• Agitation
• Delirium
• Hypertonia / myoclonus
• Tachycardia
• Tachypnoea
Common Causes
= SSRIs= MAOIs (Hyperpyrexia / Hypertensive crisis)
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Cholinergic
• Brady/tachycardia
• Confusion/reduced GCS
Common causes:= Organophosphates= Physostigmine= Some mushroom= Nerve gas
Toxidromes
• Confusion/reduced GCS
• Pinpoint pupils
• Seizures
• Weakness
• SLUDGE--------------�
• Pulmonary oedema
S sweating ,salivationL lacrymationU urinary frequency
urgencyD diarrhoeaG gastrointestinal discomfortE eyes pinpoint
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Organophosphate
Mechanism of action
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• Clinical Syndrome
• Acute Cholinergic:
– Central
– Peripheral Muscarinic
Clinical Syndrome
Respiratoryfailure
+ Death
– Peripheral Muscarinic
– Peripheral Nicotinic
• Intermediate Syndrome
• OPIDN: Delayed peripheral neuropathy
• Neurocognitive dysfunction
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Signs and Symptoms of
Organophosphate poisonings
- diarhea,abdominal pain,vomitting
- blurred vision
Clinical Findings:Clinical Findings:- S alivation- L acrimation- U rination- D iarrhea- G astroenteric disorders- E yes pinpoint
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CNS effects
• Malaise
• Memory loss
• Confusion
• Disorientation• Disorientation
• Delirium
• Seizures
• Respiratory centre depression or dysfunction
• Coma
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ManagementThe priorities in management are :
I.General & Specific poisoning management
II.Antidotes:
= Atropin
= Oximes= Oximes
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Atropine• Loading
– Doubling dose regime e.g. 2 , 4, 8, 16 mgs every 5 minutes
• Maintenance– Continuous infusion < 3mg/hr
– 10-20% of loading dose/hour
• Endpoints• Endpoints– Clear chest on auscultation with no wheeze
– Heart rate >80 beats/min
• Withdrawal– Atropine toxicity
– Clinical Improvement
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What if you give too much Atropine ?
• Anticholinergic Syndrome:
– Hot as hell
– Blind as a bat
– Red as a beet
– Dry as a bone
– Mad as a hatter
• A sensitive indicator for ingestion, but poor predictor for toxicity.
• Full syndrome is rare
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Paracetamol• Very common: 40% poisons admissions
• Often asymptomatic
• Can be lethal –-���� 200-300 deaths/year
Paracetamol metabolism
Metabolised by glucuronidation (60%),Sulphation (35%) and oxidation (10%)
= A minor but highly active metabolite (N-acetyl-p-benzoquinone imine = NAPQI) is usually neutralized by gluthathione,but in case of overdosis,the amount of gluthathione is not enough------- hepatotoxicity
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Who are at High Risk ?
• Increased oxidation
– Chronic alcohol use
– Drugs
• Reduces glutathione stores
– Malnutrition
– Eating disorders
– Chronic liver disease
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N-acetylcysteine
• Most effective within 8 hours
• Precursor for glutathione production
• Dosage:
= 150 mg/kgbw,given in bolus in 60 minutes
Treatment of Paracetamol intoxication
= 150 mg/kgbw,given in bolus in 60 minutes
in 50 or 200 ml of diluted Hidonac®
= followed by subsequent doses at slow infu-
sion,every 4 hours for at least 72 hrs
Adverse drug reaction: -urticaria,skin rash,angioedema,-bronchospasm,nausea,vomitting,fever.
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SalicylateLife-threatening of salicylate poisoning:
= predominantly;- acid-base abnormalities
= CNS dysfunction
= other effects: - nephrotoxic,ototoxic= other effects: - nephrotoxic,ototoxic
= Metabolic and acid-base disturbance= Complex= Respiratory alkalosis – direct stimulation to over
breathe=Metabolic acidosis- acid, impaired normal
metabolism, production of lactic acid & excretion ofNaHCO3 thru’ the kidney
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Salicylate overdose management
• Tailor treatment to symptoms
• Fluids--� IV Na+HCO3
• Reduce absorption:• Activated charcoal
• Tailor treatment to symptoms
• Fluids--� IV Na+HCO3
• Reduce absorption:• Activated charcoal• Activated charcoal
• Gastric lavage (>500 mg/kg and <1 hour)
• Increase elimination:• Urinary alkalinisation
• Cooling
• Glucose if hypoglycaemic
• Activated charcoal
• Gastric lavage (>500 mg/kg and <1 hour)
• Increase elimination:• Urinary alkalinisation
• Cooling
• Glucose if hypoglycaemic
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Salicylate overdose management
• <350mg/L: oral fluids
• >350mg/L: urinary alkalinisation
• >700mg/L: haemodialysis
Severity of ingested dose:>150 mg/kg: mild>250 mg/kg: moderate>500 mg/kg: severe
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PHARMACOLOGIC THERAPYFOR CIRCULATORY FAILURE
Circulatory Failure:
= the inability of the circulatory system to
adequately supply metabolic substrate to
the cells of the body.the cells of the body.
What the doctors must do?
----� act quickly to restore the blood flow to an adequate level.
How?
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Not only by:
= increasing the blood pressure or
= the cardiac out put
But also:
= must achieve adequate perfusion to = must achieve adequate perfusion to all important vascular beds, …But
= must not stress the CVS or induce further injury
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β- Adrenergic Receptor Agonists
- Dopamine
- Dobutamine
- Adrenaline
- Noradrenaline- Noradrenaline
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Receptor Selectivity of SympatomimeticReceptor type
α1 α2 β1 β2 D1
AGENT Vasocon- Presynaptic Increases Vasodilates Low dose
stricts pe- inhibition HR,inotro- peripheral vaso dilaripheral at NA synap pic,diasto- vessels te renalvessels ses lic relaxat. Veselsvessels ses lic relaxat. Vesels
-Dopamine + ++ ++ ++-Dobutamine +/- ++ +
-Adrenaline ++ ++ ++ ++ -Noradren. ++ ++ ++
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Dopamine
- Is an endogenous sympatomimetic amine
- Function as a neurotransmitter
- Is a biosynthetic precursor of adrenalin and noradrenalin.
- Activates cardiac β1-adrenergic receptor--����
= increase contractility
= increase heart rate
Unlike noradrenaline, at low doses,dopamine:
= vasodilator effect in periphery,because;
-it stimulates dopaminergic D1 receptors inrenal and mesenteric vascular beds----���� reduce afterload
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At intermediate doses,dopamine:
= causes more widespread vasodilatation----
���� greater reduction in systemic vascular resistance
At higher doses,dopamine:
= activation of α1-receptors predominates---����
generalized vasoconstriction---���� increased
afterload
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INDICATIONS
In low and intermediate doses;
= in cardiogenic shock
= in CHF
But now has been supplanted by
= dobutamine or
= phosphodiesterase inhibitors
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Dobutamine- A synthetic sympatomimetic amine.
- The predominant overall effects is agonist at
cardiac β1-receptors ---���� modest peripheral vasodilatation via agonist action at peripheral β2- receptors
COMT rapidly metabolize dobutamine------����t½ is about 2,5 minutes
Side-effects:- cardiac arrhytmia--����supra-ventriculartachyarrhytmia, BUT less than DOPAMINE
==���� dobutamine is preferred in cardiac shock
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Adrenaline (Epi)
=non-selective adrenergic agonist
= exogenously administered Epi stimulates:
- β1-,β2-,α1- and α2- receptors
- the net effects depend on the dose
= At all dose levels Epi is a potent ,β1- agonist
----���� - positive inotropic,chronotropic and lusi-----���� - positive inotropic,chronotropic and lusi-tropic (diastolis relaxation) effects
= Low dose: stimulates peripheral β2-
Higher dose: stimulate α1- ,--���� vasoconstr.
tachycardia
===���� high dose Epi is less desirable
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Indication of Noradrenalin:
1.In the setting of resuscitation ofcardiac arrest
2.Non cardiovascular:= bronchospasm (via β2-mediated
bronchial relaxationbronchial relaxation= potentiation of the effect of
local anaesthesia ( via local α1-mediatedvasoconstriction
= treatment of allergic hypersensitivereactions
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Phosphodiesterase Inhibitors
= Increase cardiac contractility by raising
intracellular cAMP level----���� indirectly
increase calcium intracellular
PDE-I ---����inhibit PDEPDE-I ---����inhibit PDE
cAMP intracel.
Ca++ intracel
Contractility
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PDE3-Inhibitors :- Amrinone- Milrinone- Aminophylline
- Theophylline
PDE3-Inhibition: -----���� cAMP
-Contractility-HR
Inotropic +I
II. –peripheral dilatation
PDE3-I -----���� -ino-dilators
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