patologi

Pharmacology therapy in acute poisoning
Datten Bangun, Aznan Lelo

Dep. Farmakologi & Terapeutik,
Fakultas Kedokteran

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!!
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
Specific Management Options-1
. DECREASING DRUG ABSORPTION
Gastric Lavage
Absorbants
TREATMENT OF ACUTE POISONING
Treat the patient, not the poison", promptly
Supportive therapy essential
Maintain respiration and circulation – primary
Judge progress of intoxication by:
Measuring and charting vital signs and reflexes

PREVENTION OF ABSORPTION OF POISON
Decontamination from skin surface
Emesis: indicated after oral ingestion of most chemicals;
must consider time since chemical ingested
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
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
PREVENTION OF ABSORPTION OF POISON
Chemical Adsorption
1 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 form
adsorbent in intestines may interrupt enterohepatic circulation
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 water

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 physiologic mechanisms may of little clinical value; titration difficult
Use of antibodies
Acute poisoning,a dynamic process
Prehospital emergency care
Decreasing the ‘free medical interval’
Diagnosis or approximation of diagnosis
Evaluation of severity, recognition of risk factors
Supportive treatment
Specific treatment? antidotes?
Prevention of early complications
Orientation (Hospital, ICU)
As early as possible
Antidotes drugs
Atropine
Beta-blockers
Calcium gluconate
Dicobalt edetate
Digoxin antibodies
Ethanol
Glucagon
Glucose
Hydroxocobalamin
Isoprenaline
4-methylpyrazole

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 treat a 70-Kg patient?
Toxidromes

Patterns of signs and symptoms

Useful to help in diagnosis and treatment of unknown poisons




DEFINITIONS
Opium
Fluid obtained from the poppy plant
Opiate
a substance derived from opium
Opioid
substance with morphine-like actions, but not derived directly from the poppy plant

In the class of opioid/opiate substances, all of the following can be prescribed legally except for heroin.
Heroin*
Morphine
Codeine
Methadone
Oxycodone
OxyContin
Percodan
Percocet
Hydrocodone
Vicodin
Fentanyl
Hydromorphone
Dilaudid


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)
Depressed respiration
Bradycardia (slow heart rhythm)
Euphoria
Floating feeling
Rescue breathing
Many agencies teach mouth to mouth
Naloxone (Narcan)
Opioid antagonist which reverses opioid related sedation and respiratory depression and may cause withdrawal
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

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
Sympathomimetics / Stimulants
Agitation/delusions/paranoia
Fight/Flight response
Tachycardia
Hypertension
Arrhythmias
Dilated pupils
Seizures
Hyperpyrexia
Common causes
Cocaine
Amphetamines
Decongestants
Ecstasy
Anticholinergic
Tachycardia
Arrhythmias
Pupils: mid-point or dilated / divergent
Confusion / drowsiness / coma
Seizures
Dry flushed skin
Urine retention
Hypertonia, Hyper-reflexia, Myotonic jerks
Common causes

Antidepressants-Tricyclics
Antihistamines
Atropine
Antipsychotics
Antispasmodics

Serotonin Syndrome

Similar to anticholinergic syndrome
loss of consciousness: uncommon
sweating and tremor : common
Agitation
Delirium
Hypertonia / myoclonus
Tachycardia
Tachypnoea
Cholinergic
Brady/tachycardia
Confusion/reduced GCS
Pinpoint pupils
Seizures
Weakness
SLUDGE--------------
Pulmonary oedema
Organophosphate
Clinical Syndrome
Clinical Syndrome
Acute Cholinergic:
Central
Peripheral Muscarinic
Peripheral Nicotinic
Intermediate Syndrome
OPIDN: Delayed peripheral neuropathy
Neurocognitive dysfunction
Signs and Symptoms ofOrganophosphate poisonings
- diarhea, abdominal pain, vomitting
- blurred vision
CNS effects
Malaise
Memory loss
Confusion
Disorientation
Delirium
Seizures
Respiratory centre depression or dysfunction
Coma
Management
The priorities in management are :
I.General & Specific poisoning management
II.Antidotes:
= Atropin
= Oximes


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
Clear chest on auscultation with no wheeze
Heart rate >80 beats/min
Withdrawal
Atropine toxicity
Clinical Improvement

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
Paracetamol
Very common: 40% poisons admissions
Often asymptomatic
Can be lethal –- 200-300 deaths/year

Who are at High Risk ?
Increased oxidation
Chronic alcohol use
Drugs

Reduces glutathione stores
Malnutrition
Eating disorders
Chronic liver disease
N-acetylcysteine
Most effective within 8 hours
Precursor for glutathione production
Dosage:
= 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


Salicylate
Life-threatening of salicylate poisoning:
= predominantly;- acid-base abnormalities
= CNS dysfunction
= other effects: - nephrotoxic,ototoxic






Salicylate overdose management
Tailor treatment to symptoms
Fluids-- IV Na+HCO3
Reduce absorption:
Activated charcoal
Gastric lavage (>500 mg/kg and <1 hour)
Increase elimination:
Urinary alkalinisation
Cooling
Glucose if hypoglycaemic


Salicylate overdose management
<350mg/L: oral fluids
>350mg/L: urinary alkalinisation
>700mg/L: haemodialysis

PHARMACOLOGIC THERAPYFOR CIRCULATORY FAILURE
Circulatory Failure:
= the inability of the circulatory system to
adequately supply metabolic substrate to
the cells of the body.
What the doctors must do?
---- act quickly to restore the blood flow to an adequate level.
How?
Not only by:
= increasing the blood pressure or
= the cardiac out put
But also:
= must achieve adequate perfusion to all important vascular beds, …But
= must not stress the CVS or induce further injury
β- Adrenergic Receptor Agonists
Dopamine
Dobutamine
Adrenaline
Noradrenaline
Receptor Selectivity of Sympatomimetic
Receptor type
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;


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
INDICATIONS
In low and intermediate doses;
= in cardiogenic shock
= in CHF

But now has been supplanted by
= dobutamine or
= phosphodiesterase inhibitors
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


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-tropic (diastolis relaxation) effects

= Low dose: stimulates peripheral β2-

Indication of Noradrenalin:
Phosphodiesterase Inhibitors
= Increase cardiac contractility by raising
intracellular cAMP level---- indirectly
increase calcium intracellular

PDE-I ---inhibit PDE
PDE3-Inhibitors :- Amrinone - Milrinone
- Aminophylline
- Theophylline