1. Barbiturate poisoning

2. Babiturate poisoning
Substituted derivative of barbituric acid (derived from urea-malonic acid)
Classification
Long
Barbital, Phenobarbital
Intermediate
Amo barbital, Buta barbital
Short
Pento barbital
Seco barbital
Ultra short
Thio
Methohexital

3. Mechanism of action Acts at GABA-BZD receptor-Cl- channel complex
Potentiate GABAnergic inhibition by increasing life time of Cl- channel opening
Increased conc barbiturate   Cl- conductance  depress Na+/K+ channels

4. Properties Long Inter Short Ultrashort Barbital Pheno barbital Amo
Buta
Pento
Seco
Thio
Metho
Pka
7.74
7.25
7.7
7.96
7.9
7.6
Detoxi-fication
Renal
Hepatic
Duration (hr)
>6
3-6
<3
0.3
Half life (hr) X
24-140
8-42
34-42
21-42
20-28
6-46
1-2
Fatal dose (gm) 10 5 30 x

5. Clinical features of over dose
sign and symptom are variable and depend on stage of intoxication
Significant toxicity 4mg/dl(long acting) ,2mg/dl(short)
Mild - Resembles Alcohol intoxication
Moderate - depression of mental status, response to painful stimuli, deep tendon reflex & slow resp
Severe- coma & loss of all reflexes except light reflex planter extensor, hypothermia & hypotension
Both acute / chronic intoxications are seen but the chronic form occurring at dose higher (ten times) than those required for acute.

6. A. Central N system Act as depressant
Primary feature : impaired level of consciousness
Main features include : restlessness, insomnia, delirium, hallucinations, confusion, slurred speech, ataxia, convulsions, coma.
Increased intoxications
Increased depth of coma
Increased loss of neurological function

7. Clinical features of over dose (contd…)
B. Respiratory system
Direct depressant action : on respiratory centre(medulla)
Decreased respiratory rate, hypoventilation
Cyanosis and shallow respiration
Loss of hypoxic drive / influence on sensitization of chemoreceptors
Later part  develop pneumonia, non-cardiogenic pulmonary edema

8. Clinical features of over dose (contd…)
C. Cardiovascular
decreased myocardial contractility
Direct vascular smooth muscle relaxation (vasodilatation)
Excessive capillary exudation  venous pulling  hypovolemia  decrease BP  shock
severe cases : medullary depression of CVS regulation
D. Hypothermia
Significant
Due to depression of hypothalamic temp regulation centre
vasodilatation effects
During recovery : pyrexia occurs

9. Clinical features of over dose (contd…)
E. Skin
Occurs at an early stage
Bullous
Not specific
: over pr points & dorsum of fingers

10. Clinical features of over dose (contd…)
F. Ocular
Nystagmus / dysconjugate eye movements
Miosis  early manifestation
Later hypoxia + paralysis of pupillary sphincter  Mydriasis
G. Gastrointestinal system
Assess the severity of poisoning
Unconsciousness+lack of bowel sounds severely poisoned

11. Clinical features of over dose (contd…)
H. Renal system
Severe hypotension with hypothermia  significant impairment of renal function
ARF shock& hypoxia 16% death
Judicious use of vasopressor drugs like dopamine / dobutamine and timely hypotension correction can prevent rental shut down

12. Clinical features of over dose (contd…)
I. Laboratory evaluation
Investigations
CBC, serum electrolyte, urea,, creatinine, glucose, ABG analysis, chest x-ray
Serum barbiturate level
Urine level (common)

13. If other drugs present :interference in measurement
Depth/duration of coma depend on concentration of barbiturate in brain (not plasma level)
Recently
Gas liquid chromatography 
Based on influence of pH on UV absorption spectrum of drug

14. Management No specific antidote supporting therapy is adequate
Removal of the source
gastric lavage
Activated charcoal (1gm/kg)
Repeat every 2-4 hourly
slow continuous administration till patient improves

15. Management of barbiturate poisoning (contd…)
2. Supportive care
Assessment and stabilisation of the airway oxygenation, mechanical ventilation if required
Maintenance of blood volume / correction of dehydration, fluid infusion and use of vasopressor
Rewarming
3. Forced alkaline diuresis
long acting barbiturate poisoning (phenobarbitone), eliminated primarily by renal excretion
pt adequately hydrated, with stable CVS / renal status
Frusemide 250mg in with IV NaHCO3 (1.4%)
Urinary pH , but plasma pH <7.5
Barbiturates are acidic, ionise in alkaline urine, not absorbed back and hence excreted

16. Management of barbiturate poisoning (contd…)
4 Hemodialysis and hemoperfusion : (activated charcoal or other adsorbents)
- Remove long &short acting barbiturates
use of analeptics abandoned
Instead of emphasizing the termination of coma, attention directed at
Intensive supportive therapy
Respiratory care / support
Cardiovascular support

17. Thank You