Somniferous poisons

Dr M. Malleswari Asso. prof NRI MEDICAL COLLEGE

Opium cultivation in India

OPIUM
Obtained from Papaver somniferum white poppy plant in India Each plant produces around 5-8 capsules Unripe capsule rich in alkaloids Ripe capsule minimal or no alkaloids Opium is a coagulated air dried latex juice obtained by longitudinal incisions of the unripe capsule of white poppy plant Air dried to obtain dark brown opium

Capsule of papaver somniferum

Capsule incision

Incised capsule oozing latex

Removing the extract from capsule

 Unripe capsule rich in alkaloids

Ripe/ dry capsule minimal traces sedative /

narcotic
Dry capsule poppy seeds kus kus
Strong pungent odour and bitter taste
carminative

Poppy seed oil seeds no alkaloid at all

Indian poppy plants 40% alkaloids 10%

morphine Asia minor plants( Turkey, Afghanistan, Pakistan) 20% of morphine content India produced under license Ghaziapur - limited

Poppy seeds kus kus

Alkaloids in two groups

Phenanthrene group Isoquionline group
Narcosis Mild analgesia, no narcosis

1. Morphine (10%)
2. Codeine 3. Thebaine

1. Narcotine (noscapine

6%) 2. Papaverine

Classification
1.
2. 3.

Natural: morphine, codine

Semi-synthetic: Synthetic:
heroin, hydromorphine, oxymorphone

methodone, meperidine, levarphanol tartrate, fentanyl, propoxyphene

Action/ metabolism
Opiod receptors in body and especially in CNS and spinal cord
Endogenous opioids endorphins / enkephalins / dynorphins
Opiod receptors:
1. 2. 3. 4.

Mu Euphoria / supraspinal analgesia / respiratory

depression / constipation Kappa Spinal analgesia / CNS depression / miosis Sigma Psychomimetic effects (dysphoria, hallucination, delusions, increased HR, BP, RR) Delta - Analgesia

 Route ingested, inhaled, I.V, I.M, subcutaneous Symptoms with IV much faster than smoking
Circulated in body, metabolized by the liver
Conjugated with glucuronic acid to form glucuronides

Opioids decrease GI motility constipation

Decreased gastric emptying

increased duration of toxin extraction

Active secretion of morphine to stomach when

taken by whatever route

Acute poisoning
Similar to morphine poisoning Within few mins of injection and hr post ingestion Causes dermatitis if applied on skin on some individuals hypersensitivity, erythema, urticaria. Stages of acute poisoning:
1. Stage of excitement or euphoria
2. Stage of stupor 3. Stage of narcosis or coma

I. Stage of excitement (euphoria)

Euphoria

Very short duration and not seen in huge intake

Increased sense of well being, increased mental

activity, freedom from anxiety Talkative, restlessness Hallucinations In children convulsions

INTOXICATION OR WITHDRAWAL?

Always look at the pupils; the pupil size can give very good clinical information.

INTOXICATION OR WITHDRAWAL?

Withdrawal

Intoxication

II. Stage of stupor

Headache, nausea and vomiting

Incapacity for exertion,

characteristic

heaviness in limbs very

Giddiness and drowsiness

Decreased sensations
Intense desire to sleep Constricted pupils

Face and lips cyanosed

Smell + Pulse & respirations normal

III. Stage of narcosis / coma

Deep unarousable coma Flaccid muscles and areflexia
Later pupillary dilatation terminal anoxia

PIN POINT pupils

no light response

Decreased brain stem response to CO2 Slow shallow pulse with clammy peripheries

and dry mucous membranes All secretions suspended except sweat Death due to respiratory paralysis Smell +

Morphinism/ morphinomania
Young adults 3 to 6 g/ day Tolerance to its effects increased dose Aphrodisiac and euphoric later on impotence Dry skin with tattoos, features of skin popping, mainlinig Initial euphoria anhedonia and depression Insomnia, memory loss, decreased intellect, hallucinations + Constipation, contracted pupils, emaciation Fatal addiction

DD for opium poisoning

1. OPIUM POISONING smell, pinpoint pupils, dry

MM with wet skin, low temperature and decreased R. Triad of coma, pinpoint pupils, respiratory depression

2. Barbiturate poisoning
blisters pupils

dilated pupils, barbiturate smell, dilated reacting

3. Acute alcohol intoxication 4. Carbolic acid poisoning

5.
6.

carboluria, smell, whitened mucous membranes

Carbon monoxide poisoning convulsions, cherry red discoloration, carboxyHb Epileptic coma seizures +, frothy mouth, tongue may be bitten, rapid recovery

7. 8. 9. 10. 11.

12. 13. 14. 15.

Uraemic coma ammonical smell, features of renal failure, cheyne-stokes breathing Diabetic coma known DM, low temp, acetone breath, increased glu. levels in blood and urine CNS trauma head injury, bleeding +, cheyne stokes, unequal pupils, SCH Cerebral malaria fever e chills, spleen +, PF + Heat hyperpyrexia high temperature exposure, dry hot skin, congested conjunctiva with contracted pupils, Circulatory collapse CVAaccidents Encephalitis Hysterical coma Meningitis

CONDITION
Opium poisoning Barbiturate poisoning Acute alcohol intoxication Carbolic acid poisoning Epileptic coma Uraemic coma Diabetic coma CNS trauma Cerebral malaria Heat hyperpyrexia

FEATURES
smell, pinpoint pupils, dry MM with wet skin, low temperature and decreased R.
dilated pupils, barbiturate blisters smell, dilated reacting pupils carboluria, smell, whitened mucous membranes

Carbon monoxide poisoning convulsions, cherry red discoloration seizures +, frothy mouth, tongue may be bitten, rapid recovery ammonical smell, features of renal failure, cheyne-stokes breathing known DM, low temp, acetone breath, increased glu. levels in blood and urine
head injury, bleeding +, cheyne stokes, unequal pupils, SCH

fever e chills, spleen +, PF + high temperature exposure, dry hot skin, CVS collapse

Treatment of acute poisoning

ABC Removal of unabsorbed poison: GIT

Gastric lavage

Useful in delayed cases also and it decreases

gastric emptying 1:5000 KMnO4 in water oxidizes opium unabsorbable Useful even if drug injected or inhaled Activated charcoal

General measures IVF, temperature control,

antibiotics

OPIOD ANTAGONISTS Competes with opioids at the receptor sites naloxone 2 mg I.V repeated every minute, upto a total dose of
10- 20 mg I.V

Useful Reverses respiratory depression, analgesic and euphoric actions of opioids Delusions, dysphoric and hallucinogenic activity of synthetic opioids Infusion in case of long acting opioids Given to correct respiratory depression but not

to precipitate withdrawal Nalmefene long action time COMA COCKTAIL

Post mortem features

Intense lividity bluish discoloration

Initial smell- later degraded

RS signs of asphyxia (congestion, cyanosis,

Petechial haemorrhages)
Lumps of opium may be present in GIT
Lab morphine and analogues (rarely detected)

Marquis Test
H2SO4 + Formalin + substance = purple- violet / blue

Skin popping

Mainlinig

Treatment of chronic addiction Supportive therapy Nutritional rehabilitation Gradual withdrawal of drug Replacement with a less addictive opiod to control withdrawal symptoms (methadone) Use of B blockers to reduce anxiety and craving
WITHDRAWAL SYMPTOMS Nausea and diarrhea Lacrimation, midriasis, goose flesh, increased sympathetic drive, YAWNING, CRAVING Peaks in 36-72 hrs, disappears in 5-8 days

HEROIN
Brown sugar Diacetyl morphine

 White, brown and black tar Smack, junk or dope

Speed balls (Powerballing) heroin and cocaine

Smoked, chasing the dragon

Injected, or snuffed skin popping, mainlining

 Diacetyl to acetyl to morphine

No oral rapidly hydrolysed Post injection monoacetymorphine and

morphine only seen Tolerance in days Preferred over morphine due to its high euphoria CNS depression main cause of death

HEROIN

Fatal dose50 mg

SIGNS AND SYMPTOMS as morphine TREATMENT ABC/ Antagonist / Methadone to prevent withdrawal symptoms POSTMORTEM Nonspecific Needle marks, perivenus fibrosis Contaminants like talc etc foreign body granulomas in lung and liver, Sudden cardiac death cardio toxic Heroin lung congested frothy lung Brampton's cocktail morphine/ heroin/ CPM/ OH terminal CANCER Drug users elbow MYOSITIS OSSIFICANS

Meperidine

Hypnotics
Barbiturates
Used by the Nazis during WWII for euthanasia

Benzodiazepines

Miscellaneous agents Chloral hydrate

Phenobarbitone Pentobarbitone Hexobarbitone Thiopentone

Classification
Long acting Phenobarbitone Onset - 2hr Action; 6-12 hr (Ac)
Intermediate acting

Pentobarbitone

Onset hr

Action 3-6 hr

Short acting

Hexobarbitone
Thiopentone
(A)

Onset quick

Action - <3hr

Ultra short acting

Onset immediate

Action 5-10min

Absorption, fate and excretion GI / IV / PR Detoxified by alkylation and oxidation in liver Renal excretion upto 1 week post intake
Recreational use Intoxication similar to alcohol (mild to moderate)
Slurred speech Decreased motor coordination Impaired judgment

Rapid tolerance to the drug

Physical dependence Psychological dependence Amount intake coma amount - death

MECHANISM OF ACTION
Phenobarbital and other barbiturates Enhance the inhibitory actions of GABA Interact with different receptor site on Cl- ion channel Increased duration of Cl- ion channel opening

GABA binding site Barbiturate binding site

GABA

SYSTEM
CNS

FEATURES
Drowsy, confused, delirious, hallucinations (+) Slurred speech, stupor, muscular incordination Coma and barbiturate automatism; Pupils little contracted & reacting to light Hypothermia Depresses myocardium and causes smooth muscle relaxation and medullary depression Low cardiac output, hypotension, cold peripheries

CVS

RS

Respiratory depression with decreased Minute volume (3-4L/min) Rapid and shallow or slow and laboured

Signs & symptomsAcute poisoning

Confusion, excitement, delirium, hallucinations, ataxia Stupor progressing to deep comaloss of reflexes

Resrapid and shallow or slow and laboured Cvs cardiac output, cvs collapse,

Barbiturate blisters

Treatment of Barbiturate poisoning

Deaths due to respiratory depression/ VF
ABCScandinavian method Gastric lavage (8hr post ingestion) KMnO4 + charcoal Bowel evacuation Analeptics CNS stimulants (amphetamines) Hemodialysis or peritonialdialysis Alkaline diuresis & promoting diuresis symptomatic treatment

Postmortem features non specific

Withdrawal
Barbiturates
REM Rebound Excitation Tremors Insomnia Nausea Hallucinations Convulsions

TOXICITY Additive CNS depression When used with Alcoholic beverages Antihistamines Antipsychotic drugs Opioid analgesics Tricyclic antidepressants

Acute withdrawal from medication GTC, grand mal, disability and even death Lethal Uses
Physician assisted suicide (PAS) - euthanasia Legal punishment Barbiturates + muscle relaxants

Signs and symptoms

Depending on amount and duration of intake CNS, CVS, RS main Single large or repeated small doses

Methaqualone (Mandrax)
Anxiolytic and sedative recreational drug Dr M L Gujral during malarial research Relaxation, euphoria, drowsiness, incordination Delirium, convulsions and hyperreflexia Crosses BBB/ hypotension/ MI Similar to barb poisoning but has more motor difficulties and low cardiac and RS depression Symptomatic management Treated with BDZs or anticonvulsants Street Names: Ludes, Qualudes, Vitamin Q, The Love Drug, Wallbangers, Whore Pills

Chloral hydrate

Depressant, colorless, powder with pungent odour Absorbed through GIT and rectum also Metabolized in liver to trichlorethanol hypnotic Conjugated with glucuronic and excreted Signs and symptoms
Similar to barbs Retrosternal burning pain, albuminuria Rashes and respiratory centre paralysis

Treatment
Lavage, dialysis, flumazenil symptomatic

Knockout drops

Alcohol + Chloral hydrate`Mickey Finn`

CNS stimulants
Amphetamines and caffeine
Euphoria, increased energy, alertness and loss of appetite Aggressive behavior, confused thinking exhaustion and

sleepiness Hallucinations, delusions and paranoia seizures, coma and death Most commonly abused substances Recreational drugs and designer drugs

Amphetamines
Alpha methyl phenethylamine Speed or crank club drug CNS stimulant Derived from ephedrine abuse potential

Uses Appetite suppressant Narcolepsy Attention deficit hyperactivity disorder Recreational and performance enhancement

Types Methylene dioxyamphetamine (MDA love drug) Methylene dioxyeth-amphetamine (MDEA eve) Methylene dioxyeth methamphetamine (MDMA) ECSTASY - designer drugs All metabolized to amphetamine stimulant Oral or inhalational uses Mechanism of action
Inhibit release + inhibit reuptake of Ach and H but not glutamate in CNS, catecholamine release Increased excitatory NT - excitation

 Onset of fatigue and sleepiness delayed

Loss of appetite only initially Increased talkativeness and awareness,

insomnia, tremors, dilated pupils, increased HR and BP Agitation, paranoid delusions, hallucinations, convulsions and coma Ecstasy
Hallucinogenic and stimulant/ trismus + bruxism

Treatment Supportive/ sedation/ B blockers

Caffeine (trimethyl xanthines)

Most commonly used mood altering drug Tea, coffee, chocolate, cool drinks Brewed coffee 100 mg (6oz) Instant coffee 70 mg Brewed tea 40 mg Instant tea 30 mg Soft drinks 40 mg Dark chocolate 30 mg (1oz) Analgesics 30 -60 mg Toxic amount = 1 to 2 g

 Stimulates acid, pepsin secretion Direct on myocardium increased excitability

and rate increased CO and SV Reduces tiredness and sleep Increases BMR by 10% Diuresis

Caffeine and anxiety 200 mg% - anxiety and induces panic attacks Caffeine and sleep At bedtime or throughout the day Sleep onset delayed, total time decreased, normal stages of sleep altered and decreased quality

Caffeine and health Delayed conception, LBW Caffeine intoxication/ withdrawal/ dependence Caffeine withdrawal 12 24 hours post termination Headache, fatigue, sleepiness, depressed Decreased concentration, irritability, impaired psychomotor, vigilance and cognitive functions On high levels seizures and cardiac arrest
Treatment General measures, sedatives

Thank you