NEUROTOXICOLOGIC

DISORDERS
 OBJECTIVES

• to identify the different naturally occurring and synthetic substances that may affect the
function of the nervous system
• to describe the adverse effects of naturally occurring and synthetic substances on the nervous
system
• to describe the possible treatment options for the adverse effect of the identified substances
 REFERENCES

• Ropper et. al., Adam’s & Victor’s Principles of Neurology 10th ed.,
• J B Harris, PG Blain, Neurotoxicology: What the neurologist needs to know., 2004
 NEUROTOXICOLOGY

• defined as the science that deals with the adverse effects of naturally occurring and synthetic
chemical agents on the structure or function of the nervous system
• Neurotoxin is a naturally occurring or synthetic chemical agent that can cause a functional or
structural change in the nervous sytem
 GENERAL PRINCIPLES OF
NEUROTOXICOLOGY
• rational use of drugs requires knowledge of:
• the best route of administration
• the drug’s absorption characteristics
• distribution in the nervous system and other organs
• biotransformation
• excretion of the drugs
• all systems of neurons are not identical
• each neuron has it’s own vulnerability to particular drugs and toxic agents
• drugs may target different parts of the neuron like the terminal axons, dendrites or receptors in
the synaptic surfaces
• however, it must not be assumed the modes of action of drugs on nerve cells is exclusive for a
particular mode of action
 GENERAL PRINCIPLES OF
NEUROTOXICOLOGY
• Bioavailability
• oral medications
• majority of drugs acting on the nervous system are ingested
• factors affecting the intestinal absorption is taken into account
• other routes of drug administration may be used
• a drug/ toxic agent to enter the extracellular compartment must be able to cross the:
• capillary-endothelial barrier (blood-brain barrier)
• blood & cerebrospinal fluid (blood-CSF) barrier
• solubility characteristics of a drug determines it’s rate of diffusion
 OPIATES & SYNTHETIC ANALGESIC
DRUGS
• includes all the naturally occurring alkaloids in opium prepared from the seed capsules of the
poppy Papaver somniferum
• for clinical purposes:
• Opiate: refers to the alkaloids that have a high degree of analgesic effect (morphine)
• Opiod & narcotic analgesic: designate drugs w/ actions similar to those of morphine
• Clinical effects of opioids:
• Acute poisoning/ Opioid Overdose
• Addiction
 OPIOID OVERDOSE

• may be a frequent occurrence due to it’s illicit use

• may result from:
• accidental ingestion or injection
• suicidal intent
• errors in dose calculation
• use of substitute
• contaminated street product
• unusual sensitivity of the user
• sensitivity is increase in:
• children
• adults w/ myxedema, addisons disease, chronic liver disease & pneumonia
 OPIOID OVERDOSE

• Clinical manifestation:
• unresponsiveness
• shallow respiration
• slow respiratory rate ( 2 - 8/ min) or periodic breathing
• pinpoint pupils
• bradycardia
• hypothermia
• pulmonary edema or aspiration pneumonia may arise later
• immediate cause of death:respiratory depression w/ consequent asphyxia
 OPIOID OVERDOSE

• Clinical manifestation:
• Mild degree of intoxication may manifest with:
• anorexia
• nausea & vomiting
• constipation
• loss of sexual interest
• Toxicology screens may be useful in the diagnosis but treatment have to be initiated before
the results are completed
 OPIOID OVERDOSE

• Treatment
• ventilatory support
• Naloxone (Narcan) 0.05 mg w/ increasing doses every 2 mins up to a dose of 15 mg IV
• for children:
• initial dose 0.1 mg/kg is recommended
• failure of the effect of naloxone should cast doubt on the diagnosis of opioid overdose
• once patient responds to the naloxone w/c is seen as:
• adequate respiration
• pupillary response
• patient is observed for 24 hours and further naloxone (50% higher the the previous dose) is
given IM as needed
• patient may remain drowsy for many hours
 OPIOID OVERDOSE

• Treatment
• gastric lavage
•done in cases where the drug was ingested
•this may be done many hours after ingestion
•since one of the effects of opioid intake is illeus
• once awake patient may complain of:
•pruritus
•sneezing
•tearing
•piloerection
•diffuse body pains
•yawning
•diarrhea
 OPIOID OVERDOSE

• Treatment
• But the antidote must be used with caution for addicted patients
• use of antidote in addicted patients may induce withdrawal effects
 OPIOID ADDICTION

• Etiology & Pathogenesis

• factors that may contribute to the onset of addiction
• socioeconomic
• psychologic
• pharmacologic factors
• most susceptible are:
• young men
• living in an economically depressed area
• onset:
• usually adolescent
• peaks at 17 - 18 years old
• 90% engage in criminal activity
• many have psychiatric disturbances
 OPIOID ADDICTION

• Etiology & Pathogenesis

• Phases of opioid addiction
1. intoxication/ euphoria
2. pharmacogenic dependence/ drug-seeking behavior (addiction)
3. propensity to relapse after a period of abstinence
• repeated self-administration is the most important factor in the onset of addiction
• the need to increase the dose in order to obtain the original effects is known as tolerance
• physical dependence: refers to symptoms & signs that appear when the drug is withdrawn
following a period of continued use
 OPIOID ADDICTION

• Opioid Abstinence syndrome/ withdrawal syndrome

• depends on:
•dose of the drug
•duration of addiction
• appearance of symptoms depends on the last exposure to the drug
•morphine: 240 mg daily x 30 days or more may show moderately severe withdrawal
symptoms
•15 mg 3 x a day for 3 days may manifest with mild symptoms
 OPIOID ADDICTION

• Opioid Abstinence syndrome/ withdrawal syndrome

• 1st 8 - 16 hours: asymptomatic
• > 16 hours:
•yawning
•rhinorrhea
•sweating
•piloerection
•lacrimation
• symptoms are initially mild and increases in severity over the next several hours to several
days
• patients are able to sleep during early abstinence period but is restless and thereafter
insomnia remains a prominent feature
 OPIOID ADDICTION

• Opioid Abstinence syndrome/ withdrawal syndrome

• other symptom between 16 hours to 36 hours
• pupillary dilatation
• recurring waves of “gooseflesh”
• muscle twitching
• generalize body aches
• 36th hour
• restless becomes severe
• nausea and vomiting
• diarrhea develops
• Temperature, RR and BP are slightly elevated
• all symptoms peak intensity 48 - 72 hours after withdrawal before it subsides
 OPIOID ADDICTION

• Opioid Abstinence syndrome/ withdrawal syndrome

• rarely fatal
• after 7 - 10 days clinical signs of abstinence are no longer evident
• some complains after 10 days:
•insomnia
•nervousness
•weakness
•muscle aches
• Habituation substitution of a drug-seeking activities for all other aims and objectives in life
•this feature fosters the relapse to use the drug after the physiologic abstinence changes
seem to have disappeared
 OPIOID ADDICTION

• Opioid Abstinence syndrome/ withdrawal syndrome

• Characteristics of addiction and abstinence are qualitatively similar w/ all drugs of the opiate
group
• the difference is in the dosage, potency and length of action of the opiate
• Diagnosis of addiction is made when patient admits to using and needing drugs
• without admission of addiction, collateral evidence such as:
•mitosis
•needle marks
•emaciation
•abscee scars
•chemical analysis
•may also be apparent when treatment of acute opiate intoxication precipitates a
characteristic abstinence syndrome
 OPIOID ADDICTION

• Opioid Abstinence syndrome/ withdrawal syndrome

• Treatment of Opioid Abstinence Syndrome
•Methadone use as a substitute for opioid
•
a long acting full opioid agonist
•
action: pain relief
•
dosing ratio:
•
1 mg methadone: 3 mg morphine or 1 mg heroin or 20 mg meperidine
•
dose sufficient to suppress abstinence sypmtoms
•
Clonidine
•
counteracts most of the nonadrenergic withdrawal symptoms
•
dose: 0.2 - 0.6 mg BID x 7 days
 OPIOID ADDICTION

• Opioid Abstinence syndrome/ withdrawal syndrome

• Treatment of Opiate Habituation
•methadone: 60 - 100 mg daily
•given under supervision day by day for months or years
•plus various psychotherapy and social counseling
 OPIOID ADDICTION

• Medical and Neurologic complications of Opioid use

• in addition to the toxic effects of opioids, addicts may suffer from other neurologic &
infectious complications due to:
•contaminated by adulterants
•infectious agents
• infectious complications include:
•HIV infection
•
most important
•
because of the use of unsterile needles
•Septicimia
•endocarditis
•viral hepatitis
 OPIOID ADDICTION

• Medical and Neurologic complications of Opioid use

• Neurologic complication: cerebral leukoencephalopathy
•due to inhalation of heated heroin vapor known as “chasing the dragon”
•clinical presentation: stupor, coma and death
• acute generalized myonecrosis w/ myoglobinuria
•with renal failure
•due to injection of adulterer heroin
•sequelae of venous thrombosis due to IM injection of adulterer heroin
•
Brawny edema
•
fibrosis myopathy
 SEDATIVE-HYPNOTIC DRUGS

• Barbiturates
• Mechanism of Action:
• derived from barbituric acid
• potency of each drug is a function of the ionization constant & lipid solubility
• the higher the lipid solubilit
• the greater is the CNS potency
•the faster is the action
•drug action is shorter
• acts by suppressing neuronal transmission by:
•enhancing GABA inhibition at pre- and postsynaptic potentials
•reduce excitatory postsynaptic potentials
• results into: impaired consciousness/ coma due to inactivation of neurons in the reticular
formation of the upper brainstem
 SEDATIVE-HYPNOTIC DRUGS

• Acute Barbiturates Intoxication

• signs & symptoms vary with
•the type and amount of drug
•
Pentobarbitlal & Secobarbital
•
quick effect but recovery is faster
•
Phenobarbital
•
slower effect and recovery is slower
•length & time from ingestion
•most fatalities are related to intake of:
•
secobarbital
•
amobarbital
•
pentobarbital: potential fatal dose is 6 to 10 g
 SEDATIVE-HYPNOTIC DRUGS

• Acute Barbiturates Intoxication

• signs & symptoms vary with
•severe intoxication
•
occurs w/ ingestion of 10 - 20 times the oral hypnotic dose
•
manifest w/
•
comatose
•
slow, shallow or irregular respiration
•
pulmonary edema
•
cyanosis
•
(-) tendon, corneal nor gag reflex
 SEDATIVE-HYPNOTIC DRUGS

• Acute Barbiturates Intoxication

• Management
•mild to moderate
•
recovery usually occurs
•
no special treatment required except prevent aspiration
•
if patient is unresponsive: intubate the patient
•hemodialysis/ hemifiltration w/ charcoal used for
•
ingestion of long-acting barbiturates
•
also indicated for anuric patients
 SEDATIVE-HYPNOTIC DRUGS

• Barbiturate Abstinence or Withdrawal syndrome

• there is an initial improvement 8 - 12 hours after symptoms of intoxication diminish
• symptoms that may appear after 12 hours
• nervousness
• tremor
• insomnia
• postural hypotension
• weakness
• for chronic phenobarbital use, withdrawal symptoms appear after 48 - 72 hours after the final
dose
• generalized seizures w/ loss of consciousness- 2nd & 4th day of abstinence
• increase sensitivity to photic stimulation - causing seizure episodes
• delirium may follow such episodes including death
 ANTIPSYCHOSIS DRUGS

• originally referred to as Tranquilizers

• use for control of:
• schizophrenia
• psychotic states associated w/ organic brain syndromes
• affect disorders (depression or bipolar disorders)
• mechanism of action
• blocks postsynaptic mesolithic dopamine receptors & serotonin receptors
• side effects includes:
1. Parkinsonian syndrome
2. Acute dyskinetic & dystonic reactions
3. Akathisia
4. Tardive dyskinesias
 ANTIPSYCHOSIS DRUGS

• side effects: Parkinsonian syndrome

• most common complication
• manifest with:
• masked fancies
• slight symmetric tremor
• reduced blinking
• generalized rigidity
• shuffling gait
• slowness of movement
• symptoms appear after several days of drug therapy
• basis of symptoms: suppression of dopamine in the striatum
 ANTIPSYCHOSIS DRUGS

• side effects: Acute dyskinetic & dystonic reactions

• occurs early in the administration of the drug
• but decreases dramatically with:
• discontinuation of the drug
• IV administration of diphenhydramine or benztropine
• manifestations:
• involuntary movement of the lower facial muscles (mainly around the mouth)
• protrusion of tongue (buccolingual/ oral-masticatory syndrome)
• dysphagia
• tonic spasm of a limb
 ANTIPSYCHOSIS DRUGS

• side effects: Akathisi

• associated w/ intake of molindone
• treated w/ propranolol
• manifest as restlessness reflected by:
• persistent shifting of the body and feet
• inability to sit still
• pacing or jiggling of legs
 ANTIPSYCHOSIS DRUGS

• side effects: Tardive dyskinesias

• group of late & persistent complications of neuroleptic therapy
• may persist even w/ discontinuation of medication
• may be due to hypersensitivity of dopamine receptors in the basal ganglia secondary to
prolonged blockage of the receptors
• manifest as:
• lingual-facial-buccal-cervical dyskinesias
• choreoathetotic & dystonic movements of trunk and limb
• diffuse myoclonus
• personal tremor (“rabbit” syndrome)
• dysarthria or anarthria
 ANTIPSYCHOSIS DRUGS

• side effects: Neuroleptic Malignant Syndrome

• most dreaded complication of phenothiazine and haloperidol
• mortality rate is 15 - 30% if not promptly recognized
• may occur days, weeks or months after neuroleptic treatment started
• manifestations:
• hyperthermia
• rigidity
• stupor
• unstable BP
• diaphoresis
• other sympathetic overactivity
• elevated creatine kinase (CK) up to 60,000 units
• renal failure
 ANTIPSYCHOSIS DRUGS

• side effects: Neuroleptic Malignant Syndrome

• Treatment:
• prompt recognition of altered consciousness w/ rising temperature
•bromocriptine 5 mg TID (up to 20 mg tid)
•if patient cannot tolerate oral intake may give
•dantrolene 0.25 - 3.0 mg IV
• once coma has supervened, shock and anuria may prove fatal or leave the patient in a
vegetative state
 ANTIPSYCHOSIS DRUGS

• Treatment of Neuroleptic Side Effects

• cessation of the offending drug
• antiparkinsonian drugs of the anticholinergic type
• Amantadine 50 - 100 mg TID
 ANTIDEPRESSION MEDICATIONS

• Monoamine Oxidase Inhibitors

• adverse effect
•
excitement
•
restlessness
•
agitation
•
insomnia
•
anxiety
•
Mania & convulsions
•
combined w/ other medications like phenothiazines & CNS stimulants induces:
•
hypertension
•
atrial & ventricular arrhythmia
•
pulmonary edema
•
stroke or death
 ANTIDEPRESSION MEDICATIONS

• Tricyclic Antidepressants
• adverse effect
• early morning awakening
• decrease appetite and libido
• orthostatic hypotension
• urinary bladder weakness
• drowsiness
• confusion
• blurred vision
• dry mouth
• mortality is associated w/ tachyarrthymias & atrioventricular block
• Treatment: gastric aspiration w/ activated charcoal
• physostigmine
 ANTIDEPRESSION MEDICATIONS

• Serotonin Syndrome
• results from excessive intake of serotonin selective reuptake inhibitors
• manifestation
•confusion & restlessness
•tremor
•tachycardia & hypertension
•clonus & hypereflexia
•shivering & diaphoresis
• treatment:
•discontinue medication reduced temperature & hypertension
•benzodiazepines controls agitation
 STIMULANTS

• Amphetamines
• adverse effects:
•
restlessness
•
excessive speech and motor activity
•
tremor
•
insomnia
•
hallucinations
•
delusions
•
changes in affect and thought processes
•
cerebrovascular complications like: intracebral & subarachnoid hemorrhage
 STIMULANTS

• Amphetamines
• Chronic use withdrawal may present with:
•
prolonged sleep: disproportionate amount of REM sleep
•
on awakening patient experiences:
•
ravenous appetite
•
muscle pain
•
profound fatigue
•
depression
•
Treatment:
•
discontinue use
•
antipsychotic medication
•
antihypertensive when needed
 STIMULANTS

• Coccaine
• manifestation of dependence are subtle and hard to recognize
• manifest with:
•insomnia
•restlessness
•anorexia
•depression
•hyperprolatinemia
•signs of dopaminergic hypersensitivity
•intracerebral hemorrhage due to acute hypertension from the sympathomimetic actions of
coccaine
 STIMULANTS

• Coccaine
• manifestation of dependence are subtle and hard to recognize
• manifest with:
•plus amphetamine can cause generalized vasospasm leading to cortical infarcts
• anxiety, paranoia and other manifestations psychosis may also develop
• Treatment: antipsychotic medication: haloperidol
 HALLUCINOGENS

• Marijuana
• intake of small doses mimics mile alcohol intoxication
• drowsiness, euphoria, dulling of senses and perceptual distortions
• increasing dose effects are similar to LSD
• higher doses may cause severe depression and stupor
• withdrawal after chronic use may manifest w/:
• reduced congnitive performance
 HALLUCINOGENS

• Synthetic Cannabinoids
• binds more avidly to cannabinoid receptors than the original drug
• produces a heightened stimulant effect
• effects include:
•agitation
•delusions
•paranoia
• Treatment of intoxication:
•diane-ines
•haloperidol
 DISORDERS CAUSED BY BACTERIAL
TOXINS
• Most common causes:
• Tetanus
• Botulism
• Diptheria
• each is caused by a powerful bacterial toxin that acts on the nervous system
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• anaerobic, spore-forming rod Clostridium tetani

• present in feces of humans and animals particularly horses
• spores may remain dormant for months to years
• but when introduced to wounds if a foreign body or purulent bacteria, are converted into the
vegetative forms
• vegetative forms produce exotoxins: tetanospasmin
• in some developing countries, tetanus may be introduced via the umbilical cord causing
tetanus neonatorum
• Tetanus toxin is proposed to spread by:
• migration of toxins through the peripheral nerves
• but may also be disseminated by blood or lymphatics
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Mode of Action of Tetanus Toxins

• the toxin is a zinc-dependent protease
• block neurotransmitter release by cleaving surface proteins of the synaptic vesicles
• thus preventing normal exocytosis of neurotransmitters
• toxin acts by blocking inhibitory transmitters at the presynaptic sites of the spinal cord and
brainstem
• main inhibitory transmitter affected is GABA
• Renshaw cell is preferentially affected
• patients w/ tetanus manifest w/ trismus or lockjaw - due to failure of the inhibitory
mechanism that activates the masseter muscles
• the masseter muscle innervation seems to be the most sensitive to the toxin
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Mode of Action of Tetanus Toxins

• afferent action is exaggerated
• reciprocal innervation is lost allowing bot agonist and antagonist muscles to contract
resulting into a muscular spasm
• besides the general effect on the brain and brainstem skeletal muscle at the point where the
axon forms the endplate is affected
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Clinical Features: based on clinical types

• Generalized Tetanus
• most common form
• begins as a local tetanus becoming generalized in the next few days or may be diffuse
from the beginning
• manifestation:
•Trismus is frequently the 1st manifestation preceded by stiffness of jaw/ neck
•fever
•other general symptoms of infection
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Clinical Features: based on clinical types

• Generalized Tetanus
• manifestation:
•eventually causing unremitting rigidity in all involved muscles
•
abdomen is board-like
•
legs rigidly extended
•
lips pursed/ retracted
•
eyes partially closed
•
eyebrows elevated
•superimposed are paroxysms of tonic contraction/ spasm of muscles (tetanic seizures)
in response to the slightest external stimulus
•this spasms are extremely painful
•no lost of consciousness is seen
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Clinical Features: based on clinical types

• Generalized Tetanus
• manifestation:
•Opisthotonus - due to tonic contraction of groups of muscles
•
forward flexion of the trunk
•
flexion and adduction of the arms
•
clenching of the fists
•
extension of the legs
•Laryngeal & pharyngeal spasm plus respiratory muscles
•
causes the threat of apnea or suffocation
•Fever and pneumonia are common complications
•Diaphoresis w/ large swings in BP and heart rate w/ diaphoresis are typical
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Clinical Features: based on clinical types

• Generalized Tetanus
• Death is usually due to:
•asphyxia from laryngospasm
•heart failure
•shock due to action of toxin on the hypothalamus and sympathetic nervous system
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Clinical Features: based on clinical types

• Local Tetanus
• most benign form
• initial symptoms:
• stiffness
• tightness
• pain in the muscles surrounding the wound
• followed by twitching w/ brief spasms of affected muscles
• sustained tautness of the affected muscles and resistance of the part to passive
movement
• diagnostic maneuver: repetitive voluntary movements such as opening and closing of the
hand results to:
• gradual increase in tonic contractions of affected muscles
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Clinical Features: based on clinical types

• Local Tetanus
• symptoms may persist in localized form for weeks or months
• but may eventually improve/ disappear without residue
• complete recovery is to be expected
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Clinical Features: based on clinical types

• Cephalic Tetanus
• follows wounds of the face and head
• incubation period is 1 - 2 days
• affected muscles are weak or paralyzed
• spasms may involve the:
• tongue
• throat
• many cases are fatal
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Diagnosis:
• clinical features
• history of preceding injury
• injury may be trivial, forgotten and is healed
• organisms may/ may not be recovered from the wound
• Lab test:
• EMG
• serum CK may be moderately elevated
• death rate is about 50% overall
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Treatment:
• antitoxin: 3,000 - 6,000 u of tetanus immune human globulin
• Procaine Penicillin: 1.2 Million units daily
• Metronidazole 500 mg every 6 hours IV or 400 mg rectal
• immediate surgical treatment of wound and tissue around wound is injected with antitoxin
• Tracheostomy indicated for:
• patients w/ recurrent generalized tonic spasms
• must not be delayed until apnea and cyanosis has occurred
• prevent any external stimulus by placing patient in:
• dark & quiet room
• judicious use of sedation
•benzodiazepines: diazepam 120 mg/dl
•barbiturate
 DISORDERS CAUSED BY BACTERIAL TOXINS:
TETANUS

• Prevention:
• Immunization
• booster dose of toxoid every 10 years
• toxoid injection when injuries are in danger of being infected w/ tetanus
• 2nd dose of toxoid after 6 weeks if booster dose was not given in the preceding year
• if booster dose has never been given or a person w/ no previous immunization:
• tetanus toxoid
• human antitoxin
 DISORDERS CAUSED BY BACTERIAL TOXINS:
DIPTHERIA

• acute infection caused by Corynebacterium diptheriae

• Clinical form of the disease:
• Faucial-Pharyngeal form
• characterized by formation of an inflammatory exudate of the throat and trachea
• exudate contains the bacteria that produce an exotoxin
• exotoxin affects the heart & nervous system in about 20% of cases
• Nervous system involvement:
• palatal paralysis:
• manifestation:
•
nasal voice
•
regurgitation
•
dysphagia
• appears between 5th - 12th day of illness
 DISORDERS CAUSED BY BACTERIAL TOXINS:
DIPTHERIA

• Faucial-Pharyngeal form:
• Nervous system involvement:
•Ciliary body paralysis
•
loss of accommodation
•
blurring of vision
•
w/ preserved light reaction
•
appears in the 2nd and 3rd week
• toxins reaches the schwann cells in most vascular parts of the peripheral nervous system
w/in 24 - 48 hours of infection
• toxin causes demyelination in the proximal parts of the spinal nerves in the:
•dorsal root ganglia
•spinal roots
• cardiac muscles and conducting system of the heart undergo mild focal necrosis
 DISORDERS CAUSED BY BACTERIAL TOXINS:
DIPTHERIA

• Extrafaucial source of diphtheric infection

• penetrating wound
• skin ulcer
• umbilical infection in neonates
• Treatment:
• no specific treatment
• antitoxin within 48 hours from onset of symptoms
 DISORDERS CAUSED BY BACTERIAL TOXINS:
BOTULISM

• food borne illness caused by an exotoxin of Clostridium botulism

• most common cause is ingestion of bacteria from home-preserved
• canned products
• vegetables
• home-cured ham
• primary site of action of the toxin
• neuromuscular junction on the presynaptic membrane
• Toxin effect:
• interferes w/ the release of acetylcholine from the peripheral motor nerves at the
neuromuscular synapse
 DISORDERS CAUSED BY BACTERIAL TOXINS:
BOTULISM

• Symptoms appear within 12 - 36 hours from ingestion of contaminated food

• anorexia, cause & vomiting are most common
• blurred vision and diplopia - initial neural symptoms, followed by:
•ptosis
•strabismus
•extra ocular muscle paralysis
•lost of light accomodation
• nasality of voice
• hoarseness
• dysarthria
• dysphagia
• inability to phonate
 DISORDERS CAUSED BY BACTERIAL TOXINS:
BOTULISM

• Symptoms appear within 12 - 36 hours from ingestion of contaminated food

• progressive weakness and respiratory insufficiency may follow within 2 - 4 days
• severe constipation is a characteristic of botulism which may be due to paresis of the
smooth muscles of the intestines
• Diagnosis is confirmed by electrophysiologic studies
• reduced amplitude of evoke muscle potential
• increase in amplitude w/ rapid repetitive nerve stimulation
• for patients who recover
• improvement begins within a few weeks
• ocular movement is the 1st to recover followed by other cranial nerve function
• complete recovery of paralysis may take many months
 DISORDERS CAUSED BY BACTERIAL TOXINS:
BOTULISM

• Three types of botulinum toxins but clinical effects are indistinguishable

• Treatment of antitoxin covers for all three toxins/ trivalent antiserum
• initial dose: 10,000 u IV after negative skin testing followed by 50,000 u IM/ day until
improvement of symptoms appear
• Penicillin or Metronidazole used to eradicate the organism in a wound
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND
STINGS

• Ergotism
• Lathyrism
• Mushroom Poisoning
• Buckthorn poisoning
• Neurotoxin Fish Poisoning
• Venoms, Bites and Stings
• Tick Paralysis
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND STINGS
ERGOTISM

• poisoning with ergot, drug derived from rye fungus Claviceps purpurea
• used to:
• control postpartum hemorrhage
• migraine
• Parkinsons disease
• repeated use of the drug may cause ergotism
• acute overdosage: causes hypertension
• two types of ergotism
• gangrenous
• caused by vasospastic, occlusive process in the small arteries of the extremities
• convulsive/ neurogenis
• characterized by fasciculations, myoclonus and muscle spasm followed by seizures
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND STINGS
ERGOTISM

• pathologic changes degeneration of the

• posterior columns
• dorsal roots
• peripheral nerves
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND STINGS
LATHYRISM

• a neurologic syndrome characterized by:

• acute onset of pain
• paresthesia
• weakness of the lower extremities
• progression to a permanent spastic paraplegia
• caused by a toxin contained in the chickling vetch pea, Lathyrus
• legume that is consumed in excess quantities during famine
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND STINGS
MUSHROOM POISONING

• mostly would cause transient gastrointestinal symptoms but some may elaborate toxins that
may be fatal
• most important toxin: cyclone-tides coming from severe species of
• Amanita phalloides
• mascara
• accounts for 90% of fatal mushroom poisoning
• toxin disrupt RNA metabolism causing hepatic and renal necrosis
• symptoms appear between 10 - 14 hours after ingestion
• nausea & vomiting
• colicky pain
• diarrhea
• followed by: irritability, restlessness, ataxia hallucinations convulsions and coma
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND STINGS
MUSHROOM POISONING

• other mushroom toxins:

• methylhydrazine found in Gyromitra species
• clinical presentation similar to cyclopeptide poisoning
• muscarine found in Inocybe and Clitocybe species
• symptoms appear within 30 - 60 minutes from ingestion
• characterized by parasympathetic stimulation
•miosis
•lacrimation
•salivation
•nausea & vomiting
•diarrhea
•perspiration
•bradycardia
•hypotension
•Tremor, seizure & delirium for severe poisoning
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND STINGS
MUSHROOM POISONING

• Treatment:
• no effective antidote available
• induce vomiting if it has not occurred, use ipecac
• followed by activated charcoal to bind toxins left in the GIT
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND STINGS
BUCKTHORN POISONING

• rapidly progressive , sometimes fatal paralysis after ingestingbuckthorn shrub

• toxin causes a predominantly motor polyneuropathy
• disorder resembles Guillain-Barre syndrome and tick paralysis
• recognition depends on the history if ingestion of the fruit in endemic areas
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND
NEUROTOXIN FISH POISONING

• marine toxin that blocks neural sodium channels

• results from eating fish that fed on a toxin-containing microscopic flagellate
• dinoflagellates are ingested by reef fish and shellfish in high concentrations
• flagellates may color the surrounding water red - red tide
• initial symptoms appear minutes to hours after ingestion
• diarrhea
• vomiting
• abdominal cramps
• followed by:
• paresthesias beginning personally followed by the limbs
• hot/cold sensation associated w/ electrical-like or burning paresthesia in the mouth
• muscle aches and shooting pains may also be present
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND
NEUROTOXIN FISH POISONING

• as in Puffer fish poisoning or in other advanced stages of poisoning

• weakness
• respiratory failure
• coma
• Diagnosis:
• history of ingestions in endemic areas
• ingestion of imported fish
• symptoms may be mistaken for Guillain-Barre syndrome
• Perioral paresthesia should suggest the correct diagnosis
• Treatment:
• supportive treatment
• mannitol is said to hasten recovery
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND STINGS
VENOMS, BITES & STINGS

• symptoms associated w/ venoms may range from:

• respiratory depression
• paralysis
• pupillary dilatation
• ptosis
• tissue necrosis
• circulatory collapse
• symptoms associated with stings mainly result into
• hypersensitivity
• anaphylaxis
• several reports of cerebral & myocardial infarction have been reported
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND STINGS
TICK PARALYSIS

• results from toxin secreted by the gravid tick

• identified tick:
• Dermacentor andersoni - wood tick
• Dermacentor variables - dog tick
• most cases occur in children
• small body mass renders them susceptible to the effects of a small amount of toxin
• symptoms:
• generalized, flaccid areflexia paralysis
• appears after 1 - 2 days
• may mimic Guillain-Barre syndrome
• CSF is normal
 POISONING CAUSED BY PLANTS, VENOMS, BITES AND STINGS
TICK PARALYSIS

• Tick tend to attach to the hairlines/ in the matted hair of the scalp, neck and pubis
• careful search is need to reveal them
• diagnosis:
• identification of the tick
• endemic area
• Treatment:
• removal of the tick
Thank you