Toxicology

Question 1

What is the Pathophysiology of a Opioid Overdose

Answer 1

Opioids modulate nociception in the terminals of afferent nerves in the CNS and PNS and GI tract. They are agonists at the μ (OP3), κ (OP2), and δ (OP1).

OP3 receptors divide into 2 subtypes which result in analgesia, respiratory depression, cough suppression, and euphoria:

The clinical role of OP1 receptors are largely unknown. There is a localised release of dopamine in the mesolimbic pathway (“pleasure pathway” resulting in euphoria).

Question 2

What is the Pathophysiology of a Tricyclic Antidepressant Overdose

Answer 2

TCA toxicity results in:

 Inhibits Na+ (Sodium)  channels:
-  Wide QRS and bradycardia
Treat with NaHCO3- as it causes alkalaemia and
- ↑Na+ which reverses Na+ blockade 
Inhibits K+ (potassium) channels:
- Prolonged QT 
Inhibits GABA (inhibitory) receptors:
- seizure
Inhibits histamine and muscarinic receptors:
-  Sedation, confusion, dry mouth, tachycardia, HT 
Inhibits NA re-uptake:
- Agitation, tachycardia, HT 
Inhibits α adrenergic receptors:
- Sedation,hypotension,tachycardia
Inhibits serotonin re-uptake:
- Sedation, hyperreflexia

Question 3

What is the Pathophysiology of a Sedative

GHB, Benzodiapines

Answer 3

Benzodiazepines
Benzodiazepines are psychotropic drugs - drugs that affect the mind and are mood altering. They are commonly known as minor tranquilizers and are prescribed mainly for anxiety and sleeping problems. In the past benzodiazepines were thought to be harmless and non-addictive. However, many studies have reported that they are actually drugs of dependence and potentially lethal when taken in overdose quantities.

GHB:
A drug commonly found in the dance scene and is sometimes referred to as liquid ecstasy due to its stimulating, euphoric and supposed aphrodisiac qualities. Chemically- speaking, it is not related to MDMA at all. Mildly salty in flavor, yet colourless and odourless, it’s also used a date-rape drug – when mixed with alcohol, it can intoxicate quickly.
GHB is naturally occurring neurotransmitter and a psychoactive drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. It acts on the GHB receptor and is a weak agonist at the GABA-B receptor

Question 4

What is the Pathophysiology of a psychostimulants.

• Ecstasy (MDMA)
• Methamphetamine
• Cocaine

Answer 4

General Knowledge
Amphetamines are thought to enter the nerve terminal via the transporter, disrupt storage vesicles of dopamine and reverse the direction of the dopamine transporter through which large amounts of dopamine are released

Ecstasy
The primary mode of action of MDMA is as an indirect serotonergic agonist, increasing the amount of serotonin released into the synapse. MDMA acts on the serotonin transporter and is transported into the nerve terminal. This promotes release of serotonin through the serotonin transporter by a process of transporter-mediated exchange. Whilst within the terminal, MDMA interferes with the storage of serotonin within the vesicles and thus increases the amount of serotonin available to be released

Methamphetamines:
Methamphetamine promotes the release of monoamine neurotransmitters dopamine, serotonin, and norepinephrine within central (CNS) and peripheral nerve endings. It also blocks re-uptake of dopamine similar to cocaine, and it may act as a false transmitter. This explains its euphoric effects in the CNS and sympathomimetic effects such as tachycardia and hypertension.

Cocaine
- is a stimulant and has a similar effect to amphetamines like speed and ice, but produces a more intense effect and shorter “high‟ depending upon dosage.
Cocaine also enhances the activity of dopamine. It does this by blocking its reuptake into the nerve terminal via the transporter and thus increasing the amount of dopamine available to act at receptors in the synapse

Question 5

What is the Pathophysiology of Organophosphate Poisoning

Answer 5

The primary mechanism of action of organophosphate pesticides is inhibition of carboxyl ester hydrolases, particularly acetylcholinesterase (AChE). AChE is an enzyme that degrades the neurotransmitter acetylcholine (ACh) into choline and acetic acid. ACh is found in the central and peripheral nervous system, neuromuscular junctions, and red blood cells

Once AChE has been inactivated, ACh accumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic receptors. Clinical effects are manifested via activation of the autonomic and central nervous systems and at nicotinic receptors on skeletal muscle.

Question 6

What is the Pathophysiology of a Snake Bite

• Red Belly
• Tiger
• Eastern Brown

Answer 6

• Neurotoxins interfere with nerve signalling in a number of ways, the most common of which is competitive binding. In this scenario, the toxin binds to a specific receptor in a manner that blocks neurotransmitters from binding the receptor.
• Cytotoxicity broadly describes a toxic effect on cell function. Technically speaking, this also means that many neurotoxins
  Myotoxic a non-enzymatic mechanism that leads to severe muscle necrosis

Bites from species of venomous snakes occurring within Victoria can result in

Neurotoxic/Myotoxic – leading to paralysis and progressing to respiratory arrest – requiring intubation/assisted ventilation.

Cardiovascular effects – hypotension

Coagulopathy - causing a massive uncontrolled activation of the clotting pathway and essential clotting factors are rapidly consumed, the patient is unable to clot any further and is therefore prone to haemorrhage.

Red belly
The venom has predominantly anticoagulant and myotoxic effects, and symptoms of envenomation include bleeding and/or swelling at the bite site, nausea, vomiting, headache, abdominal pain, diarrhoea, sweating, local or general muscle pain and weakness, and red-brown urine (due to myoglobin being released from damaged muscle tissue).

Eastern Brown
Clinically, the venom of the eastern brown snake causes venom-induced consumption coagulopathy; a third of cases develop serious systemic envenoming including hypotension and collapse, thrombotic microangiopathy, severe haemorrhage, and cardiac arrest.[61] Other common systemic symptoms include nausea and vomiting, diaphoresis (sweating), and abdominal pain. Acute kidney injury and seizures can also occur.

Tiger
Myotoxicity, neurotoxicity, thrombotic microangiopathy and systemic symptoms.

Question 7

What is the Pathophysiology of Blue Ring octopus Sting

Answer 7

Blue-ringed octopuses produce a potent neurotoxin called tetrodotoxin.
First, the venom blocks nerve signals throughout the body, causing muscle numbness. Other symptoms include nausea, vision loss or blindness, loss of senses and loss of motor skills. Ultimately, it will cause muscle paralysis—including the muscles needed for humans to breathe, leading to respiratory arrest