Pharm Review (work in progress)

Question 1

What are the phases of pain signaling and processing?

Answer 1

• Transduction
• Conduction
• Transmission
• Perception
• Modulation

Question 2

Fast nerve fibres?

Answer 2

A delta fibers

Question 3

Slow nerve fibres?

Answer 3

C fibers

Question 4

What is transduction?

Answer 4

When pain stimuli is converted into an action potential

Question 5

What is conduction/transmission?

Answer 5

Conduction is when a pain signal is sent from a peripheral nerve to the spinal cord along either A delta fibres (fast) or C fibres (slow) to the spinal cord and then transmission sends the pain signal to the brain via a spinothalamic tract (ascending pathway) in the spinal cord.

Question 6

What is perception (as pertains to pain signal and processing)?

Answer 6

Occurs in the cerebral cortex as pain is located and identified.

Question 7

What is pain modulation?

Answer 7

The brain is able to modulate pain through the use of a descending pathway that releases inhibitory neurotransmitters that hinder pain transmission in the spinal cord. Pain is also modulated with endogenous opioids.

Question 8

When there is damage to tissue, pain generation is modulated by?

Answer 8

• Activators (Receptor potential, pH drop, Kinins, Capsaicin, think topical lidocaine)
• Facilitators (Substance P, Nitrous Oxide, Glutamate)
• Potentiators (Prostaglandins, COX, think NSAIDS)
• Itch (Histamine)
• Inhibitors (Opioids, Cannabinoids. Neuropathic pain can be inhibited by Serotonin, Norepi, and GABA)

Question 9

With tissue damage, explain the signal transduction of nociceptors.

Answer 9

• Action potential arrives at neuron
• Generates calcium flux into cell
• Causes vesicle of neurotransmitters to be released into synapse
• Neurotransmitters interact with postsynaptic receptors
• Generate an action potential
• Travels down neuron

Question 10

Briefly describe the pain pathway in terms of tracts, fibres, and regions of spinal cord and brain.

Answer 10

Pain stimulus is received at a nociceptor, it travels down A-delta or C fibres, through the dorsal root ganglion, to the dorsal grey horn of spinal cord, it synapses then crosses to other side of cord and up a spinothalamic (ascending) tract to the thalamus, and then to the cerebral cortex for perception. A descending tract in the spinal cord links the brain to the dorsal grey horn at the synapse where it can release inhibitory neurotransmitters.

Question 11

Opioids can affect pain pathways at?

Answer 11

At the dorsal root creating an inhibitory effect reducing ascending pain signals. It can also affect the emotional processing of pain. They’re considered “Inhibitors” for pain modulation.

Question 12

How do opiates like morphine or fentanyl modulate pain?

Answer 12

They bind to MU receptors causing K+ efflux in post synaptic neurons which causes hyperpolarization (more negative) thus increasing the threshold making it harder to illicit an action potential. They also limit calcium influx in the presynaptic neuron thus reducing the release of neurotransmitters. Together this reduces pain signal transmission to the brain.

Question 13

What is the difference between depolarizing and nondepolarizing paralytic agents?

Answer 13

Depolarizing agents (like succinylcholine) bind to Ach receptors in the neuromuscular junction causing depolarization. They have an higher affinity to the receptors than actual Ach, and are resistant to acetylcholinesterase, and so while bound they prevent repolarization and so paralysis. Nondepolarizing agents (like rocuronium) bind and block the Ach receptors without causing depolarization. While they are bound they prevent depolarization and so illicit paralysis.

Question 14

What are the receptors of interest that you would think about targeting when treating nausea and vomiting?

Answer 14

• Serotonin (5HT-3)
• Histamine (H1)
• Muscarinic (M1)
• Dopamine (D1/D2)
• Neurokinin (NK1)

Question 15

What areas of interest are there when treating nausea and vomiting?

Answer 15

• Vomiting Centre
• ChemoTriggerZone (CTZ)
• Vestibular System

Question 16

Were are the vomiting centre and CTZ located?

Answer 16

In the medulla oblongata/brain stem.

Question 17

Which receptors in the vestibular system cause nausea and vomiting? What is your drug of choice to combat that?

Answer 17

Both H1 and M1 receptors. Your first choice is gravol (dimenhydrinate) for it’s antihistamine and muscarinic antagonist (anticholinergic) properties. Benadryl (diphenhydramine) also targets these receptors.

Question 18

Will zofran work to reduce nausea and vomiting in patients suffering from motion sickness?

Answer 18

NO. Motion sickness is due to a vestibular issue. The vestibular apparatus uses H1 and M1 receptors to illicit nausea and vomiting. Zofran works on serotonin 5ht-3 receptors. There for it will not help the issue.

Question 19

Give an example of a patient you would use haldol on to treat nausea and vomiting. Why would it work?

Answer 19

Cannabinoid hyperemesis. Like most drugs, weed effects dopamine in the brain. Dopamine can stimulate the CTZ. So pukey pukey. Haldol elicits a strong postsynaptic blockade of CNS dopamine receptors D1/D2, so, less pukey.

Question 20

Your patient is complaining of gastrointestinal upset after receiving chemotherapy. What antiemetic might you give? Why would it work?

Answer 20

You would give zofran. It is a 5HT3 receptor antagonist acting both peripherally on the vagus nerve and centrally at the CTZ. Chemotherapy irritates these areas. 5HT3 receptors bind serotonin to induce nausea and vomiting. So blocking them stops that. Serotonin also plays an active role in GI tract stimulation of the vomiting center and so zofran can be used in other cases as well.

Question 21

Why might maxeran work as an antiemetic? When would you use it?

Answer 21

It acts on D2 (like haldol), 5HT3 (like zofran), M1 (like gravol), and 5HT4. As such, it targets some of the same areas as other antiemetics and so we can see how it would be effective. In EMS we generally use it as treatment for nausea with migraines and headaches of vascular origin. DON’T GIVE TO PARKINSON’S PATIENTS

Question 22

Why might opioids like morphine cause nausea and vomiting?

Answer 22

The chemoreceptor trigger zone (CTZ) contains mu receptors. Opioids act on these receptors thereby stimulating vomiting. Morphine in particular can cause a histamine release, and histamine can also stimulate nausea.

Question 23

You give haldol and your patient starts presenting with Parkinson’s type tremors. Why? How do you fix this?

Answer 23

Haldol inhibits dopamine receptors. A balance between dopamine and acetylcholine is required for smooth muscle movements. With less effective dopamine, the Jedi force is strong in Ach. Give benadryl (the anticholinergic of the dark side), this reduces effectiveness of Ach thus balancing the universe.

Question 24

Your patient was given too much benzos, how can that be reversed?

Answer 24

Flumazenil

Question 25

What can be given to reverse a nondepolarizing agent like rocuronium?

Answer 25

Neostigmine

Question 26

You gave succinylcholine and now your patient is presenting with Malignant hyperthermia. What drug is given at hospital to reverse this?

Answer 26

Dantrolene

Question 27

Coagulation Pathway

Answer 27

Learn it my friends. God Speed. Sounds like it’ll be a long answer question. Learn all about TXA while you’re at it.