The Mechanism for the Major Therapeutic and Toxic Effects of Opioids

Question 1

What is the target of opioid drugs?

Answer 1

The opioid receptor, has subunits mu, delta, kappa. Exogenous agonists most often have their effects mediated by the mu receptor.

Question 2

What are the depressant effects of opioid drugs?

Answer 2

Inhibition of adenylate cyclase which produces cAMP, leading to a decrease in cellular activity.
Inhibit Ca ion entry into the cell, which causes a decreased stimulus for exocytosis (exact effect depends on the cell).
Enhances K ion efflux, leading to hyperpolarisation, reducing depolarisation and hence activation.

Question 3

Describe the pain pathway, including the different nodes

Answer 3

Sensory neurons take the info from periphery to dorsal horn where they synapse with spinothalamic neurons and head to the thalamus, which receives all the pain signals. The thalamus stimulates the cortex and PeriAquaductal Grey region. PAG stimulates Nucleus Raphe Magnus which signals to dorsal horn, diminishing pain signal.

Question 4

Describe the role of the Nucleus Reticularis Paragigantocellularis in the pain pathway

Answer 4

The NRPG is activated before the thalamus by the spinothalamic neuron and it activates the NRM before the signal reaches the brain. It functions like a shortcut. Its aim is to diminish pain signals as quick as possible.

Question 5

Describe the role of the Cortex in the pain pathway

Answer 5

The cortex is stimulated by the thalamus and it has the role of processing the signal and regulating the pain tolerance signal generated by the PAG. Cortex will access memories, and modulate the signal given to the PAG.

Question 6

Describe the role of the PAG region in the pain pathway

Answer 6

The PAG is activated by the thalamus and is the integrating centre for the pain tolerance pathway. Relays info onto the Nucleus Raphe Magnus

Question 7

Descirbe the role of the Nucleus Raphe Magnus in the pain tolerance pathway

Answer 7

The NRM is the effector arm of the pain tolerance pathway. It is stimulated by the PAG and its job is to send the signal down to the periphery for the response to the pain signal (ie. hurt alot or not much). It will do this by its neurons projecting onto the dorsal horn and diminishing the original pain signals from the periphery

Question 8

Describe the role of the hypothalamus in the pain tolerance pathway

Answer 8

The hypothalamus is responsible for the monitoring of general health which impacts pain tolerance ie. good health = better pain tolerance.

Question 9

Describe the role of the Locus Coeruleus in the pain tolerance pathway

Answer 9

Part of the effector arm of the sympathetic nervous system. Can directly inhibit the transmission of pain signal to the spinothalamic neurons in the dorsal horn. Works so that in a fight or flight situation youre not distracted by pain signals.

Question 10

Describe the role of the Substantia Gelatinosa in the pain pathway

Answer 10

The Substantia Gelatinosa is a part of the dorsal horn and sensory neurons have to pass through this section when transmitting the signal. The SG modulates the signal, and its ability to do this is enhanced by neurons from the NRM.

Question 11

In the PAG region, and the NRPG, opioids will be increasing the firing rate of the neurons in these regions. But, opioids are depressants, so how do they do this?

Answer 11

Opioids depress the activity of GABA interneurons. GABA is an inhibitory neurotransmitter, and often found in regions of the brain which have activities that we don’t want constitutively activated, such as nausea or euphoria. If opioids inhibit inhibitory inter neurons, the end neuron will be stimulated. This is called disinhibition.

Question 12

How do opioids have an anti tussive effect?

Answer 12

It prevents coughing. Opioids decrease the activation of afferent neurons relaying the cough stimulus from the airways to the brain. This is a direct depressant effect.

Question 13

How do opioids induce nausea?

Answer 13

They increase activation of neurons projecting from the chemoreceptor trigger zone by disinhibiton.

Question 14

What is the major toxic effect of opioid drugs and how is it produced?

Answer 14

Respiratory depression leading to suffocation. Opioids depress central chemoreceptors so less signal goes to respiratory control centre. Also depress respiratory control centre which reduces inhale/exhale stimulus to the lungs.

Question 15

What’s the role of the central chemoreceptor and respiratory control centre?

Answer 15

Central chemoreceptor sends info such as CO2 levels to respiratory control centre which generates and maintains rhythm and alters depth of breathing.

Question 16

How can the concept of full and partial agonism be used to treat opioid addiction?

Answer 16

Analgesia is produced at a lower dose than respiratory depression because it is the therapeutic effect. That means that we can use partial agonists to provide the analgesic effect, but never reaching the fatal side effect.