Opioid Analgesics

Question 1

Major action of opioids is in the CNS, act on:

Answer 1

Ascending pathway in pain transmission

Descending pathway for pain suppression

Question 2

Opioids also act on:

Answer 2

emotional reaction to pain

Question 3

Regions with neurons involved in pain suppression:

Answer 3

Brain: Hypothalamus and Hyppocampus (every others part also)

Spinal cord

Question 4

Opioids receptors:

Answer 4

miu (u) ***** (most involve in pain relief)
Delta
Kappa

Question 5

Opioid structure determining the activity:

Answer 5

• Hydroxyl site on the benzene ring (Big effect on affinity of the drug for the receptor, particularly position 3 on the benzene)
• Amine site (changes the efficacy of the drug)

Question 6

Where are the opioid receptor on the synapse?

Answer 6

-Pre-synaptic receptors (opioids cause a decreased release of transmitter –> least to cause the stimulation of pain up to the brain)
-Post-synaptic receptors (opioids cause the cell to hyperpolarize –> least chance of sending an impulse of pain up to the brain)
(both in ascending and descending pathways)

Question 7

In the pre-synaptic, the opioids act on:

Answer 7

the GPC u receptor (change the intake of calcium, least depolarization –> least transmitter released)

Question 8

In the post-synaptic, the opioids act on:

Answer 8

K+ channels (releasing more K+, which hyperpolarize the post-synaptic membrane and also affecting calcium –> decrease the chance of firing an action potential)

Question 9

By changing the intake of calcium in the pre-synaptic and releasing more K+ with the intake of Opioids, the fibers that transmitting the pain signal into the spinal cord are:

Answer 9

Least firing. There are fewer fibers that are firing.

Question 10

Others neurotransmitter related to inhibiting the cell

to send the impulse to the brain: (ascending pathway)

Answer 10

Serotonergic and Enkephalinergic neurons

Question 11

Others neurotransmitter related to inhibiting descending pain pathways:

Answer 11

Serotonin and noradrenaline

Question 12

Usually when there is injury, even if serotonin and noradrenaline inhibit the sensation of pain (inhibitory system), the body is made to ensure that we feel pain so we can get yourself out of dangerous situations. Which system is responsible?

Answer 12

GABAminergic systems

Question 13

Intake of Opioid effect on the GABAaminergic neurons:

Answer 13

Least GABA is released onto subsequent neurons. So normal inhibitory system (serotonin and noradrenaline) is acting as usual, inhibiting the sensation of pain.

Question 14

u (miu) receptors are (which type of receptor)?

Answer 14

GPCRs

Question 15

Activation of u receptors causes:

Answer 15

Post-synaptic hyperpolarization

Question 16

Morphine metabolite is excreted by:

Answer 16

kidney, need to be careful when giving morphine to patients with kidney problems.

Question 17

Why opioids have a role play in the GI tract?

Answer 17

opioids receptors on neurons in the wall of the intestine (myenteric plexus). So if taking opioids, it is inhibiting the function of there neurons, and inhibiting the propulsive activity.

Question 18

Combination of Codeine and Aspirin cause an?

Answer 18

Synergistic effect

Question 19

Codeine is converted to Morphine by:

Answer 19

CYP2D6

Question 20

If you cannot metabolize codeine into morphine with CYP2D6, what happen?

Answer 20

It will conjugate it into a glucuronide which can be eliminated.

Question 21

People deficient in CYP2D6, cannot have the pain relief from codeine but also it affect other important drugs such as>

Answer 21

Tamoxifan, drugs for tx breast cancer.

Question 22

Example of opioid partial agonist:

Answer 22

Buprenorphine or Methadone

Question 23

Loperamide opioids special effect:

Answer 23

It Can not pass through the BBB. So act on the GIT only for the tx of diarrhea.