15. Natural opiates, opioid receptors

Question 1

difference in opoids classfication and function

Answer 1

• natural, semi synthetic, and synthetic
• classified based on their interaction with the opoid receptor
• relieve pain, analgesia, they are widely distributed in body tissue, cross placental barrier and exert effect on fetus

Question 2

metabolism of opoids

Answer 2

hepatic enzymes, to inactive glucorunide conjugates before renal elimination

• with alcohol ingestion we’ll see an increase in peak serum levels in several opoids (hydromorphone, oxymorphone)
• meperidine metabolized to normeperidine which causes seizures at high plasma levels
• elimination half life will increase in patients with liver diseases

Question 3

receptors location, and function

Answer 3

-located primarily afferent and spinal cord pain transmission neurons in mid brain and medulla
(descending pathway) and they function in pain modulation
- other receptors are involved in reactivity to pain located in basal ggl, hypothalamus, limbic structure and cerebral cortex

Question 4

receptor subtypes and overall function

Answer 4

the mu receptor, kappa receptor, and delta receptor
all 3 are involved in antinociceptive and analgesic mechanisms at spinal and supraspinal levels
receptors are activated endogenously by peptides under physiological conditions

Question 5

function of mu receptor

Answer 5

activation in this receptor leads to respiratory depressant action, together with kappa activation lead to slowing of G.I motility

Question 6

function of kappa receptor

Answer 6

sedative action

Question 7

function of delta receptor

Answer 7

development of tolerance

Question 8

endogenous peptides

Answer 8

these include endorphin (have the highest affinity to Mu R.’s) endorphin’s catogorized into:
b-endorphins
enkephalins: highest affinity at the delta R.
dynorphins: highest affinity at the kappa R.

Question 9

what is ionic mechanism

Answer 9

opoid analgesics inhibit synaptic activity partly through direct activation of opoid R. through the release of endogenous opoid peptides leading to inhibition of all neurons

• all three R’s are g protein coupled
• at post synaptic level: activation of phospholipase c or inhibition of adenyl cyclase leading to K ch opening -> hyperpol.
• at presynaptic level: closing of voltage gated Ca ch. which inhibits neurotransmitter release

Question 10

central actions of morphine

Answer 10

• analgesia (inhibition of pain transmission)
• respiratory depression (most important toxic effect ) with increasing dose leads to lower breathing frequency -> hypoxia, increase in PC02 leading to increase in blood flow and increase in ICP (C.I in pts with head injury)
• euphoria and sedation
• pupil constriction (muscarinic blocking action, no tolerance to this and can be blocked by opoid ATG)
• ** exceptions:
• severe hypoxia -> pupil dilate
• opoid poisoning with meperidine
• dysphoria: opposite to euphoria kappa AG more probably to case this
• antitussive effect
• nausea, vomiting (especially with movement caused by activiation of chemoreceptors
• convulsiuons: moniter if pt has epilepsy, some are C.I in epileptic pts (MEPERIDINE, TRAMADOL)
• truncal rigidity

Question 11

Peripheral actions of morphine

Answer 11

• constipation
• smooth muscle
• bradycardia ( can be good in HF, added w/ diuretics)
• hypo tension
• endocrine alteration ( inhibit release of LH, GH, higher release of ADH and prolactin)

Question 12

what about constipation caused by morphine

Answer 12

its dose dependant
decrease in intestinal peristalsis b/c there are opoid receptors in enteric neurons
(i) antidiarrheal agent
no tolerance
higher dose leads to stronger constipation
abdominal pain, cramps leading to opoid bowel syndrome

Question 13

smooth muscle effect by morphine

Answer 13

all with the exception of meperidine
contraction of biliary tract sm.m -> biliary colic/ spasm
increase in urethral & bladder sphincter tone
decrease in uterine tone (prolongs labor)

Question 14

hypotensive effect of morhpine

Answer 14

in LVHF there will be edema in lungs and dyspnea will be a symptom and there will be an increase in respiratory frequency and anxiety
opoids will decrease the respiratory frequency

Question 15

chronic effects of opiods

Answer 15

• tolerance

- dependence

Question 16

explain tolerance

Answer 16

to all the above except miosis and constipation, maybe because of Receptor uncoupling

• ATG of glutamate NMDA receptor and delta R ATG can block opoid tolerance
• cross tolerance between different opoid AG, but this is not complete, opoid rotation -> analgesia is maintained by switching from one drug to another

Question 17

dependence

Answer 17

physical dependence can occur especially to the strong agonists, it is revealed on abrupt discontinuance as abstinence syndrome
these include: rhinorrhea, lacrimation, chills, muscle aches, diarrhea, yawning, anxiety and hostility
*** a precipitated withdrawal results when an opoid ATG is administered to a physically dependent individual

Question 18

what leads to toxicity and what can be some symptoms

Answer 18

-over dose: a triad of pupillary constriction, comatose state and respiratory depression, I.V injection of Naloxone ATG drug, ventilatory support may reverse the action
-drug interaction: additive CNS depression with ethanol, sedative hypnotics, anesthetics, antiphsychotics, TCA’s & antihistamines
meperidine with MOA inhibitors leads to hyperpyrexic coma, also cause serotonin syndrome when used with SSRI’s