Treat physiologic specific pain sensation and psychologic suffering aspects

Stimulation of opiate receptors leads to G-protein coupled decrease in adenylate cyclase and a decreased Ca2+ influx: leads to decreased neuronal excitability,

decreased neurotransmitter release ( decreased glutamate, ACh, 5-HT, NE and substance P/

1. opiate receptors all over.

2. endogenous opiate peptides that act as agonists at opiate receptors.

3. central analgesic actions in periqueductal grey matter.

4. works on Pain fibers in the spinal cord - inteneurons: decreases the release of substance P which is an excitatory  neurotransmitter in pain pathway in substantia gelatinosa.

5. electrical stimulation of enkephalinergic neurons (or acupuncture) will cause analgesia.

1. analgesic at all locations,
2. respiratory depressant: spinal supraspinal and peripheral-- (freq cause of death).
3. Antidiarrheal
4. sedation
5. euphoria

what opiate receptors does respiratory depressant?

a) mu

b)kappa

c) delta

 a) mu

c) delta

1. analgesia at peripheral & spinal
2. antidiarrheal
3. sedation,
4. diuresis
5. psychotomimesis (mimics psychosis: dysphoric, unpleasant effect)

1. analgesic
2. respiratory derpressant
3. antidiarrheal

what opiate receptors does sedation? pick 2

a) mu

b)kappa

c) delta

a) mu

b) kappa

all 3 opiate receptors mu, kappa, delta does which of the following? pick 2

a) analgesia

b) anti-diarrheal

c) sedation

d) euporia

2) respiratory depressant

a) analgesia

b) anti-diarrheal

what opiate receptors does psychomimesis and diruresis?

a) mu

b)kappa

c) delta

what opiate receptors does euphoria?

a) mu

b)kappa

c) delta

1. opium poppy
2. abuse (hypodermic)
3. "CURES"
4. analgesia
5. increased dose = increased subjective effects to reliever severe pain: more euphoria or dysphoria, decreased respiration
6. pupil- miosis- pinpoint
7. respiration: respiratory derpession
8. emetic and nauseant effects (direct stimulation of chemoreceptor trigger zone)
9. convulsions at high doses
10. Cardiovascular system: Dilate resistance and capacitance vessels. causes orthostatic hypotension. so do not use for shock.
11. GI tract: marked constipation

rapid first pass metabolis (75%) so not effective orally,

glucuronide conjugation;

enterohepatic recirculation,

well absorbed subcutaneously, intramucular and IV (60% within 30mins SC)

naltrexon (ReVia)

naloxone (Narcan)

effetive in overdose of opiate

what are the endogenous opiate peptides?

they are produced by nerves and act as agonists at opiate receptor.

1. Met. Encephalin
2. Leu. Encephalin
3. Beta-endorphin (runner's high)
4. dynorphi

helps to intensify or minimize pain.

there is a big placebo effect to pain. can have central control over painful stimuli

• shows central control of tolerance: no suffering!!
• because the pt knows there is an end to the pain and the experiment will stop
• therefore higher threshold stimulus (than suffering or psychologic aspect)

painful stimuli generated in periphery (e.g. trauma, burn e.t.c)

• impulses sent from peripheral tissues through nociceptors that go up into scpical cord through nociceptive pthway.

Bradykinin: causes pain sensation when released

Prostaglandins: cause pain sensation or enhances painful response to other mediators.

1. neuropeptides released in substantia gelations also mediators of pain receptors: substance P, CGRP.
2. Nitric Oxide: enhance painful stimuli as it travels along
3. Nitric oxide: part

• Act peripherally in spinal cord to decrease release of painful mediators[substance P] and neurotransmitters [NE, 5-HT]

• Act centrally (more effective at above)
• Activate descending inhibitory periaqueductal gray pathway to decrease painful responses coming up into the CNS.

inhibit prostalandin synthesis.

decreases the amount of prostaglandin produced and thus decreases activity of prostaglandins.

codeine is metabolized to morphine, hence analgesic actions.

used frequently for antitussive actions.

Same as morphine's effect and toxicities.

orally effective, subcutaneous and parenterally.

1/10th morphines potency

severe pain: effective if injecting.

Used in combo with acetaminophen or ASA.

which opiate is more likely to be abused?

a) morphine,

b) codeine,

c) detromethorphan

Dextro form is non-narcotic antitussive or non opiate cough supressant= euivalent to codeine.

Levo form = analgesic, close to codiene

Acts as non-Opoid receptor

No respiratory depression, No analgesia,

no euporia

Thus, dependence is not a problem.

Equal to morphine & orally effective, easily abused.

Most frequently  prescribed drug for pain relife. NSAIDs block prostaglandin production tor eleive maid.

Same as ocycodon excpt -OH group added

1. Used only as and analgesic (LESS antitussive and anti diarrheal!
2. more risk of convulsant effects,
3. available for IM,IV, and oral administration.
4. 1/10th to 1/14 the morphine potency with an equal efficacy for side effects (less spasmogenic- less colic)
5. Easily crosses PLACENTA, decr. respiration in fetus.

1. anti-diarrheal,
2. atropine added to decrease abuse
3. Schedule 5: requires prescription

is equal to diphenoxylate as an antidiarrheal, has a lower abuse potential.

AVAILABLE OVER THE COUNTER!

Its poor lipid solubility prevents CNS effects: although still an opiate, effect localized to GIT.

excellent analgesic,

same actions and toxicities as morphine.

Prep: oral or injected.

Potency= equaly to morphine BUT longer duration after repeated dose.

Used in opiate maintenance programs: stops the heroin from giveing the feeling of euporia, pt is still addicted to opiates taking methadone.

less potent than codeine,

orally active, opiate drawbacks without increased,

not on market

• equal to morphine as an analgesic, flood receptor site with another opiate and prevent fast onset of heroin

• much less abuse, blocks receptor in morphine dependent pts.

• Partial agonist at Mu receptor

• Weak antagonist at kappa receptor.

Good analgesia via kappa agonist receptor,

• weak agonist at mu receptor,

low addiction liability,

less nausea and vomiting than morphine.

• good for chronic pain management.

1/4 to 1/2 morphine potency

Admin: subQ or oral

Parenteral,

reverses morphine/ other opiate effects, including endogenous opiates.

Short duration.

No work on its own unless opiate is present.

new anlagesic

weak opiate mu receptor agonist binding,

weak inhibition of NE & 5-HT uptake,

antidepressant actions,

active metabolite analgesic activity (mu).

low abuse potential, can cause physical dependence.

1. head trauma ( incr pCO2 leads to vascular dilation -> incr intracranial pressure
2. asthma and other chronic respiratory diseases: histmaine release with IV & IM morphine, and more hypoxia
3. Convulsive/seizure disorders or CNS stimulants (opoid convulsant action enhanced with stimulants.

Opoid Tolerance and physical dependence

• rapid tolerance (depends on dose & schedule)

• Lethal respiratory depression impressive,

• Analgesia = tolerance problem in chronic tx.

• Cellular form of tolerance is expected

• LITTLE tolerance to miosis and constipation!!

body needs drug to operate normally. remove opiate and state is abnormal: withdrawal sydndrome starts aiwth rebound once opiate removed.

Withdrawl effects are opposit to morphine eff.:

1. diarrhea
2. increased CNS activity
3. agression,
4. anxiety,
5. relieved by giving an opiate or wirthdrawal dissipiates over time
6. duration and severity of withdrawal syndrom edepends on the particular agent and pattern of use and abuse.

which drug will relieve symptoms of morphiine withdrawal?