Opioid Autacoids

OPIOID

An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. The receptors in these organ system mediate both the beneficial effects and the side effects of opioids.

Classification Opioid drugs include:

Full agonists

Partial agonists

Antagonists

Partial agonists can displace full agonists and produce antagonistic effects.

MorphineHeroinCodeineThebaineEtorphine FentanylMeperidine (Pethidine)MethadoneOpioid peptides

Pentazocin

NaloxoneNaltrexone

Endogenous Opioid Peptides

Some regions in the brain contain peptides with opioid-like properties (endogenous opioid peptides).

Endogenous opioid peptides have been implicated in pain modulation.

They can be released during stressful conditions such as pain or the anticipation of pain.

Opioid Receptors

Three classes of opioid receptors ( µ, δ, κ) have been identified.

All are members of the G protein-coupled family.

Some opioids, can produce an agonist effect at one receptor subtype and an antagonist effect at another.

The opioids act on neurons by: Closing voltage-gated ca2+ channels on presynaptic

nerve terminals and reducing transmitter release. Hyperpolarizing and inhibiting postsynaptic neurons by

opening K+ channels.

Opioid Receptors Cont,d

Analgesia, euphoria, respiratory depression, and physical dependence result from actions at µ receptors.

Opioid analgesic effects also include interaction with kappa and delta receptors.

All three major receptors are present in high concentrations in the dorsal horn of the spinal cord.

Organ System Effects

Analgesia Pain consists of both sensory and emotional

components. Opioids reduce both aspects of the pain.

Euphoria Pleasant floating sensation with lessened anxiety

and distress.

Dysphoria An unpleasant state characterized by

restlessness and malaise, may sometimes occur.

Organ System Effects Cont,d

Sedation Drowsiness and clouding of mentation are

frequent concomitants of opioid action. Combination of morphine with other central

depressant drugs results in very deep sleep.

Cough suppression.

Organ System Effects Cont,d

Respiratory depression The respiratory depression is dose-related. It is possible to partially overcome respiratory

depression by stimulation of various sorts. Meperidine produces less respiratory

depression, in newborn infants (useful in obstetric).

Miosis No tolerance develops for miosis. It is valuable in the diagnosis of opioid

overdose.

Organ System Effects Cont,d

Gastrointestinal tract Constipation

Biliary tract Constriction of biliary smooth muscle, which may

result in biliary colic. Renal

Increased sphincter tone may precipitate urinary retention, especially in postoperative patients.

Ureteral colic by a renal calculus may be made worse by opioids.

In this case (and biliary colic) the dose of opioid should be increased.

Clinical Use of Opioids

Paine relief Severe, constant pain is relieved. Sharp, intermittent pain is not controlled. Fixed interval administration (regular dose at

regular time) is more effective than dosing on demand.

Stimulant drugs (amphetamine) enhance the analgesic actions of the opioids (useful in chronic pain).

Clinical Use of Opioids Cont,d

Acute pulmonary edema.

Cough suppression: Obtained at doses lower than those needed

for analgesia.

The effect is also produced by isomers of opioids that are devoid of analgesic and addiction effects.

The opioids used are: dextromethorphan & codeine

In patients taking MAO inhibitors hyperpyrexic coma may happen.

Clinical Use of Opioids Cont,d

Anesthesia In cardiovascular surgery where a primary goal is to

minimize cardiovascular depression. Diarrhea

Diarrhea from almost any cause can be controlled. Diphenoxylate as an antidiarrheal drug, is used in

combination with atropine.

The usual dose is two tablets to start and then one tablet after each diarrheal stool.

Not suitable treatment for all kinds of diarrhea.

Contraindications

Contraindications and cautions in therapy: Use of pure agonists with weak partial

agonists.

Use in patients with head injuries.

Use during pregnancy.

Tolerance Tolerance begins with the first dose of an opioid.

Tolerance clinically appears after 2–3 weeks of frequent exposure.

The degree of tolerance may be up to 35 fold.

60 mg of morphine causes respiratory arrest in a nontolerant person.

In addicts, 2000 mg of morphine may not produce respiratory depression.

M.H.Farjoo

High Tolerance No Tolerance

Analgesia Miosis

Euphoria, dysphoria Constipation

Mental clouding Convulsions

Respiratory depression

Sedation

Nausea & vomiting

Cough suppression

Antidiuresis

Withdrawal or Abstinence Syndrome

Manifestations: Rhinorrhea Lacrimation Yawning Chills Piloerection Hyperventilation Hyperthermia

Mydriasis Muscular

aches Vomiting Diarrhea Anxiety Hostility

Withdrawal or Abstinence Syndrome Cont,d

Morphine or heroin: Signs start within 6– 10 hr. After the last dose. Peak effects are seen at 36–48 hr. By 5 days, most of the effects have disappeared, but

some may persist for months. Methadone:

Several days are required to reach the peak effects. It may last as long as 2 weeks.

After the abstinence syndrome subsides, tolerance also disappears.

Craving for opioid may persist for many months.

Opioid Overdose

Injection of pure opioid antagonist drugs.

Intravenous injection of naloxone reverses coma due to opioid overdose but not that due to other CNS depressants.

Naloxone has a short duration of action (1–2 hours).

A depressed patient may recover after a single dose of naloxone and appear normal, but relapses into coma after 1–2 hours.

Tramadol Tramadol is a strong analgesic which blocks

serotonin reuptake. It is a weak µ receptor agonist, so can be used

with full agonists for chronic neuropathic pain. It induces seizures and is relatively

contraindicated in patients with a history of epilepsy.

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