3a - Opiods

Nocipathy Pain

Results from actuation of Nociceptors (pain receptors) due to tissue injury or inflammation.

Neuropath Pain

Damage or dysfunction of the nervous system itself (peripheral nerves, spinal cord or brain)

Opiods

A class of drugs derived from morphine or synthesized to mimic it's effects. used primarily for moderate to severe pain.

Natural Opioids 

Directly derived from opium. Morphine, Codine.

Semisynthetic Opioids

Modified natural compounds. Oxycodone, Hydromorphone, Heroin

Synthetic opioids

fully manufactured in labs. fentanyl, Methadone, tramadol.

µ (Mu) receptor: Location

brain, spinal cord, periphery

µ (Mu) receptor: Function

Conduction of heat-related nociceptive pain, mechanichal pain, and chemical pain

µ (Mu) receptor: Effects

Strong analgesia, euphoria, respiratory depression, dependence

µ (Mu) receptor: Natural ligand

Endorphins

Κ (Kappa) receptor: Location

dorsal horn of the Spinal cord

Κ (Kappa) receptor: Function

Softens the response to thermal and chemical nociceptive pain

Κ (Kappa) receptor: Effects

Analgesia, sedation, dysphoria

Κ (Kappa) receptor: Natural ligand

Dynorphins

δ (Delta) receptor: Location

Periphery & some brain regions

δ (Delta) receptor: Function

Linked to enkephalins, modulates analgesia & mood regulation. Endogenous activists.

δ (Delta) receptor: Natural ligand

Enkephalins

Enkephalins

Small peptides that bind to opioid receptors, acting as natural painkillers and mood regulators in the body.

What happens to calcium channels when Gi receptors are activated presynaptically? They close, less calcium enters, less neurotransmitter release

How do Gi receptors affect adenylyl cyclase postsynaptically? They inhibit it, lower cAMP, reduced PKA activity

What ion channel do Gi receptors open postsynaptically? Potassium channels, K+ leaves the cell, hyperpolarization

What is the overall effect of Gi receptor activation on neurons? Inhibition: less neurotransmitter release and reduced excitability

What type of receptor agonist is morphine?

Strong μ-opioid receptor agonist; also activates κ-receptors

Where does morphine bind in the body?

CNS, gastrointestinal tract, and bladder

What neurotransmitters does morphine inhibit to reduce pain?

Substance P and glutamate

Where is codeine naturally found?

In opium

How does codeine compare to morphine in receptor activity?

Weak μ-opioid receptor agonist

How does morphine alter pain perception?

Raises spinal pain threshold and reduces brain perception; pain awareness remains but less distressing

What emotional effect does morphine cause?

Euphoria (cheerfulness, satisfaction, well-being)

What is the most dangerous side effect of morphine?

Respiratory depression, dose-dependent, leading to apnea

What is the antidote for opioid overdose?

Naloxone (opioid antagonist)

What is the classic pupil sign of opioid use?

Pinpoint pupils (miosis)

Do patients in deep coma always have pinpoint pupils?

No, they may present with dilated pupils

How does morphine affect GI motility?

Decreases motility → constipation, antidiarrheal effect

How does morphine affect the gallbladder?

Causes contraction, worsening gallstones

What happens at high doses of morphine?

Hypotension, bradycardia, increased intracranial pressure (dangerous in brain/spinal trauma)

What allergic-type effects can morphine cause?

Urticaria, sweating, vasodilation

Why is morphine risky in asthmatic patients?

Histamine release can cause bronchoconstriction

How does morphine affect hormone secretion?

Decreases GnRH, increases prolactin, increases ADH → urinary retention

How does morphine affect uterine contractions?

Decreases force, length, and frequency → prolongs stage II of labor

What happens to morphine when taken orally (PO)?

Significant first-pass effect in the liver, making PO administration unstable

How is oral morphine usually given to improve stability?

In extended-release form, providing more stable plasma concentrations

What type of pharmacokinetics does morphine follow?

Linear pharmacokinetics (higher dose → greater effect)

How is morphine distributed in the body?

Rapidly disperses throughout all tissues and crosses the placenta

Which opioids are most lipophilic compared to morphine?

Fentanyl and methadone (morphine is least lipophilic, penetrates brain the least)

How is morphine metabolized in the liver?

Conjugated to glucuronic acid

What is the active metabolite of morphine?

Morphine-6-glucuronide (analgesic effect)

What is the excitatory metabolite of morphine?

Morphine-3-glucuronide (causes CNS excitation)

Why is morphine dangerous in newborns?

They lack the ability to conjugate morphine → toxic accumulation

How are morphine metabolites excreted?

Mainly in urine, small portion in feces

What is the typical duration of morphine’s action?

4–5 hours

How does epidural morphine differ in duration?

Much longer, due to slow clearance from epidural space

Why are older patients more sensitive to morphine?

Slower metabolism, less fatty tissue, decreased renal activity → prolonged activity

What is the natural origin of codeine?

Found naturally in opium

What type of pain is codeine effective against?

Mild to moderate pain

How is codeine metabolized in the body?

Converted to morphine by CYP2D6 (P450 enzyme)

Why can codeine be dangerous in ultra-metabolizers?

They produce high levels of morphine → risk of toxicity

With what drug is codeine usually combined for pain relief?

Acetaminophen (paracetamol)

How is codeine used in over-the-counter (OTC) medicine?

As a cough suppressant in low doses

Why has codeine been replaced by dextromethorphan in OTC cough medicines?

Dextromethorphan does not cause analgesia and prevents addiction

What type of opioid is oxycodone?

Semi-synthetic opioid

How does oxycodone’s potency compare to morphine?

About 2 times stronger than morphine

How is oxycodone usually administered?

Orally (PO), often combined with aspirin or acetaminophen (Percocet)

How is oxycodone metabolized and eliminated?

Metabolized by P450 enzymes and secreted through the kidneys

What is a major risk associated with oxycodone?

High risk of addiction

What type of opioid is oxymorphone?

Semi-synthetic opioid

How potent is oxymorphone compared to morphine when given IV?

About 10 times stronger than morphine

How potent is oxymorphone compared to morphine when given orally?

About 3 times stronger than morphine

What are the release forms of oxymorphone?

Immediate-acting (4 hours) and extended-release (12 hours)

What type of opioid is fentanyl?

Synthetic opioid

How potent is fentanyl compared to morphine?

About 100 times more potent

Why does fentanyl act quickly?

It is highly lipophilic, with onset and dismantling in 15–30 minutes

How is fentanyl administered?

IV injection, epidural, oral (PO), transdermal patches

When is fentanyl used IV?

During surgery and for pain after surgery

When is fentanyl used in cancer patients?

For breakthrough pain (only in patients already on opioids)

Why must fentanyl only be given to opioid-experienced patients?

Otherwise it can cause apnea

What happens with subcutaneous fentanyl administration?

Forms a reservoir lasting about 12 hours

How is fentanyl metabolized?

By P450 enzymes

How is fentanyl excreted?

Through urine

What type of opioid is meperidine?

Synthetic opioid, different from morphine

What receptors does meperidine act on?

Weak μ-opioid agonist > κ-opioid agonist

What additional property does meperidine have?

Anticholinergic → can cause delirium

How does meperidine’s duration compare to morphine?

Shorter acting than morphine

Is meperidine lipophilic?

Yes, it is very lipophilic

Into what metabolite is meperidine broken down?

Normeperidine

How is meperidine excreted?

Through the kidneys

What toxic effects can meperidine cause?

Neurotoxicity → seizures and decreased blood pressure

Why is meperidine dangerous in elderly patients?

Impaired kidney function → accumulation of toxic metabolite

What is the maximum recommended duration of meperidine use?

Up to 48 hours only

What type of opioid is methadone?

Synthetic opioid, similar in potency to morphine

How does methadone’s euphoria compare to morphine?

Causes less euphoria than morphine

How long is methadone’s duration of action?

Has a longer half-life (shelf life) than morphine

How is methadone absorbed?

Well absorbed orally (PO)

What receptors does methadone act on?

μ-opioid receptor agonist, NMDA receptor antagonist, and SNRI (serotonin-norepinephrine reuptake inhibitor)

What is methadone used for clinically?

Treatment of withdrawal from heroin and morphine

How does methadone affect the biliary system?

Raises biliary pressure

What gastrointestinal side effect does methadone share with morphine?

Causes constipation

How is methadone metabolized?

In the liver, partly by P450 enzymes → complex and unpredictable metabolism

How is methadone excreted?

Through the urine

Is methadone lipophilic?

Yes, it is lipophilic and accumulates in adipose tissue