Opioids

Opiates are commonly used medications that stimulate opioid receptors to reduce the sensation of pain.  These medications are used to treat painful conditions and to assist in pain management during surgeries or sedation.

Opiates are addictive and the side-effect profile of respiratory depression makes this class of medication particularly dangerous to prescribe and administer without careful thought and planning.  Overdose of opiates (intentionally or accidentally) can occur easily and can result in death from apnea (cessation of breathing).  Many individuals have died of opiate overdose from both prescribed, diverted (opioid pills obtained by prescription, then sold), or illegally obtained sources (e.g. heroin).  

Due to the dangerous side-effect profile of opioids, limited quantities should be prescribed and opiates should be avoided when possible in the treatment of chronic pain.  

Class Drugs

• Alfentanil

• Codeine

• Fentanyl

• Hydrocodone

• Hydromorphone

• Meperidine

• Methadone

• Morphine

• Oxycodone

• Oxymorphone

• Remifentanil

• Sufentanil

Class Mechanism of Action

Mechanism mediated by interaction between the mu, kappa, and delta receptors

• Mu Receptors

Responsible for response to thermal, mechanical, and chemical pain stimuli

• Kappa Receptors

Located in the dorsal horn

• Responsible for response to chemical and thermal pain stimuli

• Delta Receptors

Located in periphery

Opioids activate the opioid receptor, which affects the pre- and postsynaptic neurons

• Presynaptic neuron

Activation of the presynaptic neuron opioid receptors, decreases calcium influx into the presynaptic neuron

• Decreased calcium levels inhibit the release of neurotransmitters (glutamate) thereby reduction transmission of excitatory pain stimuli

• Postsynaptic neuron

Activation of the postsynaptic neuron opioid receptors, increases potassium efflux from the postsynaptic neuron

• Decreased potassium levels, decrease the response to excitatory neurotransmitters

Class Application

Analgesia

• Alters perception of pain centrally

• Increases pain threshold at the spinal cord

Euphoria

• Produces sense of well-being

Antitussive

• Decreases cough reflex

Anti-Diarrheal

• Decreases motility and increases tone of GI smooth muscle

• Often produces constipation

Class Adverse Effects

Respiratory depression

• Reduces sensitivity of respiratory center neurons to carbon dioxide, resulting in decreased respirations

• Effect is increased with co-administration of other sedative medications

• Epidemic of opioid related deaths from prescription drugs

Care should be taken in prescribing medications to opioid naïve patients, patients with other sedative prescriptions, obstructive sleep apnea, and individuals at high risk of medication abuse

• Naloxone is a reversal agent, which saves lives in treatment of opioid overdose

Miosis

• Causes pinpoint pupils

• Clue in deciphering cause of altered mental status

Hypotension/bradycardia

• Effect seen at large doses

Histamine release

• Primary effect is pruritus

• May cause vasodilation, sweating, urticaria, and bronchoconstriction

Opioid withdrawal

• Rarely life threatening (except in neonatal period)

• Body aches, diarrhea, nausea, chills are hallmark symptoms

Drug Table

Drug Name	Application	Comments	Image
Alfentanil		Synthetic; More potent than fentanyl; Used primarily for surgical procedures	"Alfalfa" "Nail"
Codeine		Natural; Much weaker than morphine; Some individuals are rapid metabolizers, which can lead to toxicity and respiratory depression; Antitussive properties	"Coding"
Fentanyl		Synthetic; 100x as potent as morphine; Rapid onset and short half-life; Serotonin syndrome in patients taking SSRIs	"Fence" "Nail"
Hydrocodone		Semi-synthetic; Oral form 8x as potent as morphine; Preferred in patients with renal dysfunction as results in less accumulation of metabolites	"Water" "Coding"
Meperidine		Mechanisms; -Kappa agonist; -Mild Mu agonist; -Anticholinergic properties; Properties; -Synthetic; -Less potency than morphine; Adverse Effects; -Metabolite normeperidine causes neurotoxicity; -Hyperreflexia; -Delirium; -Seizures; -Only use for short-term <48 hours; -Serotonin syndrome; -Use caution in elderly or those with renal insufficiency	"My Pear" "Dining"
Methadone	Adjunct for focal seizures	Mechanisms; -Acts on Mu receptors; -Antagonizes NMDA receptors; -Norepinephrine and serotonin reuptake inhibitor; -Impacts both nociceptive and neuropathic pain by impacting both Mu receptors and norepinephrine and serotonin receptors; Properties; -Synthetic; -Non-linear morphine equivalent conversion; -Provides less euphoria and has a longer duration of action than morphine; -Long-half life results in prolonged times to reach steady-state in patients: 1.5 days - 2 weeks; -Toxicity can develop if careful titration is not performed; Adverse Effects; Prolongs QT interval	"Meth" "Done"
Morphine		Properties; -Natural occurring; -Standard of comparison for other opioids	"Morphing caterpillar"
Oxycodone		Properties; -Semi-synthetic; -Oral form 2x as potent as morphine; -Extended release form (oxycontin) is often crushed and abused	"Oxygen" "Coding"
Oxymorphone		Properties; -Semi-synthetic; -Oral form 3x as potent as morphine	"Ox" "More Phone"
Remifentanil		Properties; -Synthetic; -Less potent than fentanyl; -Used primarily for surgical procedures	"REM CD" "Fence" "Nail"
Sufentanil		Properties; -Synthetic; -Less potent than fentanyl; -Used primarily for surgical procedures	"SUE" Fence" "Nail"