Used in the past to refer to morphine and morphine like analgesics with dependence 

Recently referes to any drug that causes dependence 

Phenanthrene- morphine, codiene 

Benzylisoquinoline- papaverine 

Mu

Kappa

Delta

Brain 

Spinal Cord

Periphery 

Located in the Substancia gelatinosa

Rex Laminae 2-3

Enkephalins

Endorphins

Dynorphins 

Respond to endorphins

Mu1 and Mu2

Spinal and Supraspinal Analgesia 

Euphoria

Low abuse potential

Miosis- constriction

Spinal Analgesia

Ventilatory Depression

Bradycardia

Physical Dependence

Constipation 

Suprspinal and spinal analgesia

Sedation, dysphoria

Miosis

Less respiratory depression

Respond to Dynorphin

Agonists inhibit neurotransmitter via N calcium channels 

Spinal and Supraspinal analgesia

Modulates Mu receptor activity

Depression of ventilation

Physical Dependence

Responds to enkephalins 

Increase K+ conductance

This inhibits neurotransmitter release and hyperpolarizes the cell

Inhibit Ca++

Results in suppression of neurotransmitter release 

Increasing K+ conductance

Hyperpolarizes the Cell 

Decreases MAC

Depresses EEG to a certain point

Motor and Sensory evoked potentials are not effected

Auditory evoked potentials are effected somewhat 

Miosis

Reduces Shivering Threshold and Supresses Shivering 

Causes Pruritis

Decrease Ventilatory Drive and Airway Reflexes

Decrease repsonse to DL 

Increase bronchomotor tone in asthmatics 

Depression of Respiration 

High Doses

Elderly- high plasma concentration on a weight basis

Neonates- incomplete BBB

CNS depressants additive- ETOH, Barbs, VA, Benzos, IV sedatives and Hypnotics 

Renal Insufficiency

Decreased Hepatic Blood Flow

Hyperventilaiton

Hypocapnia- increased un-ionized drug

Rewarming, shivering, motion allows secondary peaks due to reuptake from tissues 

Hypotension

Diminshed response to baroreceptors 

Bradycardia (exception demerol)

Histamine release (morphine)-vasodilation

Neuroendocrine stress response- hemodynamic instability

Intra-op and post-op catabolism

Reduce stress response by inhibiting HPA 

Decrease urge to void- relaxes detrusor

Especially with intrathecal 

Decreased biliary, pancreatic, and intestinal secretions

Delayed gastric emptying

Decreased Intestinal Motility- constipation

Triggers CTZ- nausea

Spasm of sphinchter of Oddi- looks like stones, give glucagon

True Allergic reactions are extremely rare

Local reactions are to histamine release (morphine) and preservatives

Prevents increase in IOP 

Even with Succinylcholine 

Need to increase dose of opioid to achieve the same analgesic effect

Cross tolerance between all opioids

Caused by down regulation of opioid receptors and Up regulation of cAMP pathways

Enzyme induction of CYP450 causes increased rate of metabolism (not really tolerance) 

Receptors are present in the substania gelatinosa of spinal cord 

Analgesia is more visceral rather than somatic 

Highly lipophilic of opioids is reason or post op analgesia- reflection of systemic absorption 

Diffuses across dura to CSF

Cephalad movement of opioids depends on lipid solubility 

Vascualr absorption insignificant 

Dose dependent

Caused by opioid in CSF or circulation 

Pruritis- most common

Urinary Retention

Ventilatory Depression

Viral Reactivaiton

Reactivation of herpes 2 to 5 days of opioid administration

Underlying mechanism involves cephalad mirgration of opioid to CSF and interaction with traigeminal nerve 

2 hr after injection

Most likely from systemic absorption 

Occurs more than 2 hours after injection

Reflects cephalad migration in the CSF and interaction with opioid recptors in the ventral medulla 

Detect with pulse ox

Most reliable sign is depressed level of consciousness

Treated with supplemental O2 and Naloxone