Opioids Flashcards
What are different types of pain?
Nociceptive pain
(Well-localized pain)
Neuropathic pain
(Direct injury to nerve or not well managed chronic nociceptive pain)
Inflammatory pain
(Associated with tissue damage)
Define opiates
Naturally occurring alkaloids such as morphine
Define opioid
Broadly describes all compounds that work at the opioid receptor
Define endorphin
Used to describe endogenous opioid peptides
What is the function of the mu receptor stimulation?
Supraspinal and spinal analgesia
💤Sedation
🚫Inhibition of respiration
📉Bradycardia
N/V
Slowed gastric motility
Modulation of hormone/NT release
What are the functions of delta GPCR
Supraspinal + spinal analgesia
Modulation of hormone + NT release
Slowed gastric motility
What are functions of kappa GPCR
Spinal analgesia
Dysphoria
What are 4 classes of opioids?
Phenanthrenes
Phenylpiperidines
Diphenylheptanes
Atypical opioids
What opioids are phenanthrenes?
Codeine
Morphine
Hydromorphone
Hydrocodone
Oxymorphone
Le orphan old
Buprenorphine
Nalbuphine
Butorphanol
What drugs are phenylpiperidines?
Fentanyl
Alfentanil
Sufentanil
Meperidine
What drug is diphenylheptane?
Methadone
What drugs are atypical opioids?
Tapentadol
Tramadol
Where do opioids act?
Spinal cord = ascending pathway to inhibit pain transmission
Brain = descending modulation pathway (dec. perception of pain)
Peripheral action (topicals)
What happens after opioid agonist binding to GPCRs?
Alpha-GTP can inhibit adenylyl cyclase and dec. intracellular cAMP = dec. Ca
= dec. NT release
What do post-synaptic opioids do in spinal cord?
Ascending pathway
Increase potassium conductance
= chloride influx and potassium efflux
= dec. response to excitatory neurotransmitters
What does GABA do in the endogenous pain regulatory system?
GABA inhibits the “off” process of pain …. allows your body to feel pain
Turning off GABA = less pain
What is PAG?
Periaqueductal grey matter
Primary control center for descending modulation
Opioids inhibit GABA via PAG
What does modulation in the descending inhibitory pathway do?
Decreases pain
Where do opioids distribute?
Localize in tissues with highest perfusion
Low blood to fat tissues, but accumulation may be an issue with lipophilic opioids
What is significance of morphine metabolites?
M3G = can lead to tremors, twitching = accumulation in renal failure can lead to CNS seizures
M6G = analgesia 4-6x more powerful than parent
Differentiate metabolism of meperidine and fentanyl
Meperidine
= hepatic metabolism, renally cleared
Fentanyl
= metabolized in liver and then further by small intestine (when PO)
No active metabolites
What are specific effects of opioids?
Analgesia
Euphoria
Dysphoria
Respiratory depression
Sedation
Sleep disturbances Cough relief (dec. reflex)
Dyspnea relief (dec. resp. Drive) GI: N/V, constipation
Describe respiratory depression effect of opioids
Dose-related - Reversal is possible w/ naloxone
When levels of CO2 accumulate, body stimulates to breath
Opioids: brain is unaware of inc. pCO2 and under stimulates breathing..
this decrease is well tolerated in “most” patients
Whos at risk for opioid-related respiratory depression?
Elderly
Sleep apnea/obese
Smokers, COPD, emphysema, asthma
+use sedatives, benzodiaz., EtOH
Opioid naive
Escalating dose (self-titration)
Long acting opioids
Pain relief
