Opioid Analgesics Flashcards
What is the source of opioids?
Plants: The opium poppy
Animals: endogenously occurring
What are the endogenous opiods?
Enkephalins- short peptides. Act as neuromodulators at synapses. Derived from pro-enkephalin
Endorphins: Hormones that can act more systemically. Derived from proopiomelanocortin. Beta endorphin is the most active endorphin.
Dynorphin: Derived from prodynorphin. dynorphin A is most biologically active Kappa selective
Endomorphines- mu receptor selective
(Nociceptins- bind to opioid-like receptors and regulate pain transmission)
What antagonizes the effects of enkephalin, endorphin, and dynorphins?
Naloxone
Where do opioids bind?
Exogenous: transmembrane domains
Endogenous: transmembrane and extracellular
What are the different types of opioid receptors?
mu, delta, kappa, others
What is the signaling mechanism of the opioid receptor.?
G-protein coupling decrease neuronal excitability. Inhibition of pre-synaptic Ca channel activation of potassium channel inhibition of cAMP synthesis
What is the mechanism of inhibition in pain pathways?
- Inhibit neurotransmitter release in the presynaptic terminal in spinal cord/ascending pathway. Also inhibits post-synaptically through opening of K channels.
- Activation of descending pathway. Mediated by serotonin and norepinephrine.
What is the mechanism of inhibition in pain pathways?
- Inhibit neurotransmitter release in the presynaptic terminal in spinal cord/ascending pathway. Also inhibits post-synaptically through opening of K channels.
- Activation of descending pathway. Mediated by serotonin and norepinephrine, as well as Enkephalin.
What type of pain are opioids effective in treating?
Nociceptive pain, not neuropathic pain
Relieve dull, constant pain (2nd pain), not sharp pain (1st pain)
What are the typical uses of opioids?
Pain with malignancy painful diagnostic procedures post-operative pain obstetrical anesthesia patient-controlled analgesia (PCA) cough (lower doses) : separable from analgesic actions
What are the behavioral effects of opioid drugs?
Euphoria (mu receptors- VTA, NAcc)
Dysphoria- hallucinations (Kappa receptors)- rare
Sedation, lethargy, confusion- very common, overall CNS depression
What are the behavioral effects of opioid drugs?
Euphoria (mu receptors- VTA, NAcc)
Dysphoria- hallucinations (Kappa receptors)- rare
Sedation, lethargy, confusion- very common, overall CNS depression
Behavioral Excitation- sign of acute toxicity
What is the most dangerous side effect of opioids?
Respiratory depression- primary cause of death.
Decreased sensitivity to blood CO2 levels.
Opioids contraindicated in case of suspected head injury, because of vasodilation from increased CO2
What are the effects of opioids on the brainstem?
Nausea and vomiting?????????????? Cough suppression: doses lower than necessary for analgesia and respiratory depression- some don't even have analgesic effects Pupillary constriction (miosis)- excitation of edinger-westphal nucleus. "pinpoint pupils"
What are the effects of opioids on GI system?
Constipation- very little tolerance develops
Therapeutic- anti-diarrheal like loperimide (imodium)
Can also use antagonists (that don’t get absorbed systemically) to treat opioid induced constipation
What are the effects of opioids on histamine?
Can cause histamine release from mast cells and basophils- can lead to itching, urticaria, local vasodilation, headache. Peripheral vasodilation can lead to reduced blood pressure.
What are the effects of opioids on CV system?
Decrease in cardiac work load
Inhibition of baroreceptor reflex
Use opioids with caution if pt is hypovolemic
Therapeutic- myocardial infarction to control pain and decrease cardiac load. Also, pulmonary edema associated with cardiac dysfunction
What are the contraindications to opioid use?
Respiratory depression of any cause Suspected head injury Hypotension Shock (because endogenous opioid system is involved in the shock response) Impaired hepatic function Histamine Release Hypothyroidism
How are opioids absorbed?
?
How are opioids distributed?
?
How are opioids Metabolized?
?
Discuss morphine
Widely used to relieve severe pain
Discuss heroin
rapid onset- not approved for medicinal use
Discuss codeine
Metabolized to morphine. Often combined with tylenol or aspirin. Less potent than morphine- toxicity at high doses. High oral bioavailability.
