Pharmacologic Treatment of Pain Flashcards
How is B-endorphin synthesized? What is the most important opioid receptor for pain relief?
B-endorphin: Derived from POMC –> ACTH (fast-acting) & B-endorphin (slow-acting). The most important opioid receptor for pain relief is “Mu.”
What is the MOA of endorphins in the CNS? PNS? What are the proposed mxns of release?
CNS: Inhibiting GABA & thus disinhibiting dopamine. Receptors are in descending pain circuit: amygdala, mesencephalic reticular formation, PAG, rostral ventral medulla. PNS: Inhibition of substance P & tachykinin release at peripheral sensory nerve fibers and dorsal root ganglia. Central release involves the hypothalamus, midbrain, rostral medulla; cell bodies of opiodergic neurons in the median eminence of the hypothalamus. Peripheral release is mediated by stress and co-release of ACTH. Corticotrophs in the anterior pituitary synthesize ACTH & B-endorphin in equal amounts and release during stress. Release mediators are: 5-HETE, LTA4, LTB4, other lipoxygenase products, Angiotensin II, 5-HT. This involves activation of cAMP by B-adrenoreceptor activation.
What is opioid-induced hyperalgesia?
Opioid-induced hyperalgesia (AKA opioid-induced abnormal pain sensitivity or paradoxical hyperalgesia) is a phenomenon usally associated with the long term use of opioids in which individuals develop an increasing sensitivity to noxious stimuli, even evolving a painful response to previously non-noxious stimuli (allodynia). Some studies on animals have also demonstrated this effect occurring after only a single high dose of opioids.
What is the MOA of NSAIDs? Which are better for less stomach irritation? Whih causes irreversible inhibition and is used to prevent what? Fever is cause by which prostagland? All NSAIDs cause? Why use NSAIDs versus opiods?
NSAIDs inhibit cyclooxygenase (COX), which converts arachidonic acid metabolites to prostaglandins and thrombaxane, leading to inflammation. COX2 inhibitors lead to less gastric irritation. Aspirin is an irreversible COX inhibitor and is used to prevent coronary artery occlusion & colorectal cancer. Fever is caused by PGE2. All NSAIDs cause decreases in renal blood flow; prostaglandins cause vasodilation. Opiods are for “10/10” pain and will make a patient “less concerned” about pain. Still, both opiods and NSAIDs are for inflammatory pain (versus neuropathic pain, which should be addressed with AEDs and TCAs).
In general, what do antiepileptic drugs do?
Lower a neuron’s ability to fire via hyperpolarization & disallowing depolarization.
What nerve fibers are for noxious heat & chemical stimuli? What about noxious mechanical stimuli?
C. Ad.
What happens when there is a subthreshold pain response? What happens during a full pain response? If this system goes awry, what happens? What is this called? Knowing this, how could we block painful excessive nociception in central sensitization?
Small Ca2+ influx noted –> Significant Ca2+ & Na+ influx noted –+> Significant Ca2+ & Na+ influx with Glutamate release In essence, the circuits become “glued together” and there is a an excessive or chronic pain response. This is called “central sensitization.” To relieve this: Ca2+ blocker, Na+ blocker, Glu blocker.
What are AEDs that can be used in pain management? Side effects?
Na+ channel blockers: Carbamazepine [for trigeminal neuralgia] (aplastic anemia, p450 3A4 inducer), Lamotrigine [no pain approvals] (SJS rash), Topiramate [migraines] (weight loss, acidosis, oligohydrosis, glaucoma). Ca2+ blockers: Gabapentin [diabetic neuropathy] (weight gain, sedation), Pregabalin [diabetic neuropathy] (mild addiction, weight gain, sedation).
Why do SSRIs & SNRIs help pain? Name 2 SNRIs and a TCA that can be used for pain. Cite side effects.
If descending NE projections are weak, pain can occur. Descending NE pathways usually release NE, which causes release of GABA, which will inhibit ascending afferent pain fibers. Using an SSRI/SNRI to increase NE will strengthen this descending pathway. SNRIs: Duloxetine, Milnacipran (serotonin side effects: HAs, GI distress, insomnia, fatigue, sex/weight gain; NE effects: N, HTN, dr mouth, app suppression). TCA: Amitryptiline (5HT & NE side effects as above, anticholinergic sed effects, Na+ blockade – may prolong heart QTc and cause MI).
What are the three neuropsychological aspects of pain suffering?
Sensation, Perception, Affect
