Pharm final

Julien’s Rules (3 meds to use before opioids)

1 → analgesic/anti-inflammatory

2 → antidepressants w/ norepinephrine potentiary action

3 → mood stabilizing anticonvulsants w/ analgesic action

Pain receptors

delta, mu, kappa

Chemistry of nociception

nociceptor → glutamate (released in spinal cord) → activate all 5 pain pathways (each nociceptor activates a specific pathway; pain → cortex)

Glutamate and pain

to modulate → antagonize post-synaptic receptors in the spinal cord

NMDA receptor → ketamine selective antagonist (low dose to stay in spinal cord (local anesthetics), if high levels, affect brain (hallucinations)

THC → CB1 partial agonist (blocks release of glutamate)

Pain management: opioids - receptors (delta, mu, kappa)

delta (spinal) - in brain and spinal cord

lets out potassium (K+) like mu receptors; K+ efflux creates IPSP, Na+/K+ to Ca2+ channel due to no action potential

drug addiction can be prevented by not acting on mu

Norepinephrine (NSRIs)

depression and pain respond best to NSRI

causes opioid release in spinal cord

Journavax (Suzetrigine)

shouldn’t produce addiction

FDA approved in 2025

Nociceptor’s specific voltage gated Na+ channel (Na+ V1.8)

V1.8 is not expressed

V1.8 expressed in PNS on nociceptors and not other sensory neurons (only in nociceptors in PNS)

approved for acute moderate to severe pain

grapefruit interaction (cannot be taken w/ CYP3A inhibitors)

blocks channels at action potential at node of ranvier (stops it; never releases glutamate)

Treating pain and minimizing addiction risk

suboxone → naloxone surrounds opioid (morphine, oxytocin, etc.), stomach acid breaks down naloxone, opioid slowly absorbed (prevents addiction w/ slow onset; can’t inject because grinding it down cancels out opioid), more time to use drug before addiction starts

High Trait Anxiety

less activity in ventral PFC (more emotional/reactive)

more activity in the amygdala (increases CRF levels)

external for good things, internal for bad things; overemphasize negative, underemphasize positive

higher risk factors for vulnerability

Low Trait Anxiety

more activity in ventral PFC (suppressing anxiety/ inhibit emotions)

less activity in amygdala (turned off from GABA(inhibits anxiety), better control over CRF release (less))

Autonomic Nervous System

controlled by hypothalamus

increased breathing, heart rate → anxious → CRF release

feelings; facial expressions

thermal (shiver → fear)

Feeling, Behavior, Physiological Response

PFC → Amygdala → Hypothalamus

CRF - stress (degree of change in environment) good stress v bad stress (ex. marriage vs divorce; produce same amount of CRF)

Maternal anxiety during pregnancy

babies had larger VPFC and amygdala, but only on right side (all were right handed)

Classic Anxiolytics (First Generation)

ex. benzodiazepines, valium, barbiturates

all GABA-A receptor agonists

GABA-A receptor agonists (1st gen. anxiolytics)

produce Cl- current (producing IPSP)

present 90% of neurons - brain

cortex - release of GABA - inhibit emotions (ie anxiety)

GABA also present in VTA — release of dopamine in N.acc (causes release of dopamine indirectly + euphoria)

same effects of alcohol; addictive

addition of CNS depressant (self-medicate alcohol, marijuana) before being prescribed anxiolytics (cross tolerance and dependency) → ¼ being treated for anxiety classified as alcoholic