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Neurogenesis in adults can occur here
- - dentate gyrus of the hippocampus
- - olfactory bulb
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Opiods
- - centrally acting analgesics
- - mu agonist (work on same receptor as endorphins)
- - work on ascending and descending pain tracts
- -(down) DISinhibit GABAs inhib. actions on Ser and NE
- - (up) block NT release from presyn. via blocking Ca channels and hyperpolarize postsyn. via opening K channels
- - Morphine- full mu agonist, full efficacy
-
epicritic pain
- easily discriminable and well localized
-
protopathic pain
- not localized and can only be described generally
-
ASA
- - irreversible COX inhibitor
- - anti-inflammatory, fever, pain, and thrombotic effects
- -**increased risk of bleeding**
-
NSAIDS
- - reversible COX inhibitors
- - inhibit pain and inflammation
-
APAP
- - COX inhibitor in spinal cord and brain
- - reduces pain and fever
- - NO effect on inflammation
-
When is combonation therapy ok
- when MOA of the drugs is different
-
Steroids
- prevent inflammatory mediator production by working on hormone receptors
-
Local anesthetics
- - block neuronal firing
- - effective against nociceptive and neuropathic pain
-
local analgesics
- - nociceptive and neuropathic pain
- - Lidocaine- Na channel blocker- slow rapid firing of voltage gated Na ion channels
- -Capsacin- substance P- stimulates C fibers- overstimulation causes temporary nerve ending damage, reducing ability to send pain signals
-
enkephalins
- - act on delta receptors for distraction of pain
- - Nucleus Raphe Magnus will stimulate the release of enkephalins(via seratonin) from inhibitory neurons in spinomesencephalic tract after pain signal reaches PAG via
-
NMDA-r antagonist
- - block Ca influx
- - Ketamine- serious side effects like dysphoria and hallucinations
-
Catecholamine synthesis
L-tyrosine--(tyrosine hydroxylase** + BioH4)--> L-DOPA
L-DOPA--(DOPA decarboxylase+B6)--> DA
DA--(Cu+ Vit C)--> NE--(SAM)--> Epi
**= irreversible regulatory step
-
Inactivation of catecholamines and indoleamines
- -taken back up into nerve by high affinity uptake Na cotransport**
- 1. MOA- oxidative deamination
- 2. COMT- methylation
- **= transporter is rate limiting step
-
Indoleamine synthesis
- L-Trp--(Trp hydroxylase+BioH4)--> 5-OH-Trp
- 5-OH-Trp--(decarboxylase+B6)-->5-HT(seratonin)
-
MAOIs
- - can cause HTN when exposed to foods containing tyamine(cheese and redwine)
- - MAO-A for 5-HT(seratonin)
- - MAO-B for DA
-
amitryptiline
- - tricyclic antidepressant
- - inhibit high-affinity uptake of NE and 5-HT(seratonin)
- - approved for use in neuropathic pain
- - side effect- anticholinergic effects
- - not for patients over 65
-
SSRI
- inhibit uptake of 5-HT only
-
cocaine and methylphenidate
-inhibit uptake of DA,NE and 5-HT
-
amphetamine
- releases DA and 5HT from nerve terminals
-
Barbituates
- stimulate GABA-A receptor
- - cause increase in Cl conductance
- - hyperpolarize
-
Benzodiazepines
- - sensitize GABA-A receptor
- ** no suicide risk**
- - increase Cl conductance
- - hyperpolarize
-
duloxetine
- - SNRI (seratonin, NE reuptake inhibitor
- - approved for peripheral diabetic neuropathy
-
gabapentin and pregabalin
- - anticonvulsant
- - blocks Ca influx by binding to alpha 2 delta s/u of Ca ion channel
- - blocks release of glutamate and substance P
-
Thalamic pain syndrome
- lesions to posterior thalamus may cause chronic pain
-
methylphenidate
- - binds to DAT
- - reduces rate of uptake and increases extracellular DA
- - cocaine works this way
-
Mixed amphetamine salts
- - triggers phosphorylation of DAT causing reversal of DA and subsequent increase
- - inhibits uptake and increases release of DA
-
Dx for inattention
- - 6 or more for 6 months
- -often loses thing, creless mistakes, difficulty sustaining attention, poor listener, forgetful, easily distracted, etc
-
Dx for hyperactivity
- - 6 or more for 6 months
- - fidgety, cant remain seated, runs about, etc
-
dorsal anterior cinculate cortex (dorsal ACC)
-regulates selective attention
-
dorsolateral prefrontal cortex
- sustained attention
-
prefrontal motor cortex
- involved in hyperactive sx
-
orbital frontal cortex
- involved in impulsive sx
-
NE in ADD
- - modulates attention processes through arousal networks in the prefrontal cortex
- - also important in behavioral inhibition
-
haloperidol
-D2 receptor antagonist
-
COMT
- - ez involved in DA metabolism
- -polymorhic (val/met) substitution at gene level increases activity
- - more activity--> less DA
-
Seratonin
- -synth in rapha nuclei
- - involved in mood, sleep and psychosis
- - can act as excitatory or inhibitory
- - ionotropic or metabotropic
- - therapy target for migraines, anxiety, depression and OCD
-
Fluoxtine
- -Seratonin Reuptake Ihnibitor (Ser/Na cotrans inhib)
- - can be used to heal (temporary tx)
-
ACh
- - ligand and metabotropic receptors
- - receptors in basal ganglia, cortex and hippocampus
- -loss of central muscarinic cholinergic neurons-> AD
-
diphenhydramine
- -histamine blocker
- - not for pt over 65-> can cause delirium
-
NE
- - made in locus coeruleus in pons
- - function- arousal, sleep/wake cycle, pain, inflammation, emotions, learning and memory
-
Clonidine
- - dampens NE tone
- - used in opiate withdrawl
- - can be used in tx of ADD, ax, depresson
-
GABA
- A- ionotropic receptor, increase Cl conductance
- B- metabotropic receptor, increase K conductance
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