Term
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Definition
epilepsy, schizo, neurodegen disorders
major cause of brain damage after stroke |
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Term
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Definition
1) IONOTROPIC: NMDA, AMPA, Kainate
2) METABOTROPIC |
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Term
| NMDA R. ion permeability = |
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Definition
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Term
| selective agonists of NMDA R. = |
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Definition
NMDA, glycine
(glycine = necessary co-agonist with NMDA or glutamae) |
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Term
| NMDA R. competitive antagonist = |
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Definition
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Term
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Definition
TETROMER
2 x NR1 = glycine binding site
2 x NR2 = glutamate binding site |
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Definition
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Term
| AMPA R ion permeability = |
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Definition
Na+ in
K+ out
Ca2+ perm depends on what subunits make AMPA R. |
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| AMPA R selective agonist = |
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Definition
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Term
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Definition
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Definition
TETRAMER
GluR5-7, KA1, KA2 |
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Term
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Definition
| Na+ in K+ out Ca2+ perm depends on what subunits make kainate R. |
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Term
| Kainate R selective agonists |
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Definition
| Kainate (natural substance in seaweed) |
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Term
| Kainate R competitive antagonist |
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Definition
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Term
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Definition
| ...Mg2+ at RMP (80mV), and can only block the NMDA channel when the channel is open ( need glycine and glutamate/NMDA to be present and bound to NMDA R.) |
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Term
| Why are activated NMDA R and AMPA R's often expressed together? |
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Definition
| activated AMPA R = depo of mb = remove Mg2+ block of NMDA R = activate NMDA R |
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Term
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Definition
| Ca2+ and Na+ influx = EPSP (excitatory post synaptic potential) |
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Term
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Definition
| ...synaptic plasticity (imp in learning and memory. |
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Term
| Long term potentiation (LTP) = |
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Definition
| incr. strength/ long term enhancemnt of signal by incr Ca 2+ influx (when NMDA R activated) |
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Term
| Long term depression (LTP) = |
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Definition
| if nerve not activated alot get a decr in Ca2+ influx when NMDA R's are activated = weaker signal |
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Term
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Definition
| excessive Ca2+ entry = neuronal cell death/stroke |
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Definition
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Term
| NMDA R are expressed on sensory neurones and therefore are involved in... |
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Definition
| ...transmission of pain responses ( NMDA R anatgonists v. gd at pain relief, better than morphine, but hasnt reached clinic yet) |
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Term
| low affinity uncompetitive NMDA R anatgonists = |
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Definition
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Term
| mechanism of action of Ket as a NMDA R uncompetitive antagonist |
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Definition
Like Mg2+ blocks NMDA R when open (blocks NMDA R at high transmission)
Fast dissociation rate = no prolonged blocking effect |
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Term
| Effects of Ket as a NMDA R uncompetitive antagonist = |
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Definition
| Dissociative GA = sedation, immobility and analgesia Used a s an anaesthetic for birds, small animals and large animals SIDE EFFECTS: hallicinergic, loose function of bladder, raised intra-ocular press, mm tremors and involuntary movements, seizures (rare) |
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Term
| Memantine advantage over ket = |
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Definition
| v. low affinity channel blocker = v well tolerated |
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Term
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Definition
| ...tx of memory impairment in modeate to severe alzheimers (alzheimers = no uptake of glutamate by glial cells = over stim of NMDA R's) |
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Term
| high affinity uncompetitive NMDA R anatgonists |
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Definition
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Term
| adverse effects of MK-801 = |
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Definition
1. hallicinations
2. memory impairment
3. can bind for so long = channel closes and MK-801 trapped in channel, take a few times of NMDA channel opening and closing for MK-801 to unbind, therfore NMDA R is blocked for a long time, preventing normal synaptic transmission |
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Term
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Definition
| ...blocking pain, but isnt used in vetmed due to its adverse effects |
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Term
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Definition
6-11mg/kg IM for restraint or mild sedation (can be sprayed in mouth)
22-33mg/kg IM or 1-2mg/kg IV for GA
Give IM see effects in 10mins, give IV see effects in 1min |
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Term
| Ket transdermal patch to tx... |
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Definition
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Term
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Definition
| 2mg/kg IV with a mm relxant (eg xylazine) |
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Term
| ket is contraindicated in... |
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Definition
...1. hypertensive patients
2. eye injurys
3. patients with liver/kidney dz (as cant excrete or metab drug well)
4. known history of seizures |
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Term
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Definition
IM is painful
eye remains open so should be lubricated to prevent damage to eyes surface by drying |
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Term
| glutmate activates metabotropic R's = |
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Definition
| Activate PLC = Activate mobilistaion of IC Ca2+ |
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Term
subtypes of
a)group 1
b) group 2
c) group 3
metabotropic glutmate Rs |
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Definition
a) mGlu 1 & 5
b) mGlu 2 & 3
c) mGlu 4, 6, 7 and 8 |
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Term
signal transduction of metabotropic Rs
a) group 1
b) group 2
c) group 3 |
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Definition
a) + Gq = +PLC = inc IC Ca2+
b) + Gi/Go = - AC = decr cAMP
c) + Gi/Go = - AC = decr cAMP |
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Term
| mGlu Rs (metabotropic Rs) regulate... |
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Definition
...ionotropic Rs and K+ and Ca2+ channels
(as mGlu autoRs control depo of presynaptic nerve = control release of glutamte) |
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Term
| post synaptic group 1 mGlu R mediate... |
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Definition
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Term
| presynaptic group 2 & 3 mGluR's... |
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Definition
| ...decr glutamate release = AUTORECEPTERS (block release of own transmitter) |
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Term
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Definition
necrotic lesions in retina
elevated extracellular glutamate = persistant neuronal depo = excitotoxicity |
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Term
| 3 key elements leading to cell death = |
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Definition
1. NA+ influx (incr water influx = cell lysis = glutamate released = incr neuronal cell death) - reversible if stimulus removed (eg glutmate)
2. Ca2+ influx (release glutamate=incr extracellular glutamate = inr neuronal cell death - primarily responsible for delayed neurodegen)
3. Excocystoiss of glutamate = spread and incr neurodegenerative porcess |
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Term
| SOD (superoxide dismutase) normally... |
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Definition
| ...destroys superoxide (superoxide produces free radicals) |
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Term
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Definition
| =mitochondria mop up XS IC Ca2+ = uncoupling of ATP production =production of free radicals (eg superoxide) instead of ATP |
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Term
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Definition
| Failure of ATP dependant NA+/K+ exchanger = loose balance of ions across mb = glutamate transporters reverse ( as need 3Na+ in and 1K+ out for glutamate uptake) = glutamate pumped out of cell. |
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Term
| therapeutic time windoe in stroke is how long? |
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Definition
| 3-6hrs (tx should be givin within 3-6hrs after stroke to maximise effectiveness of tx, b4 reperfusion damage has time to take place) |
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Term
| protect neurones from excitotxixity by... |
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Definition
| ...txing immediately with glutamate R antagonists or glutamate release inhibitors (NMDA R anatagonists have shown to decr extent of brain lesion in animals but failed to live up to their promise in clinical trials) |
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Term
| side effects of glutmate antagonists |
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Definition
1. hallucinations
2. amnesia
3. ataxia
4. vacuolation of neurones |
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Term
| name an environmental toxin that causes neurodegen |
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Definition
| DOMoic acid (in sp. of plankton/algae) |
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Term
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Definition
| (shell fish eat algae and then mammal eats shell fish) = crosses BBB = incr NA+ and CA2+ into cell = neuronal cell death = amnesic shell fish poisoning |
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Term
| Domoic acid/Domoate mech = |
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Definition
| v. potent AMPA and KAINATE R agonist that can cross BBB |
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Term
| clincial signs of domoic acid poisoning = |
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Definition
loss of short term memory (activate hippocampus)
motor weakness/lethargy (activate motor neurones)
seizures
=death |
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Term
| is there an antidote for domoic acid poisoning? |
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Definition
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