parkinsons Flashcards
_ disease
degeneration of dopaminergic neurons projecting from substantia nigra to the striatum
parkinson’s diease
parkinson’s
normally, activativation of _Galphai receptors in the striatum affect ACh and GABA release. degeneration of this neurons projecting to the striatum attenuates dopamine release and leads to a loss of proper control of motor fxn
dopamine D2
L-DOPA - what is left of the projections, they provide more DA to the synapse -
L-DOPA crosses BBB
Dopamine does not cross BBB
generally L-DOPA treatment good for _ years
sometimes need to diminish does over time because of side effects
patients become lesss responsive(more degenerative)
3-4years
when given L-DOPA we give it with carbidopa a peripheral dopa decarboxylase inhibitor
why
get more drug into CNS because Da doesn’t cross BBB
without it 80% of patients experience nasusea and vomiting due to activate of Da receptors in gut
some advantages of Da agonists over L-DOPA
not as toxic as L-DOPA
dont require neuron from substantia nigra for delivery
parkinson’s also treated by metabolic enzyme inhibitors
_ and _
MAO and COMT inhibitors
goal of anticonvulsants - epilepsy
phenytoin and other anti-seizure drugs block _
block high frequency firing APs
they look a lot like LA
sustains Na channel is refractory state
some anti-convulsants potentiate the effects of _ to dampen synaptic nerve impulses
GABA
can inhib gaba transaminase - metabolism of GABA
inhib GABA reuptake
_ are favored by dentists in ER treatment of seizure or epileptic episode
GABA potentiation
benzodiapines
anti-convulsants
barbs also safe way to treat epilepsy - sedative effects limit utility
blockade of T-type calcium channels
drugs that block these in the thalamus are effective as _
anti-convulsants
sedative hypnotic drugs, anti-anxiety drugs, central acting muscle relaxing drugs primarily are _ and _
barbiturates(more toxic) and benzodiapines
anxiolysis
sedation - without loss of consciousness
hypnosis - depressed sleepy state - impaired sensory responsive
anesthesia - unconsciousness without possibility of arousal
resp failur
what do we give for muscle sparms barbs or benzodiapines
benzodiazepines - potentiate GABA
which gaba receptor do barbs and benzos bind to
gaba A receptor - ligand gated ion channel - mediate Cl- conductance
gaba b - g protein coupled
barbs and benzo are allosteric regulators of GABA A - CL
_ increase the duration of GABA mediated channel opening - increase duration of Cl-
_ increase the frequency of GABA mediated channel opening
barbiturates increase opening of channel more Cl- - knock out everything
benzodiazepines increase frequency (less toxic) - more anti-anxiety - better therapeutic index,less potential for abuse
both cause membrane hyperpolarization
CNS depression
at higher dose barbs or benzos can act as GABA mimetic
barbiturates at high dose can mimetic GABA
Valium is a long acting _
benzodiazepine
Flumazenil is a barb or benzo antagonist
benzodiazepine
structurally unrelated to benzodiazepines but bind to same site on GABA
sedation within 15min - used to tx insomina
ambein(zolpidem)
barbs or benzo
although a general downer on the CNS, the reticular formation is especially sensitive - arousal,attention,sleep,awareness
barbiturates
_ are first line of tx of Bipolar disorder
more effective in treating manina but does augment other anti-depressants
lithium salts
do they work - don’t really know
decrease adrenaline and increase serotonin
toxic at high dose
