Pharmacology

Front 1

what are the three main subtypes of glutamate-gated ion channels?

Back 1

1. AMPA
2. NMDA
3. Kainate

Front 2

AMPA receptors

Back 2

found throughout CNS
- NA influx (excitatory)

Front 3

Kainate receptors

Back 3

found throughout CNS
- NA influx and K efflux
- may be used to code for pain intensity

Front 4

NMDA

Back 4

- hippocampus, cerebral cortex and spinal cord
- receptor opening requires simultaneous binding of glutamate and glycine
- requires depolarization to get rid of Mg block even after NT binding
- K, Na, and Ca influx

Front 5

memantine

Back 5

non competitive NMDA receptor antagonist that does not cause the side effects associated with competitive receptor antagonists
- 'use dependent'!

Front 6

give the mechanism for apoxic injury

Back 6

mit are not able to maintain ionic gradients, and the Na couple glutamate-Na coupled transporters don't work.
- increased glutamate causes increased opening of NMDA channels
- increase Ca, Na, and K influx
- increased Ca actiaves many Ca dependent degredation enzymes (DNAse, proteases, phosphatases, phospholipases)

Front 7

memantine

Back 7

noncompetitive NMDA receptoror antagonist that has few side effects.
- is use dependent
- allows low levesl of receptor activation during physiologic stimulation but prevents higher levle sof activation

Front 8

how do AMPA receptor antagonists help against ischemic injury?

Back 8

- don't let Ca entry through AMPA receptors
- added effect of preventing depolarization --> reduced activation of NMDA receptors and voltage-activated Ca channels

Front 9

hyperalgesia

Back 9

extreme sensitivity to pain
- modulated by NMDA receptors

Front 10

Lamotrigine

Back 10

used to treat refractory complex partial seizures
- stabilizes the inactivated state of the voltage-gated Na channel --> reduces membrane excitability

Front 11

pathogenesis of ALS

Back 11

defect in glutamate transporters in the spinal cord and motor cortex --> increased [glutamate] --> motor neuron death via excitotoxicity

Front 12

riluzole

Back 12

voltage-gated Na channel blocker for treatment of ALS --> decrease glutamate release
- cerebroprotective, antiepileptic, and analgesic effects

Front 13

CNQX

Back 13

AMPA receptor antagonist for treatment of ALS

Front 14

amantadine

Back 14

noncomeptitive blocker of NMDA receptor channels
- used to treat Parkinson's disease

Front 15

synthesis of GABA

Back 15

depends on the glutamic acide decarboxylase (GAD)
-decarboxylation of glutamate to GABA in nerve terminals

Front 16

cofactor for GAD

Back 16

pyridoxal phosphate (Vitamin B6)

Front 17

Difference between GABA_A and GABA_B

Back 17

ionotropic GABA_A: fast IPSPs
metabotropic GABA_B: slow IPSPs

Front 18

GABA_A

Back 18

ligand gated Ca channel that opens immediately after GABA binding

Front 19

GABA_B

Back 19

7 membrane G protein receptor. Opens K channels
- expressed at lower elvels than GABA A
- found primarily in spinal cord

Front 20

baclofen

Back 20

GABA_B receptor agonist

Front 21

gabaculine

Back 21

inhibits GABA-T: enzyme responsible for degredation of GABA ot succinic semialdehyde
- anticonvulsive effects

Front 22

Allylglycine

Back 22

inhibits glutamic acid decarboxylase --> lowered GABA levels --> convulsant

Front 23

Isoniazid

Back 23

inhibits pyridoxal kinase (antivitamin B6) --> lowered GABA levels --> convulsant at high doses

Front 24

Tetanus Toxin

Back 24

inhibit GABA and glycine release --> convulsant

Front 25

Muscimol

Back 25

GABA_! receptor agonist --> mimics psychosis

Front 26

Baclofen

Back 26

GABA_B receptor agonist --> muscle relaxant

Front 27

Bicucullin

Back 27

competitve receptor antagonist --> convulsant

Front 28

Picrotoxin

Back 28

noncompetitive GABA antagonist --> convulsant

Front 29

Benzodiazepines

Back 29

potentiate GABA binding --> anticonvulsant, anxiolytic

Front 30

Barbituates

Back 30

increase GABA efficacy, weak agonist --> anticonvulsant, anesthetic

Front 31

where do sedative/anxiolytic and hypnotic drugs act?

Back 31

at the GABA_A receptor. The receptor also has a
1. barbiturate binding site (that also binds IV general anesthetic and CNS depressants)
2. a bezodiazepine binding site
3. a steroid binding site

Front 32

how do benzodiazepines and barbiturates act?

Back 32

primarily by alering the interaction between GABA_A receptor and GABA.

Front 33

barbiturates

Back 33

increased GABAergic trasnmission at the brainstem: suppression of the reticular activating system --> sedation, amnesia, and loss of consciousness
increased GABAergic transmission at the motor neurons in the spinal cord --> releases muscles and suppresses reflexes
- decrease activation of AMPA receptor by glutamate

Front 34

which are used more in clinical settings: benzodiazepines or barbiturates?
Why?

Back 34

benzodiazepine:
- cause less tolerance
- have fewer withdrawl symptoms
- have less impact on drug-metabolizing enzymes
- higher selectivity and less toxic potential

Front 35

why are barbiturates dangerous?

Back 35

synergize with GABA at GABA_A receptors
- independently activate GABA_A channels!!

Front 36

what are barbiturates good for?

Back 36

anti-epileptics
phenobarbital hyperpolarize the neuron --> decrease neuronal excitability --> raise seizure threshold.

Front 37

relationship between barbiturates and P450 oxidases

Back 37

P450 inducer

Front 38

how do you treat barbiturate overdose?

Back 38

- respiratory and cardiovascular support
- activated charcoal for drug chelation
- alkalinization of urine to increase barbiturate clearance

Front 39

why are benzodiazepines safter than barbiturates?

Back 39

benzos increase the frequnecy of channel opening instead of increaseing the duration of Cl channel opening (barbit).
- benzos increase the likelihood of opening by increasing the binding affinity between GABA and the GABA_A receptor
- benzos have no intrinsic agonist activity

Front 40

flumazenil

Back 40

used to treat benzodiazepine overdose
- competitive blocker of benzo bindng to GABA_A receptor

Front 41

diazepam and aprazolam

Back 41

benzos used for:
- chronic severe anxiety
- anxiety that accompanies depressiona nd schizophrenia

Front 42

mechanism of benzodiazepine tolerance

Back 42

decreased expressin of GABA_A receptors

Front 43

ethanol molecular targets

Back 43

believed to have some effect on GABA_A as well.
- inhibition of NMDA receptor activation (endogenous ligand: glutamate)