CNS neuropharmacology Flashcards Preview

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Flashcards in CNS neuropharmacology Deck (56):
1

Behaviors linked to pre frontal cortex

executive function and attention, motor, pain, negative symptoms (guilt, suicidality)

2

Behaviors linked to basal forebrain

memory

3

Behaviors linked to nucleus accumbens

delusions, hallucinations, reward

4

Behaviors linked to striatum

motor

5

Behaviors linked to thalamus

pain, sensory relay

6

Behaviors linked to hypothalamus

sleep

7

Behaviors linked to cerebellum

motor

8

Behaviors linked to spinal cord

pain

9

Behaviors linked to hippocampus

memory

10

Behaviors linked to amygdala

fear, anxiety panic

11

List the precursors and key enzymes for the synthesis of acetylcholine

Acetyl-CoA + Choline > ACH + CoA (catalyzed by choline acetyl transferase)

12

Describe the inactivation mechanisms for acetylcholine

acetylcholinesterase

13

Which receptors does Ach bind to and what are its actions

Muscarinic receptors: (M1-M3: Gq stimulate PLC activity) (M2-M4: Gi/o inhibit adenylyl cyclase activity). Nicotinic receptors: Nn opens receptor-gated cation channel [ionotropic]

14

CNS location of ACH

Produced in cell bodies in brain stem and basal forebrain of neurons that widely project to cerebral cortex and hippocampus

15

Name compounds that affect ACH release, activation and degredation

Botulism decreases release, black widow spider venom increases release, Nicotine (nicotinic agonist), Benztropine (muscarinic antagonist) and diphenhydramine (muscarinic antagonist) all work at the receptor. Donepezil is an ACHE inhibitor

16

List the precursors and key enzymes for the synthesis of biogenic amines

Catecholamines: Tyrosine > tyrosine hydroxylase converts to L-Dopa (rate limiting) > dopamine > Norepinephrine > epinephrine. Indoleamine (5-HT): Tryptophan > tryptophan hydroxylase converts to 5-OH-tryptophan (rate limiting) > 5-HT > 5-HIAA

17

How are monoamines stored

Transmitter is taken-up into storage vesicle via the vesicular monoamine transporter (VMAT) where it is packaged for release and protected from
degradation by intraneuronal monoamine oxidase (MAO).Transmitter is taken-up into storage vesicle via the vesicular monoamine transporter (VMAT) where it is packaged for release and protected from
degradation by intraneuronal monoamine oxidase (MAO).Transmitter is taken-up into storage vesicle via the vesicular monoamine transporter (VMAT) where it is packaged for release and protected from
degradation by intraneuronal monoamine oxidase (MAO).

18

Monoamine termination of action

reuptake by presynaptic membrane: dopamine transporter (DAT), norepinephrine transporter (NET), serotonin transporter (SERT)

19

List receptors/second messengers for norepinephrine

α1 adrenergic: Gq stimulation of phospholipase C activity. α2 adrenergic: Gi/o inhibition of adenylyl cyclase activity, K+ channel opening. β1 adrenergic: Gs stimulation of adenylyl cyclase activity. β2 adrenergic: Gs stimulation of adenylyl cyclase activity

20

List receptors/second messengers for dopamine

D1 dopamine receptor: Gs stimulation of adenylyl cyclase activity. D2 dopamine receptor: Gi/o inhibition of adenylyl cyclase activity

21

List receptors/second messengers for serotonin

5HT1A, 1B, 1D: Gi/o inhibition of adenylyl cyclase activity and K+ channel opening. 5HT2A, 2B, 2C: Gq stimulation of phospholipase C activity - closing of Ca++ channel. 5HT3: Ligand-gated cation channel - excitatory [ionotropic]. 5HT4: Gs stimulation of adenylyl cyclase activity

22

CNS location for dopamine, norepinephrine and serotonin

 Dopamine: Substantia nigra > neostriatum pathway (nigrostriatal), ventral tegmental area >
limbic cortex (mesolimbic), ventral tegmental area > frontal cortex pathway (mesocortical),
hypothalamus > pituitary (tuberoinfindibular pathway).  Norepinephrine: Cell bodies in pons and brain stem (locus ceruleus) projecting to all levels of brain  Serotonin: Cell bodies in raphe regions of pons / upper brain stem that project to all levels of brain.  Dopamine: Substantia nigra > neostriatum pathway (nigrostriatal), ventral tegmental area >
limbic cortex (mesolimbic), ventral tegmental area > frontal cortex pathway (mesocortical),
hypothalamus > pituitary (tuberoinfindibular pathway).  Norepinephrine: Cell bodies in pons and brain stem (locus ceruleus) projecting to all levels of brain  Serotonin: Cell bodies in raphe regions of pons / upper brain stem that project to all levels of brain.  Dopamine: Substantia nigra > neostriatum pathway (nigrostriatal), ventral tegmental area >
limbic cortex (mesolimbic), ventral tegmental area > frontal cortex pathway (mesocortical),
hypothalamus > pituitary (tuberoinfindibular pathway).  Norepinephrine: Cell bodies in pons and brain stem (locus ceruleus) projecting to all levels of brain  Serotonin: Cell bodies in raphe regions of pons / upper brain stem that project to all levels of brain.

23

Function of dopamine, norepinephrine and seretonin

dopamine: initiate voluntary movement, rewar related behaviors, working memory, control of attention. Norepi: arousal, attention, vigilance, sleep wake cycle, fear, anxiety. Serotonin: sleep, arousal, attention, sensory info processing, emotion/mood, pain, eating/drinking

24

List drugs that work on norepi action via synthesis, storage, release or termination

a-methyl-p-tyrosine decreases synthsis. Reserpine inhibits storage (VMAT). Amphetamine increases release (NET). Cocaine-Bupropion-Venlafaxine inhibit termination (NET) and Phenelzine inhibits termination (MAOa)

25

Where do pseudoephedrine, clonidine, mirtazapine and propranolol act

α1 > Pseudoephedrine [indirect ag]
α2 > Clonidine [ag] / Mirtazapine [antag]
β 1-2 > Propranolol
α1 > Pseudoephedrine [indirect ag]
α2 > Clonidine [ag] / Mirtazapine [antag]
β 1-2 > Propranolol
α1 > Pseudoephedrine [indirect ag]
α2 > Clonidine [ag] / Mirtazapine [antag]
β 1-2 > Propranolol

26

Synthesis of GABA

glutamate > glutamic acid decarboxylase converts to GABA (gamma-aminobutyric acid)

27

Termination of GABA

reuptake into presynaptic nerve and glial cells by GABA transporter

28

List 3 drugs that work on GABA at the synapse and their functions

Benzodiazepines: Bind to GABAa (on post-synaptic membrane) receptor to facilitate GABA inhibitory action. Tiagabine: Inhibits reuptake of GABA by
transporter. Vigabatrin: Inhibits degradation by GABA-T (GABA transaminase)Benzodiazepines: Bind to GABAa (on post-synaptic membrane) receptor to facilitate GABA inhibitory action. Tiagabine: Inhibits reuptake of GABA by
transporter. Vigabatrin: Inhibits degradation by GABA-T (GABA transaminase)Benzodiazepines: Bind to GABAa (on post-synaptic membrane) receptor to facilitate GABA inhibitory action. Tiagabine: Inhibits reuptake of GABA by
transporter. Vigabatrin: Inhibits degradation by GABA-T (GABA transaminase)

29

GABA receptors and second messengers

GABAa: Opens ligand-gated Cl- channel > decreases neuronal excitability (IPSPs) [ionotropic]. GABAB : Gi/o > inhibit adenylyl cyclase, decrease Ca++ conductance, open K+ channel

30

GABA location/ function

brain and spinal cord - major inhibitory neurotransmitter of CNS

31

Glutamate synthesis

Glutamine > converted to glutamate by glutaminase

32

Glutamate termination

reuptake by neuron via neuronal glutamate transporter, or uptake by glial cell transporter where it is converted to glutamine by glutamine synthetase, then taken up by neuron

33

Glutamate receptors and second messengers

NMDA: Increase Ca++ influx. AMPA: Increase Na+ and Ca++ influx. Kainate: Increase Na+ influx. R1-R5 (Group I): Gq > stimulation of phospholipase C activity. R2-R3 (Group II): Gi/o > inhibition of adenylyl cyclase activity-inhibit VSCC-activate K+
channels. R4-R6-R7-R8 (Group III): Gi/o > inhibition of adenylyl cyclase activity-inhibit VSCCNMDA: Increase Ca++ influx. AMPA: Increase Na+ and Ca++ influx. Kainate: Increase Na+ influx. R1-R5 (Group I): Gq > stimulation of phospholipase C activity. R2-R3 (Group II): Gi/o > inhibition of adenylyl cyclase activity-inhibit VSCC-activate K+
channels. R4-R6-R7-R8 (Group III): Gi/o > inhibition of adenylyl cyclase activity-inhibit VSCC

34

Alzheimer's disease pathology and treatment related to cholinergic pathway

Pathology: decreased muscarinic-cholinergic function
Treatment: cholinesterase inhibitors: DonepezilPathology: decreased muscarinic-cholinergic function
Treatment: cholinesterase inhibitors: Donepezil

35

Parkinson's disease pathology and treatment related to cholinergic pathway

Pathology: muscarinic-cholinergic overactivity
Treatment: muscarinic antagonist: Benztropine Pathology: muscarinic-cholinergic overactivity
Treatment: muscarinic antagonist: Benztropine

36

Psychoses pathology and treatment related to cholinergic pathway

Pathology: [??] decreased nicotinic-cholinergic function. Treatment: nicotinic agonist: Nicotine

37

Depression pathology and treatment related to adrenergic pathway

Pathology: decreased NE activity in cortical areas
Treatment: increase NE activity (acutely) by
1. decrease termination (NET)( Venlafaxine-Amitriptyline), 2. decrease degradation > increase storage - release (MAOA)(Phenelzine) or 3. increase release >α2 antagonist ( Mirtazapine)Pathology: decreased NE activity in cortical areas
Treatment: increase NE activity (acutely) by
1. decrease termination (NET)( Venlafaxine-Amitriptyline), 2. decrease degradation > increase storage - release (MAOA)(Phenelzine) or 3. increase release >α2 antagonist ( Mirtazapine)

38

Pain pathology and treatment related to adrenergic pathway

Pathology: abnormal neurotransmission in pain pathway (NE). Treatment: decrease termination (NET): Venlafaxine-Amitriptyline

39

Anxiety pathology and treatment related to adrenergic pathway

Pathology: excessive NE neuronal activity. Treatment: β1-β2 antagonist: Propranolol
Pathology: excessive NE neuronal activity. Treatment: β1-β2 antagonist: Propranolol

40

Describe roles of L-dopa, amphetamine, Ropinirole, aripiprazole, haloperidol, cocaine and bupropion on the dopaminergic synapse

L-Dopa increases synthesis, amphetamine increases release, Ropinirole is a D2 agonist, Aripiprazole is dopamine partial agonist, haloperidol is D2 antagonist, cocaine inhibits reuptake and bupropion inhibits reuptake (NDRI)

41

Parkinson's disease pathology and treatment related to dopaminergic pathway

Pathology: decreased DA activity in nigrostriatal pathway. Treatment: increase striatal dopamine levels by 1. increase synthesis: L-dopa. 2. increase receptor activation: Ropinirole. 3. decrease degradation, increase storage - release: Carbidopa (DDC) -Selegiline (MAOB) - Entacapone (COMT)

42

Psychoses pathology and treatment related to dopaminergic pathway

Pathology: increased DA activity in mesolimbic pathway. Treatment: dopamine D2 antagonist: Haloperidol

43

Describe the roles of Fenfluramine, Buspirone, sumatriptan, clozapine, ondansetron, propranolol, fluoxetine, venlafaxine and clomipramine on the serotoninergic system

Fenfluramine increases release, Buspirone is a 5HT1A Partial Agonist, Sumatriptan is a 5HT1D Agonist , Clozapine is a 5HT2A Antagonist, Ondansetron is a 5HT3 Antagonist, Propranolol is a β1-β2 Antagonist, Fluoxetine is a SSRI inhibitor, Venlafaxine is a SNRI inhibitor, Clomapramine is a TCAD reuptake inhibitor

44

Depression pathology and treatment related to seretonin pathway

Pathology: decreased 5HT activity in cortical areas
Treatment: increase 5HT activity (acutely) by 1. decrease termination (SERT): Fluoxetine-Venlafaxine. 2. decrease degradation: increase storage - release: (MAOA): PhenelzinePathology: decreased 5HT activity in cortical areas
Treatment: increase 5HT activity (acutely) by 1. decrease termination (SERT): Fluoxetine-Venlafaxine. 2. decrease degradation: increase storage - release: (MAOA): Phenelzine

45

Pain pathology and treatment related to seretonin pathway

Pathology: abnormal neurotransmission in pain pathway. Treatment: decrease termination (SERT): Venlafaxine-Duloxetine

46

anxiety pathology and treatment related to seretonin pathway

Pathology: excessive amygdala activity (low 5HT activity). Treatment: increase 5HT activity (acutely) by 1. decreaseing termination (SERT): Fluoxetine-Venlafaxine. 2. Partial agonist at 5HT1a: Buspirone

47

Roles of Diazepam-zolpidem, phenobarbital-alcohol, sevoflurane, flumazenil, baclofen, vigabatrin and tiagabine on the GABAergic pathway

Diazepam-zolpidem, phenobarbital-alcohol and sevoflurane are all GABAa agonists, Flumazenil is a GABAa antagonist, Baclofen is a GABAb agonist, Vigabatrin inhibits degradation and Tiagabine inhibits reuptak

48

Seizure pathology and treatment related to GABA pathway

Pathology: depressed GABA activity leads to increased spread. Treament: GABA agonists: BDZs-Barbituates

49

anxiety pathology and treatment related to GABA pathway

Pathology: excessive amygdala activity (low GABA activity). Treatment: GABA agonist: benzodiazepines

50

Insomnia pathology and treatment related to GABA pathway

Path: excessive amygdala activity/decreased GABA activity. Treatment: GABA agonist: Z drugs (zolpidem)- benzodiazepam

51

Anesthesia related to GABA pathway

Barbituates used to increase GABA

52

Roles of lamotrigine, memantine, ketamine, alcohol on glutamatergic pathway

lamotrigine decreases release, memantine, ketamine, and alcohol are NMDA antagonists

53

Alzheimers pathology and treatment related to glutamate pathway

Pathology: increased neuronal excitotoxicity
Treatment: decrease excitotoxicity via NMDA-R block: Memantine

54

Pain pathology and treatment related to glutamate pathway

Pathology: abnormal neurotransmission in pain pathway. Treatment: decrease Glu activity via NMDA-R block: ketamine

55

Seizure pathology and treatment related to glutamate pathway

Pathology: enhanced Glu activity leads to increased spread of excessive neuronal discharge. Treatment: decrease Glu release via VSCC block: Lamotrigine

56

Anesthesia related to glutamate pathway

nitrous oxide decreases glut activity via NMDA-R block