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Flashcards in Exam 4 Deck (126):
1

cause of Parkinson's

degeneration of dopamine neurons in substantia nigra

2

symptoms of parkinsons

1. resting tremor - goes away with activity
2. bradykinesia/akinesia and slow speech
3. postural instability
4. muscular rigidity

3

besides decrease in dopamine what else occurs in parkinson's?

1. loss of substantia nigra cells/loss of pigment
2. lewy bodies in substantia nigra

4

role of synuclein

inhibits dopamine - forms aggregates --> proteasome degrades

5

mutations of synuclein are what kind of mutation? what happens?

gain of function (Parkinson's)

form aggregates - major protein in lewy bodies

6

role of parkin?

ubiquinates proteins --> degradation

7

mutations of parkin are what kind of mutation? what happens?

loss of function (recessive)

Parkin not active, proteins accumulate into lewy bodies

8

Drug therapy targets for parkinson's?

1. stimulation of dopamine D2 receptor
2. block muscarinic receptors

9

Drugs that are dopamine and NE precursors for treating Parkinson's?

L-DOPA, levodopa

10

what enzyme converts L-DOPA to dopamine

DOPA decarboxylase

11

what is levodopa usually paired with, what does it do?

carbidopa (levodopa + carbidopa = Sinemet)

inhibits DOPA decarboxylase in the peripheral NS --> more L-DOPA enters CNS b/c not consumed by peripheral neurons

12

L-DOPA particularly ameliorates what?

bradykinesia and decreases mortality

13

bromocriptine and pergolide

Parkinson drugs that are dopamine agonists - D1 and D2

14

1. trihexyphenidyl
2. benzatropine mesylate
3. diphenhydramine

muscarinic antagonists for Parkinson's

15

effect of taking muscarinic antagonist?

modest (usually adjuncts to L-DOPA)

improve tremor and rigidity

16

common side effects for Parkinson's drugs

GI - nausea, anorexia, vomiting (constipation and urine retention for muscarinic)

confusion, hallucinations

17

physiologic and essential tremor treatment

propranolol - beta antagonist

18

autosomal dominant (gain of function mutation) neurodegenerative disorder

- paternal transmission = more severe and rapid

Huntington's

19

neuron effected in Huntington's

acetylcholine (cholinergic) neuron

Gaba neuron

- DA is enhanced

20

how is the brain effected by Huntington's

atrophy of caudate nuclei

enlargement of ventricles

21

Genetics of huntington's?

CAG (Gln) repeats (polyglutamine)

normal: 9-37
disease: 37-86

- multiple glutamine residues causes beta protein aggregates and abnormal helices leading to neuronal cell death

22

Huntington's symptoms

choreic movements and dementia

23

Treatments for Huntington's?

alleviate symptoms:

1. tetrabenazine (reserpine)
2. haloperidol (clozapine)
3. carbamazepine

24

treatment for Huntington's that is a dopamine depleting agent - decrease chorea/falls

tetrabenazine (reserpine)

25

treatment for Huntington's that is a D2 antagonist antipsychotic agent - control movement (low dose) and psychosis (high)

haloperidol (clozapine)

26

treatment for Huntington's that is a anti epileptic agent that limits neuronal firing

carbamazepine

27

early symptoms of alzheimer's

memory loss
decreased vocab

28

moderate symptoms of alzheimer's

difficulty understanding complex topics

fragmented/meaningless sentences

29

severe symptoms of alzheimer's

disoriented

can't perform simple tasks

incontinence

loss of physical coordination

30

what NT neuron is effected in alzheimer's

Ach

degeneration of subcortical cholinergic neurons (basal forebrain)

31

how is the brain effected by alzheimer's

cerebral atrophy

sulci enlarged

ventricular dilation

32

what is a cellular level hallmark of alzheimer's

neuritic and amyloid plaques

33

in alzheimer's what do the neuritic/amyloid plaques contain?

1. Tau (helical protein from neuron)
2. Apo-E
3. Amyloid precursor protein (APP)
4. neurotransmitters

34

what causes neurofibrillary tangles?

clumps of Tau filaments in neurons

35

what normally prevents Tau from pairing (neurofibrillary tangles)?

Apo-E

36

pramipexole and ropinirole

Parkinson's D2 and D3 agonists

37

in alzheimer's what happens to the amyloid precursor protein (5-7% of early onset FAD)

APP normal cut into soluble APP by alpha secretase which protects the neurons

in Alzheimers APP cut incorrectly into beta-AP by beta/gama secretase

38

what mutation is found in 20-50% of early onset FAD

presenilin 1 mutation - autosomal dominant

39

chromosomes presenilin 1 and 2 mutations are on

chromosomes 14 and 1

40

Presenilin is part of what enzyme?

gama secretase

41

PS-1 deficient mines showed decrease production of ____?

beta AP

42

what does Apo-E do?

normally binds to beta-AP preventing it from forming aggregates

43

what form of Apo-E has a high probability of developing Alz?

50% of late onset AD

Apo-E4

44

what does beta AP do?

may bind receptors on neurons

45

current treatment approach for Alz

augment cholinergic function - inhibitors

46

tacrine

- Alz
- centrally acting inhibitor
- 4x daily
- hepatotoxicity, nausea, diarrhea

47

donepezil

- Alz
- inhibitor
- more CNS specific than tacrine - reduced side effects
- 1x daily
- nausea, diarrhea

48

rivastigmine
galantine

- Alz
- inhibitor

49

memantine

- Alz
- NMDA receptor blocker
- inhibits effects of NT glutamate --> main excitatory NT (too much stimulation causes degeneration)

50

role of dopamine

movement and attention

51

effect of increased dopamine

schizophrenia

anxiety

52

effect of decreased dopamine

parkinson's

53

role of serotonin

mood
sleep
appetite
impulse
aggression

54

effect of decreased serotonin

depression

some anxiety disorders

55

role of NE

eating

alertness

56

effect of increased NE

schizophrenia

57

effect of decreased NE

depression

58

role of Ach

memory
learning
voluntary motion
sleep

59

effect of increased Ach

depression

60

effect of decrease Ach

dementia

61

role of GABA

inhibits excitation and anxiety

62

effects of decreased GABA

anxiety

63

in an fMRI what hemoglobin is paramagnetic (for hemodynamic response)

deoxyhemoglobin - activated state (line up in magnetic field)

64

for depression where would you expect to see high and low levels of activity

high: ventromedial prefrontal cortex

low: dorsolateral prefrontal cortex

65

depression: NT?

Increased: Ach
Decreased: NE, DA, Ser

66

schizophrenia: NT?

Increased: NE, DA

67

Anxiety: NT?

Increased: DA
Decreased: Ser, GABA

68

decreases in what can lead to depression?

1. 5-HT = serotonin
2. TPH = trytophanhydroxilase (serotonin is a hydroxylated tryptophan)
3. 5-HTR = serotonin receptor
4. 5-HTT = serotonin transporter
5. BDNF = brain-derived neurotropic factor

69

what BDNF leads to a decreased response to serotonin?

Met

70

what BDNF leads to an increased response to serotonin and depression/anxiety but also memory

Val

71

anxiety symptoms

intense fears
excessive worrying
hyper vigilance

72

parts of brain affected by anxiety - what do they do?

amygdala - alert brain of threats and trigger fear/anxiety; emotional memories stored here --> anxiety involving phobias

hippocampus - store memories of threatening events; smaller in people of abuse or military

73

decreases in what can lead to anxiety

1. DAT = DA transporter
2. DRD2 = DA receptor on presynaptic neuron
3. COMT = DA degrading enzyme

losses of these cause increase in DA in the synapse

74

how is brain affected in bipolar disorder

not as much sulci or branching

75

positive symptoms of schizophrenia (presence of abnormal behavior)

1. hallucinations
2. delusions
3. disorganized speech/thinking
4. disorganized behavior
5. catatonic behavior

76

negative symptoms of schizophrenia (absence of normal behavior)

1. social withdrawal
2. isolation
3. poor self care
4. blunted mood or facial expression
5. lack of spontaneous thinking

77

how is brain affected in schizophrenia

connection between regions of the brain are altered in patients with schizo

78

phenothiazines

thioxanthenes

dibenzazepines

butyrophenones

antipsychotics

79

phenothiazine

1st synthetic drug for psychosis - tricyclic

80

drugs that block anxiety (general term)

anxiolytics

81

what in the brain may cause someone who has anxiety to be hyper emotional

amygdala activated = increase emotional content

frontal cortex suppressed = decreased intellect and socializing

82

what is the main adrenal hormone elevated with anxiety

cortisol

83

what is the risk of prolonged anxiety?

leads to neurosis and biochemical changes in CNS

84

classifications of clinical anxiety

1. Panic disorders
2. Simple phobias
3. Social phobias
4. OCD
5. Generalized anxiety disorder
6. PTSD

85

what types of drugs have shown to effectively control panic attacks?

tricyclic antidepressants

MAO inhibitors

Benzodiazepines

86

For general anxiety what is the drug of choice

benzodiazepines

87

benzodiapenes is used in a dose dependent manner. list high to low for treatment purposes

1. anesthetics
2. sedative-hypnotics
3. muscle relaxants/anxiolytics
4. anticonvulsants

88

chlordiazepoxide

prototype - benzodiazepine

anxiolytic and treats alcohol withdrawal

89

diazepam

benzodiazepine

90

problems/side effects of diazepam and other benzodiazepines

1. dependence develops
2. rebound anxiety problem
3. increased appetite
4. sedating effects with EtOH

91

Benzodiazepines:
long-acting?

intermediate acting?

shorter-acting?

long: clonazepam (anticonvulsant too)

intermediate: estazolam

short: alprazolam (Xanax), lorazepam (Ativan)

92

mechanism of action of benzodiazepines

binds to GABA-BZD-picrotoxin multi-subunit receptor/Cl- ion channel (inhibitory)

--> increases Cl- ion conductance through the channel complex into neurons (hyperpolarize)
- enhances activity of GABA to inhibit action on CNS function

93

what GABA receptor subunit mediates sedation-hypnosis

alpha 1

94

what GABA receptor subunit mediates anti-anxiety effects

alpha 2

95

zolpidem (ambien)

- anxiolytic
- sedative-hypnotic
- GABA receptor/channel alpha1 subunit selective
- causes sedation without anxiolytic activity

96

besides zolpidem, what is another anxiolytic?

serotonin 5-HT1A receptor agonists/partial agonists

- take longer to set in

97

buspirone (BuSpar)

-BZD alternative
- partial agonists at 5 HT1A
- antagonists of DA receptor
- no affinity for BZD/GABA sites
- act in limbic system (hippocampus and amygdala)

98

depression is related to a functional deficiency of ____ (primarily NE and 5-HT)

monoamines

99

reserpine
alpha-methyl DOPA

antihypertensives

depleted NE

produced depression

100

isoniazid

iproniazid

antidepressant effects

MAO inhibitor

first "anti depressants"

101

MOA for tricyclic antidepressants (TCAs)

block the reuptake of CNS monoamines by inhibiting the monoamine transporters

102

imipramine
amitriptyline
doxepin

- TCA
- affects NE and 5-HT uptake

103

general TCA side effects

arise from antagonistic interactions with central and peripheral receptors (Ach, alpha1, alpha2, H1 receptor blockade)

Ach blockade --> dry mouth, blurred vision, urine retention, decreased sweating, constipation, memory impairment

104

fluoxetine (Prozac)

selective 5-HT (re-)Uptake inhibitors (SSRIs)

antidepressant

current 1st line antidepressant

105

Amantadine

Parkinson's
- alter DA uptake and release
- mildly enhance DA neurotransmission
- acts on glutamate NMDA receptor
- adjunct to L-DOPA

106

Selligline

Parkinson's
- inhibits
- adjunct to L-DOPA

107

seizure?

finite episode of brain dysfunction resulting from:

abnormal
paroxysmal (sudden/sharp)
rhythmic
synchronous

discharging of a large population of cerebral neurons

108

The epilepsies are disorders of neuronal excitability. For a seizure to occur you need: ???

1. predisposed brain (hypoxia-ischemia, trauma, infection, hemorrhage, tumor, congenital defect)

2. an acute precipitant (fever, sleep deprivation, stress of illness, idiopathic)

"forest fire" analogy
- 1. dry timber
- 2. spark

109

where do seizures arise from

cerebral cortex - behavioral manifestations are determined by the cortical site where seizure arises

110

partial seizure

begin focally at a specific cortical site

111

generalized seizure

involve both hemispheres widely from the outset

involve reciprocal firing from cerebral cortex and thalamus

112

types of partial seizures

simple

complex

partial w/ secondarily generalized tonic-clonic

113

Seizure? commonality?

- impaired consciousness last 30 sec to 2 minutes
- localized effect
- temporal lobe (emotion and memory)

complex partial

most common (35%)

114

seizure? commonality?

- preservation of consciousness
- localized
- staring
- diverse manifestations determined by region of cortex activated by seizure

simple partial

3rd most common (20%)

115

seizure?

- evolves into tonic-clonic seizure
- loss of consciousness
- sustained contraction (tonic)
alternating sustained muscle contraction and relaxation (clonic)

partial with secondarily generalized tonic clonic

116

seizure?

- abrupt onset of impaired consciousness
- lasts ~30 sec
- staring
- common in school age children

absence (petit mal)

117

seizure?

- brief shock like contraction of muscles - may be localized or general

myoclonic and clonic

118

seizure? commonality?

- sustained contractions of muscles
- contraction alternates with relaxation

tonic-clonic (grand mal)

2nd most common

119

3 major MOA for seizures and what types of seizures does the MOA treat

1. limit sustained firing of neurons - promote inactivate voltage-activated gated Na+ channels
- partials and tonic clonic

2. Enhance GABA activity
- partials and tonic clonic

3. Limit activation of the T-current, voltage activated Ca2+ channel
- generalized: absence and myoclonic clonic

120

name a drug that treats partial or tonic clonic seizures by limiting sustained firing of neurons by inactivate Na+ voltage-activated gated channels

phenytoin (PHT)
- 2nd choice because S.E. (diplopia, sedation, gingival hyperplasia)

carbamazepine
- 1st choice
- S.E. = rash, personality change, upset stomach

121

name a drug that treats partial or tonic clonic seizures by enhancing GABA activity

how does it enhance GABA activity

phenobarbital
- top choice for infants/toddlers
- binds to GABA receptor --> enhances Cl- influx --> synaptic inhibition

122

name 1st and second drug of choice for treating generalized seizures

what are the MOA

ethosuximide
- 1st choice for absence
- decrease thalamic Ca2+ current --> inhibits thalamic neurons pacemaker action --> inhibits T-currents

valproic acid (valproate)
- 2nd choice for absence
- dual action (phenytoin and ethosuximide)
- inactivate Na+ channel and T-type Ca2+ channels --> inhibits sustained repetitive firing induced by depolarization of neurons

123

what happens when GABA is activated

Cl- channel opens --> Cl- influx --> hyperpolarization --> decrease firing

124

types of antidepressants

MAO inhibitors (-zid)
- iproniazid, isoniazid

Tricyclic antidepressants (TCAS) --> block CNS monoamine transporters (re-uptake)
- imipramine, amitriptyline, doxepin

SSRIs (-ine;-one)
- fluoxetine

125

types of antipsychotics

- phenothiazines
- chlorpromazine
- thioxanthenes

126

types of anxiolytics

benzodiazepines (-pam) = binds to GABA-BZD receptor
- chlordiazepoxide
- diazepam
-zolpidem (alpha1)

serotonin 5-HT1A receptor agonist
- buspirone