Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology 2 > 10.9 PD, HD, MS, ALS > Flashcards

10.9 PD, HD, MS, ALS Flashcards

1
Q

Parkinsonism

A

bradykinesia or hypokinesia,
Akinesia (marche a petite pas)
poor arm swing,
micrographia,
facial hypomimia (mask like facies),
dec eye blinking rate (inc schiz),
resting tremors (pill rolling in hand, head titubation),
volition abolishes rest tremors with cortical over-red,
muscle rigidity (cogwheel or lead pipe),
impairment of pstural balance;
Propulsion,
retropulsion falls forward or back when pushed,
gait: shuffling or festinant gait (in a hurry),
dementia and depression and usually found in association with PD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Extrapyramidal motor system

A

outside the pyramidal (corticospinal) motor pathways —for control of movement and balance,
EPS important: antigravity and posture maintenance (phylogenetically older moter system, more prominent after attainment of bipedalism in hominids/great apes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Extrapyramidal motor system (EPS) vs Corticospinal

A

corticospinal/corticobulbar – monosynaptic direct motor activation which synapses with lower motor neuron LMN,
EPS indirect (multisynaptic) motor activation pathway–no synpase with LMN, cerebral cortex communicates with basal ganglia and vv (CS, GP)
–> thalamus that communicates with cerebral cortex and vv - spinal cord,

Role –coordination of movement force, velocity, agonist/antagonist muscle actions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Nigrostriatal dopaminergic pathways

A

gultamate induced excitotoxicity (inc Ca),
oxidative stress (ROS),
apoptosis,
lead to dopamine neuron loss in SN,
Pathway to striatum,
mitochondrial defects in MPTP –PD,
this stratal cholinergic overactivity –impaired control of fine movement basal ganglia, (
n-methyl1234-phenyltetrahydor pyridine) a “street drug” produced accidentally in attempted synthesis of meperidien –severe, sudden irreversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Micrographia and deterioratinc had writing

A

due to hypkinesia and poor control of distal muscles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

biochemical basis of Parkinsonism

A

a balance btw excitatory cholinergic and inhibitory dopamine is essential for motor control,
apoptotic degeneration of nigrostriatal dopamine pathway causes imbalance btw dopamine (dec) and ach (inc) activites causing a striatal cholinergic excess,
an imbalance btw the two, result in movement disorder, loss of force, velocity, agonist/antagonist muscle contraction regulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Pharmacotherapy aimed at

A

increasing dopaminergic activity,

decreasing cholinergic activity or both

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Levodopa

A

replacement of dopamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

bromocriptine

A

D1 D2 agonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

selegaline

A

MAO B inhibitor, dec catabolism of neuronal dopamine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Entacapone

A

COMT inhibitor, dec met

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Anticholinergics

A

dec striatal Ach

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Miscellaneous durgs

A

glutamate antagonists, Vit-E, Amantidine – release DA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Levodopa (L-dopa)

A

a levorotatory isomer of dopa and a prodrug,
corsses the BBB and taken up by surviving dopaminergic neurons in the striatum,
then converted to DA by
AAAD (aromatic amino acid decarboxylase) or
dopa decarboxylase to restore DA activity
in the corpus striatum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Levodopa in the CNS

A

dopamine in the CNS interacts with postjucntional dopamine D2 and D3 receptors and activate inhibitory G proteins (Gi coupled), inhibits adenylyl cyclase, decrease cAMP, and open postassium channel (K),
so levodopa thereby increases the amount of dopamine release by these neurons in pts with parkinson’s and it serves as a form of replacement therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Levodopa pharmakokinetis

A

orrally absorbed and metabolized in the intestine by MAO and decarboxylation (90%) metabolized in the periphery by COMT and decarboxylation (99%), so only about 1% enters the brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Absorbtion of levodopa

A

absorbed rapidly from the small intestine in empty stomac (food decreases bioavailability, F),

high protein food interferes with the absorption and also transport of levodopa into the CNS,

should be taken on an empty stomach (usually 45 min before a meal)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Half life of Levodopa

A

has an extremely short half-life (1-2 hours), hence causes fluctuations in plasma concentration,
leading to “on-off” phenomenon, (high peath to through = inc cmax/cmin conc ratio)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Carbidopa

A

inhibits the peripheral metabolism of levodopa and increases the CNS bioavailability of the drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

administration of Levodopa

A

levodopa is always administered with peripheral decarboxylation inhibitor.
Peripheral decarboxylation inhibitors are

carbidopa and
benserazide.

These are incapable of crossing BBB.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Pyridoxine

A

dopa decarboxylation is pyridoxine (Vit B6) dependent and Vit B6 may decrease the effectiveness of L-dopa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

carbidoap with Levodopa helps in

A

reduction of dose of l-dopa, decreased incidnece of nausea, vomiting, orthostatic hyptension, and cardiac arrhythmia, if DC inhibitor is used approx 10% of L-dopa enters the brain (if not inhibitor then only 1% of l-dopa reaches the brain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

ratio of Carbidopa to L-dopa

A

ratio of 1:4 or 1:10 soooo__. 25:100 mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

adverse effects of L-dopa

A 
dyskinesias, 
peripheral nausea, 
vomiting, 
abdominal cramps, 
on off effect, 
psychosis, 
postural hypotension, 
cardiac arrhythmia, 
pathological gambling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

dyskinesias

A

major limiting factor in therapy, characterized by a variety of repetitive involuntary abnormal movements (dystonia, tics, ballisms, tremor, myoclonus (repetitive jerks) affecting the face, trunk and limb, occurs in 70% of pts, may be relived by decreasing the dose of levodopa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Peripheral effects

A

nausea, vomiting, abdominal cramps, palpiations, –due to inc l-dopa metabolism peripherally —if these are common,

increased carbidopa does helps (to reduce L-dopa conc in tissues) C/LD 25/100 mg or controled release tab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

central effects

A

nightmares, orthostatic hypotension, dissiness, hallucinations,
psychosis (clozapine/quetiapine treated),
haloperidol worsens the PD if used to treat psychosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

on-off effect

A

a rapid fluctuation btw showing no beneficial effects of levodopa and showing beneficial effects with dyskinesias, may be a sign of the later stage of dopamine neuron degeneration, clinical improvement can be obtained with continuous IV infusion and in some instances, with sustained release formualtions of levodopa/carbidopa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

psychosis

A

hallucinations, vivid dreams and distorted thinking (with chronic use), probably due to excessive dopamine concentrations in mesolimbic pathway

30
Q

Postural hypotension

A

due to activation of vascular dopamine receptors D1

31
Q

Nausea and vomiting

A

in 80% of pts, attenuated if l-dopa given along with carbidopa, with food, in divided doses, or with nonphenothiazine antiemetics, this effect is due to the direct effects of dopamine on the CTZ in the CNS and also on the GIT

32
Q

Cardiac arrhythmia

A

due to dopaminergic action on the heart

33
Q

Pathological gambling and other effects

A

gambling is more common with dopamine agonists, compulsive shopping, binge eating, hypersexual behaviour, or compulsive repetitive behaviors such as endless writing, singing or talking have also been associated with levodopa therapy

34
Q

Drug holiday

A

in the treatment, helps alleviating neurological and behavioural adverse effects
—range from 3-21 days,

efficacy–mainly dec bradykinesia rigidity, less effect on tremors, bed ridden pts may be ambulatory

35
Q

drug interactions with L-dopa

A

drugs that delay gastric emptying (anticholinergics) delay its absorption,

while drugs which promote gastric emptying such as antacids, cisapride may increase levodopa bioavailability,

Vit B6 (pyridoxine) increases the peripheral breakdown of levodopa and decreases its effectiveness

36
Q

Levodopa should not be given with

A 
MAO inhibitors (Phenelzine, Traylocypromine) as can cause severe hypertensive crisis, 
Antipsychotic drugs block dopamine receptors and may reduce the effectiveness of levodopa
37
Q

Limitations of Levodopa

A

for the first 2-5 years of treatment, levodopa produces a sustained response, but as the disease progresses, the duration of benefit from each dose becomes shorter (the wearing off effect) and still later some pts develop sudden unpredictable fluctuations btw mobility and immobility (the “on-off” effect),

after about 5-8 yrs, the majority of pts have dose-related clinical fluctuations and dose-related dyskinesias (chorea, dystonia),

as the disease progresses, levodopa-resistant motor problems including difficulties with balance, gait, speech and swallowing and non-motor symptoms including autonomic, cognitive and psychiatric difficulties become more prominent.

Sudden discontinuation or abrupt reduction of Levodopa dosage for several days may cause a severe return of parkinsonisma symptoms

38
Q

Dopamine receptor agonist in basal ganglia – Ergot derived agonists

A

bromocriptine,

Pergolide (D1, D2 receptors)

39
Q

Dopamine receptor agonist in basal ganglia – nonErgot derived agonists

A

ropinirole,
pramipexole,
rotigotine

40
Q

Dopamine receptor agonists

A

no decarboxylation required,
used as an adjunct to levodopa in advanced disease,
they may permit a reduction in levodopa dosage,
less effective than levodopa for motor symptoms of PD,
but are less likely to cause dyskinesia or motor fluctionations,
ineffective in pts who have shown no therapeutic response to levodopa

41
Q

Bromocriptine and Pergolide

A

are ergot alkaloids – D2 agonist,
pergolide is more potent,
these ergot compounds are known to cause pulmonary cardiac valvular and retroperitoneal fibrosis,
bromocriptine is mainly used in Hyperprolactinemia (for suppression of lactation) and acromegaly,
Bromocriptine is still marketed in the US;
pergolide was taken off the market bc its used was associated with cardiac-valve regurgitation

42
Q

COMT inhibitors

A

block the conversion of L-dopa to 3-O-methyldopa (3-O-MD) in the gut and liver,
extens the effect of L-dopa (prolonging the half life of Levodopa and decrease parkinsonian disability, reduce the “wearing off” and “on off” effects with Levodopa bc they reduce formation of 3-o-MD wich competes with levodopa for transport into brain tissue

43
Q

the combination of Levodopa and COMT

A

can however increase dyskinesia, a reduction in levodopa dosage may be required to avoid dyskinesia

44
Q

COMT inhibitors

A

Entacapone and
Tolcapone
(cause dyskinesia, nausea, diarrhea (more often with Tolcapone))

45
Q

Tolcapone

A 
long acting, 
more potent COMT inhibitor, 
Fatal hepatotoxicity can occur, 
hence reserved for pts with fluctuations who have not responded to Entacapone, 
not available in Canada
46
Q

Entacapone

A

short acting preferred over tolcapone as no risk of hepatotoxicity

47
Q

use of tolcapone

A

requires pt written concent and hepatic monitoring twice per month for the first 6 monts and periodically thereafter,
since these drugs are used in combination with levodopa, the levodopa dose may have to be decreased in pts who develop dyskinesia, nausea or hallucinations

48
Q

MAO-B inhibitors

A

Rasagiline, Selagiline

49
Q

MAO-B is predominantly seen in the

A

CNS

50
Q

MAO-B inhibitors fn

A

decrease dopamine metabolism in the CNS and prolong its synaptic action,
used as initial treatment and also as adjunct to levodopa,
used as montherapy in early disease, it cana delay initiation of levodopa treatment

51
Q

MAO-B adverse effects

A

dyskinesia and psychosis,
mild amphetamine-like stimulating action (selegiline is metabolized to amphetamine),
nausea and orthostatic hypotension

52
Q

MAO-B precaution

A

in pts taking SSRIs,
TCAs and meperidine
(chance of “serotonin syndrome”)

53
Q

what will be the effect of selagiline on prolactin secretion and nausea and vomiting?

A

no idea

54
Q

Anticholinergics (muscarinic blockers) work to

A

control mainly resting tremors and drooling

55
Q

drug of choice in drug induced Parkinsonism (anticholinergics)

A 
benztropine, 
trihexylphenidyl, 
diphenhydramine, 
procyclidine, 
biperiden, 
ethopropazine 
--> these drugs are used in initial stages of mild parkinsonism, often in combination with L-dopa, decrease tremor and rigidity, but have little effect on bradykinesia and postural reflexes
56
Q

Anticholinergic adverse effects

A

atropine like

57
Q

Amantadine

A

antiviral drug used in prophylaxis and treatment of Influenza,
slightly blocking Dopamine uptake and inc presynaptic release from axoplasm,
also inhibits glutaminergic NMDA receptors,
whose excitation may paly a role in the degeneration of the nigrostriatal system in Parkinson’s disease,
Also has muscarinic blocking action

58
Q

Amantadine adverse effects

A 
common--confusion, 
dizziness, 
dry mouth, 
hallucination, 
also causes livedo reticularis (reddish blue molting of the skine with edema around ankel) and 
other atropine-like adverse effects
59
Q

Novel therapies for Parkinsonism

A

NMDA antagonists,
VitE and other antioxidants,
neuronal growth factors,
neuronal transplant

60
Q

Surgical treatment of Parkinsonism

A

should be reserved for PD pts with major dyskinesia or clinical fluctuations on Levodopa treatment,
surgery does not help pts who are unresponsive to Levodopa,
deep Brain Stimulation of the subthalamic nucleus or globus pallidus with high frequency electrical stimuli from implanted electrodes is employed for PD

61
Q

choice treatment for PD

A

Levodopa combined with carbidopa remains the most effective symptomatic treatment for PD,

dopamine agonists, the next most effectiv drugs after levodopa in decresing symptoms, can be used alone before the introduction of levodopa, or as an adjunct to levodopa,

addition of peripherally -acting COMT inhibitor or an MAO-B inhibitor to levodopa can reduce motor fluctuations in pts with advance disease,

Anticholinergics are rarely used bc of theri side effects, but can be useful addition to levodopa for control of tremor and drooling,

bilateral subthalamic deep brain stimulation is an option for pts with more advanced motor fluctuations and intact cognition

62
Q

Huntingoton’s disease

A

abnormal gene on chromosome 4 with polyglutamine expansion
(encoded by CAG repeats)
–> inc huntingtin protein and other molecules
–> glutamate excitotoxicity
–> apoptotic oxidative neuronal damage in cortex + stratum
–> degeneration of GABAergic neurons in the striatum and cortex (path for control of movement). Loss of GABA nurons leads to excessive dopaminergic activity in the basal ganglia.

63
Q

Huntingtons is characterized

A

by abnormally expansive or choreo-arthetoid movements (dance-like movements) of limbs, rhythmic movements of tongue and face, and mental deterioration that lead to personality disorders, psychosis, and dementia.
Pts are usually in their late 30s when the disease begins, and progressive respiratory depression usually causes death in 10-15 yrs

64
Q

no specific treatment exists fo huntingtons but

A

drugs which block NMDA receptors may block the toxic effects of excess glutamate.

65
Q

Treatment of Huntingtons includes

A

tetrabenazine (VMAT inhibitor) for reduction of chorea?,
Dopamine antagonist – Haloperidol,
Gaba facilitatory drugs –like benzodiazepines help in reducing excessive movements?

66
Q

Multiple Sclerosis

A

is characterized by the demyelination of neurons in the CNS.
Begins with optic neuritis commonly.
Although etiology unknown; the disease is postualted to have an autoimmune or viral origin.
Demyelination accompanied by inflammatory responses leads to disruption of nerve transmission and formation of plaques in the brain

67
Q

pathology of MS

A

disseminated patches of demyelination in the CNS (brain and spinal cord) which occurs at different places at different times (fibrous gliosis),
both sensory and motor dysfunctions occurs,

S/S depends on the part of brain involved – includes visual, ocular palsies, pain, spasticity, weakness, ataxia, problems with speech, gait and bladder function

68
Q

MS goal

A

reduce frequency and severity of exacerbations and remissions.

Symptomatic.

Corticosteroidss
(prednisone,
methylprednisolone-IV)

Immuno modulatory agents 
(IFN-B1b IFNbeta1A, 
Glatiramer acetate, 
Natalizumab monthly infusion (dec WBC entry to brain) 
anti-alpha 4 integrin ab,

Immunosuppressants:
Mitoxanthrone,

Antispastic drugs:
Baclofen (GABAb agonists),

Pain (sensory neuropathy):
Gabapentin, TCA, carbamazepine

69
Q

ALS – Amyotrophic Lateral Sclerosis

A

also called Lou Gherig disease, a progressive disorder of the motor nurons characterized by muscle wasting, weakness, and respiratory failure. A defect in the superoxide dismutase enzyme that scavenges super oxide radicals.

70
Q

ALS treatment

A

not specific, only treat symptoms,

Riluzole,
Baclofen,
Insulin like growth factors

71
Q

Riluzole in MS

A

blocks the sodium channle and decrease the release of glutamate,
protects the motor neurons from the neurotoxic effects of glutamate

72
Q

Baclofen (gaba B agonist)

A

to control spasticity

Pharmacology 2 (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions