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Neuro pharmacology > Múltiple Sclerosis Pharm Treatment > Flashcards

Múltiple Sclerosis Pharm Treatment Flashcards

1
Q

MS is a disease of…?

A

The CNS

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2
Q

Which cells does MS attack?

A

oligodendrocytes

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3
Q

Is MS chronic?

A

Yes

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4
Q

Secondary progressive MS is characterized by what?

A

The development of permanent neurological deficits and the progression of clinical disability

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5
Q

Primary progressive MS is characterized by what?

A

When the disease is progressive from the onset

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6
Q

What characterizes the initial stages of MS?

A

Reversible episodes of neurological deficits (relapses) that usually lasts for days or weeks

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7
Q

What is clinical isolated syndrome?

A

What a patient presents with an initial attack of inflammatory demyelination (clinical symptoms and radiological evidence)

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8
Q

What is primary progressive multiple sclerosis?

A

A patient with a disease course characterized by progression from onset , 1 year of disability progression independent of clinical relapse

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9
Q

What is secondary progressive MS?

A

A patient who over time, develops a permanent neurological deficit and with the progression of clinical disability that becomes prominent

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10
Q

What is radiologically isolated syndrome?

A

A patient with the presence of radiological signs of demyelination but no clinical evidence of disease

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11
Q

What is relapsing remitting MS?

A

When a patient has short symptomatic periods followed by periods of full or partial remission

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12
Q

What is rapid evolving aggressive disease?

A

A patient with early accumulation of disability along with high relapse frequency and highly active disease on MRI

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13
Q

What is aggressive MS naive patient?

A

A patient who has 2 or more relapses with incomplete recovery in the past year

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14
Q

do we have axonal injury and inefficient remyelination?

A

Yes

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15
Q

Is there mitochondrial dysfunction is MS?

A

Yes

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16
Q

What is the goal for MS treatment?

A

Ameliorate symptoms of disease, reduce the accumulation of disease, and improve quality of life of MS patients

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17
Q

What are the NEDA features?

A

No new or enlarging T2-weighted lesions
No new gadolinium-enhancing lesions
No relapses
No confirmed worsening or expanded disability status scales scores

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18
Q

The treatment of MS can be divided into what types of drugs?

A

Disease modifying and symptomatic treatments

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19
Q

What is the treatment for acute relapses of MS?

A

3-5 days of IV methylprednisolone (500-1,000mg) or IVIG infusion. Also consider plasmapharesis

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20
Q

What is the first line treatment for a clinically isolated syndrome?

A

Interferon beta and glatiramer acetate

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21
Q

What is a second like treatment drug used to treat clinically isolated syndrome?

A

Teruflonamide

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22
Q

If we have a patient with relapsing remitting MS who has a moderately active disease, what is a first line drug used?

A

Interferon beta, glatiramer acetate, teriflunamide,dimethyl fumarate

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23
Q

If we have a patient with relapsing remitting MS who has a moderately active disease, what is a second line drug?

A

fingolimod and siponimod

24
Q

What drugs are used for a patient who has relapsing remitting MS who had an active disease?

A

Fingolimod, siponimod, natalizumab, cladribine, ocrelizumab

25
Q

What drugs are used for a patient with Relapsing remitting MS who also have a rapidly evolving aggressive disease?

A

Natalizumab, alentuzumab, ocrelizumab

26
Q

what does progressive MS mean?

A

It means that it has been a year since the patient has been in treatment and the patients condition continued to worsen

27
Q

What drugs are used to treat secondary progressive MS?

A

INF-beta 1a, and 1b subcutaneous

28
Q

What drugs are used to treat primary progressive MS?

A

Ocrelizumab IV, Biotin (vitamin B7), siponimod

29
Q

What is required in a patient with MS before pregnancy?

A

Washout period of at least 6 months

30
Q

When it comes to pregnancy, what therapies are indicated after the second trimester?

A

Immune reconstitution therapies

31
Q

What drugs can be given to a patient with MS while breastfeeding?

A

IVIG, methylprednisolone

All disease modifying drugs are contraindicated

32
Q

What is a first line drug for pediatric patient with MS?

A

Fingolimod

33
Q

What are second in line drugs used to treat MS?

A

INF-beta 1a, teriflunomide, dimethyl fumarate

34
Q

What type of interferon beta has the highest success when it comes to reducing the annualized relapses rate?

A

Pegylated INF-Beta 1a subcutaneously

35
Q

What is the mechanism of action of Interferon beta?

A

Induces a series of beneficial transcriptional JAK/STAT pathway changes. Decreases antigen presentation as well as proliferation of inflammatory T cells. Changes the expression of cytokines and matrix metalloproteinase (MMP)

36
Q

How is interferon beta eliminated in the body?

A

Via the liver and the kidneys

37
Q

Interferon beta can cause a rise in what?

A

Body temperature

38
Q

What are some adverse effects of interferon beta?

A

Flu-like symptoms, depressed bone marrow functions, formation of specific neutralizing antibodies that appear 6-18 months of treatment and depressive symptoms

39
Q

What is glatiramer acetate?

A

Immunomodulator that consists of the acetate salts of synthetic polypeptides, containing four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine

40
Q

What is the mechanism of action of glatiramer acetate?

A

Exhibits strong and promiscuous binding to MHC molecules and consequent competition with various myelin antigens for their presentation to T cells

41
Q

Glatiramer acetate also work by…

A

Inducing specific suppressor cells of the T helper 2 cell type

42
Q

Glatiramer acetate inhibits which types of cells?

A

Dendritic cells and monocytes

43
Q

Which MHC molecules variants does glatiramer acetate bind to?

A

HLA DRB1 variants

44
Q

What is teriflunomide?

A

An active metabolite of lefunomide and it acts as an immunomodulatory agent by inhibiting pyramidine synthesis

45
Q

What is the mechanism of action of teriflunomide?

A

Inhibits pyramidine synthesis by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase

46
Q

Teriflunomide is contraindicated in what?

A

Pregnant women and in women in childbearing age due to the risk of teratogenicity. Also contraindicated in severe hepatic impairment due to hepatotoxicity, hepatic failure and death

47
Q

What is dimethyl fumarate?

A

Non steroidal anti-inflammatory drug

48
Q

what is the mechanism of action of dimethyl fumarate?

A

Degraded to it’s active metabolite nonmethyl fumarate (MMF)
MMF up regulates the nuclear factor (erythroid-derived 2)- like 2 (Nrf2) pathway that is activated in response to oxidative stress

49
Q

Dimethyl fumarate is rapidly hydrolyzed by what type of enzymes?

A

Esterases

50
Q

What are the main metabolites of the metabolism of dimethyl fumarate?

A

MMF, glucose, citric acid, Fumaric

51
Q

What is an important adverse effect of dimethyl fumarate?

A

Liver damage and allergic reactions

52
Q

What is the mechanism of action of fingolimod and siponimod?

A

It is a sphingosine 1-phosphate receptor modulator that exerts its mechanism of action in MS by binding to various sphingosine 1-phosphate receptors. It suppresses the release of lymphocytes from the lymph nodes leading to a lower level of circulation lymphocytes in the peripheral circulation

53
Q

Fingolimod metabolism occurs via 3 major metabolic pathways which are?

A

Phosphorylation, oxidation, and fatty acid like metabolism

54
Q

Siponimod is metabolized mainly by which enzyme?

A

CYP2C9 enzyme and subsequently by the CYP3A4 enzyme

55
Q

What are some adverse effects of fingolimod?

A

Hypotension, bradycardia, cardio toxicity, heart block, skin cancer

56
Q

What are some adverse effects of siponimod?

A

Carcinogenesis, mutagenesis, infertility, feral harm

Neuro pharmacology (4 decks)

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