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MSK 06 Flashcards

1
Q

What is DMARDs?

A

Disease-modifying anti-rheumatic drugs (DMARDs)

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2
Q

What are the important characteristics of DMARDs?

A

They reduce inflammation

They have ability to reach in joints capsules in a therapeutic concentration without reaching toxic levels in serum.

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3
Q

Methotrexate uses for RA?

A

It is really an anticancer drug

But we use as very low level that do not show any side effects.

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4
Q

But hypothetical MOA for Methotrexate is?

A

We don’t know the exact MOA for this drug but likely multi-factorial.

i. Inhibit AICAR=> Inhibit degradation of Adenosine=> anti-inflammatory effects.
ii. Inhibit proinflammatory cytokine production
iii. Inhibit dihydrofolate reductase=> anti- proliferative effects of immune cells
iv. Induces apoptosis (pack in a bag and destroy cancer cells

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5
Q

Side effect of Methotrexate is?

A

It reduces DHF in human body so need folate during therapy.

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6
Q

Methotrexate anti-inflammatory properties?

A 
Inhibit proinflammatory cytokines 
Inhibit purine biosynthesis
And stimulate adenosine 
Decrease new erosions appearance
Improve survival

Onset 2-3 weeks
Route Orally or SC weekly

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7
Q

What are the side effects of Methotrexate?

A

Stomatitis (inflamed or ulcer under the chick or lips) painful or painless
Hepatotoxicity
Diarrhea
Teratogenic (abnormality following fetus) so contraindicated in pregnancy.

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8
Q

How Methotrexate inhibit folic acid?

A

They are folic acid antagonist
It leads to folic acid deficiency
As a result, cause toxicity.

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9
Q

Which dose of folic acid is appropriate for Methotrexate treatment for OA?

A

Folic acid 1-2mg Daily

Folinic acid 2.5-5mg once weekly and at least 8-12 hours after MTX

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10
Q

What is the mechanism of Hydroxychloroquine?

A

It is usually antimalarial drug
MOA unknown=>However they suppress T-cells, by inhibiting leukocyte chemotaxis, inhibit DNA & RNA synthesis.
Onset 6 weeks taken by oral route
Fun fact is that, it has favourable effects on glucose and lipid metabolism beyond anti-inflammatory effect

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11
Q

Side effect of Hydroxychloroquine?

A

Ocular toxicity
Dizziness, headache, insomnia.
Rash
May be used in pregnancy

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12
Q

Sulfasalazine use for OA?

A

It is a prodrug and cleaved by bacteria in colon to sulphapyridine & 5 amino salicylic acid

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13
Q

What is the MoA of Sulfasalazine?

A

Inhibit B cell proliferation by inhibiting IgA & IgM RF by the use of Sulfasalazine.
Onset is 2 months

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14
Q

What are the Side effects of Sulfasalazine?

A 
GI: N/V/D 
May cause liver toxicity
Cause blood problem by reducing neutropenia
Oligospermia (depletes sperm)
Hypersensitivity reaction like rash
Safe in pregnancy
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15
Q

What is Leflunomide?

A

It is a prodrug and its active metabolite is A77-1726

Taken orally

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16
Q

What Leflunomide inhibits?

A

It inhibits Dihydroorotate dehydrogenase & inhibit protein synthesis
It is also inhibitor of pyrimidine synthesis as a result decrease lymphocyte proliferation & modulation of inflammation.

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17
Q

Does leflunomide has similar efficacy like MTX?

A

Yes

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18
Q

What is the half-life of Leflunomide?

A

15-20 days

Onset of action is 4-6 days

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19
Q

What are the Leflunomide Side effects?

A

Teratogenic effect in pregnancy
Hepatotoxicity
Hypertension
Diarrhoea GI upset.

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20
Q

What if patients want to be pregnant after using leflunomide?

A

Before becoming pregnant patient should use Cholestyramine to washout leflunomide. What it does is it binds with leflunomide. 8 gm 3 times daily for 11 days.

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21
Q

What DMARDs target?

A

Inflammation

HCQ SSZ & LFE drugs in combination give very good effect.

22
Q

Which DMARDs are contraindicated in pregnancy?

A

MTX

LEF(Leflunomide)

23
Q

HCQ has what kind of toxicity?

A

Ocular

24
Q

Sulfasalazine turn colour of urine into?

A

Skin and urine yellow and orange.

25
Q

What are biologics?

A

They are large and complex PROTEINS

Genetically engineered from living system.

26
Q

What biologics do for RA?

A

They modify disease by slowing down or halt joint damage.

27
Q

How biologics effect on RA?

A

Block inflammatory response
Target and inhibit proinflammatory cytokines TNF alpha, IL-1, IL-6
Highly specific action.

28
Q

What is Tocilizumab blocks?

A

IL-6

29
Q

What is Rituximab block which cells?

A

B cells

30
Q

What is the meaning of Mab?

A

means Monoclonal antibodies

31
Q

Zu=> means

A

humanized antibodies

32
Q

Xi=> means

A

chimeric antibodies

33
Q

Characteristics of the TNF alpha inhibitor?

A

Intercept: Target TNF alpha, half-life 3-5 days, fusion protein 50 gm weekly SC

Infliximab: Target TNF alpha, 8-19 days Chimeric mAb dose: 3mg/kg every 6-8 weeks Route IV infusion

Adalimumab: TNF alpha inhibitor, 10-20 days, Human mAb, 40mg every 2 weeks SC.

34
Q

What is Etanercept?

A

Humanized protein bind TNF alpha and reduce TNF activity

Onset 1-4 weeks

35
Q

What are the side effects of Etanercept?

A

Risk of opportunistic TB which is serious
Infusion injection site reaction
Neutropenia

36
Q

What is Infliximab?

A

Chimeric monoclonal antibody

Bind both soluble and membrane bound TNF alpha

37
Q

What is the mechanism of action of Infliximab?

A

Infliximab bind TNF alpha in the circulation and in the joint and reduces its activity

38
Q

Onset of Infliximab?

A

Days to weeks

39
Q

What are the side effects of Infliximab?

A

Can cause Infusion related, Cytokine release syndrome during infusion? But it can be solved by reducing the infusion rate.
Can develop anti-infliximab antibody
Sepsis
Need to be TB tested before applying this drug because this drug can activate previous TB toxins

40
Q

What is Adalimumab & Golimumab?

A

Monoclonal antibodies
TNF alpha blocker
Bind both soluble and membrane bound TNF

41
Q

What is the mechanism of Adalimumab & Golimumab?

A

Adalimumab and Golimumab bind with TNF alpha in the circulation and in the joint and inhibit interaction with cell surface TNF alpha receptor as a result decrease TNF alpha activity.
Onset is weeks to months

42
Q

What are the Side effects of Adalimumab & golimumab?

A

UTI
Opportunistic TB infection
Injection site reaction

43
Q

What is the target of Tocilizumab?

A

Bind soluble and membrane bound IL-6 receptor Given by IV

Onset 3 months longer effect

44
Q

What is the target for Abatacept?

A

T cell activation given by IV/SC

45
Q

What is the target of Rituximab?

A

B-cell Depletion given by IV

onset 21 days

46
Q

What are the side effects of Tocilizumab?

A

Elevated liver enzymes
Elevated lipids
Neutropenia
GI perforation

47
Q

What is Rituximab?

A

Genetically engineered monoclonal antibody specifically targets CD20 on B cell surface
So CD20 is an ideal target for RA to stop inflammation.

48
Q

Mechanism of Action of Rituximab?

A

It depletes B cell by 3 mechanisms
By B cell lysis
By Cytotoxicity via macrophages and natural killer cells
By Apoptosis

49
Q

What are the Side effects of Rituximab?

A

Infusion reaction

2 months onset

50
Q

With all the biologics treatment what safety considerations we need to monitor?

A 
Serious infection
Opportunistic TB
Skin cancer
Hematologic abnormalities
Heart failure
Infusion reaction

MSK (17 decks)

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