MSK 06

Question 1

What is DMARDs?

Answer 1

Disease-modifying anti-rheumatic drugs (DMARDs)

Question 2

What are the important characteristics of DMARDs?

Answer 2

They reduce inflammation

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

Question 3

Methotrexate uses for RA?

Answer 3

It is really an anticancer drug

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

Question 4

But hypothetical MOA for Methotrexate is?

Answer 4

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

Question 5

Side effect of Methotrexate is?

Answer 5

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

Question 6

Methotrexate anti-inflammatory properties?

Answer 6

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

Onset 2-3 weeks
Route Orally or SC weekly

Question 7

What are the side effects of Methotrexate?

Answer 7

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

Question 8

How Methotrexate inhibit folic acid?

Answer 8

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

Question 9

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

Answer 9

Folic acid 1-2mg Daily

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

Question 10

What is the mechanism of Hydroxychloroquine?

Answer 10

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

Question 11

Side effect of Hydroxychloroquine?

Answer 11

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

Question 12

Sulfasalazine use for OA?

Answer 12

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

Question 13

What is the MoA of Sulfasalazine?

Answer 13

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

Question 14

What are the Side effects of Sulfasalazine?

Answer 14

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

Question 15

What is Leflunomide?

Answer 15

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

Taken orally

Question 16

What Leflunomide inhibits?

Answer 16

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

Question 17

Does leflunomide has similar efficacy like MTX?

Answer 17

Yes

Question 18

What is the half-life of Leflunomide?

Answer 18

15-20 days

Onset of action is 4-6 days

Question 19

What are the Leflunomide Side effects?

Answer 19

Teratogenic effect in pregnancy
Hepatotoxicity
Hypertension
Diarrhoea GI upset.

Question 20

What if patients want to be pregnant after using leflunomide?

Answer 20

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.

Question 21

What DMARDs target?

Answer 21

Inflammation

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

Question 22

Which DMARDs are contraindicated in pregnancy?

Answer 22

MTX

LEF(Leflunomide)

Question 23

HCQ has what kind of toxicity?

Answer 23

Ocular

Question 24

Sulfasalazine turn colour of urine into?

Answer 24

Skin and urine yellow and orange.

Question 25

What are biologics?

Answer 25

They are large and complex PROTEINS | Genetically engineered from living system.

Question 26

What biologics do for RA?

Answer 26

They modify disease by slowing down or halt joint damage.

Question 27

How biologics effect on RA?

Answer 27

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

Question 28

What is Tocilizumab blocks?

Answer 28

IL-6

Question 29

What is Rituximab block which cells?

Answer 29

B cells

Question 30

What is the meaning of Mab?

Answer 30

means Monoclonal antibodies

Question 31

Zu=> means

Answer 31

humanized antibodies

Question 32

Xi=> means

Answer 32

chimeric antibodies

Question 33

Characteristics of the TNF alpha inhibitor?

Answer 33

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.

Question 34

What is Etanercept?

Answer 34

Humanized protein bind TNF alpha and reduce TNF activity | Onset 1-4 weeks

Question 35

What are the side effects of Etanercept?

Answer 35

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

Question 36

What is Infliximab?

Answer 36

Chimeric monoclonal antibody | Bind both soluble and membrane bound TNF alpha

Question 37

What is the mechanism of action of Infliximab?

Answer 37

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

Question 38

Onset of Infliximab?

Answer 38

Days to weeks

Question 39

What are the side effects of Infliximab?

Answer 39

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

Question 40

What is Adalimumab & Golimumab?

Answer 40

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

Question 41

What is the mechanism of Adalimumab & Golimumab?

Answer 41

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

Question 42

What are the Side effects of Adalimumab & golimumab?

Answer 42

UTI Opportunistic TB infection Injection site reaction

Question 43

What is the target of Tocilizumab?

Answer 43

Bind soluble and membrane bound IL-6 receptor Given by IV | Onset 3 months longer effect

Question 44

What is the target for Abatacept?

Answer 44

T cell activation given by IV/SC

Question 45

What is the target of Rituximab?

Answer 45

B-cell Depletion given by IV | onset 21 days

Question 46

What are the side effects of Tocilizumab?

Answer 46

Elevated liver enzymes Elevated lipids Neutropenia GI perforation

Question 47

What is Rituximab?

Answer 47

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

Question 48

Mechanism of Action of Rituximab?

Answer 48

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

Question 49

What are the Side effects of Rituximab?

Answer 49

Infusion reaction | 2 months onset

Question 50

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

Answer 50

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