Pharma 6 -2😂

Question 1

Gc mechanism of action

Answer 1

• prevent interleukin (IL)–1 and IL-6 production by macrophages
• inhibit all stages of T-cell activation

Question 2

Azathioprine
 mechanism of action

Answer 2

Purine antimetabolite, converted to 6-MP; may inhibit synthesis of DNA, RNA, and proteins; interferes with cellular metabolism; may inhibit mitosis

Question 3

Azathioprine immunosuppressants side effect

Answer 3

• Bone marrow suppression

– Monitor FBC

• Increased risk of malignancy All immunosuppressants

– Esp transplanted patients -NHL

• Increased risk of infection
• Hepatitis

– Monitor LFT

Question 4

Ciclosporin & tacrolimus
 mechanism of action

Answer 4

• active against helper T cells, preventing the production of IL-2 via calcineurin inhibition
• Ciclosporin binds to cyclophilin protein
• Tacrolimus binds to tacrolimus-binding protein
• Drug/protein complexes bind calcineurin
• Calcineurin normally exerts phosphatase activity on the nuclear factor of activated T cells. This factor then migrates to the nucleus to start IL-2 transcription

Question 5

Calcineurin inhibitors:
 adverse effects

Answer 5

• Nephrotoxicity
• Hypertension
• Hyperlipidemia
• Nausea, vomiting, diarrhea
• Hypertrichosis, gingival hyperplasia,
• Hyperuricemia.
• Multiple drug interactions are possible, primarily with agents affecting the cytochrome P-450 system

Question 6

Mycophenolate mofetil
 mechanism of action

Answer 6

I • Is a prodrug derived from fungus Penicillium stoloniferum

• inhibits the enzyme inosine monophosphate dehydrogenase (required for guanosine synthesis)
• impairs B- and T-cell proliferation
• spares other rapidly dividing cells (because of the presence of guanosine salvage pathways in other cells)

Question 7

Cyclophosphamide

Answer 7

• Alkylating agent -cross links DNA so that it cannot replicate
• Many immunological effects:

– suppresses T cell activity

– suppresses B cell activity

🔫🔫🔫Indications:

– lymphoma, leukaemia

– lupus nephritis

– Wegener’s granulomatosis

– Polyarteritis nodosum

Question 8

Methotrexate: mechanism of action in malignant

Answer 8

• Methotrexate competitively and reversibly inhibits dihydrofolate reductase (DHFR)
• The affinity of methotrexate for DHFR is 1000X that of folate for DHFR.
• Dihydrofolate reductase catalyses the conversion of dihydrofolate to the active tetrahydrofolate the key carrier of one-carbon units in purine and thymidine synthesis
• Methotrexate, therefore inhibits the synthesis of DNA, RNA and proteins
• Methotrexate acts specifically during DNA and RNA synthesis, and thus it is cytotoxic during the S-phase of the cell cycle. It therefore has a greater toxic effect on rapidly dividing cells (such as malignant and myeloid cells, and GI & oral mucosa), which replicate their DNA more frequently

Question 9

Methotrexate: mechanism of action non malignant

Answer 9

• Mechanism of action in non-malignant disease e.g. RA, psoriasis is not clear
• Mechanism is not via anti-folate action
• Possible mechanisms include – inhibition of enzymes involved in purine metabolism, leading to accumulation of adenosine, a purine nucleoside that is elaborated at injured and inflamed sites. Adenosine is a regulatory autocoid that is generated as a result of cellular injury or stress, interacts with specific G protein-coupled receptors on inflammatory and immune cells to regulate their function.

– the inhibition of T cell activation activation

– suppression of intercellular adhesion molecule expression by T cells

Question 10

Methotrexate: pharmacokinetics

Answer 10

• Mean oral bioavailability is 33% (13-76%)
• Mean intramuscular bioavailability is 76%
• Administered PO, IM or S/C
• In patients taking PO with partial response or with nausea then swap to s/c
• WEEKLY NOT DAILY DOSING, metabolized to polyglutamates with long half lives
• 50% protein bound -NSAIDs displace
• Renal excretion

Question 11

Sulfasalazine (sulphasalazine)

Answer 11

• A conjugate of a salicylate (5aminosalicylic acid, 5ASA) and a sulfapyridine molecule
• Developed in 1940s
• RA or ‘rheumatic polyarthritis’ believed to be infectious
• Designed to relieve pain & stiffness (5-ASA = anti-inflammatory)
• And to fight infection (sulfapyridine = sulfonamide)

Question 12

Sulfasalazine: immunological effects

Answer 12

• T cell

– inhibition of proliferation

– possible T cell apoptosis

– inhibition of IL-2 production

• Neutrophil

– reduced chemotaxis

– reduced degranulation

Question 13

Sulfasalazine: immunological effects

Answer 13

• T cell

– inhibition of proliferation

– possible T cell apoptosis

– inhibition of IL-2 production

• Neutrophil

– reduced chemotaxis

– reduced degranulation

Question 14

Effects of blocking TNF-α

Answer 14

Etanercept ,infliximab ,
Adalimumab
اتنر اكسبت تو يوز ماب لان يخاف يموت بالصحراء
ETANER acCEPT to use MAB”

👾👾• ↓ Inflammation

Cytokine cascade Recruitment of leukocytes to joint

• elaboration of adhesion molecules
• production of chemokines
• ↓ Angiogenesis

VEGF and IL-8 levels

• ↓ Joint destruction

MMPs and other destructive enzymes Bone resorption and erosion Cartilage breakdown

Question 15

Etanercept ,infliximab ,

Adalimumab

Answer 15

• anti-TNF therapy does not appear to increase the overall risk of malignancy in RA
• increased risk of new malignancy in those anti-TNF treated patients with prior malignancy
• risk of serious infections
• Anti-TNF increases risk of skin/soft tissue infections
• ✨TB reactivation and other intracellular bacterial infections –post marketing surveillance