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Pharmacology > Rheumatology > Flashcards

Rheumatology Flashcards

0
Q

Corticosteroid ADRs

A 
Cushingoid presentation 
Growth retardation
Cataracts
Osteoporosis 
Avascular necrosis
Infection
Psychiatric disorders
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1
Q

Corticosteroids mechanism

A

Prevent IL-1 and IL-6 production by macrophages

Inhibit all stages of T-cell activation

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2
Q

Azothioprine uses

A

Maintenance therapy in SLE and vasculitis.
IBD
Bullous skin diseases
Atopic dermatitis

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3
Q

Azathioprine mechanism

A

Cleaved to 6-mercaptopurine (6-MP)
This is an anti metabolite
Reduced DNA and RNA synthesis

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4
Q

Azathioprine metabolism

A

6-MP metabolised by TMPT
Gene is highly polymorphic
Myelosuppression risk in those with low/no TMPT.

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5
Q

Azathioprine ADRs

A

Hepatitis
Infection
Increased risk of malignancy
Myelosuppression

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6
Q

Ciclosporin mechanism

A

Binds to cyclophillin protein
Inhibits calcineurium
Prevents IL-2 production in T-helper cells

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7
Q

Tacrolimus mechanism

A

Binds to tacrolimus binding protein
Inhibits calcineurium
Prevents IL-2 production in T-helper cells

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8
Q

Uses of ciclosporin and tacrolimus

A

Transplant mechanism
Atopic dermatitis
Psoriasis
RA and SLE patients with cytopaenias (no effect on bone marrow)

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9
Q

Ciclosporin and tacrolimus ADRs

A 
Hyperuricaemia
Hypertrichosis
Gingival hyperplasia 
GI complaints
Hyperlipidaemia
Nephrotoxicity
Hypertension
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10
Q

Mycophenolate mofetil mechanism

A

Inhibits inosine monophosphate dehydrogenase - required for guanosine synthesis
Impairs B and T cell proliferation
Spares other rapidly dividing cells, as they have guanine salvage pathways

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11
Q

Mycophenolate mofetil uses

A

Transplantation

Lupus nephritis

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12
Q

Mycophenolate mofetil ADRs

A

Myelosuppression
GI
Risk of toxicity in hepatic or renal failure

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13
Q

Ciclosporin and tacrolimus DDIs

A

CYP450 metabolism

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14
Q

Cyclophosphamide mechanism

A

Alkylating agent
Cross linking prevents DNA replication
Suppresses B and T cell activity

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15
Q

Cyclophosphamide uses

A

Haematological malignancies
Lupus nephritis
Wegeners granulomatosis
Polyarteritis nodusum

16
Q

Cyclophosphamide pharmacodynamics

A

Pro-drug converted by CYP450 to active forms
Active metabolites- 4-hydroxycyclophosphamide, aldophosphamide
Acrolein- toxic to the bladder, causes haemorrhagic cystitis.
Excreted by kidney

17
Q

Cyclophosphamide ADRs

A

FBCs
Infertility
Lymphoma, leukaemia
Bladder cancer

18
Q

Methotrexate mechanism

A

Inhibits dihydrofolate reductase
Prevents purine and thymidine synthesis-toxic in the S-phase, so worse for rapidly dividing cells
Role unclear in non-malignant disease-not via antifolate action, possibly a build up of adenosine causing GPCR signalling to reduce activity of T cells

19
Q

Methotrexate uses

A 
Gold standard for RA
Malignancy
Psoriasis
Crohns
Unlicensed in inflammatory myopathies, vasculitis, steroid sparing in asthma
20
Q

Methotrexate pharmacokinetics

A 
Can be administered PO, IM, SC
Weekly dosing - active metabolites (polyglutamates) have long half lives (but own T1/2 8 hrs) 
50% protein bound - displaced by NSAIDS
Renal excretion
Oral bioavailability 13-76%
21
Q

Methotrexate ADRs

A 
Mucositis and myelosuppression - reduced by folic acid supplements 
Pneumonitis 
Infection
Teratogenic, abortifacient
Hepatitis, cirrhosis
22
Q

Sulphasalazine and mesalazine mechanism

A

Conjugate of a salicylate and a sulfapyridine molecule
Salicylate is anti inflammatory
Sulphapyridine fights infection
T-cell - inhibit proliferation, promote apoptosis, prevent IL-2 production
Neutrophil - reduced chemotaxis, reduced de granulation

23
Q

Sulphasalazine and mesalazine metabolism

A

Cleaved in large bowel, so good for IBD
Sulphapyridine absorbed
Salicylate largely unabsorbed

24
Q

Sulphasalazine and mesalazine ADRs

A

Rash
Hepatitis
GI
Myelosuppression

25
Q

Anti TNF therapy uses

A

Clinically active RA

Withdrawn if no improvement/adverse effect within 6 months

26
Q

Anti TNF therapy effects

A

Reduced inflammation
Reduced angiogenesis
Reduced joint destruction

27
Q

Adolimumab
Etanercept
Ifliximab

A

Anti TNF

28
Q

Rituximab

A

Monoclonal antibody against CD20

Pharmacology (20 decks)

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