Musculoskeletal System

Question 1

Drugs (DMARDs) used to treat Rheumatoid Arthritis (RA) (5)

Answer 1

Methotrexate, Sulfasalazine, Infliximab, Rituximab, Adalimumab

Methotrexate when used in RA (different mechanism to when used in cancer) is used at lower doses than in chemotherapy. Side effects of hair loss, nausea and headaches are still common. In RA, it is believed that the inhibition of enzymes involved in purine metabolism leads to the accumulation of adenosine. This adenosine inhibits T cell activation and suppresses intercellular adhesion molecules expressed by T cells, selectively downregulates B cells and leads to deactivation of enzyme activity relevant to immune system function. It also inhibits the binding of IL-1 to its cell surface receptor.

Sulfasalazine and its metabolite (5-ASA) are poorly absorbed from the small intestine and its main mode of action is believed therefore to be in the intestine. ADRs include depression, folate deficiency, megaloblastic anaemia and temporary infertility. Mechanism of action is not understood.

Infliximab - a monoclonal antibody against TNF-Alpha used to treat autoimmune diseases. It prevents the TNF-Alpha from binding to its receptor in the cell, thus preventing an inflammatory response. ADRs include risk of serious infection, re-activation of Hepatitis B and TB in infected patients, psoriasis and vitiligo.

Rituximab - another monoclonal anti body but against the protein CD20 which is primarily found on the cell surface of B cells. Rituximab therefore destroys B cells and so is used in lymphomas, leukaemias, transplant rejection and autoimmune conditions such as RA. ADRs include cardiac arrest, re activation of Hep B and other viral infections, pulmonary toxicity, bowel obstruction and perforation, cytokine release syndrome.

Adalimumab is another anti-TNF medication like Infliximab. ADRs include deactivation of latent conditions such as TB (due to immune system suppression).

Question 2

Anticholinesterases (2)

Answer 2

Neostigmine and Pyridostigmine

Neostigmine is a reversible acetylcholinesterase inhibitor used to treat Myaesthenia Gravis. By inhibiting acetylcholinesterase, the acetylcholine neurotransmitter remains in the synaptic cleft longer, leading to an increased post synaptic response despite reduced numbers of receptors and a wider synaptic cleft.

Pyridostigmine works in the same manner.

ADRs of both include sweating, diarrhoea, nausea, vomiting, abdominal cramps, increased salivation, constricted pupils, facial flushing as a result of vasodilation, erectile dysfunction.

Question 3

Drugs used to treat osteoporosis (4)

Answer 3

Bisphosponates (e.g. Alendronic acid), calcium, Vitamin D, Oestrogens

Question 4

NSAIDs (4)

Answer 4

Ibuprofen, Naproxen, Diclofenac, Celecoxib (also aspirin but not technically an NSAID)

Non-steroidal anti-inflammatory drugs (NSAIDs) are a drug class that provide analgesia, antipyretic and in higher doses, anti-inflammatory effects. They mostly inhibit activity or COX-1 or COX-2 enzymes and therefore inhibit synthesis of prostaglandins and thromboxanes. It is thought that the inhibition of COX-2 leads to the anti-inflammatory, analgesics and antipyretic effects whilst the inhibition of COX-1 (particularly aspirin) may cause GI bleeding and ulceration.