DRUGS: Pharmacology of Inflammation and Immunosuppression Flashcards
Adalimumab
Human Anti-TNFα mAb, used in rheumatoid arthritis.
Adrenaline
In case of anaphylactic shock, adrenaline is administered intramuscularly/intravenously to counteract systemic vasodilatation and reduction in tissue perfusion.
Relieves bronchospasm.
Alemtuzumab
mAb, binds to CD52, used in treating chronic lymphocytic leukaemia, cutaneous T-cell lymphoma and T-cell lymphoma.
Anakinra
Recombinant IL-1 receptor antagonist, used in rheumatoid arthritis.
Aprepitant
An antiemetic drug that inhibits the NK1 receptor.
Used to treat chemotherapy induced nausea and vomiting.
Arthrotec
Combination of misoprostol and diclofenac, used in chronic treatment of rheumatoid arthritis to prevent peptic ulcer formation.
Aspirin
Irreversible NSAID that is used additionally to lower the risk of platelet aggregation.
Irreversible because it acetylates a serine at position 530.
Auranofin
Used to treat rheumatoid arthritis.
Research also being done into its effect on HIV infection, tuberculosis and ovarian cancer.
Azathioprine
Inhibits DNA synthesis in cells lacking a nucleotide salvage pathway (B- and T- cells), used as an immunosuppressant.
Basiliximab
mAb against CD25 alpha subunit of the IL-2 receptor, used as an immunosuppressant.
Beclametasone
Commonly used inhalable corticosteroid used in the prophylactic treatment of asthma, not used as bronchodilator in acute attacks.
Betamethasone
A corticosteroid used to treat dogs with dermatitis, applied as a topical treatment.
Botulinum toxin A
Can be administered as a prophylactic for migraines, but only advisable for patients that have been suffering from migraines for several years who experience headaches 15+ days a month.
Catumaxomab
Used to treat ascites in cancer patients.
Has been termed trifunctional because the Fc portion can bind the Fc receptors on macrophages and other cells.
Ciclosporin A
Binds to CpN, inhibits IL-2 transciption, can be used as an immunosupressant.
Cimetidine
Also known as Tagamet.
H2-receptor antagonist (reduces gastric acid secretion), one of the first drugs successful in treating peptic ulcers.
Can inhibit cytochrome p450.
Clarithromycin
Antibiotic, can be used to eradicate Helicobacter pylori, which causes peptic ulcers in many cases in humans.
Cyclophosphamide
Commonly used alkylating agent prodrug (converted by P450 enzymes in liver to phosphoramide mustard).
Phosphoramide mustard kills dividing T and B cells and therefore has an immunosuppressive effect, however it has multiple side effects.
Side effects include bone marrow depression and bladder irritation.
Dexamethasone
Corticosteroid, binds to glucocorticoid receptors, used as anti-inflammatory and in immunosuppression.
Diclofenac
NSAID component of arthrotec.
Dolasetron
5-HT3 receptor antagonist used to treat nausea and vomiting following chemotherapy.
Reduces activity of the vagus nerve, which activates the vomiting center in the medulla oblongata.
Ecallantide
Used in the treatment of HAE (hereditary angioedema)
An inhibitor of the protein kallikrein and a 60 amino-acid polypeptide.
Ergotamine
Non-selective 5-HT1 partial agonist.
Etanercept
Fusion protein of the soluble TNFα receptor and IgG1, used in rheumatoid arthritis.
Etoricoxib
COX-2 selective inhibitor, reserved for chronic inflammation in patients not thought to have a substantial cardiovascular risk.
Fexofenadine
Third generation antihistamine (H1-receptor antagonist)
Active component of prodrug terfenadine
Lacks cardiac side effects of earlier generations of antihistamines
Main uses include treating hay fever and urticaria
In cattle, antihistamines have little use in treating hypersensitivity reactions - different underlying pathology.
Fluticasone
Commonly used inhalable corticosteroid used in the prophylactic treatment of asthma, not used as bronchodilator in acute attacks.
Formoterol
Long acting β2-adrenoreceptor antagonist, used prophylactically for the treatment of asthma.
Duration of action of 8-12 hours.
Hydrocortisone
Short acting corticosteroid (>24 hours).
A 1% topical cream can be used to treat eczema.
Hydroxychloroquine
Usually used in treatment of malaria, but can also be administered to patients refractory to other DMARDs in rheumatoid arthritis.
As a lipophilic weak base, hydrochloroquine accumulates in cytoplasmic vesicles, which can reduce antigen presentation by macrophages and reactive oxygen species generation in neutrophils.
Ibuprofen
Non-selective COX inhibitor, used as an analgesic, antipyretic and anti-inflammatory.
Icatibant
Bradykinin B2 receptor antagonist used in treatment of HAE (hereditary angioedema - mutation in gene encoding C1-INH causing excessive levels of bradykinin and resulting in sufferers experiencing periods of severe and painful swelling)
Imatinib
Tyrosine kinase inhibitor.
FDA approved for use in treating mastocytosis.
Only efficacious in patients not presenting with common D816V c-Kit mutation.
Indacaterol
Ultra-long acting β2-adrenoreceptor agonist used in treating COPD.
Infliximab
A chimeric antibody that sequesters TNFα (like etanercept), used in rheumatoid arthritis.
Ipratropium
Muscarinic antagonist that produces bronchodilation by inhibiting M3 receptors on the smooth muscle.
Occasionally used in the treatment of asthma, also used in treating COPD.
Lasmiditan
A non-triptan 5-HT-1F agonist, currently under investigation.
Lexipafant
PAF (platelet activating factor) receptor antagonist.
Proved successful in treating pancreatitis in rats, but less so in clinical trials in humans.
Loratadine
Third generation antihistamine (H1-receptor antagonist)
Lacks cardiac side effects of earlier generations of antihistamines, non-drowsy
Main uses include treating hay fever and urticaria
In cattle, antihistamines have little use in treating hypersensitivity reactions - different underlying pathology.
Meloxicam
NSAID with analgesic and fever reducing effects.
Mepyramine
First generation antihistamine (H1-receptor antagonist)
Rapidly permeated blood-brain barrier and caused drowsiness and so not suited for systemic use
Used in creams for treating insect bites
Methotrexate
Dihydrofolate reductase inhibitor used as a DMARD in rheumatoid arthritis.
Acts as a folic acid antagonist (inhibition of dihydofolate reductase and competition with folic acid transport into cells).
Methysergide
5-HT2 receptor antagonist that can be used (rarely) as a prophylactic in acute migraine attacks.
Metoclopramide
Commonly used to treat nausea and vomiting, to help with the stomach emptying of people with delayed stomach emptying, and to help with gastroesophageal reflux disease.
Metronidazole
Antibiotic, can be used to eradicate Helicobacter pylori, which causes peptic ulcers in many cases in humans.
Misoprostol
PGE1 analogue.
Component of arthrotec, used in the chronic treatment of rheumatoid arthritis.
Acts as a prophylactic against NSAID-induced ulceration.
Can be administered to dogs, where ulcers have been induced through prior NSAID administration.
Muromonab-CD3
Murine mAb that targets CD3 and was the first mAb to be approved for clinical use in humans to reduce acute transplant rejection.
Mycophenolic acid
Inhibits IMPDH (inosine monophosphate dehydrogenase), an enzyme crucial for de novo guanosine synthesis. Mainly used to diminish transplant rejection.
Naproxcinod
A combination of an NSAID and NO donor.
Naproxen
NSAID, non-selective COX inhibitor.
Naratriptan
Selective 5-HT1 agonist.
Longer duration of action than sumatriptan, can cross the blood brain barrier and has less cardiac effects.
Ofatumumab
Human mAb targeting CD20.
Approved for treating chronic lymphocytic leukaemia.
Omalizumab
Recognises IgE and acts to decrease mast cell activation, because allergen bound IgE induces mast cell degranulation when bound to its receptor FCεRI
Used to treat Dermatographic urticaria, a condition where the triple response is exaggerated (generally treated with H1 receptor antagonists)
Omeprazole
Proton pump inhibitor used in treatment of peptic ulcers
Authorised for use in treating peptic ulcers in horses.
Ondansetron
5-HT3 receptor antagonist used to prevent and treat vomiting (chemotherapy induced).
Paracetamol
Analgesic/antipyretic COX inhibitor that does not cause the anti-inflammatory actions of classical NSAIDs.
Penicillamine
DMARD, may act by decreasing IL-1 and collagen synthesis
Phenylbutazone
NSAID for use in animals.
No longer allowed for use in humans because of severe side effects.
Prednisolone
Longer acting corticosteroid than hydrocortisone, shorter acting than dexamethasone.
Proglutamide
Inhibits CCK2 receptors (cholecystokinin-2), produces an inhibition of histamine release from ECL (enterochromaffin-like) cells
Histamine release is enhanced by gastrin released from G cells that acts at CCK2 receptors
Promethazine
First generation anti-histamine (H1-receptor antagonist)
Sedative, can be used to treat motion sickness, severe morning sickness and is added to certain cold/flu medications
Propanolol
β-adrenoreceptor antagonist.
Used to treat migraines.
Rantidine
Also known as Zantac
H2-receptor antagonist (reduces gastric acid secretion)
Primary drug for treatment of peptic ulcers
Rituximab
mAb that targets CD20 that is primarily expressed by B cells, and can be used in the treatment of moderate rheumatoid arthritis, its therapeutic effect being through B cell destruction.
Robenacoxib
NSAID for use in cats and dogs.
Rofecoxib
COX-2 inhibitor.
Associated with increased myocardial risk.
Rupatadine
Combined H1 and PAF receptor antagonist.
Used in treating hay fever and urticaria.
Salbutamol
Short-acting β2-adrenoreceptor agonist
Used in treatment of asthma through mast cell inhibition (raising [CAMP] inhibits mast cell degranulation), although main therapeutic action via bronchodilation
Salmeterol
Long-acting β2-adrenoreceptor agonist
Used prophylactically in treatment of asthma through mast cell inhibition (raising [CAMP] inhibits mast cell degranulation), although main therapeutic action via bronchodilation
Scopolamine
Used in treatment of motion sickness and postoperative nausea and vomiting.
Drowsiness is a common side effect.
Competitve antagonist at muscarinic ACh receptors
Sirolimus
Also called rapamycin.
Macrolide antibiotic which like tacrolimus binds to FKBP, however it does not inhibit CaN but instead binds to mTOR, a serine/threonine kinase involved in cell cycle progression and protein synthesis.
Inhibition of mTOR results in decreased T cell activation and proliferation and a decreased immune response.
Used to prevent transplant rejection and put in the coating of coronary stents to prevent restenosis.
Sodium aurothiomalate
DMARDs, work by largely unknown mechanisms.
Sodium cromoglycate
Mast cell ‘stabilizer’ which acts to inhibit degranulation
? Inhibits an inward Cl- conductance that is required to maintain a negative enough membrane potential to enable sustained influxes of extracellular calcium ? (because decreased calcium influx observed)
Can be used to treat mastocytosis
Available as eye drops for treatment of hay fever (e.g. Opticrom)
Occasionally used in treatment of asthma
Sulfasalazine
DMARD, used to treat both rheumatoid arthritis and inflammatory bowel disease.
Administered orally and broken down by colonic bacteria to produce sulfapyridine and 5-aminosalicylic acid.
Taken daily in tablet form, therapeutic benefits are not usually observed until after 3 months.
Unwanted effects include gastrointestinal disturbances, tears and contact lenses can be stained yellow and urine can appear orange.
Sumatriptan
5-HT(1B/D/F) agonist used in the treatment of migraine.
Tacrolimus
Binds to FKBP, inhibits IL-2 transcription, can be used as an immunosuppressant
Terfenadine
Second generation H1-receptor antagonist, can not cross blood-brain barrier
Used to treat hay fever between 1985-1996
Side effects: people developing torsade de points syndrome (prolonged QT interval), reports of sudden cardiac death.
Cardiac effects caused because terfenadine inhibits Kv11.1/hERG - important for the repolarisation of the action potential.
Especially dangerous in conditions of diminshed p450 3A4 activity (as terfenadine = prodrug, p450 3A4 converts it into the active compound fexofenadine)
p450 3A4 inhibited by numerous drugs, including bergamottin, the active component of grapefruit juice.
Tanezumab
Monoclonal antibody that blocks the action of NGF (nerve growth factor) in treatment of inflammatory pain.
An issue in clinical trials has been that the pain relief is so great that patients overuse damaged joints and exacerbate damage.
Theophylline
Phosphodiesterase inhibitor
Used prophylactically in treatment of asthma through mast cell inhibition (raising [CAMP] inhibits mast cell degranulation), although main therapeutic action via bronchodilation
Tocilizumab
mAb that sequesters IL-6, which like IL-1 is upregulated in rheumatoid arthritis.
Topiramate
Anti-epileptic.
Acts on numerous ion channels including voltage-gated sodium channels and GABA-A receptors.
Trastuzumab
Also known as herceptin.
Used to treat HER2 positive breast cancers.
Causes disruption of HER2 signalling and targeting of tumour cells for ADCC.
Trastuzumab emtansine
A combination of trastuzumab with a derivative of the antimicrotubule compund maytansine.
Binding of T-DM1 to HER2 causes internalisation, lysosomal degradation and release of DM1, which can bind to tubulin and prevent polymerisation causing cytotoxicity.
T-DM1 also retains the basic actions of trastuzumab; disruption of HER2 signalling and targeting of tumour cells for ADCC.
Zafirlukast
CysLT1 receptor antagonist, used in treatment of asthma
Zileuton
5-lipoxygenase inhibitor, used in some countries for the treatment of asthma
