Drugs List Block 12 Flashcards
Azathioprine
Azathioprine acts to inhibit purine synthesis, and therefore inhibit DNA and RNA synthesis leading to an inhibition of cell proliferation. It is used to treat auto-immune diseases, and also transplant recipients.
Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol.
Blood tests and monitoring for signs of myelosuppression are essential in long-term treatment with azathioprine
DMARD for RA and crohn disease
Diclofenac
Diclofenac is a NSAID. As such it has analgesic due to the inhibition of both COX-1 and COX2 enzymes.
Examples of conditions in which Diclofenac is prescribed are pain, dysmenorrhea, and ocular inflammation.
Diclofenac is still used but the least favoured of the non-cox specific NSAIDS as more Cox2 than many others. Naproxen is possibly a better choice.
Celecoxib
Celecoxib unlike most NSAIDs preferentially inhbits COX-2, reducin production of prostaglandins.
As it only targets COX-2 it does not possess anti-platelet effects, and as such is not a substitute for aspirin for cardiovascular prophylaxis.
treat rheumatoid arthritis, osteoarthritis, and familial adenomatous polyposis (FAP).
possible effects on the Cardiovascular system.
Cyclophosphamide
Cyclophosphamide is an antineoplastic, and antiimmunosuppressive agent which is activated by the cytochrome P450 isoforms, CYP2A6, 2B6, 3A4, 3A5, used to treat multiple cancers including myelomas and leukaemiaís. It has three mechanism of action
1) Attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes. This stops DNA synthesis and RNA transcription from the damaged DNA.
2) Crosslinking of DNA to prevent DNA transcription
3) Induction of DNA mispairing leading to mutations.
Alkylating agents are non cell cycle specific, and as such all induce cell death.
Vitamin D
once it is metabolised to 1,25- dihydroxycholecalciferol is is hormonally active. This metabolic change occurs in two steps,
1. In the liver: cholecalciferal is hydroxylated to 25-hydroxycholecalciferol by 25-hydroxylase.
2. Within the kidney, 25-hydroxycholecalciferol is metabolised to 1,25-dihydroxycholecalciferol,
due to the action of 1- -hydroxylase.
25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol are hydrophobic, and as such are transported in blood bound majorly to the carrier protein vitamin D-binding protein. The halflife of 25-hydroxycholecalciferol is several weeks, while that of 1,25-dihydroxycholecalciferol is only a few hours
25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol bind to vitamin D receptors, with 1,25- dihydroxycholecalciferol possessing a 1000 times higher affinity for the receptor than that for 25- hydroxycholecalciferol. Once bound to the receptor, the receptor will form a complex with the retinoid-X receptor and then modulate gene expression as the complex can act as a transcription factor.
Ciclosporin
immunosuppressive agent, used for the prophylaxis of graft rejection in organ and tissue transplantation.
It binds to cyclophilin, which causes the inhibition of calcineurin, which is responsible for activating the transcription of IL-2.
reversible inhibition of immunocompetent lymphocytes, in the G0 or G1 phase of the cell cycle. T-lymphocytes are preferentially inhibited, with the T1-helper lymphocyte is the main target, although it may also inhibit the T1-suppressor cell.
Aurothiomalate
There are indications that free thiols play an important role. Free thiols can react with reactive aldehydes, lessening the cell destructive properties of reactive aldehydes.
As a therapy Aurothiomalate is given as a intramuscular injection, with benefit not expected until about 300-500 mg has been given. It is important to avoid complete relapse since second courses of gold are not usually effective.
DMARD
This is no not widely used, as has been superceded by other DMARDs,
Chloroquine
Chloroquine is more widely know as an anti-malarial drug.
inhibit the parasitic enzyme heme polymerase, causing a build up of toxic heme within the parasite.
treatment for Rheumatoid arthritis, its mechanism of action is not understood. However it is thought to be able to reduce the levels of inflammatory agents such as IL-6, IL-1b and TNF either by blocking their release, or by reducing their transcription.
Methotrexate
Methotrexate inhibits folic acid reductase which converts folic acid to tetrahydrofolic acid. Tetrahydrofolic acid is required for both purines and pyrimidine biosynthesis, Thus, DNA synthesis cannot proceed
affects the most rapidly dividing cells
used at low dose in the management of severe, active, classical, or definite rheumatoid arthritis.
Sulfasalazine
Sulfasalazine is an anti-inflammatory agent which is used to treat Ulcerative colitis and rheumatoid arthritis.
its mode of action is unknown. Sulfasalazine is brokendown into its active metabolite (5-Aminosalicylic acid (5-ASA) and sulfapyridine (SP) within the body. In ulcerative colitis, the major therapeutic action via 5-ASA.
Sulfasalazine, has been replaced to a certain expent by Mesalazinr. Mesalazine has the same active metabolite but no longer contains the sulphur group and so is better tolerated by some patients.
Calcitonin/Salcatonin
Calcitonin is produced by the thyroid gland, and is important in the control of the calcium concentration within blood.
The calcitonin receptor is an example of a GPCR. This activates the cAMP and calcium signalling pathways, leading to the enhance production of vitamin D producing enzymes (25- hydroxyvitamine D-24-hydroxylase), greater calcium retention and enhanced bone density. net increase in bone mass and a reduction in plasma calcium levels. In addition to affecting osteoclasts, in also stimulates bone building by osteoblasts.
Calcitonin also promotes the renal excretion of calcium, phosphate, sodium, magnesium, and potassium ions
Prednisolone
heavily prescribed corticosteriod. derived from cortisone,metabolised in the liver to its active form, prednisolone. can cross the cell membrane and can bind to the corticosteriod receptor.
leads to changes in DNA transcription reducing the production of inflammatory proteins. specific example the reduction in activity of phospholipase A2, leading to the reduced production of arachodonic acid. also affect the cell membrane altering ion permeability, and also can affect neurohormone production
Raloxifene
produces estrogen-like effects on bone and lipid metabolism, while antagonizing the effects of estrogen on breast and uterine tissue.
in the bone, binds to the estrogen receptors, resulting in reduced bone resorption and increased bone mineral density in postmenopausal women, slowing the rate of bone loss.
This is achieved via activation of transforming growth factor-3, which is a bone matrix protein with antiosteoclastic properties. In addition Raloxifene can inhibit the proliferation of preosteoclastic cells
Raloxifene also antagonizes the effects of estrogen on mammary and uterine tissue. effects is not fully understood, but there are two possibilities
1) Raloxifeneís tissue-specific estrogen agonist or antagonist activity is dependent on the structural differences between the raloxifene-estrogen receptor complex and the estrogen- estrogen receptor complex.
2) The presence of at least 2 estrogen receptors (ER, ER) may determine the tissue specificity of Raloxifene.
Raloxifene is much less commonly used, as the incidence of hormonal treament of post-menopausal symptoms is less common.
Alendronic acid
Alendronate, strengthens bone and as such is used to treatcorticosteroid-induced osteoporosis and Paget’s disease, and to prevent osteoporosis in postmenopausal women. Nitrogen containing bisphosphonates inhibit farnesyl pyrophosphate (FPP) synthase by acting as analogues of isoprenoid diphosphate lipids. Inhibition of this enzyme in osteoclasts prevents the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins, such as Rac and Rho. This causes a reduction in osteoclast activity reducing bone resorption and turnover. Furthermore osteoclast survival is also affected, further increasing the ability of the bone to be rebuilt. Therefore, in postmenopausal women, it reduces the elevated rate of bone turnover, causing a net gain in bone mass.
Digoxin
Digoxin is used to treat congestive heart failure, and supraventricular arrhythmias. Its mode of action is via inhibition of the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium. This alteration in calcium concentration is thought to promote activation of contractile proteins (e.g., actin, myosin).
Digoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.
Still used in Atrial Fibrillation, third line treatment option. Rarely used in heart failure as much better drugs available
