AZ Guide u Medicine

ADENOSINE A2 antagonist

In Parkinson’s patients, the decreased activity of the dopaminergic system leads to a compensatory increase in GABA system.
A2-antagonists reduce GABA-activity, restoring the dopaminergic / GABA balance.

ALENDRONATE

• Alendronate is a drug for osteoporosis, belonging to bisphosphonates.

• Ceftriaxone is an injectable antibiotic.
• Ceftriaxone has obtained the approval for treatment of acute otitis media. Acute otitis media is mainly caused by three pathogens:

• Streptococcus pneumoniae
• Haemophilus influenzae
• Moraxella catarrhalis.

• The most common side effects of Ceftriaxone are: diarrhoea, nappy rash, rash, injection site pain, and vomiting.
  A significant increase in diarrhoea (approximately 40%) in patients who received a second injection of Ceftriaxone was observed.

[Rocephin^® (Roche), a trade mark of Ceftriaxone]

ETANERCEPT

• Etanercept is a genetically engineered fusion protein consisting of two identical chains of the recombinant human TNF-receptor p75 monomer fused with the Fc domain of human IgG1.
  It binds and inactivates TNF.

¨ RHEUMATOID ARTHRITIS

Methotrexate is the main treatment for rheumatoid arthritis.
However, in many patients Methotrexate alone does not result in satisfactory control of the disease.
89 patients with persistently active rheumatoid arthritis despite at least 6 months of Methotrexate therapy (15-25 mg per week) were enrolled.
The patients were randomly assigned to two groups:

The primary end-point for efficacy was the American College of Rheumatology (ACR) criteria for a 20% improvement in rheumatoid arthritis (ACR20) at 24 weeks.

The only adverse events associated with Etanercept were mild injection site reactions and no patient withdrew from the study because of adverse effects associated with Etanercept.
The combination of Methotrexate and Etanercept offers a promising new alternative for patients who have persistently active rheumatoid arthritis.

[Weinblatt M.E. et al., N Engl J Med 1999; 340: 253-259]

ETIDRONATE

• Etidronate, an bisphosphonate, is indicated for the prevention of bone loss in postmenopausal women at risk of developing osteoporosis, particularly those who are unable to take HRT.
• Etidronate has shown an increase in bone mineral density of about 2.5 - 3.9%, similarly to that produced by HRT.
• Etidronate is also used for the prevention of corticosteroid-induced osteoporosis.

FLAVONOIDS

• Flavonoids are polyphenolic compounds whose main dietary sources are fruit and vegetables and whose consumption has been linked to protection against heart disease and cancers.
• Flavonoids are powerful antioxidants in the oxidation of LDL and provide a possible mechanism for the beneficial epidemiologic effect of dietary fruit and vegetables on heart disease.
• Epidemiologic studies have shown consistent associations between consumption of fruit and vegetables and protection against a range of cancer,

• Block G. et al, Nutr Cancer 1992; 17: 1-29
• World Health Organization, World Health Organ Tech Rep Ser, 1990; 797: 204-312
• Ziegler R., Am J Clin Nutr 1991; 53 (suppl): 251S - 259S,

ischemic heart disease,

• Gramenzi A. et al., Br Med J 1990: 300: 771-773

and type 2 diabetes

• Colditz GA et al, Am J Clin Nutr 1992; 55: 118-123

• Flavonoids may be important factors for health that coexist with the more familiar antioxidant vitamins (i.e. vitamin E, beta-carotene)
• Quercetin is one of the most widespread and also most potent antioxidant flavonoids.

MARIMASTAT

• Marimastat is a matrix metalloproteinase (MMP) inhibitor.
  MMPs (i.e., collagenases, stromelysins, gelatinases) are able to degrade the components of the extracellular matrix.
  High levels of MMPs are expressed in a wide variety of cancer cells and are implicated in various stages: metastasis, invasion and angiogenesis.

METRIFONATE

• Metrifonate is an acetylcholinesterase (AChE) inhibitor for Alzheimer’s disease.
• Side effects include: nausea, diarrhoea and leg cramp.

OPRELVEKIN

• Oprelvekin is a recombinant version of human interleukin-11.
• It is indicated for promoting platelet production in cancer patients with solid tumours or lymphoma who are undergoing chemotherapy.
• Side effects of Oprelvekin are mainly associated with fluid retention: peripheral oedema, dyspnea, tachycardia and conjunctival redness.

[Neumega^® (American Home Products), a trade mark of Oprelvekin]

ORLISTAT

• Orlistat is a lipase inhibitors which blocks the absorption of about 30% of ingested fat.
• Indication
  Orlistat is indicated in association with a mildly hypocaloric diet for the treatment of obese patients with a body mass index (BMI) > 30 Kg/m², or overweight patients (BMI > 28) with associated risk factors (such as hypercholesterolaemia, hypertension or non-insulin dependent diabetes).
• Dosage
  The recommended dose is one 120 mg capsule taken immediately before, during or up to one hour after each main meal.
  (Daily dosage: 120 mg x 3)
• Adverse effects
  Gastrointestinal side effects are the most common adverse reaction of Orlistat and may increase when the diet is high in fat (> 30% fat composition). Among them, the most frequent adverse effects are the following: oily spotting from the rectum, faecal urgency, fatty/oily stools, oily evacuation, increased defecation, faecal incontinence.
• Interactions
  

Ø Warfarin: INR values must be monitored.
Ø Pravastatin: increased Pravastatin plasma concentrations. Dose adjustment of Pravastatin may be necessary.
Ø Orlistat may impair the absorption of fat soluble vitamins (A, D, E, K).
To ensure adequate nutrition, the diet should be rich in fruit and vegetables and multivitamin supplements must be used.

PAROXETINE

• Paroxetine is a selective serotonin reuptake inhibitor (SSRI), used in the management of depression.
• A randomized controlled trial has evaluated Paroxetine in the treatment of generalized social phobia (social anxiety disorder).
  Fifty (55%) of 91 persons taking Paroxetine (20 mg/die with increases of 10 mg/die weekly after the second week of treatment to a maximum of 50 mg/die) and 22 (23.9%) of 92 persons taking placebo were much improved or very much improved at the end of treatment (11 weeks).

[JAMA 1998; 280: 708-713]

PHENTOLAMINE

• Phentolamine is an alfa-adrenergic antagonist.
• Phentolamine is used in the control of hypertension in patients with pheochromocytoma.
• Intracavernous injection of Phentolamine has been proposed as a treatment for male sexual dysfunction.

PRESENILIN INHIBITORS

Mutant presenilins are the most common cause of familial, early-onset Alzheimer’s disease.
They act by altering g -secretase activity, an enzyme that cleaves b -amyloid precursor protein – the final step in the generation of amyloid b peptide, which accumulates in the cerebral cortex of patients with Alzheimer’s disease.
Presenilins have a role in Notch activity.
Notch is a development signal transduction molecule activated by presenilin-1-dependent, g -secretase.
Presenilins could be the target for slowing the development of Alzheimer’s disease.
Inhibition of presenilin should be (parziale) in order to avoid interference with haematopoiesis.
Blocking Notch signalling could result in T-cell disorders, leukaemia, or CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy).

PHYSOSTIGMINE

• Physostigmine is an acetylcholinesterase (AChE) inhibitor for Alzheimer’s disease.
• The most common side-effects are: nausea and vomiting.

RALOXIFENE

• Raloxifene is a drug for the prevention of osteoporosis in post-menopausal women.
• It is a selective oestrogen receptor modulator (SERM).
• Breast cancer risk of Raloxifene has not been determined.
  Tamoxifen has a similar mode of action to the SERMs. It may cause new tumour formation in women treated for breast cancer and endometrial cancer with longer use.
  Cases of endometrial cancer have been reported during the Raloxifene trials.
• Raloxifene may cause thromboembolic events.
• The most common adverse effects of Raloxifene are: hot flushes, leg cramps.

RISEDRONATE

• Risedronate is a new bisphosphonate.
• It is indicated for:
• Paget’s disease
• osteoporosis.
• Paget’s disease/Trial: Risedronate vs Etidronate.
  In the 18-month pivotal trial, 123 patients with moderate to severe Paget’s disease were randomised to receive Risedronate (30 mg daily) or Etidronate (standard dose).
  Reduction of levels of serum alkaline phosphatase (SAP) to normal.

RITUXIMAB

• Rituximab is a chimenic monoclonal antibody for the treatment of relapsed or refractory low-grade or follicular B-cell non -Hodgkin’s lymphoma.
• Rituximab is administered as a series of four infusions over a 22-day period.
• In preliminary studies, Rituximab has produced a 48% overall response rate.
• The most common side effect of Rituximab is mild-moderate flu-like symptom, mainly during the first infusion.

[Rituxan^® (IDEC/Genentech/ Roche), a trade mark of Rituximab].

RIVASTIGMIN

• Rivastigmin, an acetylcholinesterase inhibitor, is indicated for the treatment with mild to moderately severe forms of Alzheimer’s disease.

SIBUTRAMINE

• Sibutramine, an anti-obesity drug, is a serotonin and noradrenaline reuptake inhibitor.
• Sibutramine is recommended for obese patients with an initial body mass index (BMI) equal to or more than 30 Kg/m² or 27 Kg/m² in the presence of other risk factors, such as hypertension, diabetes and dyslipidaemias.
• The recommended dose is 10 mg daily, increasing to 15 mg in the subjects who do not lose enough weight.
• Sibutramine is associated with increases in both blood pressure and heart rate. Monitoring at regular intervals is required for all patients.
  In those with substantial increases in blood pressure, the dose may be decreased or treatment discontinued.
  Other side-effects associated with Sibutramine are: dry mouth, constipation, headache and insomnia.
• Sibutramine should not be used in patients with a history of stroke, coronary artery disease, arrhythmias, congestive heart failure or uncontrolled hypertension.

TROVAFLOXACIN

Trovafloxacin is a broad-spectrum quinolone with a complete coverage of respiratory pathogens with high efficacy in eradication of Streptococcus Pneumoniae and Haemophilus Influenzae.

ZANAMIVIR