Pharmacological action Pravastatin 40 mg
Pravastatin Lipid-lowering drugs of the statin, an inhibitor of HMG-CoA reductase inhibitors. By the principle of competitive antagonism statin molecule binds to a receptor that part of coenzyme A, which attaches the enzyme. Another part of the molecule inhibits the transformation of statin gidroksimetilglutarata to mevalonate, an intermediate in the synthesis of molecules of cholesterol. Inhibition of HMG-CoA reductase leads to a series of sequential reactions that result in reduced intracellular cholesterol content and is a compensatory increase in activity of LDL receptors and thus accelerate the catabolism of cholesterol (Xc) of LDL.
Lipid-lowering effect of statins is associated with lower levels of total cholesterol by LDL-C. Reduction in LDL cholesterol is dose-dependent and is not linear, but exponential.
According to the controlled studies of pravastatin, increased HDL-C level to 10%.
Statins do not affect the activity of lipoprotein lipase and hepatic, no significant effect on the synthesis and catabolism of free fatty acids, so their effect on triglycerides and again vicariously through their main effects on reducing LDL-C. A moderate reduction in triglycerides in the treatment of statins appears to be associated with expression of remnantnyh (apo E) receptor on the surface of hepatocytes involved in the catabolism LPPP, which include those of about 30% of the TG.
In addition to lipid-lowering actions, statins have beneficial effects in endothelial dysfunction (pre-clinical sign of early atherosclerosis) in the vascular wall, the state of atheroma, improves blood rheology, have antioxidant, antiproliferative properties.
Pharmacokinetics Pravastatin 40 mg
After oral administration, rapidly absorbed 30-54% of the administered dose of pravastatin, the bioavailability is 15-20%. Pravastatin undergoes the effect of “first pass” through the liver. Admission for 1 hour before or with meals reduces the systemic bioavailability and specific activity. Plasma concentration is directly proportional to administered dose. Cmax plasma levels reached after 1-1.5 h. Plasma protein binding is 50%. Excreted in breast milk. Metabolized in several ways: isomerization to 6-and 3-epipravastatina gidroksiizomera, the enzymatic hydroxylation of the ring and subsequent oxidation to ketone, oxidation of air or carboxyl ends of the chain conjugation. The main products of metabolism (3-gidroksiizomery) have a specific activity, which is 1 / 14 to 1 / 10 of the original.
T1 / 2 – 1.3-2.7 hours kidneys remove 20% of the bowel – 70%. 47% of the total clearance accounted for 53% kidney, and – in extrarenal way. Due to the elimination of the two paths may gain compensatory removal on one of them in violation of another, as well as the development of accumulation of pravastatin and its metabolites in renal and / or liver failure.
Statement Pravastatin 40 mg
Hyperlipoproteinaemia types IIa and IIb (in ineffectiveness of diet and exercise) combined hypercholesterolemia and triglitseridemiya.
Dosage regimen Pravastatin 40 mg
Individual. For intake – 10-40 mg 1 time / day for the night. Elderly patients, as well as severe liver or kidney disease should start treatment with a dose of 10 mg.
Side effect Pravastatin 40 mg
From the central and peripheral nervous system: dizziness, headache, taste disturbance, involuntary eye movements, facial nerve paresis, peripheral polyneuropathy, tremor, anxiety, insomnia, depression, amnesia, paresthesia.
On the part of the vision: the progression of cataracts, ophthalmoplegia.
Part of the digestive system: nausea, vomiting, diarrhea, abdominal pain, bloating, constipation, elevated liver transaminases (2-3 times compared to normal) and alkaline phosphatase, hyperbilirubinemia, hypercreatininemia (3-fold higher than ULN), and in some cases – hepatitis (including chronic active and cholestatic), fatty liver, cirrhosis or hepatic necrosis, hepatoma, acute pancreatitis.
From the hemopoietic system: thrombocytopenia, leukopenia, hemolytic anemia, eosinophilia.
On the part of the musculoskeletal system: increased activity of CPK, myalgia, myopathy, myositis, rhabdomyolysis.
Allergic reactions: skin rash, itching, lupus-like syndrome, anaphylactic shock, angioedema, dermatomyositis, vasculitis, purpura, toxic epidermal necrolysis (Lyell’s syndrome), malignant exudative erythema multiforme (Stevens-Johnson syndrome).
Dermatological reactions: alopecia, discoloration of the skin, photosensitivity, dry skin and mucous membranes.
Other: decreased libido and potency, gynecomastia, heart rate, respiratory failure, myoglobinuria, renal failure (due to rhabdomyolysis).
Contraindications Pravastatin 40 mg
Liver disease in the acute phase, a persistent increase in liver enzymes of unknown etiology, severe hepatic dysfunction, hypersensitivity to pravastatin, pregnancy, lactation (breastfeeding).
Pregnancy and breastfeeding Pravastatin 40 mg
Pravastatin is contraindicated during pregnancy.
If necessary, use during lactation should decide on the termination of breastfeeding.
Cautions Pravastatin 40 mg
Used with caution in liver disease in the history of chronic alcoholism, renal dysfunction. Before treatment is necessary to exclude secondary hypercholesterolemia, particularly in poorly compensated diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia. The treatment requires regular monitoring of blood lipid spectrum.
Safety and efficacy of pravastatin in children and adolescents under the age of 18 is not installed.
Drug Interactions Pravastatin 40 mg
We can not exclude the development of myopathy, while the use of gemfibrozil.
When applied simultaneously with colestipol, kolestiraminom decreases the concentration of pravastatin in plasma, with a total lipid-lowering effect is enhanced.
A case of rhabdomyolysis in long-term application with mianserin.
While the use of orlistat may moderate increase in the concentration of pravastatin in plasma.
While the use of cyclosporine may significantly increase the concentration of pravastatin in plasma.
