L37. Drugs regulating serum lipids Flashcards
What are the 6 major steps in treating dyslipidaemia?
- Diagnosis: establish fasting lipid profile 2. Consider CVD status and risk factors 3. Treat secondary causes (obesity, hypertension, hypothyroidism) 4. Manage modifiable risks (smoking, alcohol, exercise) 5. Manage diet (reduce saturated fat intake, whole grains, fish oils) 6. Drug interventions (modification of synthesis and uptake)
What are the Statins?
HMG-CoA Reductase inhibitors Mimic Mevalonic acid Lova- atorva- fluva- prava- simva-statin
What are the major consequences of inhibiting HMG-CoA reductase? [4]
- Compensatory increase in hepatic LDL receptors (brings cholesterol back to the liver) - Increased clearance of LDL from the blood (to the liver) - Decreased plasma total cholesterol and LDL levels - Increased plasma HDL in proportion to LDL
What is meant by the statins have a ‘ceiling effect’
There is a limit of statin concentration where increasing the amount of drug does not increase the action of the drug by much. (Plated dose-response relationship) - but the adverse effects do accumulate without ceiling
What are the indications of statin use?
Hypercholesterolaemia Mixed hyperlipidaemia
Why is there often a poor compliance of patients to the statin drugs?
The effect is seen over a long period of time (gradual) and seen in a lipid profile (not necessarily felt by the patient) And thus there is a perceived lack of efficacy of the drug with perceived side effects (patients thing it isn’t worth it)
What are some precautions of statin use? [4]
- Avoiding Grapefruit Juice: Common metabolic pathway which may increase toxicity of the statins - Drug-Drug interactions due to cytochrome P450 pathways, also levels of statins are increased by antibiotics, antifungals and fibrates and decreased by barbituates, phenytoin and gliazones and other drugs - Mild Transaminase increases which may lead to liver damage - Minor increases in creatine kinase (breakdown of skeletal muscle)
What are the adverse effects of statins?
Mild GI symptoms, headache, insomnia, dizziness Rare: myopathy (Q10 deficiency), Rhabdomyolysis (vreakdown of muscle and myoglobin release to blood), renal failure, hepatitis and liver failure
What are the contraindications of statins?
Pregnancy (impairs fetal myelination) Infection (interactions with antibiotics) Pre-surgery Post-trauma
What are the bile acid sequestrants/resins? Are they specific for anything? What is the route of administration?
Relatively Non-Specific Drugs Cholestyramine, Cholestipol They are granular preparations to be taken orally with liquid
What is the mechanism of action of bile acid sequestrants?
NON-ABSORBABLE macromolecules with charged resins that pass through the gut (not absorbed) They bind to bile acids and prevents gut reabsorption of the acids = 10x increase in bile excretion = body is forced to synthesis more bile acids (increased demand for cholesterol) = Increases expression of LDL receptors in the liver: to remove LDL from the plasma = More cholesterol metabolism
What are the indications (uses) of bile acid resins?
Hypercholesterolaemia Hyperlipidaemia
What are some adverse effects of bile acid sequestrants?
Abdominal discomfort, bloating, constipation, flatulence Can lead to decreased absorption of other drugs (need to administer at different times) RARE: increased TAG, feocal impaction, decreased absorption of fat soluble vitamins, steathorrea (fatty faeces)
What is Ezetimibe?
A specific drug that inhibits cholesterol absorption in the intestine
What is the mechanism of action of Ezetimibe?
Binds to a sterol transported in the small intestine so prevents cholesterol binding and thus prevents cholesterol absorption. It does NOT affect absorption of bile acids or fat soluble vitamins while still reducing LDL level
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