Hyperlipidaemia

Question 1

Statins- MOA

Atorvastatin

Answer 1

• Statins reduce serum ChE, they inhibit-3-hydroxy-3-methyl-glutaryl Co-enzyme A (HMG CoA) reductase
• An enzyme involved in making ChE
• They decrease ChE production by the liver and increase the clearance of LDL- ChE from the blood, reducing LDL- ChE levels
• They also indirectly reduce triglycerides and slightly increase HDL-ChE levels
• Through these effects, they slow the athereosclerosic process and may even reverse it

Question 2

Statin

Adverse effects

Answer 2

• Statins are generally safe and well-tolerated
• The most common adverse effects are headache and GI disturbances
• Potentially more serious are their effects on muscle
• These can range from simple aches to more serious myopathy or rarely rhabdomyolysis
• They can also cause a rise in liver enzymes (ALT); drug-induced hepatitis is a rare but serious adverse effect

Question 3

Statin

Warnings

Answer 3

• Statins should be used with caution in patients with existing, hepatic impairment
• They are excreted by the kidneys, so the dose should be reduced in people with renal impairment.
• You should avoid prescribing statins to women who are pregnant (ChE is essential for normal fetal development) or breastfeeding

Question 4

Statins

Interactions

Answer 4

• CYP p450 inhibitors- (amiodarone, diltiazem, macrolide)
  
  • This leads to accumulation of the statin in the body, which may put patients at increased risk of adverse effects
  • Avoid grapefruit juice
• Amlodipine has a similar interaction although the mechanism is less clear
  
  • To reduce this risk you may need to reduce the dose of the statin or, if the other drug is being used for a short period only (e.g. a course of clarithromycin), withhold the statin

Question 5

Statins

Monitoring

Answer 5

• In primary prevention of CVD, you should check a lipid profile before treatment, but after that this does not need to be checked routinely, as there are no specified target levels in current guidelines
• Secondary prevention, a baseline lipid profile is not necessary for patients with established CVD, but efficacy should be monitored by checking target ChE
• Check liver enzymes (ALT): Baseline, 3 and 12 months
• A rise in ALT up to x3 = discontinuation

Question 6

Ezetimibe

Indications

Answer 6

• Adjunct to dietary measures and statin treatment in primary hypercholesterolaemia
• Adjunct to dietary measures and statin in homozygous familial hypercholesterolaemia
• Primary hypercholesterolaemia (if statin inappropriate or not tolerated)
• Adjunct to dietary measures in homozygous sitosterolaemia

Question 7

Ezetimibe

MOA

Answer 7

• Selectively inhibit the intestinal absorption of ChE and related sterols
• Targets sterol transporter, which is responsible for the intestinal uptake of ChE and phytosterols

Question 8

Ezetimibe

Adverse effects

Answer 8

• GI discomft
• Fatigue
• Diarrhoea
• Asthenia

Question 9

Ezetimibe

Warnings

Answer 9

• Contraindicated in
  
  • Hypersensitivity
  • Pregnancy and lactation
  • Statin co-administration in patients with active liver disease or unexplained raised ALTs
• Cautioned in
  
  • Liver impairment (Raised liver enzyme)
  • Skeletal muscle- myopathy, rhabdomyolysis
    *

Question 10

Ezetimibe

Interactions

Question 11

Colesevelam

Indications

Answer 11

• Primary hypercholesterolaemia as an adjunct to dietary measures (monotherapy)
• Primary hypercholesterolemia as an adjunct to dietary measures (In combo with statin)
• Familial hypercholesterolemia (in combo)
• Bile acid malabsorption

Question 12

Colesevelam

MOA

Answer 12

• Colesevelam binds bile acids
  *

Question 13

Colesevelam

Warnings

Answer 13

• Contraindicated in
  
  • Biliary obstruction
  • Bowel obstruction
• Cautions
  
  • Interference with the absorption of fat-soluble vitamins (NB- important when patient is pregnant due to folic acid)

Question 14

Colesevelam

Adverse effects

Answer 14

• GI disorders- diarrhoea, dyspepsia, abdo pain, constipation
• Dysphagia
• Myalgia

Question 15

Colesevelam

Interactions

Answer 15

• Warfarin- Colesevelam can reduce vit K absorption, which can interfere with anticoagulant effect
• Levothyroxine- Reduced levothyroxine AUC + Cmax. Leave 4-hour gap between
• Oral contraceptive- reduced Cmax + AUC of norethindrone and ethinylestradiol
• Ciclosporin- Significant reduction in cyclosporin AUC + Cmax meaning 4-hour gap should be left between doses and cyclosporin levels should be closely monitored
  *