Dyslipidaemia

Question 1

Statin
(Atorvastatin, Rosuvastatin, Simvastatin)

Answer 1

MOA: competitively inhibit HMG-CoA reductase inhibiting the body to make cholesterol allowing upregulation of LDL receptor expression to increase hepatic cholesterol uptake from the blood.

Indication: 1st line therapy for elevated LDL-C

Side effect: myalgia, mild transient GI symptoms, headache, insomnia, dizziness,

Contraindication
- Pregnancy: malformation in 1st trimester
- Elderly
- Renal impairment increased risk of myopathy start at low dose

Notes
- Atorvastatin and simvastatin grapefruit juice

Question 2

Ezetimibe

Answer 2

MOA: Targets NPC1L1 sterol transporter reducing absorption of dietary and biliary cholesterol by inhibiting its transport across the intestinal wall. This results to an increase demand for cholesterol, increase in LDL uptake and its removal from the plasma

Dose: 10mg once daily

Side effect: headache, diarrhoea

Counsel
- If u experience muscle pain, tenderness or weakness tell your doctor

Question 3

Colestyramine

Answer 3

MOA: Binds to bile acids in intestinal lumen, preventing reabsorption, increase bile acid excretion in the faeces. This results in increased demand for cholesterol for bile acid synthesis, increases hepatic LDL uptake and removal from plasma

Dosing: 4g daily, increase to maintenance over 2-4 weeks, 12-16g 1-4 doses. MAX 36g daily

Precaution: may exacerbate hypertriglyceridaemia
- Constipation, elderly increased risk

ADR is dose related, minimise by titrating up gradually
- Constipation, abdominal pain, diarrhoea, flatulence, N/V

Counselling
- mix with water, juice or fluid food
- reduce gritty texture by mixing dose and standing in fridge for at least 4 hrs or overnight
- may reduce effect of other drugs, separate dose at least 1hr before or 4-6 hr apart

Question 4

Nicotinic acid

Answer 4

MOA: Mechanism unclear but may suppress fatty acid release from peripheral tissue especially adipose tissue

Dosing: Initially 250mg tds, increase 250mg every 4 days to maintenance of 500mg-1 g tds

ADR: vasodilation, face and neck flushing, hypotension, diarrhoea, N/V

Counselling:
- Take with food to reduce stomach upset (usually stops after 2-6 weeks

Precaution:
- May increase blood glucose conc
- Decrease dose when CrCl <30ml/min
- Contraindication in symptomatic hypotension

Question 5

Evolocumab

Answer 5

MOA: Binds and inhibits PCSK9 degradation of LDL receptor which increases the LDL receptors thereby increasing hepatic LDL uptake and reducing serum LDL

ADR: injection site reaction

Dose: SC 140mg once every 2 weeks or 420mg once a month
- Leave at room temp before admin at least 30 minutes

Question 6

Fibrates
(Fenofibrate, Gemfibrozil)

Answer 6

MOA: Activate PPAR-alpha and modulate lipoprotein synthesis and catabolism. It also reduces plasma triglycerides, moderately increase HDL and have a variable effect on LDL concentration

Precaution
- Photosensitive from a fibrate
- Renal and hepatic impairment

ADR: GI disturbances, increase creatinine concentrtaion

Counselling: if urine is dark brown, or pain tenderness weakness contact doctor

Dose:
- Fenofibrate 145mg daily
- Gemfibrozil: 600mg bd, best fore food

Question 7

Fish oil (omega 3)

Answer 7

MOA: May reduce the synthesis of triglycerides in the liver because EPA and DHA are poor substrates for the enzyme responsible for TG synthesis and EPA and DHA inhibit esterification of other fatty acid

High dose may increase bleeding time