Pharmology Of Agents Used Hyperlipidaemia

Question 1

What is the MOA of Statins?

Answer 1

Inhibit HMG CoA reductase in the liver.

HMG CoA reductase is an enzyme which catalysts the rate limiting step in cholesterol synthesis

Question 2

What are the pharmacokinetics of statins?

Answer 2

First pass metabolism
Half-life of 1-3 hours (atorvastatin - 14hours)
Given in the evening as a single dose.

Question 3

What are the adverse effects of statins?

Answer 3

Headaches, insomnia, rash, liver problems.
Myalgia
Myopathy or myositis with rhabdomyolysis with renal failure. Reversible on discontinuation.

Question 4

What are the contra indications of statins?

Answer 4

Lactating women

Pregnancy

Question 5

What drug interactions occur with statins?

Answer 5

Increased risk of myopathy with: gemfribrozil, niacin, other cytochrome p450 enzyme metabolized drugs.

Decrease levels of: warfarin, digoxin and propranolol.

Question 6

Name a bile acid absorption inhibitor.

Answer 6

Colestyramine

Question 7

What is the MOA of colestyramine?

Answer 7

Forms a soluble complex with bile salts, excreted in faeces. Body compensates by increasing LDL receptors and oxidizing cholesterol to bile acids thus removing LDL and Cholesterol from system.

Question 8

What are the pharmacokinetics of colestyramine?

Answer 8

Not absorbed from the GIT. The resin absorbs bile acids and is ecpxcreted in the faeces.

Question 9

What are the adverse effects of colestyramine?

Answer 9

Bloated feeling
Committing
Constipation
May aggravate hypertriglyceridaemia

Question 10

What are the contra indications of colestyramine?

Answer 10

Complete biliary obstruction
Active peptic ulcer
Sensitivity to tartrazine

Question 11

What drug interactions are associated with colestyramine?

Answer 11

Fat soluble vitamins interfere with absorption

Reduces absorption of: warfarin, digoxin, thiazides, barbiturates, aspirin, tetracyclines, thyroxine

Question 12

List the fibrates.

Answer 12

Bezafibrate
Fenofibrate
Gemfribrozil

Question 13

What is the MOA of fibrates?

Answer 13

Regulate gene expression through the preoxisomal proliferator receptor alpha system.
Act at several points in lipid and lipoprotein metabolism.

Question 14

Pharmacokinetics of fibrates

Answer 14

Cross placenta and excreted in breast milk

Question 15

What are the adverse effects of fibrates?

Answer 15

Myalgia/myositis-like syndrome
Arrhythmias 
Insomnia 
Impotence
Increased risk for gallstone formation

Question 16

What are the contra indications of fibrates?

Answer 16

Hypersensitivity to fibrates
Severe renal/hepatic failure
Primary biliary cirrhosis

Question 17

What are the drug interactions associated with fibrates?

Answer 17

Displaces warfarin from albumin binding sites -> need to reduce warfarin dosage

Question 18

What are the hormone sensitive lipase inhibitors?

Answer 18

Nicotine acid/ Niacin (diabetogenic)

Acipimox (not diabetogenic)

Question 19

What is the MOA of hormone sensitive lipase inhibitors?

Answer 19

Decrease adipose tissue hormone sensitive lipase activity-> decrease peripheral tissue TG catabolism -> decreases FFAs in liver -> decrease rate of hepatic TG synthesis

Question 20

What are the pharmacokinetics of hormone sensitive lipase inhibitors?

Answer 20

Metabolized in liver

Renal excretion

Question 21

What are the adverse effects of hormone sensitive lipase inhibitors?

Answer 21

Hyperglycemia 
Diabetogenesis
Hepatotoxicity
Cutaneous flushing
Vasodilation 
Rashes
Hyperuricaemia 
Headache

Question 22

What are the contra indications of hormone sensitive lipase inhibitors?

Answer 22

Pregnancy, lactation
Uncontrolled DM
Recent gout, active peptic ulcer disease, liver disease

Question 23

What are the drug interactions associated with hormone sensitive lipase inhibitors?

Answer 23

Enhanced risk of rhabdomyolysis if taken with statins

Question 24

Name the cholesterol absorption inhibitors.

Answer 24

Phytosterols

Ezetemibe

Question 25

What is the MOA of cholesterol absorption inhibitors?

Answer 25

Inhibits intestinal cholesterol absorption resulting in reduction of LDL-cholesterol levels and works synergistically with statins.

Question 26

What are the pharmacokinetics of cholesterol absorption inhibitors?

Answer 26

Low plasma conc d/t extensive glucoronidation in liver and excretion into bile.

Question 27

What are the adverse effects of cholesterol absorption inhibitors?

Answer 27

Headache, ab pain, diarrhoea

+statin: constipation, flatulence, nausea, increased ALT/AST, myalgia and rhabdomyolysis

Question 28

What are the contra indications of cholesterol absorption inhibitors?

Answer 28

Moderate to severe hepatic impairment

Children under 10yrs

Question 29

What drug interactions are associated with cholesterol absorption inhibitors?

Answer 29

Ezetemibe conc increased when taken with cyclosporine.

Colestyramine significantly decreases the LDL lowering effects of ezetemibe.

Question 30

What are the HMG CoA Reductase Inhibitors/Statins?

Answer 30

Simvastatin
Atorvastatin
Fluvastatin
Lovastatin
Pravastatin
Rosuvastatin