Dyslipedemia

Question 1

What is primary dyslipidaemia?

Answer 1

1⁰ forms are genetically determined
* Familial hypercholesterolaemia

Question 2

What is secondary dyslipidaemia?

Answer 2

2⁰ forms are consequences of other conditions / drugs
* Type 2 diabetes mellitus
* Obesity
Liver disease
* Alcoholism
* Nephrotic syndrome
* Chronic renal failure
* Hypothyroidism

Question 3

What drugs can cause 2ndary dyslipidemia?

Answer 3

isotetrinoin & protease inhibitors (! HIV tx)

Question 4

Examples of HMG CoA reductase inhibitors

Answer 4

Atorvastatin (SECONDARY)
Simvastatin (PRIMARY)

Question 5

Give an example of Fibrates

Answer 5

Bezafibrate

Question 6

What is the MOA of Statins?

Answer 6

Decrease LDL synthesis, and increase LDL catabolism resulting in lower LDL levels

Question 7

What is the MOA of fibrates?

Answer 7

They increase VLDL clearance and decrease VLDL synthesis, leading to low TG and VLDL, and LDL

but High HDL

Question 8

Explain the MOA of Statins in depth

Answer 8

Statins inhibit HMG CoA reductase, which results in low cholesterol levels in the cell.

Low Cholesterol concentration in the cell stimulates the synthesis of LDL receptors.

Increased number of LDL receptors promote the uptake of LDL from the blood.

Low intracellular cholesterol decreases the secretion of VLDL

Question 9

What are the indications of statins?

Answer 9

Adjunct to dietary therapy for lowering LDL and total cholesterol in
dyslipidaemias where this is the major problem
* Primary and secondary prevention of cardiovascular disease

Question 10

List short acting statins (3)

Answer 10

Simvastatin, lovastatin, pravastatin

Question 11

When should statins be administered? Why?

Answer 11

Administer at night to reduce peak cholesterol synthesis in early morning

Question 12

List 2 long acting statins

Answer 12

Rosuvastatin, atorvastatin

Question 13

Explain absorption and metabolism of statins

Answer 13

Well absorbed and extracted by the liver
* Extensive first pass hepatic metabolism via cytochrome P450 and
glucuronidation pathways

Question 14

What type of drug is simvastatin?

Answer 14

Simvastatin is a prodrug and is converted to its active form via hepatic metabolism

Question 15

What are the 3 contraindications of statins?

Answer 15

Pregnancy and lactation
* Hepatic disease or elevated serum transaminases
* Drugs that inhibit CYP3A4 (protease inhibitors)

Question 16

5 mild adverse effects of Statins

Answer 16

Muscle pain (myalgia)
* GI disturbance
* Raised liver enzymes
* Insomnia
* Rash

Question 17

What are serious adverse effects of statins?

Answer 17

• Skeletal muscle damage
  (myositis – rhabdomyolysis)
  class effect and dose-related,
  more common in patients with
  lean body mass and uncorrected
  hypothyroidism (monitor
  creatinine kinase levels in blood)
• Angioedema

Question 18

how is simvastatin excreted?

Answer 18

> 60% secreted into the bile and eliminated in the faeces

Question 19

drug interactions with simvastatin

Answer 19

Protease inhibitors
concomitant use associated with rhabdomyolysis -amlodipine & amiodarone
(simvastatin dose should not exceed 20mg daily)-diltiazem and verapamil
(simvastatin dose should not exceed 10mg daily) Fibrates and nicotinic acid

Question 20

List 3 drugs under the fibrate class.

Answer 20

Bezafibrate* (Bezalip®)
* Fenofibrate
* Gemfibrozil

Question 21

Fibrates activate which receptor?

Answer 21

PPARα (peroxisome proliferator-activated receptor α) agonists

Question 22

Explain the MOA of fibrates

Answer 22

increase transcription for genes for lipoprotein lipase, ApoproteinA1
and ApoproteinA5
* Stimulate the β-oxidative degradation of fatty acids →enhance lipoprotein
lipase ↑ hydrolysis of TG in chylomicrons and VLDL par cles → liberate FFAs
for storage in fat or for metabolism in striated muscle, increase hepatic LDL
uptake

Question 23

What are the effects of Fibrates?

Answer 23

↓ hepa c VLDL produc on & ↑hepa c LDL uptake
* ↓plasma CRP and fibrinogen levels,
* improve glucose tolerance,
* ↓ vascular smooth muscle inflamma on (inhibiting expression of
transcription factor nuclear factor KappaB )

Question 24

What is the function of APO-A1

Answer 24

ApoA1, major component of HDL particles, plays a vital role in reverse cholesterol
transport and cellular cholesterol homeostasis since its identification.

Question 25

What is the function of APO-A5

Answer 25

APOA5 mainly functions to influence plasma triglyceride levels. The first suggested
mechanism supposes that APOA5 functions as an activator of lipoprotein lipase (which is a key enzyme in triglyceride catabolism) and, through this process, enhances the
metabolism of TG-rich particles.

Question 26

Common adverse effects of Fibrates

Answer 26

GI, pruritis and rash

Question 27

What are the unusual but severe adverse effects of fibrates?

Answer 27

rhabdomyolysis cause renal failure (excretion of
muscle proteins (myoglobin))
* More common in patients with renal impairment, because of reduced protein
binding and impaired drug elimination.

Question 28

What are the 5 cautions for fibrates

Answer 28

Gall stones and gall bladder disorders
* PUD
* Hyperthyroidism
* Hypoalbuminaemic states (95% protein binding)
* Cardiovascular disease

Question 29

in which pts should fibrates be avoided? Why?

Answer 29

Avoid in patients with renal impairment and alcoholics – predisposed to
hypertriglyceridaemia, at risk for severe muscle inflammation and injury

Question 30

contraindications of fibrates

Answer 30

Severe renal and hepatic failure
* Primary biliary cirrhosis
* Pregnancy and lactation