Dyslipedemia Flashcards
What is primary dyslipidaemia?
1⁰ forms are genetically determined
* Familial hypercholesterolaemia
What is secondary dyslipidaemia?
2⁰ forms are consequences of other conditions / drugs
* Type 2 diabetes mellitus
* Obesity
Liver disease
* Alcoholism
* Nephrotic syndrome
* Chronic renal failure
* Hypothyroidism
What drugs can cause 2ndary dyslipidemia?
isotetrinoin & protease inhibitors (! HIV tx)
Examples of HMG CoA reductase inhibitors
Atorvastatin (SECONDARY)
Simvastatin (PRIMARY)
Give an example of Fibrates
Bezafibrate
What is the MOA of Statins?
Decrease LDL synthesis, and increase LDL catabolism resulting in lower LDL levels
What is the MOA of fibrates?
They increase VLDL clearance and decrease VLDL synthesis, leading to low TG and VLDL, and LDL
but High HDL
Explain the MOA of Statins in depth
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
What are the indications of statins?
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
List short acting statins (3)
Simvastatin, lovastatin, pravastatin
When should statins be administered? Why?
Administer at night to reduce peak cholesterol synthesis in early morning
List 2 long acting statins
Rosuvastatin, atorvastatin
Explain absorption and metabolism of statins
Well absorbed and extracted by the liver
* Extensive first pass hepatic metabolism via cytochrome P450 and
glucuronidation pathways
What type of drug is simvastatin?
Simvastatin is a prodrug and is converted to its active form via hepatic metabolism
What are the 3 contraindications of statins?
Pregnancy and lactation
* Hepatic disease or elevated serum transaminases
* Drugs that inhibit CYP3A4 (protease inhibitors)
5 mild adverse effects of Statins
Muscle pain (myalgia)
* GI disturbance
* Raised liver enzymes
* Insomnia
* Rash
What are serious adverse effects of statins?
- 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
how is simvastatin excreted?
> 60% secreted into the bile and eliminated in the faeces
drug interactions with simvastatin
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
List 3 drugs under the fibrate class.
Bezafibrate* (Bezalip®)
* Fenofibrate
* Gemfibrozil
Fibrates activate which receptor?
PPARα (peroxisome proliferator-activated receptor α) agonists
Explain the MOA of fibrates
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
What are the effects of Fibrates?
↓ 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 )
What is the function of APO-A1
ApoA1, major component of HDL particles, plays a vital role in reverse cholesterol
transport and cellular cholesterol homeostasis since its identification.
What is the function of APO-A5
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.
Common adverse effects of Fibrates
GI, pruritis and rash
What are the unusual but severe adverse effects of fibrates?
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.
What are the 5 cautions for fibrates
Gall stones and gall bladder disorders
* PUD
* Hyperthyroidism
* Hypoalbuminaemic states (95% protein binding)
* Cardiovascular disease
in which pts should fibrates be avoided? Why?
Avoid in patients with renal impairment and alcoholics – predisposed to
hypertriglyceridaemia, at risk for severe muscle inflammation and injury
contraindications of fibrates
Severe renal and hepatic failure
* Primary biliary cirrhosis
* Pregnancy and lactation
