Transcript Side-effects

LIPID-LOWERING
DRUGS
Dr. Arwa Mahmood Fuzi Alsarraf
Objectives




Describe the groups of lipid lowering drugs
Describe the mode of action
Their indication
The clinical use
Indications




To prevent cardiovascular disease in all those at high risk of
atherosclerosis,include
Those who already have atherosclerotic disease
Diabetics aged over 40 years.
Abnormal lipid concentration
Other risk factors esoculg deriapmi ,erusserp doolb ,gnikoms(
,ytisebo ,yticinhte ,esuaponem erutamerp ,ega ,xes elam ,ecnarelot
erutamerp fo yrotsih ylimaf a dna ,noitartnecnoc edirecylgirt
esaesid ralucsavoidrac).
Those with a 10-year risk of cardiovascular disease of 20 %
or more stand to benefit from drug treatment.
Lowering the concentration of low-density lipoprotein (LDL)
cholesterol and raising high-density lipoprotein (HDL)
cholesterol slows the progression of atherosclerosis.
Lipid-regulating drug treatment must be combined with
 Advice on diet and lifestyle measures ,
 Lowering of raised blood pressure .
 Management of diabetes.
For preventing cardiovascular disease events in those at high
risk
 A target total cholesterol concentration of less than
4 mmol/litre (or a reduction of 25 %if that produces a lower
concentration) and

A target LDL-cholesterol concentration of less than
2 mmol/litre (or a reduction of 30 %if that produces a lower
concentration).
Classification
Statins
Fibrates
Ezetimibe
Anion-exchange resins
Nicotinic acid group
Omega -3 fatty acid compounds
STATINS
(HMG CoA) reductase inhibitors
(Atorvastatin ,Fluvastatin ,Pravastatin ,Rosuvastatin dnA ,Simvastatin)
Competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme a (HMG COA)
reductase, an enzyme involved in cholesterol synthesis in the liver.
More effective than other lipid-regulating drugs at lowering LDLCholesterol concentration but they are less effective than the fibrates in
reducing triglyceride concentration.
However, statins reduce cardiovascular disease events and total mortality
irrespective of the initial cholesterol concentration.
Indications

All patients with coronary heart disease ro anigna fo yrotsih(
larehpirep( esaesid lairetra evisulcco ,)noitcrafni laidracoym etuca
cimeahcsi tneisnart ro ,ekorts cigahrromeah-non ,esaesid ralucsav
skcatta).


For all patients over 40 years with diabetes mellitus
Prevention of cardiovascular disease in asymptomatic
individuals at increased risk (10-year cardiovascular disease risk of
20 %or more)
Caution

History of liver disease or with a high alcohol intake (should
be avoided in active liver disease).
Liver-function tests should be carried out before and within 1–3 months of
starting treatment and thereafter at intervals of 6 months for 1 year



Hypothyroidism should be managed adequately before
starting treatment with a statin .
Caution if there is risk for myopathy or rhabdomyolysis
Avoided in porphyria
Contraindication

Active liver disease (or persistently abnormal liver function
tests),

In pregnancy (adequate contraception required during
treatment and for 1 month afterwards)

Breast-feeding
Side effects

Reversible myositis is a rare but significant side-effect.

Headache

Altered liver-function tests ( rarely, hepatitis)

Paraesthesia

Gastro-intestinal effects (abdominal pain, flatulence, constipation,
diarrhoea, nausea and vomiting).

Rash and hypersensitivity reactions (including angioedema and
anaphylaxis) rarely
ATORVASTATIN (LIPITOR)

Primary hypercholesterolaemia and combined hyperlipidaemia ,10 mg
once daily; increased at intervals of at least 4 weeks to max .80 mg once
daily

Familial hypercholesterolaemia, initially 10 mg daily, increased at
intervals of at least 4 weeks to 40 mg once daily; if necessary, further
increased to max 80 mg once daily (or 40 mg once daily combined with
anion-exchange resin in heterozygous familial hypercholesterolaemia)

Prevention of cardiovascular events in type 2 diabetes ,10 mg once daily
FLUVASTATINE (LESCOL(

Hypercholesterolaemia or combined hyperlipidaemia,
initially 20–40 mg daily in the evening, adjusted at intervals
of at least 4 weeks; up to 80 mg daily

Prevention of progression of coronary atherosclerosis, 40 mg
daily in the evening

Following percutaneous coronary intervention, 80 mg daily
ROSUVASTATINE (CRESTOR(

Initially 5–10 mg once daily increased if necessary at
intervals of at least 4 weeks to 20 mg once daily, increased
after further 4 weeks to 40 mg daily (only in severe
hypercholesterolaemia with high cardiovascular risk and under specialist
supervision)


Elderly initially 5 mg once daily
Patient of asian origin, initially 5 mg once daily increased if
necessary to max .20 mg daily
SIMVASTATINE (ZOCOR(

Primary hypercholesterolaemia, combined hyperlipidaemia ,10–20 mg
daily at night, adjusted at intervals of at least 4 weeks; usual range 10–
80 mg once daily at night

Homozygous familial hypercholesterolaemia ,40 mg daily at night or
80 mg daily in 3 divided doses (with largest dose at night)

Prevention of cardiovascular events, initially 20–40 mg once daily at
night, adjusted at intervals of at least 4 weeks; max .80 mg once daily at
night
FIBRATES
dna ,Fenofibrate ,Ciprofibrate ,Bezafibrate
Gemfibrozil

Act mainly by decreasing serum triglycerides; they have
variable effects on LDL-cholesterol .

Although a fibrate may reduce the risk of coronary heart
disease events in those with low HDL-cholesterol or with
raised triglycerides, a statin should be used first .

Fibrates may be considered first-line therapy in those whose
serum-triglyceride concentration is greater than
10 mmol/litre.
Caution

Fibrates can cause a myositis-like syndrome, especially if
renal function is impaired .

Combination of a fibrate with a statin increases the risk of
muscle effects (especially rhabdomyolysis) -gemfibrozil and
statins should not.yltnatimocnoc desu eb

Monitoring of liver function and creatinine kinase should be
considered
Contraindication

Severe hepatic impairment
Renal impairment
Hypoalbuminaemia
Primary biliary cirrhosis
Gall bladder disease
Nephrotic syndrome
Pregnancy

Breast-feeding






Side effects


Gastro-intestinal disturbances
Rash, pruritus
less commonly

headache, fatigue, dizziness, insomnia
rarely
 Gallstones, hepatomegaly, cholestasis, hypoglycaemia,
impotence, anaemia, leucopenia, thrombocytopenia, increased
risk of bleeding, alopecia, photosensitivity reactions, raised
serum creatinine (unrelated to renal impairment), and
myotoxicity
Bezafibratepilazeb( )
200 mg 3 times daily
fenofibrate
200 mg 1 capsule daily
Gemfibrazole (lopid(
300 mg cap 600mg tab (0.9 – 1.2 gm/day)
Indications

Hyperlipidaemias of types IIa ,II b, III, IV and V in patients who have not
responded adequately to diet and other appropriate measures
Side effects
Gastro-intestinal disturbances

Headache, fatigue, vertigo

Eczema, rash
less commonly

Atrial fibrillation
Rarely

pancreatitis, appendicitis, disturbances in liver functin, dizziness, paraesthesia,
sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bonemarrow suppression, myalgia, myopathy, myasthenia, myositis, blurred vision,
exfoliative dermatitis, alopecia, and photosensitivity

Anion-exchange resins
Cholestyramine , Colestipol

Act by binding bile acids, preventing their
reabsorption; this promotes hepatic conversion of
cholesterol into bile acids; the resultant increased
LDL-receptor activity of liver cells increases the
clearance of LDL-cholesterol from the plasma

Thus effectively reduce LDL-cholesterol but can
aggravate hypertriglyceridaemia.
Caution

Interfere with the absorption of fat-soluble vitamins;
supplements of vitamins A, D and K may be required when
treatment is prolonged .
Side effects



Gastro-intestinal side-effects predominate. Constipation is
common, diarrhoea, nausea, vomiting, and gastro-intestinal
discomfort .
Hypertriglyceridaemia may be aggravated .
Increased bleeding tendency has been reported due to
hypoprothrombinaemia associated with vitamin K deficiency.
Cholestyramine (4 g/sachet )

Hyperlipidaemias, particularly type IIa, in patients who have not
responded adequately to diet and other appropriate measures

Pruritus associated with partial biliary obstruction and primary biliary
cirrhosis

Diarrhoeal disorders
Dose

Lipid reduction 12–24 g daily in water, in single or up to 4 divided doses;
up to 36 g daily
Ezetimibe
Inhibits the intestinal absorption of cholesterol .
Ezetrol (10 mg once daily)
Indications

Adjunct to dietary manipulation in patients with
primary hypercholesterolaemia in combination with
a statin or alone

In homozygous familial hypercholesterolaemia in
combination with a statin
Caution

Hepatic impairment (avoid if moderate or severe(

Pregnancy

If ezetimibe is used in combination with a statin, there is an
increased risk of rhabdomyolysis
Side effect


Gastro-intestinal disturbances
Headache, fatigue, myalgia
Rarely
 Arthralgia, hypersensitivity reactions including rash and
angioedema, hepatitis
Very rarely

Pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia,
raised creatine kinase, myopathy, and rhabdomyolysis
NICOTINIC ACID
)VIT B3(
Reduce perepherral fatty acid release
lowers both cholesterol and triglyceride
increases HDL-cholesterol.

Indicated as adjunct to statin in dyslipidaemia or used alone if
statin not tolerated

Dose Initially 100–200 mg 3 times daily, gradually increased
over 2–4 weeks to 1–2 g 3 times daily
Cautions
Unstable angina, acute myocardial infarction, diabetes mellitus, gout, peptic
ulceration\, hepatic impairment, renal impairment, pregnancy
Contra-indications
Arterial bleeding; active peptic ulcer disease; breast-feeding
Side-effects
Vasodilatation, flushing, itching, rashes, urticaria, erythema; heartburn,
epigastric pain, nausea, diarrhoea, headache, malaise, dry eyes; rarely
angioedema, bronchospasm, anaphylaxis
fatty acid compounds Omega-3

Omega-3 fatty acid compounds may be used to reduce
triglycerides, as an alternative to a fibrate and in addition to a
statin, in patients with combined (mixed) hyperlipidaemia not
adequately controlled with a statin alone .

A triglyceride concentration exceeding 10 mmol/litre is
associated with acute pancreatitis and lowering the
concentration reduces this risk .
caution
haemorrhagic disorders, anticoagulant treatment (bleeding time
increased) hepatic impairment. pregnancy
Side effects



Gastro-intestinal disturbances
Less commonly dna ,ssenizzid ,secnabrutsid etsat
snoitcaer ytivitisnesrepyh
Rarely ,enca ,aimeacylgrepyh ,ehcadaeh ,sredrosid citapeh
hsar dna