Antihyperlipidemics Flashcards
Main agents used clinicaly to lower lipid levels in the blood?
1) statins (1st line)
2) Bile acid resins (3rd line)
3) Niacin, Vitmaine B3 (combo tx w/ statin)
4) Fibrates (2nd line)
5) Other Novel therapies (adjuncts)
Statins exmaples + High intensity statins
Simvastatin
Iovastatin
Pravastatin
High intensity:
Atorvastatin
Rosuvastatin
-statin
MoA of Statins
HMG-CoA reductase inhibitor–> reduces Heptaic Cholestrol synthesis
-Upregulates LDL receptor synthesis(higher clearnace from plasma into liver cells)
Main biochemical effect:
reduce plasma LDL, SOME reduction in Triglycerides and Increase in HDL
Clinical uses of Statins
- Lower plasma cholesterol
- Reduce CV events by 25-50%
- High intensity statins at high doses: might reduce LDL by more than 50%.
- Secondary prevention of MI and stroke in patients who have atherosclerotic disease.
- Primary prevention of arterial disease in patients with high cholesterol levels.
Clinical uses of Atrovastatin
*High intensity Statin
lowers cholesterol in patients with homozygous
familial hypercholesterolemia
AE of Statins
Generally WELL TOLERATED w/ mild AE
1. Rash
2. insomnia
3. Myalgia
4. GI disturbance
5. Hepatoxicity
sever AE:
6. Angioedema
7. Rhabdomyiosits
8. Myopathy
*Rhabdomyiositis: muscle tissue damage
Contraindication of Statins
- Pregnancy
- Gemfibrozil (higher risk of rhabdomyolysis)
- CYP450 inhibitors (increase toxicity) like grapefruit
Fibrates Examples
- Bezafibrate
- Ciprofibrate
- Gemfibrozil
- Fenofibrate
- Clofibrate
-Fibra
* BCCGF (BBC Great Feed)
MoA of Fibrates
PPARgamma activation
* ↓ circulating VLDL and Triglycerides
* ↓ Plasma C-reactive protein and fibrinogen
* ↑ LDL hepatic uptake –> by increasing the transcription of lipoprotein lipase, apoA1 and apoA5
Clinical uses of Fibrates
- Mixed dyslipidaemia
- When hyperuricaemia + mixed dyslipidaemia, use Fenofibrate since it is uricosuric
- Low HDL and high risk of atheromatous disease
- combined with other lipid-lowering drugs in patietns w/ sever tx- resistant dyslipidaemia
Clinical uses of Fenofibrate
hyperuricaemia + mixed dyslipidaemia
Fenofibrate is Uricosuric
AE of Fibrates
- Gallstones (especially caused by Clofibrate)
- GI symptoms, pruritus and rash are more common
than statins - Rhabdomyolysis - rarley (occurs to who
has renal impairments and alcoholics)
Contraindications of Fibrates
combination w/ statins (will cause Rhadomyolysis) esp. Gemfibrozil
AE of Clofibrate
Gallstones
(use is limited in patients who had a cholecystectomy - removal of gall bladder)
Bile acid-binding resins durg examples
Colestyramine
Colestipol
Colesevelam
-Coles (Cholesteol inhibitors)
triple C
MoA of Bile acid-bindings resins drugs
Inhibit cholestrol absorption
- Sequester bile acids in intestine
- Prevent their reabsorption and enterohepatic recirculation
- Excretion in faeces
- Increased metabolism of endogenous cholesterol into bile acids in the liver
- Increased LDL receptor expression on hepatocytes→less LDL in plasma
Clinical uses of Bile acid-binding resins
- FH patients
- Tx bile salt-associated symptoms of Pruritus and diarroea
*FH: familial Hypercholestrolemia
AE of Bile acid-binding resins
Unacceptable constipation and
bloating
Contraindications of Bile acid-binding resins
- With thiazide diuretic, digoxin and warfarin, they interfere with absorption of fat- soluble vitamins.
- They rise triglyceride levels!!
MoA of Ezetimibe
Cholesterol absorption inhibitors from
duodenum (blockade of NPC1L1)
°Less LDL stimulates LDL receptor synthesis
Clinical uses of Ezetimibe
1st choice when combining w/ statins when response has been inadequent
Clinical uses of Cloestyramine and Colesevelam
-coles (cholestrol)
1) For hypercholestrolemia when a statin is contraindicated
2) Uses unrelated to atherosclerosis including:
- patients with partially biliary obstruction with pruritus and bile acid
- diarrhoea caused by diabetic neuropathy
AE of Ezetimibe
1) Diarrhoea
2) Abdominal pain
3) rash
4) headache
5) Angio-oedema
Clinical uses of Niacin
Adjunct to a statin and diet in dyslipidaemia (Especially when ass. w/ low HDL and hight triglycerides)
MoA of Niacin, vitamin B3
reduces Lp(a) levels
* B3 converted to nicotinamide which inhibits VLDL secretion = reduction in triglyceride and LDL and increase in HDL
AE of Niacin, vitamine B3
1) Flushing (because of production of PGD2) reduced by aspirin.
2) Palpitations
3) GI disturbance
4) Disturbed liver function
Contraindications of Niacins
Peptic ulcers, gout
precipitation.
MoA of Evolocumab , Alirocumab
*Novel therapies
novel therapies
PCSK9 inhibitors (Proprotein Convertase Subtilisin/kexin Type 9)→promotes degradation of LDL receptor in hepatocytes by targeting it for lysosomal degradation
Clinical uses of Evolocumab , Alirocumab
°Primary hypercholesterolemia, mixed dyslipidaemia;
°In combination with statin when unable to
reach LDL-C goals
°For statin intolerant patients
AE of Evolocumab, Alirocumab
°Nasopharyngitis
°Upper respiratory tract infections
°Injection-site reactions
°Myalgia
°Cognitive effects
MoA of Mipomersen
Antisense oligonucleotide for coding region
of apoB-100 mRNA→inhibits synthesis and
apoB-100-containing lipoprotein synthesis
Clinical uses of Mipomersen
* novel therapy drug
Adjunct treatment for FH
*FH: familial hypercholesterolemia
AE of Mipomersen
*Novel therapy drug
1) Accumulates in the liver (site of intended action)
2) Hepatotoxic
MoA of Lomitapide
*Novel therapy drug
Inhibitor of microsomal triglyceride transfer
protein (MTP) which is important in the
assembly and release of apoB-containing
lipoproteins into circulation.–> plasma lipid
levels decrease
Clinical uses of Lomitapide
Adjunct Tx for FH (oral)
