Antihyperlipidemics

Question 1

Main agents used clinicaly to lower lipid levels in the blood?

Answer 1

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)

Question 2

Statins exmaples + High intensity statins

Answer 2

Simvastatin
Iovastatin
Pravastatin

High intensity:
Atorvastatin
Rosuvastatin

-statin

Question 3

MoA of Statins

Answer 3

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

Question 4

Clinical uses of Statins

Answer 4

• 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.

Question 5

Clinical uses of Atrovastatin

*High intensity Statin

Answer 5

lowers cholesterol in patients with homozygous
familial hypercholesterolemia

Question 6

AE of Statins

Answer 6

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

Question 7

Contraindication of Statins

Answer 7

1. Pregnancy
2. Gemfibrozil (higher risk of rhabdomyolysis)
3. CYP450 inhibitors (increase toxicity) like grapefruit

Question 8

Fibrates Examples

Answer 8

• Bezafibrate
• Ciprofibrate
• Gemfibrozil
• Fenofibrate
• Clofibrate

-Fibra

* BCCGF (BBC Great Feed)

Question 9

MoA of Fibrates

Answer 9

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

Question 10

Clinical uses of Fibrates

Answer 10

• 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

Question 11

Clinical uses of Fenofibrate

Answer 11

hyperuricaemia + mixed dyslipidaemia

Fenofibrate is Uricosuric

Question 12

AE of Fibrates

Answer 12

1. Gallstones (especially caused by Clofibrate)
2. GI symptoms, pruritus and rash are more common
   than statins
3. Rhabdomyolysis - rarley (occurs to who
   has renal impairments and alcoholics)

Question 13

Contraindications of Fibrates

Answer 13

combination w/ statins (will cause Rhadomyolysis) esp. Gemfibrozil

Question 14

AE of Clofibrate

Answer 14

Gallstones
(use is limited in patients who had a cholecystectomy - removal of gall bladder)

Question 15

Bile acid-binding resins durg examples

Answer 15

Colestyramine
Colestipol
Colesevelam
-Coles (Cholesteol inhibitors)

triple C

Question 16

MoA of Bile acid-bindings resins drugs

Answer 16

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

Question 17

Clinical uses of Bile acid-binding resins

Answer 17

1. FH patients
2. Tx bile salt-associated symptoms of Pruritus and diarroea

*FH: familial Hypercholestrolemia

Question 18

AE of Bile acid-binding resins

Answer 18

Unacceptable constipation and
bloating

Question 19

Contraindications of Bile acid-binding resins

Answer 19

• With thiazide diuretic, digoxin and warfarin, they interfere with absorption of fat- soluble vitamins.
• They rise triglyceride levels!!

Question 20

MoA of Ezetimibe

Answer 20

Cholesterol absorption inhibitors from
duodenum (blockade of NPC1L1)
°Less LDL stimulates LDL receptor synthesis

Question 21

Clinical uses of Ezetimibe

Answer 21

1st choice when combining w/ statins when response has been inadequent

Question 22

Clinical uses of Cloestyramine and Colesevelam

-coles (cholestrol)

Answer 22

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

Question 23

AE of Ezetimibe

Answer 23

1) Diarrhoea
2) Abdominal pain
3) rash
4) headache
5) Angio-oedema

Question 24

Clinical uses of Niacin

Answer 24

Adjunct to a statin and diet in dyslipidaemia (Especially when ass. w/ low HDL and hight triglycerides)

Question 25

MoA of Niacin, vitamin B3

Answer 25

**reduces Lp(a) levels** * B3 converted to nicotinamide which **inhibits VLDL secretion** = reduction in triglyceride and LDL and **increase in HDL**

Question 26

AE of Niacin, vitamine B3

Answer 26

1) **Flushing** (because of production of PGD2) **reduced by aspirin**. 2) Palpitations 3) GI disturbance 4) Disturbed liver function

Question 27

Contraindications of Niacins

Answer 27

**Peptic ulcers**, gout precipitation.

Question 28

MoA of Evol**ocumab** , Alir**ocumab** | *Novel therapies

Answer 28

**novel therapies** **PCSK9 inhibitors** (Proprotein Convertase Subtilisin/kexin Type 9)→promotes **degradation of LDL receptor** in hepatocytes by targeting it for lysosomal degradation

Question 29

Clinical uses of Evol**ocumab** , Alir**ocumab**

Answer 29

°Primary hypercholesterolemia, mixed dyslipidaemia; °In combination with statin when unable to reach LDL-C goals °For statin intolerant patients

Question 30

AE of Evol**ocumab**, Alir**ocumab**

Answer 30

°Nasopharyngitis °Upper respiratory tract infections °Injection-site reactions °Myalgia °Cognitive effects

Question 31

MoA of Mipomersen

Answer 31

Antisense oligonucleotide for coding region of apoB-100 mRNA→inhibits synthesis and apoB-100-containing lipoprotein synthesis

Question 32

Clinical uses of **Mipomersen** | * novel therapy drug

Answer 32

**Adjunct treatment for FH** | *FH: familial hypercholesterolemia

Question 33

AE of **Mipomersen** | *Novel therapy drug

Answer 33

1) **Accumulates in the liver** (site of intended action) 2) **Hepatotoxic**

Question 34

MoA of **Lomitapide** | *Novel therapy drug

Answer 34

**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**

Question 35

Clinical uses of **Lomitapide**

Answer 35

Adjunct Tx for **FH (oral)**