Antihyperlipidemic Flashcards by Ibtihal Balubaid

Hyperlipidemia (Hyperlipoproteinemia) means
———– plasma lipoproteins which is one of the
risk factors for————– ( coronary heart
disease).

increased-atherosclerosis

How well did you know this?

Not at all

Perfectly

Other risk factors include ———- as a
major risk factor for coronary disease. Also, reduced
levels of ———–, increased ———— of lipoproteins,
and stimulation of————- . , ————-also a
major risk factor, is another source of oxidative
stress. Also, and,—————-and————– .

Cigarette smoking-HDL-oxidation-thrombogenesis-Diabetes-obesity-hypertension

How well did you know this?

Not at all

Perfectly

Plasma lipids include: ———and—————and—————

cholesterol, triglycerides

(TG) and phospholipids

How well did you know this?

Not at all

Perfectly

Metabolic disorders that involve elevations in any

lipoprotein are termed———————–or ——————–

hyperlipoproteinemias or hyperlipidemias

How well did you know this?

Not at all

Perfectly

———–denotes increased levels of

triglycerides

Hyperlipemia

How well did you know this?

Not at all

Perfectly

Types of lipoproteins
——————— → formed in GIT from
dietary TG.

Chylomicrons (TGs):

How well did you know this?

Not at all

Perfectly

Types of lipoproteins
———— (TGs and cholesterol) → endogenously
synthesized in liver. Degraded by ——- into free fatty
acids (FFA) for storage in——— and for
————– in tissues such as cardiac and skeletal
muscle.

VLDL-LPL -adipose tissue-oxidation

How well did you know this?

Not at all

Perfectly

Types of lipoproteins
———— (TGs, cholesterol); and —— (cholesterol) →
derived from ——— hydrolysis by lipoprotein
lipase. Normally, about——– of LDL is removed from
plasma by —————-

IDL-LDL-VLDL-70%- Hepatocyte

How well did you know this?

Not at all

Perfectly

Types of lipoproteins
- ———— (protective) →exert several —————-
effects. They participate in ————- of cholesterol
from the artery wall and inhibit the —————- of
atherogenic lipoproteins& removes cholesterol from
tissues to be degraded in ———-.

HDL - Anti atherogenic - retrieval - oxidation - liver

How well did you know this?

Not at all

Perfectly

Etiology of hyperlipidemias
• 1- ———–(genetic origin): hereditary.
• 2- Secondary to:
• Diseases e.g. ———————
• Drugs: ———————, alcohol, ——————-

Primary - hypothyroidism - beta blocker - thiazides

How well did you know this?

Not at all

Perfectly

Types of Hyperlipidemia
• Primary Chylomicronemia (I):
Chylomicrons are not present in the serum of normal
individuals who have fasted——–hours. The recessive traits
of deficiency of——————– are usually
associated with severe lipemia.

10-lipoprotein lipase or its cofactor

How well did you know this?

Not at all

Perfectly

Types of Hyperlipidemia
• Familial Hypercholesterolemia (IIA):
Familial hypercholesterolemia is an——————–
trait. Although levels of ———– tend to increase with normal
.

autosomal dominant -LDL-VLDL

How well did you know this?

Not at all

Perfectly

Types of Hyperlipidemia
Familial Combined (mixed) Hyperlipoproteinemia (IIB):
elevated levels of———– ,————– .

VLDL-LDL

How well did you know this?

Not at all

Perfectly

Types of Hyperlipidemia
• Familial Dysbetalipoproteinemia (III):
Increased ——— resulting increased ———– and cholesterol
levels.

IDL-TG

How well did you know this?

Not at all

Perfectly

Types of Hyperlipidemia
• Familial Hypertriglyceridemia (VI):
increase———- production with normal or decreased LDL.

VLDL

How well did you know this?

Not at all

Perfectly

Types of Hyperlipidemia
Familial mixed hypertriglyceridemia (V):
• Serum ——— and ————- are increased

VLDL and chylomicrons

How well did you know this?

Not at all

Perfectly

Management of Hyperlipidemias
• I- Diet:
• Avoid —————- (animal fats) and give
—————-(plant fats).
Regular consumption of fish oil which contains
omega——- fatty acids and vitamins — and —-
(antioxidants).

saturated fatty acids-unsaturated fatty acids-3-E-C

How well did you know this?

Not at all

Perfectly

Management of Hyperlipidemias
II. Exercise:
• ————- HDL and insulin —————

increase sensitivity

How well did you know this?

Not at all

Perfectly

Management of Hyperlipidemias
III- Drug therapy: the primary goal of therapy is
to —————- levels of ——— . Also, 2nd goal, ———- in ——–
is recommended

decrease-LDL-increase-HDL

How well did you know this?

Not at all

Perfectly

HMG –COA reductase inhibitors
(statins)
Production of this enzyme and of LDL
receptors is transcriptionally regulated by
the------------------- in the cell.
• -Inhibit the  step ----------------in
cholesterol synthesis.

content of cholesterol-first enzymatic

How well did you know this?

Not at all

Perfectly

Mechanism of action of statin: - Structural analogues of HMG –COA reductase (the rate limiting enzyme in
cholesterol synthesis)
→ reduction of
cholesterol synthesis in liver →
compensatory ↑ in synthesis of —————- on hepatic and extra hepatic tissues →Increase in hepatic uptake of circulating———— which decreases plasma LDL cholesterol .
- low intracellular cholesterol decreases the secretion of —————
- Decrease TGs to some extent and ↑ HDL.
- ————–protective: vaso——— and
decrease ————- formation and
stabilize plaque.————–action.

LDL receptors-LDL-VLDL-Cardio-dilators-platelet thrombus- Anti-inflammatory

How well did you know this?

Not at all

Perfectly

Simvastatin - Rosuvastatin -lovastatin- Pitavastatin are include in which group ?

HMG –COA reductase inhibitors ( Statin)

How well did you know this?

Not at all

Perfectly

Pharmacokinetics of statin :
————, ——— (prodrugs). The others
are active as given.
- ————— & —————– are the most
potent.
- Well absorbed when taken ————-. Excreted
mainly in ———–
- T1/2= 2 hrs Except:
Atrovastatin (———), Rosuvastatin (———)
* Should be given at night except:
—————————and—————-

Simvastatin-lovastatin-Atorvastatin-Rosuvastatin-orally-bile-14 hr-19 hr
Atrovastatin and Rosuvastatin

How well did you know this?

Not at all

Perfectly

Effective in all types of hyperlipidemia except those who
are ———————————– (lack of
LDL receptors)
Usually combined with other drugs.

homozygous for familial hypercholesterolemia

How well did you know this?

Not at all

Perfectly

Adverse effects of statin: | 5

1- Increase in liver enzymes (serum transaminases should be monitored continuously ,CI in hepatic dysfunction). • 2-Myopathy and muscle damage leading to renal failure (myoglobinuria) in patients with renal dysfunction especially when combined with fibrates or nicotinic acid, erythromycin, itraconazole and cyclosporine (plasma creatine kinase level should be monitored continuously). • 3- Cataract and GIT upset. • 4- Increase in warfarin levels. • 5-CI in pregnancy and nursing mothers , lactation, children and teenagers.

The most common affect of all 5 groups ?

GIT upsets

Enumerate the high intensity statin and they lower LDL an averge of more than and equal ------? 2

Rosuvastatin Atorvastatin 50%

Enumerate the moderate intensity statin and they lower LDL an averge of more than and equal ------? 8

``` Atorvastatin Rosuvastatin Simvastatin Pravastatin Lovastatin Fluvastatin Pitavastatin 30% to less than 50% ```

Enumerate the low intensity statin and they lower LDL an averge of more than and equal ------? 5

``` Lovastatin Pravastatin Fluvastatin Simvastatin Pitavastatin less than 30% ```

FDA is revising drug label for -----------to clarify the risk of myopathy

Lovastatin

The first and cheapest anti hyperlipidemic----------------------------------.Decrease both TGs (---------------) and cholesterol (-------------) levels

Niacin; Nicotinic acid (Inhibitors of lipolysis)-VLDL-LDL

• Mechanism of action of Niacin ( Nicotinic Acid)(inhibitors of lipolysis): • It is a ------------inhibitor of lipolysis in adipose tissues → ↓ mobilization of FFAs (major precursor of ------- and needed for VLDL production) to the liver → ↓ VLDL (after few hours). • Since ------- is derived from VLDL so ↓ VLDL → ↓ LDL (after few hours). • - ↑ HDL levels ( the most potent antihyperlipidemic). • - ↓ endothelial dysfunction →↓ thrombosis

potent-TGs-LDL

The most potent antihyperlipidemic drug in raising HDL ?

- Niacin; Nicotinic acid (Inhibitors of | lipolysis)

-----------------will dec endothelial dysfunction →↓ thrombosis

- Niacin; Nicotinic acid (Inhibitors of | lipolysis)

someone use statin and has a low level of HDL which drug could he use to improve his HDL level ?

- Niacin; Nicotinic acid (Inhibitors of | lipolysis)

Pharmacokinetics of Niacin: • ----------- given, converted to--------- which does not decrease plasma lipids alone(must be incorporated with NAD).

Orally-nicotinamide

Therapeutic uses of Niacin : • Familial ------------- (type IIB) (↑VLDL and↑ LDL). • Sever hypercholesterolemia, combined with -------------- or -------------.

hyperlipidemias-fibrates -cholestyramine

Fibrates (activators of lipoprotein lipase) -------------fibrate (prodrug 20 hours) and -------------(2h)

Fenofibrate-Gemfibrozil

Mechanism of action of Fibrates : Agonists at PPAR(---------------) → expression of genes responsible for increased activity of plasma lipoprotein lipase enzyme → hydrolysis of----------- (by 30%) and chylomicrons→ ↓ serum TGs • - Increase clearance of---------(by 10%) by liver & ↑ HDL

Peroxisome proliferator activated receptor- VLDL- LDL

The most effective in reduction TGs ---------------

Fibrate

Therapeutic uses of Fibrate: | 1 thing

• Hypertriglyceridemia (the most effective in reduction TGs) - combined hyperlipidemia (type III) if statins are contraindicated.

patient who take fibrate should also becareful about Ingestion of high amount of simple sugars especially -------------enhances FFA, and formation of TGs and VLDL, thus reduction of fructose and other free sugars is an effective mechanism to lower FFA synthesis.

fructose

Fibrates-Efficacy lower TG by ----------to--------- Lower LDL-C by -----------to----------- with normal ----------- Raise HDL-C by ------- to ------- reduce progression of ------------------lesions

30 - 55 % 5-20% 18-22 coronary

Pharmacokinetics of fibrate: • - Completely absorbed after -------administration. • - ------------- bound to plasma proteins(pp), extensively metabolized, excreted in -----------

oral-Highly-urine

Adverse effects: of fibrate • --------- disturbances. • ----------- (increased biliary cholesterol excretion). • - Muscle pain and myopathy (patients with -------- impairment are at risk). • - Increase ---------- (something like warfarin) levels (compete for pp). • -CI in pregnancy (safety in pregnancy is not established), , lactating women, renal and hepatic dysfunction, gall stones.

GIT Gall stones renal coumarin

- Bile acids Sequestrants(resins): | 3 example

Cholestyramine, colestipol and colesevalem

• Mechanism of action of resins : are------- exchange resins; bind bile acids in the intestine forming complex →loss of bile acids in the stools →↑ conversion of cholesterol into------------ in the liver. Decreased concentration of intrahepatic cholesterol → compensatory increase in -------- →↑ hepatic uptake of circulating LDL → ↓ serum LDL cholesterol levels. • -Modest increase in -------------

anion- bile acids-LDL receptors-HDL

Pharmacokinetics of resins : Orally given but--------- neither ----------nor altered by intestine, totally excreted in feces

absorbed-metabolically

Bile Acid-Binding Resins efficacy - Reduce LDL-C by -------to----------- - Raise HDL-C by -----to--------- - May increase -------------concentration - Reduce major ----------- events - Reduce -------- mortality

``` 15-26% 3-6% TG concentration major coronary events coronary-CHD ```

Therapeutic uses of resins: • Of choice in treatment of type ------and ---------- hyperlipidemias (along with statins when response to statins is inadequate or they are contraindicated). • - useful for Pruritus in biliary obstruction (↑ bile acids).

IIA and IIB

------------------------useful for Pruritus in biliary obstruction (↑ bile acids).

resins(Bile acid sequestrants)

AVERSE EFFECTS of resins: • --------, -------------- but not ---------- ↓ absorption of fat soluble vitamins (----, -----, ----, -----) , ↓ Vit K → ----------------------- • ---------------is the most common adverse effect. • ↓ absorption of many drugs as digitoxin, warfarin, aspirin, phenobarbitone. Thus, these drugs should be taken -----to----- hours before , or ----to--- hours after bile acids binding resins Cholestyramine can sometimes cause ------------

``` Cholestyramine, colestipol , colesevalem k,a,d,e hypoprothrombinemia. Constipation 1-2 4-6 Hypertriglyceridemia ```

- Ezetimibe (cholesterol absorption inhibitors) Inhibits intestinal ---------- absorption → ↓ delivery of intestinal cholesterol to liver→ ↓ concentration of intrahepatic stores of cholesterol→ compensatory ↑ in LDL receptors →↑ uptake of circulating LDL →↓ serum LDL cholesterol levels( comparable or even more than statins)

cholesterol

Ezetimibe (cholesterol absorption inhibitors) | Adverse effects: 3 things

diarrhea and abdominal pain. • - CI in patients with liver dysfunction

-Therapeutic uses • ---------------May be synergistic with statins : so good for combination therapy (adjunct therapy). • Recent data suggest that --------- with Simvastatin is supperior than Simvastatin alone in reducing cardiovascular events.

Ezetimibe

Omega - 3 fatty acids Mechanism of action: • Essential fatty acids inhibit ----------and---------- • Decrease TG by ------------- with small increases in LDL and HDL. • Does ------------ CV morbidity and motality.

VLDL and TG. 25- 30 % not affect

• Adverse effects: | 2 things

• GIT disturbances. • Increase bleeding tendency with anticoagulants and antiplatelets.

Combination drug therapy: If no improvement within ------------weeks with a single drug therapy, the dose should be -------------.

6 | increased

Combination drug therapy: If no improvement after--------- months change the drug or consider combination therapy

Combination drug therapy: Bile acid resins can be safely combined with ---------- or ------------- (↓ LDL, VLDL cholesterol levels respectively). - Ezetimibe + statins → synergistic effects. • - Fibrates and statins are------- → ------------. • - Nicotinic acid and statins (must be cautiously used) → ---------------.

``` statins nicotinic acid CI myopathy myopathy ```

Efficacy of Ezetimibe Lowers LDL-C by --- to ----- May raise HDL-C by ---- to ------- Lower TG by -------- to ---------

18-20% 1-5% 5-10%

Adverse effects of Niacin : 5 things 3G 1C 1M

``` 1-Cutaneous flush (PG-mediated , dec by Aspirin 30 min before niacin ) and pruritus 2-GIT disturbances 3-Glucose intolerance 4- Gouty arthritis(hyperuricemia) 5-Myopathy (rare) ```