Antilipemic Drugs - Lecture notes 1-10 PDF

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DRUGS AFFECTING CIRCULATION: ANTILIPEMIC DRUGS 1. Relate drug therapy to physiology of hyperlipidemia. ● Lipids in blood are in different forms o Triglycerides ▪ Provide energy for cellular metabolism o Phospholipids ▪ Essential components of cell membranes o Cholesterol ▪ a components of cell membrane ▪ essential for steroid synthesis ▪ essential to form bile salts ● ● ● ●

Blood lipids are transported in plasma by specific proteins called lipoproteins. Lipids + apoproteins = lipoprotein HDLs& LDLs carry cholesterol. VLDL & chylomicron (dietary) carry triglycerides

● HDL and LDL both carry cholesterol. ● LDL cholesterol carry cholesterol TO cells. ● HDL cholesterol carry cholesterol FROM cells. Key points 1. When dietary fats go into the small intestine, gallbladder contracts to release bile into small intestine. **Remember bile is necessary for fats to be absorbed by the small intestine. ● Bile breaks fat into micelles. ● Micelles now are able to be absorbed into small intestine wall. ● Without bile, no absorption! 2. Liver processes fats into LDLs, HDLs 3. LDLs & HDLs enter circulation and reach periphery o LDL (bas cholesterol) ▪ Delivers cholesterol to peripheral tissues. ▪ Cause atherosclerosis 

▪ Atherosclerosis is a condition in which fatty material collects along the walls of arteries. This fatty material thickens, hardens (forms calcium deposits), and may eventually block the arteries. Can cause the following: ● Heart disease ● Stroke ● Hypertension ● Others ▪ Under pro-atherogenic conditions, chylomicron remnants, VLDL remnants, and small LDL deliver cholesterol to the artery wall (pro-atherogenic). o HDL (good cholesterol) ▪ Delivers cholesterol from tissues to the liver*** ▪ HDLs carry LDLs away from artery walls. L ▪ HDL removes cholesterol from the artery wall (anti-atherogenic). o The ‘traditional’ dyslipidemia typically associated with intra-abdominal (visceral) obesity includes hypertriglyceridemia, the presence of small, dense LDL, and low HDL cholesterol levels. All three abnormalities are metabolically linked. o Chylomicron and VLDL remnants (not routinely measured) are also elevated in intra-abdominal obesity. ● Dyslipidemia may be cause by… o Primary: genetic or familial - 95% o Secondary ▪ Dietary habit ▪ Diabetes mellitus ▪ Medications ● Beta blockers o Older drugs o Propanol o Atalmool o Metproanl o Cause Hyperlipidemia o Slightly increase triglycerides and decrease HDL ● Cyclosporine – immunosuppressant drug ● Oral estrogens – Increases triglycerides in liver and secretes lipid in circulation VLDL ● Glucocorticoids ● Sertraline – Antidepressant – Increases triglycerides ● Diuretics: Thiazide – Increase LDL ● AIDS drugs: protease inhibitors - Increase LDL

● Treatment goals for patients with dyslipidemia**** o Low total cholesterol ▪ Total cholesterol : Below 200 mg/dl o Low bad cholesterol ▪ LDL : below 130 mg/dl ▪ Triglycerides: below 150 mg/dl o High good cholesterol ▪ Above 35 mg/dl ● Lifestyle Changes***** o Healthy Diet: o Reduce saturated fats: red meat & dairy products o Eliminate trans fats: ‘partially hydronated vegetable oils (cookies, crackers ,cakes) o Eat high Omega 3 foods: salmon, walnuts, flax seed, Fish oil pills o Increase fiber: oatmeal, beans, apples pears o Add whey protein: Lowers LDL o Exercise and loose weight: Raise HDL

● Nursing: Summary o Lipid lowering drug: To lower cholesterol, LDL, promote HDL o Statins ▪ First line drugs ▪ Take at night ▪ SE: Muscle symptoms and hepatotoxicity ▪ Many drug-drug interactions ● Bile Acid Binding Agents ▪ Take with fluid ▪ Take other meds 1 hr. before or 4-6hr after ● Niacin ▪ SE: Flushing of the neck ▪ Take Aspirin 30 min before ▪ Take with cold water ● Cholesterol absorption inhibitors ▪ Diarrhea

● PCSK9: injection every 2 weeks

Antilipidemic Drugs Drug Name STATINS atorvastatin (Lipitor) lovastatin (Mevacor) simvastatin (Zocor) fluvastatin (Lescol)

Mechanism of Action Inhibit liver enzyme Hydroxymethylglutaryl-C oA (HMG-CoA) reductase that synthesize cholesterol

Use(s) ● ● ●

First line drugs for dyslipidemia ↓ LDL and triglycerides ↑ HDL

Adverse Effects/ Nursing Implications Contraindications in high dose (dangerous) Many drug-drug interactions: ● Elevated liver enzymes ● Antifungal drugs (hepatotoxicity) ● Cyclosporine ● Myopathy (immunosuppressant) ● Rhabdomyolysis ● Verapamil ● Muscle aches (myalgia) ● Erythromycin Careful drug-drug interactions* Drugs that increase effects of lovastatin and related drugs ● GI issues: flatulence, ● Azole antifungals(e.g., fluconazole, N/V/D (not serious & itraconazole) temporary) ● Cyclosporine ● Erythromycin ● Headache ● Fibrate dyslipidemias ● Niacin Drugs that increase effects of Fluvastatin’s ● Alcohol cimetidine, ranitidine, omeprazole Drugs that decrease effects of lovastatin and related drugs ● Bild acid sequestrant dyslipidemics ● Antacids ● Iradipine ● Rifampin ● St. John’s wort

Considerations: ● Take at night (except atorvastatin) o Rationale: production is most active at night (2-4AM) ● ●

● ●

BILE ACID BINDING AGENTS cholestyramine (Questran) colesevelam (Welchol)

Bind bile acids in intestine - Bile is made primarily from cholesterol and eliminated in feces - Liver consumes more cholesterol to make bile acids

↓ cholesterol level in blood

↑ GI effects: bloating, constipation, gas

Report therapeutic effects Monitor closely for muscle Sx; obtain baseline CK levels in elevated risk patients with renal dysfunction, liver disease, polypharmacy Monitor for Sx of hepatotoxicity Avoid giving with grapefruit juice (exacerbating factor)

statin: - Most widely used - NOT GIVEN AT NIGHT Drug interactions: ↓ absorption of fat-soluble vitamins A, E, D, K and many other meds – give meds 1 hr before or 4-6 hrs after Considerations: - Cholestyramine and colestipol may be hard to tolerate— Mix cholestyramine powder + colestipol granules with water or other fluids, soups, cereals or fruits such as applesauce; follow with more fluid - Give with food—bile acid will be secreted when foods are in the small intestine - Report therapeutic effects

niacin (Vitamin B3)

Inhibits mobilization of free fatty acids from peripheral tissues

Omega-3 Fatty Acids

↓ LDL and triglycerides ↑ HDL

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Flushing of the face and neck, itching, tingling Flushing is reported by as many as 85% of patients taking niacin

- Start out low and titrate to avoid side effects - Take at night with cold water - Take aspirin or ibuprofen 30 minutes prior - Avoid alcohol - Observe for side effects - Report therapeutic effects

↓ triglycerides

fish oil (Vascepa) Most effective for ↓ serum triglycerides and ↑ HDL

Fibric Acid Agents Fenofibrate (Tricor) gemfibrozil (Lopid) Cholesterol Absorption Inhibitors ezetimibe (Zetia) PCSK9 Inhibitors

Inhibit absorption of cholesterol in small intestine

↓ LDL

PCSK9 ↓   # of available LDL receptors ฀  ↑   LDL-C levels PCSK9 inhibitors ↑   # of available LDL receptors ฀ ↓ LDL-C levels

Newest class Primarily for those with “heterozygous familial hypercholesterolemia” genetic condition that makes cholesterol levels hard to control

Not first line drug

Back and abdominal pain Hypersensitivity reactions: rash, nausea, diarrhea Itching, bruising at injection site Kinetics: Injection every 2 weeks Limitation: Expensive

Define the following terms; 1. Lipoproteins - Any of a group of soluble proteins that combine with and transport fat or other lipids in the blood plasma. 2. Chylomicrons - Found in the blood and lymphatic fluid where they serve to transport fat from its port of entry in the intestine to the liver and to adipose (fat) tissue. ● transports dietary lipids from the small intestines to the liver 3. Very-low-density lipoproteins (VLDLs) - Lipoproteins that transport triglycerides and other lipids from the liver to various tissues in the body. 4. Intermediate-density lipoproteins (IDLs) - Remnant of VLDL 5. Low-Density liproproteins (LDLs) - Transport cholesterol to cells 6. High density lipoproteins (HDLs) - Transports cholesterol for excretion 7. Hyperlipidemia - an abnormally high concentration of fats or lipids in the blood. 8. Triglycerides - an ester formed from glycerol and 3 fatty acid groups. Triglycerides are the main constituents of natural fats and oils, and high concentrations in the blood indicate an elevated risk of stroke. 9. Metabolic syndrome - a cluster of biochemical and physiological abnormalities associated with the development of 10. Alanine aminotransferase (ALT) - (ALT) is an enzyme found primarily in the liver and kidney. It was originally referred to as serum glutamic pyruvic transaminase (SGPT). Normally, a low level of ALT exists in the serum. ALT is increased with liver damage and is used to screen for and/or monitor liver disease 11. Aspartate aminotransferase (AST) - enzyme that is normally present in liver and heart cells. AST is released into blood when the liver or heart is damaged. 12. Atherosclerosis - a disease of the arteries characterized by the deposition of plaques of fatty material on their inner walls....