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Pharm Week 2 Drugs of Hyperlipidemia, Study Guides, Projects, Research of Pharmacology

Virginia State University (VSU)Pharmacology

Pharm Week 2 Drugs of Hyperlipidemia

Typology: Study Guides, Projects, Research

2025/2026

Available from 01/09/2026

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Pharm Week 2 Drugs of Hyperlipidemia
Pharmacodynamics of antilipemic
•
Build-up of LDL and plaque formation
o
INCREASED LDL = INCREASED plaque
o
Macrophages  eat all damaged LDLs  foam cells (engorged LDLs)
▪
Accumulation of engorged foam cells = atherosclerotic
plaque
•
LIPID
=
any physiologic substance that is fat soluble
o
Lipids = HYDROPHOBIC
▪
Chylomicron
=
water soluble TRANSPORT for ingested
lipids
▪
VLDL
=
water soluble transport for synthesized lipids (TCA
mostly)
▪
IDL = unstable results of breakdown of some VLDL
•
When VLDL gives up TCA
▪
LDL
=
result of breakdown of LDL in plasma
•
IDL gives off more TCA
•
The lipid that is targeted with hyperlipidemia therapy
▪
HDL
=
picks up cholesterol from cell membranes and
transport to free cholesterol pool
•
Interacts with chylomicrons and VLDL dropping off
lipoproteins (apoE and apoCII)
o
Types of lipids
▪
CHOLESTEROL (fat soluble building blocks)
•
Primary structural compound of cell membrane
•
Precursor to bile salts and steroid hormones
▪
FATTY
ACIDS/TRIGLYCERIDES
•
Fuel
▪
GLYCEROPHOSPHOLIPIDS
•
Lipid compound
•
Provide the hydrophobic barrier between water and
cholesterol
▪
EICONSAOIDS
•
Prostaglandin precursor
▪
BILE SALTS
•
Emulsify dietary fats
o
When eat fat, need bile to break it down
o
Released in response to a meal (eating)
•
Built on cholesterol
▪
STEROID
HORMONES
▪
FAT SOLUBLE VITAMINS
•
A (vision), D (Ca2+, PO4 balance), E (anti-oxidant) & K
(clotting)
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Pharm Week 2 Drugs of Hyperlipidemia

Pharmacodynamics of antilipemic

  • Build-up of LDL and plaque formation o INCREASED LDL = INCREASED plaque o Macrophages  eat all damaged LDLs  foam cells (engorged LDLs) ▪ Accumulation of engorged foam cells = atherosclerotic plaque
  • LIPID = any physiologic substance that is fat soluble o Lipids = HYDROPHOBIC ▪ Chylomicron = water soluble TRANSPORT for ingested lipids ▪ VLDL = water soluble transport for synthesized lipids (TCA mostly) ▪ IDL = unstable results of breakdown of some VLDL - When VLDL gives up TCA ▪ LDL = result of breakdown of LDL in plasma - IDL gives off more TCA - The lipid that is targeted with hyperlipidemia therapy ▪ HDL = picks up cholesterol from cell membranes and transport to free cholesterol pool - Interacts with chylomicrons and VLDL dropping off lipoproteins (apoE and apoCII) o Types of lipids ▪ CHOLESTEROL (fat soluble building blocks) - Primary structural compound of cell membrane - Precursor to bile salts and steroid hormones ▪ FATTY ACIDS/TRIGLYCERIDES - Fuel ▪ GLYCEROPHOSPHOLIPIDS - Lipid compound - Provide the hydrophobic barrier between water and cholesterol ▪ EICONSAOIDS - Prostaglandin precursor ▪ BILE SALTS - Emulsify dietary fats o When eat fat, need bile to break it down o Released in response to a meal (eating) - Built on cholesterol ▪ STEROID HORMONES ▪ FAT SOLUBLE VITAMINS - A (vision), D (Ca2+, PO4 balance), E (anti-oxidant) & K (clotting)

Triglycerides (TCA) and Cholesterol

  • Triglycerides o TCA = once eaten or synthesized (in liver) need to get to muscle (burned off) or adipose tissue (stored as fat) o Once TCA is ingested (in gut) or synthesized has to be transported to area of action ▪ To get from ingestion to action site have to be packaged in a way that enables plasma (water) transport - Too much = fat embolus o Transport of TCA ▪ Eat  breakdown  absorb TCA  rebuild it  complex with proteins  chylomicron (proteins give the chylomicron water solubility)  circulation (into lymphatic system entering blood stream)  modified by HDL (HDL transfer proteins to the chylomicrons)  lipoprotein breakdown  apoprotein (ApoE or ApoCII) direct to muscle or stored as fat  chylomicrons breakdown and back to liver to be recycled o MAJOR DIETARY LIPID o VLDL is low density because most of the compound is triacylglycerol
  • Cholesterol o Cholesterol = found in free cholesterol pool of liver o Can’t be absorbed in epithelial cells on own ▪ Combines with bile salts in the guit o Cholesterol target = free pool of the cholesterol in liver ▪ The remnant (left over chylomicron) goes to the liver to enter the free cholesterol pool o Free cholesterol pool supplied by: ▪ Ingested cholesterol (transported by chylomicron remnant) – LEASE COMMON ▪ Synthesized cholesterol (recycled from LDL) ▪ Intracellular synthesis via the HMG-CoA reductase pathway – MOST COMMON o Maintain the cholesterol pool ▪ LDL receptors regulate based on your body need for cholesterol - Binding of LDL to the receptor = INCREASED cholesterol release in the cell  synthesis of receptors DECREASE (LDL)  more LDL circulating ▪ INCREASED cholesterol = DECREASED HMG-CoA reductase ▪ If cholesterol pool low = INCREASED synthesis receptors (LDL) HMG-CoA reductase produced and DECREASED LDL in plasma (since need in the free pool)

o Can also DECREASE triglyceride levels and increase HDL in some patients o COMPEITITVE inhibitors of HMG CoA reductase ▪ By inhibiting de novo cholesterol synthesis, they deplete the intracellular supply of cholesterol

  • Decrease causes cell to increase the number of cell surface LDL-C  plasma cholesterol is reduced, by decreased cholesterol synthesis and increased LDL-C catabolism
  • Pulls LD out of plasma therefore lowering LDL
  • Dosing o Given in the evening ▪ Cholesterol synthesis is a nocturnal event
  • Benefits o Atherosclerotic plaque stabilization o Improvement of coronary endothelial function o Inhibition of platelet thrombus formation o Vascular anti-inflammatory activity
  • FIRST LINE TREATMENT
  • These agents undergo FIRST PASS by the LIVER o Be aware of LIVER function when prescribing
  • Therapeutic use o Effective in lower plasma cholesterol levels in ALL types of hyperlipidemias o Patients with homozygous for familial hypercholesterolemia lack LDL receptors and benefit much less from statins
  • Pharmacokinetics o ALL metabolized by CYP450 in the LIVER
  • Adverse effects o ELEVATED liver enzymes ▪ Hepatic insufficiency can cause drug accumulation o Myopathy o Rhabdomyolysis ▪ Increase risk with renal insufficiency, vit D deficiency, hypothyroidism, advanced age, female, -zole anti fungals, protease inhibitors, cyclosporine, erythromycin, gemfibrozil or niacin o Can also ELEVATE effect of warfarin (coumadin) o CONTRAINDICATED: pregnancy, lactation and active liver disease
  • 2013 ACC/AHA Guidelines for treatment of blood cholesterol o Group 1: Clinical ASCVD (age 21-75 yrs)  if meet criteria  high intensity statin o Group 2: LDL > 190  meet criteria  high intensity statin o Group 3: diabetes type I or II, age 40-75yr  moderate (high) intensity statin

▪ Moderate = 75 years with diabetes type I or II ▪ High = 10 yr ASCVD with risk > 7.5% o Group 4: 10yr ASCVD estimated > 7.5% and age 40-75  meet criteria  moderate intensity statin

  • Statin categories o HIGH = 50% reduction of baseline LDL o MODERATE = 30-49% reduction of LDL o LOW = 30% ▪ No role for low intensity Niacin
  • Medications o Niacin (Niaspan, slo-niacin)
  • Mechanism o Strongly inhibits lipolysis in adipose tissue  reduces production of free fatty acids ▪ Reduced liver triglycerides levels decreases hepatic low- density lipoprotein (VLDL) production  reduces LDL-C plasma concentration
  • Reduced LDL-C by 10-20% and most effective agent for INCREASING HDL-C o Also lowers triglycerides by 20-35%
  • Can be used in combination with statins
  • Therapeutic use o Lowers plasma levels of both cholesterol and triglycerides o Treatment of familial hyperlididemias o Often used in combination with other agents
  • Pharmacokinetics o PO administration o Niacin  converts to  nicotinamide  incorporated into the cofactor nicotinamide adenine dinucleotide (NAD+) o Excreted in urine
  • Adverse effects o Intense cutaneous flush with uncomfortable feeling of warmth and pruritus o Taken with aspirin (prostaglandin-mediated) can decrease flush feeling o INHIBITS tubular secretion of uric acid  predisposes patients to hyperuricemia and gout o AVOID in active hepatic disease and peptic ulcers Fibrates – Fibric Acid Derivatives
  • Medications

o Colestipol (Colestid) o Cholestyramine (Prevalite, questran) ▪ Relieve pruritus caused by acculumation of bile acids in patients with biliary stasis

  • Lower LDL significantly o Less than observed with statins o Reduces LD by 15-30%
  • Used for chronic diarrhea than cholesterol
  • Can rise triglyceride levels
  • Mechanism of action o Binds bile acid in the gut  interrupt absorption  just excrete it ▪ DECREASE free cholesterol pool of liver o Bind to negatively charged bile acids and salts  resin/bile acid complex is excreted in feces  lower bile acid concentration ▪ Causes increase conversion of cholesterol to bile acids ▪ Intracellular cholesterol concentrations DECREASE, which activates INCREASED hepatic uptake of cholesterol- containing LDL-C particles  decrease in plasma LDL-C
  • Therapeutic use o Useful in (combination with diet or NIACIN) for treating type IIA or type IIB hyperlipidemia o Always give on EMPTY STOMACH
  • Pharmacokinetics o Insoluble in water and have large molecular weight ▪ Not absorbed or metabolically altered by the intestine o Completely excreted by feces
  • Adverse effects o GI disturbances – ALWAYS GIVE ON EMPTY STOMACH ▪ Constipation, nausea, flatulence o Interfere with absorption of vit A, D, E, K o Interfere with absorption of digoxin, warfarin and thyroid hormone ▪ Take 1-2 hours before or 4-6 hours after these medications Cholesterol absorption Inhibitor
  • Medications o Ezetimibe (Zetia) ▪ DECREASES absorption of cholesterol in gut
  • Mechanism of action o INHIBITS absorption of dietary and biliary cholesterol in small intestine  DECREASE in intestinal cholesterol to liver ▪ Reduction of hepatic (liver) cholesterol stores and increase in clearance of cholesterol clearance from the blood ▪ DECREASES absorption of cholesterol in gut  DECREASED cholesterol stores in free cholesterol pool of liver 

INCREASED LDL receptors  INCREASED LDL plasma clearance  DECREASED cholesterol

  • When you eat, bile salts attach to cholesterol
  • Metabolized in the small intestine and liver via glucuronide conjugation o Biliary and renal excretion
  • Adverse effects o Not for patients with moderate to severe hepatic insuffiency Omega-3 fatty acids
  • Only ethyl ester with cardiovascular risk reduction o For TCA >
  • Medications (found in tuna, halibut and salmon) o Docosahexaenoic and eicosapentaenoic acids (lovaza, various OTC preprations) ▪ OTC = fish oil tabs o Icosapent ethyl (vascepa) ▪ Reduces hepatic synthesis of VLDL
  • Essential fatty acids that are used for triglyceride lowering o Inhibit VLDL and triglyceride synthesis in the liver o DECREASES synthesis of VLDL  enhances lipoprotein to increase VLDL clearance
  • Adverse effects o GI effects ▪ Abdominal pain, nausea, diarrhea o Contraindicated with anticoagulants and antiplatlets agents PCSK9 Inhibitors – very expensive
  • Medications o Alirocumab (praluent) o Evolocumab (Repatha)
  • For patients with lipid disorders OR max statin therapy (combination therapy)
  • PCSK9 is an enzyme predominately produced in the LIVER o Binds with the LDL receptors on the surface of hepatocytes  degradation of LDL receptors o INHIBITING PCSK9 enzyme  more LDL receptors are available to clear LDL-C from the serum
  • PCSK9 block protein PCSK9  DECREASED degradation of LDL receptors  LDL receptors stay expressed and removal LDL from plasma (circulation)
  • Used in addition to maximize tolerated statin therapy in patients with heterozygous and homozygous familial hypercholesterolemia
  • Provides potent LDL lowering (50-70%) o In combination with other statin
  • Only available as subcutaneous injections