2. Purpose: Teach Atorvastatin to Nursing Students
• Goals:
• At the end of this presentation, Nursing students will be able to:
o Identify the pathophysiological conditions treated with atorvastatin
o Describe the pharmacokinetics of the medication
o Explain the pharmacodynamics, pharmacogenomics and possible adverse effects
o List precautions to take before using atorvastatin
3. Introduction
• Generic Name: Atorvastatin
• Brand Name: Lipitor
• Class: A member of class of drugs known as statins
• Usage: Primarily for lowering blood cholesterol and to prevent cardiovascular events
• Mode of Actions: Inhibits HMG-CoA reductase, an enzyme found in liver involved in
production of cholesterol
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4. Pathophysiological Conditions Treated with
Atorvastatin
• Hypercholesterolemia- a high-level low-density lipoprotein (high LDL
cholesterol)
• Common in patients with heart disease
• Not recommended to combine with certain other cholesterol-lowering drugs
• Daily oral dose at regular interval
• Cholesterol is a lipophilic molecule, functions as a precursor molecule in the synthesis of
vitamin D, steroids, and sex hormones (Huff, & Jialal, 2019).
5. Intended Response to Atorvastatin
• Statin medications generally decrease cholesterol production by preventing the
conversion of HMG-CoA to mevalonate (Siddique & Mclver, 2019).
• A synthetic compound, atorvastatin is a competitive inhibitor of HMG-CoA
reductase
• It increases the number of LDL receptors on the surface of hepatic cells
• Atorvastatin reduces the level of triglycerides and low-density lipoprotein (LDL)
which circulate in the bloodstream as part of lipoprotein complexes (Nordqvist, 2019).
6. Potential Interaction & Adverse Reaction
• Grapefruit juice – may increase blood level of atorvastatin
• May increase risk of liver damage
• and a rare but deadly condition called rhabdomyolysis – causes breakdown of skeletal
muscles
• Interaction with fenofibrate, clofibrate, gemfibrozil – increase risk of myopathy and
rhabdomyolysis
• Phenytoin, bosentan – CYP3A4 inducers may decrease plasma concentration of atorvastatin
• Co-administration with any CYP3A4 inhibitors such as voriconazole may increase serum
concentration of atorvastatin causing serious adverse reaction
9. Pharmacokinetics of Atorvastatin
• Absorption
• Rapidly absorbed when taken orally
• Time to maximum plasma concentration approximately 1-2 hours
• Bioavailability is low at 14% due to extensive first-pass metabolism but the systemic availability for HMG-CoA
reductase activity is approximately 30% (DrugBank, 2019).
• Distribution: Highly plasma protein bound, about 98%
• Has a volume of distribution of about 380 liters.
• Metabolism: is by cytochrome P450 3A4 hydroxylation (CYP3A4) to activate ortho and para-
hydroxylated metabolites.
• Excretion: Eliminated in the bile together with its metabolites with less than 2% seen in the urine
(DrugBank, 2019). The half-life of atorvastatin is approximately 14 hours and the active metabolites have
about 20 to 30 hours half-life (Pharmacist, November 23, 2019)
11. Pharmacodynamics
• The liver is the principal site of cholesterol synthesis and LDL clearance,
• The liver is also the primary site of action of atorvastatin.
• The extent of LDL-C reduction is dependent on the dosage of atorvastatin and
not the systemic drug concentration.
12. Pharmacogenetics
• Single nucleotide polymorphisms (SNPs) is the most common genetic variation
found in man
• It is assumed to underlie the adverse effects that serve as a barrier associated
with the effective cardiovascular risk reduction, which include:
• Increased plasma creatine kinase level
• Fatigue
• Cramps
• Myalgia
• Rhabdomyolysis (Du Souich, Roederer, & Dufour, 2017).
13. Precautions to Take Before Using Atorvastatin
• History of liver disease
• Pregnant or breastfeeding mothers
• Muscle pain or weakness
• Kidney disease
• Alcohol use
• History of stroke
14. References
Du Souich, P., Roederer, G., & Dufour, R. (2017). Myotoxicity of statins: Mechanism of action. Journal of Pharmacology & Therapeutics,
175, 1-16. doi:10.1016/j.pharmthera.2017.02.029
Huff, T. & Jialal, I. (2019). Physiology, cholesterol. In StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing. Retrieved from
https://www.ncbi.nlm.nih.gov/books/NBK470561/
Nordqvist, J. (2019). What is Lipitor? Retrieved from https://www.medicalnewstoday.com
Siddique, M. S., & Mclver, L. A. (2019). Atorvastatin. In StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing. Retrieved from
https://www.ncbi.nlm.nih.gov/books/NBK430779/
