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Cilostazol, sold under the brand name Pletal among others, is a medication used to help the symptoms of intermittent claudication in peripheral vascular disease. It may also be used to prevent stroke. In 2019, it was the 347th most commonly prescribed medication in the United States, with more than 800thousand prescriptions.
Research
Effects on longitudinal bone growth
Cilostazol has been investigated in preclinical models as a stimulator of endochondral bone growth. PDE3 is expressed in proliferating chondrocytes of the growth plate, and that Pde3b-knockout mice show enlargement of the tibia and other long bones. In embryonic mouse metatarsal explant cultures, cilostazol at 10μM increased longitudinal outgrowth over four days, expanding the round and columnar chondrocyte zones and increasing alcian-blue-stained extracellular matrix; the PDE3 inhibitors milrinone, anagrelide and olprinone produced comparable effects, while inhibitors selective for PDE2 or PDE10 did not. The authors suggested that PDE3 inhibitors might be repurposed for short-stature disorders such as achondroplasia, while cautioning that the findings are preclinical and that self-administration of cilostazol for growth purposes is unsupported and carries cardiovascular and bleeding risks. If no improvement is seen after 3 months, stopping the medication is reasonable.
Adverse effects
Possible side effects of cilostazol use include headache (the most common), diarrhea, severe heat intolerance, abnormal stools, increased heart rate, and palpitations.
A single report has been made of grapefruit juice possibly increasing the effects of cilostazol; some drug information sources list this as a possible interaction. The FDA-approved labeling of cilostazol notes that grapefruit juice (which is a CYP3A4 inhibitor) increases the drug's maximum concentration by around 50%.
Mechanism
Cilostazol is a selective inhibitor of phosphodiesterase type 3 (PDE<sub>3</sub>) with therapeutic focus on increasing cAMP. An increase in cAMP results in an increase in the active form of protein kinase A (PKA), which is directly related with an inhibition in platelet aggregation. PKA also prevents the activation of an enzyme (myosin light-chain kinase) that is important in the contraction of smooth muscle cells, thereby exerting its vasodilatory effect.