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First Aid
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First Aid for the USMLE Step 1 (2023)
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PCSK9-Inhibitors

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PCSK9-Inhibitors

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PCSK9-Inhibitors

PCS-K9 in Inhibiting-chains
JulianMagome9668
12 KEY FACTS
AVAILABLE DRUGS
Evolocumab
PC-Evolution

Evolocumab is a human monoclonal antibody from the group of PCSK9 inhibitors. It is used to treat hypercholesterolemia.

Alirocumab
Alienware-PC

Alirocumab is a drug from the group of PCSK9 inhibitors that are used to treat hypercholesterolemia.

MECHANISM OF ACTION
Monoclonal Antibodies
Monocle on Ant-tie-body

PCSK9 inhibitors are monoclonal antibodies. Monoclonal antibodies are antibodies produced by a cell line ("cell clone") derived from a single B lymphocyte. They are directed against a specific, single epitope. In this case, they target the serine protease PCSK9 enzyme.

Bind the PCSK9 Enzyme
PCS-K9

The serine protease PCSK9 has the function of binding to LDL receptors on the surface of liver cells (hepatocytes) and promoting their breakdown in the lysosomes. PCSK9 inhibitors selectively bind to circulating PCSK9 and inhibit their function. As a consequence, the enzyme can no longer bind to the LDL receptors.

Decreased Degradation of LDL-receptors
Down-arrow Degradation of Ladybug-devil Receptors

As a result of the binding of the PCSK9 enzyme, the breakdown of the LDL receptors decreases.

Increased LDL Receptors on Hepatocytes
Up-arrow Ladybug-devil Receptor on Liver

Leading to an increase of LDL receptors on Hepatocytes.

Reduction of LDL in Plasma
Reduced Ladybug-devils on Plasma-TV

The increased LDL receptors on the cell surface lead to a reduction in LDL cholesterol (LDL-C) in the blood, as it is increasingly absorbed by the liver cells.

INDICATION
Second-line Therapy for Hypercholesterolemia
Second-place-tutu on Hiker-cholesterol-burger

PCSK9 inhibitors are used as second-line therapy in patients with hypercholesterolemia. Due to the current (2019) high costs, PCSK9 inhibitors are only used in familial hypercholesterolemia, therapy-refractory hypercholesterolemia with a very high cardiovascular risk, and when the standard therapy with statins plus ezetimibe has been exhausted and the LDL value is still above 140 mg/dl.

ADMINISTRATION
Subcutaneous Injection
Sub-q-tip

The drug is administered subcutaneously.

SIDE EFFECTS
Skin Reaction at the Injection Site
Skin Reaction at the Injection Site

Skin Reaction at the Injection side is a common side effect of this drug.

Myalgia
Mayo-algae

Myalgia is a common side effect of this drug.

Neurocognitive Impairment
Cog-brain Impaired

A common side effect of this drug is neurocognitive impairment.

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