Medical Pharmacology Practice Questions: Chapter 33-34 Inhibitors of MEK kinases *serine-threonine kinases acting downstream of RAF: Trametinib (Mekinist); Cobimetinib (Cotellic)

Medical Pharmacology Practice Questions: Inhibitors of MEK kinases *serine-threonine kinases acting downstream of RAF: Trametinib (Mekinist); Cobimetinib (Cotellic)

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MEK (mitogen-activated protein kinase kinase) is a kinase enzyme that phosphorylates mitogen-activated protein kinase (MAPK). This kinase is a pharmacological target aimed at inhibiting the Ras-RAF-MEK-ERK pathway.
1. true
2. false
Trametinib is the first MEK family inhibitor approved by the FDA.
1. True
2. False
Trametinib pharmacokinetics/pharmacodynamics:
1. Orally bioavailable
2. Reversible, allosteric inhibitor
3. Both
4. Neither
Trametinib bioavailability:
1. Oral bioavailability is about 70%.
2. Oral bioavailability is decreased if taken along with a high-calorie meal.
3. Peak plasma concentrations of of trametinib is noted about 90 minutes after dosing.
4. Trametinib exhibits a half-life of about five days.
5. All of the above are correct.
Clinical use/uses of trametinib
1. :Monotherapy for patients with mutant BRAF V600E/K melanoma.
2. In combination with the BRAF inhibitor dabrafenib, trametinib is also FDA approved for mutant V600E/K metastatic melanoma.
3. In combination with the BRAF inhibitor dabrafenib, trametinib may be effective in treating metastatic melanoma (mutant V660E/K) and metastatic non-small cell lung cancer (NSCLC exhibiting mutant V600E).
4. A & B
5. B & C
6. A, B & C
Trametinib frequently noted adverse effects/effects:
1. Cutaneous rash
2. Diarrhea
3. Acneiform dermatitis
4. All of the above responses are correct.
Serious adverse effects associated with trametinib administration include interstitial lung disease, ocular toxicities, hemorrhage, cardiomyopathy and hypertension.
1. True
2. False
Trametinib administration, similar to BRAF inhibitors, is also associated with cutaneous squamous cell carcinoma.
1. True
2. False
Cobimetinib:
1. An oral bioavailable drug that reversibly inhibits MEK1/2 protein kinase activity.
2. Is associated with elimination half life range from 1 to 3 days.
3. Both
4. Neither
Cobimetinib metabolism:
1. Mediated by the cytochrome P450 drug metabolizing system; particularly by the CYP3A4 isoform.
2. Drugs that influence CYP3A4 enzymatic activity would be expected to alter cobimetinib levels in patients.
3. Both
4. Neither
Vemurafenib in combination with cobimetinib is approved for treating metastatic or unresectable melanoma exhibiting a BRAF V600E/K utation.
1. True
2. False
Common adverse effects/effects associated with cobimetinib administration:
1. Photosensitivity
2. Nausea
3. Vomiting
4. Pyrexia
5. Diarrhea
6. All of the above represent common adverse effects due to cobimetinib dosing.