Potassium channel modulators

Potasssium Channels, their subtypes and their modulation by various drugs.

1. Potassium Channel Modulators Dr. Sahil Kumar Department of Pharmacology Maulana Azad Medical College

2. Outline Introduction: Potassium Channels Types and Distribution Modulators Pharmacological Actions and Uses of KCOs Conclusion

3. Introduction: Potassium Channels Membrane spanning proteins allowing efflux of potassium ions through K+ selective pore. Role in cellular & cardiac repolarization, smooth muscle relaxation, neurotransmitter & insulin release . Channelopathies .

4. Classification of Potassium Channels Grouped based on their structure as well as physiological criteria into three families – 6 TM : includes voltage gated channels. These channels are composed of two subunits namely primary pore forming α-subunit and an associated regulatory subunit. 2 TM : ATP sensitive potassium channels 4 TM : Underlying cause for leak currents in neuronal cells.

5. Potassium Channel Terminology

6. 4TM family of K channels This family is underlying cause of leak currents in the neuronal cells.

7. Pharmacological actions + Potential Uses

8. Potassium Channel Openers Drug Dose Uses Diazoxide HTN: 13 mg/ kg I.V Bolus every 5-15 minutes – Hypoglycemia: 3-8 mg/kg QID HTN, Hypoglycemia Minoxidil 2.5 mg – 80 mg BD orally – 2%/ 5 % gel also available, apply 1 ml BD in alopecia Alopecia areata & alopecia androgenita – Malignant / refractory HTN

9. Potassium Channel Openers Drug Dose Uses Nicorandil 10-40 mg orally BD 2-6 mg/ i.v / hr Angina Pinacidil 12.5 mg BD , in combination with diuretic – 37.5 mg controlled release tablet available Angina Potassium Channel Openers

10. Potassium Channel Openers Drug Dose Uses Flupirtine 100-300 mg/day Pain, Retinal ischemia, stroke, Neurodegen . disorder Retigabine 600-1200 mg/day Epilepsy Iptakalim 5 – 20 mg/day HTN, ?Antipsychotic Potassium Channel Openers