malignant hyperthermia (MH)
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| Dantrolene pharmacological mechanism | a ryanodine receptor (RYR) antagonist (inhibits RYRs) | the main calcium-releasing channel of the sarcoplasmic reticulum | Anesth Analg 2010;111:1400–10
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| Dantrolene was synthesized as a new class of | skeletal muscle relaxant | by Snyder in 1967 | J Med Chem 1967;10:807–10
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| Name an analog of dantrolene | Azumolene | was synthesized by replacing the para-nitro-phenyl group in dantrolene sodium with a para-bromo-phenyl group | J Med Chem 1987;2:263– 6
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| What advantage an analog of dantrolene had | Azumolene is 30-fold more water soluble than dantrolene | Dantrolene sodium has low water solubility that makes its clinical use difficult | Anesth Analg 2010;111:1400–10
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| Which exact ryanodine receptors Dantrolene inhibit | Dantrolene acts directly on RYR1 and RYR3 isoforms | to inhibit the extent of channel activation by calmodulin (CaM) and decreases the Ca2 sensitivity of channel activation | Anesth Analg 2010;111:1400–10
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| What dantrolene vial include? | 20 mg dantrolene sodium, 3000 mg mannitol, and sodium hydroxide | dantrolene - anhydrous salt; and sufficient sodium hydroxide to yield a pH of approximately 9,5 when reconstituted with 60 mL | Anesth Analg 2010;111:1400–10
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| Which medication should be avoided if dantrolene is used? | Calcium channel blockers | because they may cause hyperkalemia and myocardial depression that may result in cardiovascular collapse | http://emedicine.medscape.com/article/1445509-overview#a11
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| How to Reconstitute Dantrolene? | Add 60ml of sterile Water and shake vigorously until solution is yellow-orange color and clear | Inspect carefully for cloudiness or precipitation before administration. Do not mix with other fluid or drugs. | http://lifeinthefastlane.com/book/critical-care-drugs/dantrolene/
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| How to store Reconstituted Dantrolene solution? | Keep at room temperature. Must be protected from direct light. Use solution within 6 hours of reconstitution | The solution is light sensitive | http://lifeinthefastlane.com/book/critical-care-drugs/dantrolene/
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| Signs of Malignant Hyperthermia (MH) | • Increasing ETCO2 /Cyanosis • Tachycardia / arrhythmias /tachpynea • Masseter spasm or trismus /Trunk or total body rigidity • Myoglobinuria cola-colored urine • Rapidly increasing temperature(may be a late sign) | Tachypnea, resulting from increased production of carbon dioxide, is evident early during the acute crisis in patients who are breathing spontaneously. This leads to overheating and discoloration of the soda lime of the absorption system | http://meds.queensu.ca/anesthesiology/assets/Emergency_protocols/MALIGNANT_HYPERTHERMIA_Alorithm.pdf
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| Dantrolene in clinical use for treating: | Malignant Hyperthermia (MH), neuroleptic malignant syndrome, control of chronic spasticity (PO therapy), heat stroke, ecstasy intoxication | Relaxant properties due to its ability to reduce intracellular calcium and depress excitation– contraction coupling; | Anesth Analg 2010;111:1400–10
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