SODIUM CHANNEL ANTAGONISTS AND CHLORIDE CHANNEL AGONISTS SODIUM

SODIUM CHANNEL ANTAGONISTS AND CHLORIDE CHANNEL AGONISTS

SODIUM and CHLORIDE CHANNELS Erythroxylon coca and Erythroxylon novogranatense the first local anesthetic to be discovered Cocaine

SODIUM and CHLORIDE CHANNELS COCAINE Karl Koller ophthalmologic local anesthetic Halsted regional anesthesia Sigmund Freud "I take very small doses of it regularly and against depression and against indigestion, and with the most brilliant success", Über Coca (1884) as a mental stimulant as a possible treatment for digestive disorders as an appetite stimulant in case of wasting diseases as a treatment for morphine and alcohol addiction as a treatment for asthma as an aphrodisiac as a local anaesthetic According to the Sears, Roebuck and Co. Consumers' Guide (1900), their extraordinary Peruvian Wine of Coca. . . ". . . sustains and refreshes both the body and brain. . It may be taken at any time with perfect safety. . . it has been effectually proven that in the same space of time more than double the amount of work could be undergone when Peruvian Wine of Coca was used, and positively no fatigue experienced. . . "

SODIUM and CHLORIDE CHANNELS Angelo Mariani Henrik Ibsen, Émile Zola, Jules Verne, Alexander Dumas, Robert Louis Stephenson, and Sir Arthur Conan Doyle Queen Victoria, King George I of Greece, King Alphonse XIII of Spain, the Shah of Persia, and by William Mc. Kinley, President Pope Pius X was an enthusiast, as was Pope Leo XIII

SODIUM and CHLORIDE CHANNELS Pemberton's French Wine Coca "a most wonderful invigorator of the sexual organs" “Pemberton's French wine cola” Prohibition in 1886 “Coca-Cola: the temperance drink” "a substitute for food so that people could live a month, now and then, without eating. . . " Gentleman's Magazine Federally-regulated in December 1914 - the Harrison Act

SODIUM and CHLORIDE CHANNELS Local Anesthetics rate of rise of action potential declines increase threshold for excitation -- slows impulse conduction -finally ability to generate AP is lost due to ability of local anesthetic to block Na+ channels and thus block Na+ current

SODIUM and CHLORIDE CHANNELS anesthetic binds to open channels

SODIUM and CHLORIDE CHANNELS COCAINE TOXICITY Profound Vasospasm Seizures/Intracranial Hemorrhage (2° to HTN) Myocardial Infarction/Dysrhythmias/Aortic Dissection (2° to HTN) Rhabdomyolysis leading to Acute Renal Failure

SODIUM and CHLORIDE CHANNELS Can Na+ channel inactivation account for the myriad toxic clinical symptoms? NO! Overwhelming activation of the sympathetic limb of the autonomic nervous system

SODIUM and CHLORIDE CHANNELS ALCOHOL Consumption is part of cutural history Mesopotamia Egypt India Greeks/Romans SYMPOSIUM a meeting or conference for the public discussion of some topic (in classical Greece) a drinking party with intellectual conversation, music, etc Greek sumposion, from sumpinein to drink together, from sum- syn- + pinein to drink

SODIUM and CHLORIDE CHANNELS

SODIUM and CHLORIDE CHANNELS g - aminobutyric acid (GABA) receptor/channel ligand gated Cl- channel Et. OH is an agonist 2 a: 2 b: 1 g (CNS depressant)

SODIUM and CHLORIDE CHANNELS DISULFRAM Used in the rubber industry as an antioxidant Et. OH alcohol dehydrogenase acetaldehyde workers were hypersensitive to Et. OH acetaldehyde dehydrogenase ACETALDEHYDE SYNDROME vasodilation/flushing throbbing headache nausea/copious vomiting blurred vision

SODIUM and CHLORIDE CHANNELS

SODIUM and CHLORIDE CHANNELS