Addiction Pharmacotherapy for Alcohol Use Disorders David A. Frenz, M.D. [email protected]26 September 2010 Positive cravings Acute drinking Reward circuitry activated Chronic drinking Reward circuitry dysregulated Withdrawal Negative cravings Relapse Pregabalin Oxcarbazepine Topiramate Acamprosate Ondansetron Aripiprazole Naltrexone Varenicline Baclofen Disulfiram Disease of Addiction Medication Options Adapted from: Cleve Clin J Med 2006;73:641.
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Addiction Pharmacotherapy for Alcohol Use Disorders
• Are electrochemical impulses (waves) that transmit information within neurons!
• Cause neurotransmitter release into the synapse!
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Action potential!
Signal!
Synapse!
• Synapses are specialized junctions were neurons communicate with each other and other tissues(e.g., muscles, glands)!
• Each neuron has up to 15,000 synapses!• Each cubic millimeter of cerebral cortex contains
about 1 billion synapses!• There are roughly 100–500 trillion synapses in the
brain!
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Synapse!
http://www.drugabuse.gov/jsp/MOD3/page3.html!
Neurotransmitters!
• Are chemicals that transmit information from neurons to others cells!– Other neurons!– Muscles, glands!
• Are stored in vesicles in the presynaptic neuron!• Are released into the synapse by action potentials!• Act upon the postsynaptic tissue!
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Receptors!
• Are molecules to which ligands bind!• Ligands include!
– Neurotransmitters!– Hormones!– Medications and substances that are abused!– Poisons and toxins!
• Receptor-ligand relationships are very specific—“lock and key”!
Receptor-ligand!
http://www.drugabuse.gov/jsp/MOD3/page3.html!
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Wikimedia!
Neurotransmission!
Action potential!
Neurotransmitterreleased into the synapse!
Neurotransmitters!
• Can be excitatory or inhibitory!• Excitatory neurotransmitters!
– Make postsynaptic action potentials more likely!• Inhibitory neurotransmitters!
– Make postsynaptic action potentials less likely!
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Neurotransmission—excitation!
Action potential! Action potential!
Excitatory neurotransmitterreleased into the synapse!
Muscle,!gland, et cetera!
Neurotransmission—inhibition!
Action potential!
Inhibitory neurotransmitterreleased into the synapse!
Muscle,!gland, et cetera!
Key concept!
• Psychotropic medications and substances that are abused exert their effects—both intended and unintended—by affecting neurotransmission at the synaptic level!
“ !They are restless, irritable and discontented, unless they can again experience the sense of ease and comfort which comes at once by taking a few drinks… After they have succumbed to the desire again, as so many do, and the phenomenon of craving develops… ”!
David A. Frenz, M.D.!Mental Health & Addiction Services!HealthEast St. Josephʼs Hospital!45 West 10th Street!St. Paul, MN [email protected]!651-232-3640 (department)!651-326-3730 (voice mail)!