Clapp and Wackernah Article Flashcards
Recognize changes in neurotransmitter signaling systems that are associated with acute and chronic alcohol exposure, including adaptations that lead to the expression of withdrawal symptoms
In small amounts, EtOH inhibits the flow of ions through the NMDA glutamate receptor and enhances the activity of GABA receptor channels, overall inhibitory effect on neurons. Chronic alcoholism leads to responses that increase the potential excitability of neurons through up regulation of NMDA receptors. After cessation of drinking, there is a change in the balance between glutamate and GABA signaling resulting in a hyper excitability state. Changes in GABA system contribute to the antigenic and aversive effects of EtOH withdrawal.
What 3 medications (4 if you include the one in Europe) are approved for the treatment of alcoholism
Disulfiram, acamprosate and naltrexone. The european drug is nalmefene
Mechanism of action, contraindications and serious and common adverse effects of disulfiram?
Disruption of the normal alcohol metabolism pathway in the human body. Alcohol is converted into acetaldehyde by the enzyme aldehyde dehydrogenase. Disulfiram inhibits this enzyme leading to an unpleasant reaction of N/V, throbbing HA, flushing, tachycardia and palpitations that defer the patient from wanting to drink. Serious reactions include MI, CHF, arrhythmias, respiratory depression, convulsions and death.
Mechanism of action, contraindications and serious and common adverse effects of acamprosate?
Unknown mech. However, it is believed to normalize the balance between excitatory and inhibitory pathways and help with the discomfort that comes from withdrawal. Possible NMDA antagonism and reduction in glutamate receptors. Favorable safety and tolerability profile. Avoid in severe renal impairment.
Mechanism of action, contraindications and serious and common adverse effects of naltrexone?
Interacts with dopamine and the endogenous opioid neuropeptide systems. (competitive opioid antagonist)
Primary side effect is GI discomfort (nausea). Other side effects: HA, dizziness, nervousness, fatigue, insomnia.
Contraindicated in patients currently taking opioid agonists.
Summarize the findings from the COMBINE trial that support the use of naltrexone and/or acamprosate
Acamprosate: The trial showed no benefit for acamprosate when compared to placebo in reducing alcohol use in treatment-seeking alcoholics.
Naltrexone demonstrated improvements in maintain abstinence and reducing heavy drinking. High clinical efficacy in the use in psychotherapy for short treatment periods.
Compare/contrast the effectiveness of the 3 approved medications for alcoholism with regard to treatment goals and specific drinking outcomes
Disulfiram reduces cravings and prevents relapse due to changes in neurotransmission.
Acamprosate improves abstinence rates, percent days absent and time to first drink
Naltrexone reduces the rate of heavy drinking events by 25%
