Substance dependence & withdrawal pharmacology Flashcards
List the pharmacological treatments required for acute alcohol withdrawal (try to get them in order of delivery).
Thiamine IV
Fluids & electrolytes (to correct dehydration and any imbalances).
Dextrose IV (when thiamine levels increased - prior can cause metabolic acidosis).
*Acamprosate: *administered immediately following acute withdrawal. It acts to re-establish some GABA and GLUTAMATE pathways.
Benzodiazepines: to manage discomfort, and prevent seizures and delerium.
List the pharmacological options for alcohol dependence managment / abstenence maintainence.
*Naltrexone: *acts as a partial antagonist to Opioid Mu receptors which minimises the positive reinforcers for alochol abuse such as euphoria leaving only the negative reinforcers.
Dilsulfiram: inhibits the liver enzyme, aceletylhydrogenase which functions to detoxify ethanol. This causes immedicate hangover like symptoms upon consumption of alcohol (minimising the positive reinforcers and exacerbating the negative).
Benzodiazepines: have a specific role in acute withdrawal however should be avoided in ongoing management of addition
What is phamalogically critical in prevention the progression of Wernick’s encephalopathy to Korskoff’s Syndrome?
Thiamine (B1), Thaiamine (B1) Thiamine (B1)
Why is it important to give thiamine and check levels prior to administration of dextrose to a patient with Wernicke’s encephalopathy?
The active form of thiamine acts as a coenzyme for many biochemical processes within the body including the metabolism of glucose. In the abscence of thiamine, glucose would not be metabolised down the full glycolysis pathway and thus would form lactic acid leading to metabolic acidosis.
If a patient undergoing withdrawal has a high risk of seizures, what medication should profolactically be given to the patient to prevent seizures during their withdrawal process?
Patients with high risk of seizures (history of previous withdrawal seizures, or those with moderate to high dependance) should be admisistered an antiseizure medication ie phenytoin or carbamazepine.
What is the name of the medication that can be given to reverse the effects of benzodiazepines?
Flumazenil
Flumazenil works be competitively binding benzodiazapine receptors on GABBA A receptors.
What is the general mechanism of action of Benzodiazapines.
Benzodiazapines work by allosterically binding to Benzo receptors located on GABBA A receptors (on post synaptic neurons). When Benzodiazapines bind to their receptors they induce a conformational change in the receptor which increases the GABBA A receptors affinity for GABBA thus increasing the frequency of opening of the GABBA A receptor channels allowing for hypoerpolarisation via influx of Cl-. In this hyperpolarised state GABBA neurons do not dolpolarise as readily and therefore cannot exert their inhibitory effects on other neurons in the CNS - hence benzodiazapines lead to over stimulation of the CNS including sense of euphoria.
Which medication acts as an Opioid reversal agent?
Naloxone is a long acting full opioid receptor antagoinist which competitively inhibits opioids for the Mu, Kappa and Delta opioid receptor binding sites. Thus Naloxone acts as a reversal agent for Opioids.
What two drugs used in combination (1 tablet) are considered first line for the treatment of opioid dependence?
Naloxone + Bupenorphine
Naloxone = opioid reversal agent (long acting, full antagonist of Mu (Opioid) receptors).
Bupenorphine = partial opioid agonist (long acting with ceiling effect - users cannot achieve desired effects from taking the drug as symptoms such as euphoria cannot be achieved.
List four medications important for use in the treatment of opioid dependence (including acute overdose).
Naloxone (reversal agent - long acting, full competitive antagonist at Mu (opioid) receptors.
Buprenorphine (long acting, partial competitive agoinist) with ceiling effect - desired effects ie euphoria unable to be achieved. Considered relapse prevention.
*Benzodiazepines METHADONE *- (complete agonist of of opioid receptors with long half life) used as opioid substitiution therapy which has ceiling effects ie reduced euphoria / positive reinforcers. Considered withdrawal / reduction adjunct.
*Naltrexone: *acts as a partial antagonist to Opioid Mu receptors which minimises the positive reinforcers. Relapse prevention.
