Question

Mary-Lou is a 75-year-old widow, who lost her husband to cancer over a year ago. Her family and friends have noticed that she has been very teary, has low self-esteem and has lost interest in the things she used to love such as going to bingo with her friends and gardening. Her family initially put this down to the loss of her husband and thought it would pass with time. However, they are now getting really concerned as they have noticed that her mood is not improving still. When asked by her daughter if she is sleeping well, she says she has been drinking wine every night to help her go to sleep. It makes her feel happy and relaxed. What started as one glass a night has now increased to two or three glasses a night, and she has also started drinking during the day. Her daughter has noticed that her mum’s face always appears flushed and that she has had quite a few colds lately. Mary-Lou is also losing her balance and experiencing mood swings. Her daughter is worried that she is relying too heavily on alcohol and fears that she is starting to get short-term memory loss from the alcohol consumption. She has been forgetting things such as where she put her keys, whether she turned on the washing machine, why she opened the fridge and forgetting the topic of conversation when talking with her daughter on the phone. Mary-Lou has also been getting disorientated and getting lost when she goes out on her daily walks. A neighbor rang her daughter one day to tell her that she found Mary-Lou wandering around aimlessly, and when questioned what she was doing Mary-Lou snapped and said she was trying to get home. Her daughter decided it was time to take Mary-Lou to the local GP to work out what was going on with her. After listening to the signs and symptoms Mary-Lou was experiencing, the GP diagnosed her with depression and prescribed 50 mg of Fluoxetine/Prozac daily. Based on the results of clinical and radiological assessments, the GP determined that she had early onset Alzheimer’s disease. He prescribed a cholinesterase inhibitor and gave them information on support groups and tips on what to do from here on in. He also prescribed 10 mg of Diazepam daily to help with the withdrawals from alcohol abuse.

Explain the mechanism of action of two drug types Mary-Lou is prescribed with and describe how these drug actions help mitigate some of her symptoms. In your answer, make references to the pathophysiology of the relevant diseases. Explain how these drug help to mitigate her symptoms.

Answer 1

Alzheimer's disease is characterised by deficiency of working cholinergic neurons, particularly those neurons from the nucleus basalis of Meynert (the subcortical area). As a result, there is progressive dementia. The cholinesterase inhibitor drugs, prevents the break down of acetyl choline in the synapses. Hence they enhance the levels of acetyl choline in the central nervous system. Donepezil, Rivastigmine and Galantamine are the 3 cholinesterase inhibitor drugs which are used. They delay the symptoms progression. They cross the blood brain barrier, have long duration of action.

Alcohol withdrawal is characterised by symptoms such as tremor, irritability, tachycardia, hypertension, sweating, nausea, seizures, sleeplessness, visual hallucinations and delirium tremens. Repeated alcohol use leads to necessity of more and more alcohol to produce the effects previously produced by small amounts . This is due to tolerance. Cellular tolerance occurs due to neurochemical changes that lead to relatively normal physiological function, even in the presence of alcohol. The cellular changes that occurs due to chronic ethanol exposure will not resolve immediately following cessation of alcohol intake. It will take several weeks to resolve. So rapid decrease in blood levels of alcohol within this period produce withdrawal syndrome. Alcohol being a CNS depressant and withdrawal symptoms are due to the absence of this depressant, depressant drugs such as benzodiazepines(diazepam) is used to treat withdrawal symptoms. These drugs promote binding of inhibitory neurotransmitter GABA to GABA - A receptor and thus causes inhibition at all levels of neuraxis.