Q.1 Mary-Lou is suffering from depression and the early onset of Alzheimer’s disease. The characteristic symptoms and pathophysiology of both the diseases are as following:
Depression: The characteristic symptoms of depression that Mary-Lou had included lost interest in the activities that she used to love, lowered self-esteem and excessive crying. Depression does not have actual pathophysiology but multiple hypotheses related to the depleted levels of the neurotransmitters dopamine, serotonin (5-HT) and norepinephrine (NE) in the central nervous system (CNS). The most widely accepted hypothesis is the hypothesis which states that following certain traumatic events; the neural circuits inside an individual’s brain get constricted leading to the hypoproduction and easy reuptake of these neurotransmitters produced, without their final conversion into the final product. This reuptake occurs with the help of mono-amino oxidase (MAO) enzyme. The overall decreased levels of dopamine, 5-HT and NE in the CNS leads to depression.
Alzheimer’s disease: Mary-Lou’s symptoms of Alzheimer’s disease include her depression, getting lost while wandering and her gradually impairing memory. For Alzheimer’s disease also, multiple hypotheses are present. The first one is the cholinergic hypothesis, according to which a potential cause of the disease is the lack of central cholinergic neurons and ensuing deficiency of acetylcholine, a neurotransmitter responsible for memory and learning. According to the amyloid hypothesis, part of a process of amyloid precursor proteins (APP) cleavage is impaired resulting in progressive neuronal loss in the cortex. APP is pathologically cleaved by beta-secretase, leading to the formation of extracellular insoluble amyloid-beta oligomers and plaques. Tau hypothesis states that tau proteins undergo phosphorylation and accumulate into intracellular neurofibrillary tangles, which may result in the disease.
Q.2 The mechanism of action of the two classes of drugs prescribed to Mary-Lou are as following:
Fluoxetine/Prozac: Fluoxetine, which was prescribed to Mary-Lou is sold under the brand name Prozac and belongs to the antidepressant drug group selective serotonin reuptake inhibitors (SSRIs). This category of drug works more selectively towards the inhibition of the pre-synaptic reuptake of serotonin only. Serotonin thus present can induce emotional excitation after binding to its post-synaptic receptors and can contribute to reduced symptoms of depression.
Cholinesterase inhibitors: Under normal conditions, acetylcholine (ACh) is synthesised in the brain by cholinergic neurons from acetyl coenzyme A and choline and upon the arrival of neuronal impulse, ACh is released into the synaptic cleft where ACh interacts with its receptors present on the postsynaptic neurons. Here, ACh is broken down to form acetate and choline by cholinesterase enzymes, thus terminating stimulating signals. Since Alzheimer’s disease is associated to the deficiency of ACh in the brain, cholinesterase inhibitors were interposed to alleviate the symptoms of the disease by inhibiting cholinesterase enzymes from breaking down ACh, thereby increasing both the level and duration Ach action.
a) The pharmacokinetic factors associated with Mary-Lou’s antidepressant medication Fluoxetine/Prozac are as following:
Since Fluoxetine is highly bound with protein, it is absorbed well following in taking it orally. The pharmacokinetic profile of Fluoxetine is not linear; therefore, it has to be used cautiously in case of patients who have alleviated capacity of metabolism, for example, patients have impaired hepatic function. Fluoxetine interacts with other antidepressant drugs such as MAO inhibitor drugs and these interactions can cause serious complications, leading to the serotonergic syndrome. Furthermore, it has a wide distribution volume and after ingestion, it is metabolized to norfluoxetine. The half-life for the elimination of Fluoxetine is around 1-4 days while for Fluoxetine’s metabolite, norfluoxetine, it is between 7-15 days. So, there should be at least a 2-week gap between the top of one and the start of other medication. Additionally, the pharmacokinetics of Fluoxetine is not affected by age of the patient taking it and is better suited in elderly individuals.
b) Fluoxetine can interact with other antidepressant drugs including mono-amine oxidase inhibitor drugs, and these interactions can give rise to serious complications, sometimes causing serotonergic syndrome also. So to avoid any such complication, no other antidepressant drug can be administered while the intake of Fluoxetine is continuous. There should be a gap of at least two weeks before the stop of Fluoxetine intake and the start of any other antidepressant drug to make sure that Fluoxetine has completely left the system.
Q.4 Based on Mary-Lou’s critical picture, it is clear that she is suffering from depression. Although she does not have an alcohol addiction and drinks wine only to cope with her depression. She finds the sedation from the alcohol as a sort of medication for her sadness. Therefore, it is clear that Mary-Lou’s depression had put her at a higher risk of developing alcohol problems, as in her case study also the symptoms of her depression preceded her alcohol abuse.
People with physical dependence on alcohol experience multiple withdrawal symptoms following their alcohol abstinence. Physical dependence is characterized by the consumer’s body getting adapted to the regular high doses of alcohol.
Psychological dependence, which is commonly referred to as addiction is characterized by risky, impulsive behaviours with continuous alcohol use despite its visible negative effects such as health, finance or relationships related problems.
Generally, people who suffer from alcohol or drug abuse have both physical and psychological dependence but either of these dependencies can also happen without the presence of the other. Similarly, Mary-Lou was physically dependent on alcohol, as she did not experience any ill-effects resulting from alcohol use and her doctor also prescribed her Diazepam, which was supposed to help her with the withdrawal symptoms.
Q.5 Mary-Lou is suffering from osteoarthritis in her hip joints because of which she was experiencing crepitus. Osteoarthritis is a condition that occurs in the synovial joints where two bones are separated by articular cartilages, which are responsible for the absorption of shock and the gliding between the two bones. The junction of the bones in a synovial joint is characterised by an articular capsule, which is comprised of the fibrous layer and the synovial membrane. The synovial membrane secretes the viscous synovial fluid that provides additional lubrication to the joint. In osteoarthritis, there is a progressive loss of the articular cartilage leading to the loss of joint space.
This results in the addition of a significant amount of friction in the middle of the two bones, thereby generating inflammation and triggering pain via the nerve endings in this joint space. When the condition becomes severe, bone comes over bone and bone spurs known as osteophytes are formed. In addition to crepitus, symptoms of osteoarthritis include the stiffness of joints in the morning, which generally lasts for less than an hour and comes back at the end of the day and a sharp ache or burning sensations in the joints, which worsens with activity.
Q.6 The aetiology of osteoarthritis is different from other joint diseases in numerous ways. There can be multiple causes that can be attributed to the occurrence of osteoarthritis, which is a degenerative condition of joints caused due to the wear and tear of the joints. The known factors associated with osteoarthritis are as following: ageing, genetics, gender, sports injuries, obesity and bleeding near the joints. Osteoarthritis prevails with growing age and is usually associated with elderly people. Genetics play an important role in the occurrence of the condition i.e. a person with the family history of osteoarthritis is likely to have it. Furthermore, the disease predominantly occurs in older females than males. Sports injuries such as torn cartilage, joint dislocation and injuries of ligaments can increase the risk of osteoarthritis. Wear and tear caused due to strenuous activities and overweight could also lead to arthritis because it puts additional mechanical stress on the joints and can cause the articular cartilage to wear off prematurely. Moreover, an injury leading to bleeding near a joint can make osteoarthritis worse or can develop new symptoms related to osteoarthritis.
Q.7 Mary-Lou’s fracture can take longer to heal than it would for someone who was half her age because she has decreased bone density and porous bones due to her age-related condition, osteoporosis, as diagnosed through her T-score. The healing phase of a bone is divided into three stages: inflammatory stage, repair stage and remodelling stage. Patient-related physiological factors that can influence the healing of a bone include the presence of co-morbidities, oestrogen level and the presence of vascularisation at the site of fracture. In general, fracture reunion takes longer in elderly adults because of the reduced density of bones (osteoporosis), which acts as co-morbidity hindering the healing process.
Reduced oestrogen level in post-menopausal females also contributes to delay in healing as oestrogen inhibits the process of bone resorption. Furthermore, vascularisation to the bones is reduced with age which also prolongs healing. Hip fracture in elderly adults brings along more complications than in younger adults and is often presumed to be a death sentence. One-third of adults aged over 50 years die within one year of suffering from a hip fracture and within 3 months of having a hip fracture, risk of dying increases by 5 to 8 times. This increased risk remains almost for the next 10 years. In addition to suffering pain, hip fracture in elder adults worsens the quality of their life by increasing dependency and decreasing physical functions.
Q.8 The T-score from Mary-Lou’s DEXA scan came out to be -3.0, this suggests that she is suffering from osteoporosis as a T-score of -2.5 or lower is a diagnosis of osteoporosis. Osteoporosis is a disease characterised by a higher breakdown of the old bone as compared to the formation of new bone, resulting in the formation of porous bones, which means a reduction in the bone density to the point of a potential fracture. Under normal conditions, bones are replaced every few years by the process of bone remodelling, which comprises of two steps: bone resorption, in which bone is broken down by osteoclasts; and bone formation, in which new bone is formed by osteoblasts.
The entire process of bone remodelling is highly dependent on the calcium levels of serum, which are kept in a normal range by a balance between parathyroid hormone (PTH), Vitamin D and calcitonin. When the breakdown of bone by osteoclasts is faster than its rebuild by the osteoblasts, it results in lowered bone mass and eventually osteoporosis. Treatment of osteoporosis usually relies on bisphosphonate drugs, which prevent the loss of bone density and decrease the risk of fractures. Bisphosphonates reduce osteoclast-mediated bone resorption by either stimulating osteoclast apoptosis or by inhibiting cholesterol synthetic pathway, leading to decreased osteoclast function.
Q.9 Two of the triggers for Hilda’s respiratory condition are cold temperatures and pollens. Firstly, cold weather or temperature creates the spasms within the lungs and when the air passes through the nose, unlike in non-asthmatic people, it does not get warmed up and affects the lungs badly as people with asthma already have twitchy lungs. It makes them more susceptible to having the spasm, which then constricts the lumen of the airway and makes the symptoms of asthma appear. Pollens can also be a potent trigger for asthma patients as the body’s immune system mistakes it as an invader, causing immune responses against it. The antibodies of the immune system bind to the pollens to protect the body, resulting in the release of chemicals such as histamine, thereby causing the asthma symptoms to worsen by creating an inflammatory response in the lungs and causing muscle contractions in the branches of the airways present in the lungs. These contractions that occur can cause the person to feel wheezy and tight in the chest.
Q.10 The two characteristic symptoms of Hilda’s respiratory disease are wheezing and coughing. In Asthma patients, during an asthma attack when the lungs go into spasm, the smooth muscles in the airway also spasm and constrict and the opening of the airway lumen is reduced as the muscular layer thickens and clamps down on the opening. In addition to this, the mucus layer which is present inside the smooth muscle layer also swells up in reaction to the inflammation and becomes amorphous in shape rather than a smooth round opening, which was present before the attack. This amorphous shaped mucus layer further clamps down the lumen, making it much smaller. The mucus glands present in the mucus layer also react to the immune response and get filled up with mucus, which is then secreted into the lumen making the lumen even narrower and blocked off. Between this constriction and the fluid, little bubbles are present that are responsible for the popping and wheezing during an asthma attack. This wheezing comes from both mechanical narrowing of the lumen and the extra fluid present in there. This obstruction of the airways makes it harder for the air to get in and out of the lungs making the person cough a lot.
Q.11 One of Hilda’s anti-asthma medications is the corticosteroids which were given to her in the hospital. Corticosteroids are a kind of anti-inflammatory drugs used to reduce inflammation, production of mucus and swelling in the airways of the individual suffering from asthma. This results in the airways that are less inflamed and lesser likely to react to the triggers for asthma and allows people with asthma symptoms to have better control over their disease. Corticosteroids/glucocorticoids work to decrease inflammation in multiple ways. After their passage via the cell membrane, they bind to the glucocorticoids specific receptor proteins found in the cytoplasm of the cells of our body, the cells then send signals to decrease the production of cells and proteins that promote inflammation and activate the immune system. They also activate the production of anti-inflammatory proteins. All of this makes glucocorticoids very effective anti-inflammatory medication reducing the symptoms of asthma.
Q.12 The two measures following which Hilda’s chances of contracting coronavirus can be minimised include staying safe at home and maintaining proper social distance and taking all the necessary precautions when outside, in extremely urgent situations. To prevent microorganisms from contracting to more people, the chain of infection has to be broken. This can be done at six points and the germs can be prevented from infecting any further people. The first link is the pathogen itself that acts as the agent of infection. The second link is the reservoir, which includes the places where the pathogen lives. The third link is the way of exit of the infectious agent from the infected person, such as aerosols and open wounds.
Next link is the mode of transmission of the pathogen such as inhalation, ingestion and direct/indirect contact. Furthermore, portal/way of entry of the pathogen via which the pathogen can enter a new host is also a point where the chain of infection can be broken. The last point of breaking the chain of infection is the susceptible host, who can be any individual receiving healthcare or immune-compromised. Similarly, Hilda’s chances of contracting coronavirus can be minimised by breaking the chain of coronavirus infection at any of the aforementioned points, but the most efficient point for her will be to isolate herself at home.
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