NRS 641 Pathophysiology Discussion Papers – Solution Samples

Topic 3 DQ 1

Fluid, Electrolyte, and Acid-Base Balance: Hyperkalemia.

Hyperkalemia is a medical condition characterized by elevated blood potassium levels above 5.0 mmol/L (Jafar et al., 2020). potassium is an important intracellular electrolyte required for the normal function of nerves, heart, and muscles. A disturbance in potassium levels negatively affects the functioning of these systems. This can manifest as muscle weakness, paralysis, numbness, palpitations, tingling, chest pain, and shortness of breath. Notably, potassium levels above 7 cause hemodynamic instability, while levels above 8mmol/l lead to respiratory paralysis.

NRS 641 Pathophysiology Discussion Papers

The normal range of potassium is between 3.5- 5.0 mmol/l. (Jafar et al., 2020). The balance of ranges of potassium is dependent on kidney functions and intake. The kidney plays a vital role in the excretion of excess potassium secretion through urination to maintain the balance. On the other hand, diet provides the body with potassium to avoid a deficit. The foods rich in potassium include bananas, orange juice, cantaloupe, and honeydew melon. Any dysfunction in kidney function with increased intake of potassium-rich meals creates an imbalance that increases serum potassium levels.

Kidney dysfunction can be contributed by various factors, including acute and chronic renal failure, drugs, comorbidities, and Addison`s disease (Simon et al., 2022).  Kidney failure leads to impairment of excretion, leading to the buildup of potassium and other electrolytes. Furthermore, medications such as amiodarone and spironolactone are potassium-sparing, leading to limited excretion by the kidneys.

In addition, other medications such as angiotensin-converting enzyme inhibitors and non-steroidal anti-inflammatory drugs can result in hyperkalemia due to a decrease in glomerular filtration rate and aldosterone. Hypoaldosteronism causes Addison’s disease that further worsens hyperkalemia. Likewise, the presence of commodities such as diabetes type 1 causes derangement in kidney function that leads to hyperkalemia. Finally, intravasation of potassium from extracellular space following serious burns and penetrating trauma can worsen hyperkalemia. All the mentioned process combines to cause non-specific physiologic changes manifesting as hyperkalemia features.

Patient education is an important aspect of patient care. Patients should be informed about the potential causes of hyperkalemia, including diet and drugs. Therefore, patients with hyperkalemia should limit the intake of potassium-rich meals and equivalent supplements. Also, they should stop taking medications, including potassium-sparring diuretics, NSAIDs, and ACE inhibitors, to prevent the risk of hyperkalemia (Simon et al., 2022). Patients should also be taught to check their pulse and identify early features of hyperkalemia for prompt management.  Finally, patients should have their potassium levels checked regularly as well as take all prescribed medications appropriately.


NRS 641 Pathophysiology Discussion Papers Topic 3 DQ 2

Management of hyperkalemia.

Management of hyperkalemia is subject to understanding the cause and severity of the conditions. Treatments are cause-specific aimed at increasing the excretion of potassium. As a result, several treatment modalities are present. The initial care limits the oral intake of potassium-rich meals(Khan et al., 2022). Calcium gluconate is used to stabilize the cardiac in the setting of hyperkalemia. Insulin and dextrose are used to shift potassium into cells.  Finally, loop diuretics can be used to increase urinary excretion of potassium. Details of furosemide are discussed hereafter.

Furosemide is an example of the loop diuretic used to manage hyperkalemia. Furosemide causes diuresis by inhibiting the sodium-potassium-2 chloride (Na+-K+-2Cl) co-transporter in the thick ascending loop of Henle and distal convoluted tubule (Khan et al., 2022). Therefore, it is used in conditions associated with water overload.

Such conditions include pulmonary edema, congestive heart failure, renal failure, liver failure, and ascites. Its use in the management of hyperkalemia is guided by the principle of inhibiting potassium absorption while increasing its elimination through urine. However, understanding its pharmacodynamics is necessary for monitoring this medication.

Furosemide is through either the oral or intravenous route. However, the dosage is adjusted according to renal functions. Patients with renal dysfunction or kidney failure should receive a lower dosage to lower the risk of toxicity due to a reduction in clearance(Palmer et al., 2021). Therefore, caution should be taken when prescribing medications to people above 65 years. Ototoxicity can also develop more so when administered with ethacrynic acids.

Hearing impairment can result from ototoxicity. Hence co-administration with ethacrynic acid is contraindicated.  Furthermore, furosemide causes increased water loss and electrolytes leading to dehydration and electrolyte imbalances. Those imbalances include hypomagnesemia, hyponatremia, hypokalemia, and hypocalcemia. Therefore, monitoring of renal functions is essential when taking furosemide. Other adverse effects include diarrhea, anemia, abdominal cramps, anorexia, headache, vertigo, orthostatic hypotension, hyperglycemia, and glycosuria.   

Finally, furosemide has some drug-drug interactions that must be considered. For instance, ethacrynic acid works with the same mechanism as furosemide leading to serious adverse effects when co-administered, therefore, contraindicated (Palmer et al., 2021). Furthermore, it has pharmacodynamic synergism with some agents, including gentamicin, tobramycin, streptomycin, potassium phosphate, and squill. Either of the products increases the effects of the other resulting in worsening adverse effects.


  • Khan, T. M., Patel, R., & Siddiqui, A. H. (2022). Furosemide. In StatPearls [Internet]. StatPearls Publishing.
  • Palmer, B. F., Carrero, J. J., Clegg, D. J., Colbert, G. B., Emmett, M., Fishbane, S., Hain, D. J., Lerma, E., Onuigbo, M., Rastogi, A., Roger, S. D., Spinowitz, B. S., & Weir, M. R. (2021). Clinical management of hyperkalemia. Mayo Clinic Proceedings. Mayo Clinic, 96(3), 744–762.

NRS 641 Pathophysiology Discussion Topic 4 DQ 1

HEENT: Detached Retina

Retinal detachment is a medical condition characterized by separation and pulling of the retina from the retinal pigment epithelium, potentially leading to vision loss (Chen et al., 2018). The retina is an internal layer of the eye with numerous nerve vessels that help in image focusing and transmission of information to the brain through the optic nerve to enable vision. Therefore, any dysfunction in the retina leads to interference in visual fields with resultant vision loss.

Detachment of the retina also causes deprived oxygen and nourishment supply that can potentially cause nerve cell death and vision loss (Chen et al., 2018). However, other features, including darkness, flashlights, reduced vision, and loss of peripheral visual fields, may precede visual loss and blindness.

Detachment of the retina is a process culminated by various factors and steps. Causes of detachment can be due to several factors, including inflammation, injury, damage, or structural changes. Inflammation causes exudation of fluids with or without a tear to cause increased intraocular pushes that push away the retina to cause detachment.  Other causes of exudation leading to detachment include injury to the blood vessels and age-related macular degeneration.

Furthermore, injury to the eye or eye surgery can lead to retinal tear that causes accumulation of vitreous gel that pulls the eyeball.  This process is termed rhegmatogenous; it is the most common.  In addition, patients with diabetes with poorly controlled blood sugar are predisposed to diabetic retinopathy. Retinopathy causes scarring within the eyeball, pushing away the retina, leading to its detachment. This process is called tractional detachment.

All these processes integrate risk factors for retinal detachment. Moreover, other risk factors for a detachment include genetics, previous eye surgery, severe myopia, infectious diseases, previous detachment of the eye, pre-eclampsia, cancer of the eye, and trauma.

Finally, patients with retinal detachment are prone to visual problems resulting in visual loss and falls. Therefore, patient education is necessary before or during treatment. First, the patient should be encouraged to increase lighting, remove all hazards, and ask family members to direct them while walking to prevent falls (Kwok et al., 2020). 

Secondly, patients should not rub their eyes and protect their eyes with eye patches during sleep.  Lastly, patients should sleep on either side with an elevated head to help reduce intraocular pressure and reduce the worsening of the retinal detachment.  Patients should also adhere to medications and be prepared for surgery in case of symptoms worsen.


NRS 641 Topic 4 DQ2

Treatment of Retinal Detachment.

Retinal detachment is a medical emergency that requires prompt ophthalmologist review with the initiation of care. Treatment can either be medical or surgical. Surgical treatment is the definitive management upon identification of the course (Bonfiglio et al., 2020). On the other hand, medical therapy is auxiliary aimed at relieving symptoms while reducing intraocular pressure. Common medical therapy includes acetazolamide, Tenecteplase, and triamcinolone acetonide. Acetazolamide is discussed hereafter.

Acetazolamide is a diuretic agent classified as a carbonic anhydrase inhibitor. It acts by inhibiting carbonic anhydrase activities, leading to increased carbonic acid levels (Bonfiglio et al., 2020). Elevated carbonic acid leads to a reduction in body pH with the resultant acidic body. Sodium bicarbonate and chlorides are excreted in an acidic environment with resultant loss of water. As a result, increased diuresis leads to decreased blood pressure, intracranial and intraocular pressure. Reduction in aqueous humor reduces the risk of retinal detachment and optic nerve. Therefore, this medication can be given either orally or intravenously to reduce intraocular pressure. However, monitoring of side effects is essential.

Acetazolamide causes increased water loss with loss of electrolytes, including sodium, sodium bicarbonate, and chlorides. This can result in hyponatremia, hypokalemia, and metabolic acidosis(Farzam & Abdullah, 2022). Therefore, kidney function and blood gases must be evaluated on patients taking acetazolamide. In addition, the administration of acetazolamide leads to reduced clearance of ammonia that increases the risk of hepatic encephalopathy.

Unfortunately, patients with kidney and hepatic dysfunction are at an increased rate of encephalopathy, hence monitoring is mandatory. Finally, other common side effects include dizziness, confusion, tinnitus, low libido, paresthesia, black stool, vomiting, nausea, agitation, blurred vision, and abdominal pain. Patients with sulfa allergy may develop Steven Johnson`s syndrome (SJS) by using acetazolamide.

Lastly, acetazolamide interacts with other agents when taken concurrently. For instance, acetazolamide causes increased urine pH, reducing renal clearance of amphetamines, thus increasing its toxicity (Liao & Zhu, 2019). When administered with acetazolamide, other medications with reduced clearance include phenytoin, primidone, and quinidine. In contrast, acetazolamide increases lithium’s excretion, resulting in reduced efficacy of lithium. Furthermore, there is a risk of kidney stones formation on administering acetazolamide with sodium bicarbonate. Finally, the prescription of more than one carbonic anhydrase is discouraged due to the risk of pharmacodynamic synergism that may cause worse adverse effects.


  • Bonfiglio, V., Reibaldi, M., Macchi, I., Fallico, M., Pizzo, C., Patane, C., Russo, A., Longo, A., Pizzo, A., Cillino, G., Cillino, S., Vadalà, M., Rinaldi, M., Rejdak, R., Nowomiejska, K., Toro, M. D., Avitabile, T., & Ortisi, E. (2020). Preoperative, intraoperative, and postoperative corticosteroid use as an adjunctive treatment for rhegmatogenous retinal detachment. Journal of Clinical Medicine, 9(5), 1556.
  • Farzam, K., & Abdullah, M. (2022). Acetazolamide.
  • Liao, L., & Zhu, X.-H. (2019). Advances in the treatment of rhegmatogenous retinal detachment. International Journal of Ophthalmology, 12(4), 660–667.

NRS 641 Topic 5 DQ 1

Cardiovascular and lymphatic system: Arteriovenous Malformations.

Arteriovenous malformations (AVM) are abnormal fistula formation between arteries and veins without a capillary bed (Bokhari & Bokhari, 2021). Arteries functions to pump blood to other parts of the body while veins return the blood to the heart to complete a cycle. Capillaries allow for normal connections between arteries and veins while facilitating the supply of oxygen and essential nutrients to the body. In AVM, abnormal communication interrupts the normal function of arteries, veins, and capillaries. Lack of capillary bed leads to deprived oxygen and nutrients to tissues due to high flow of blood that disrupts nutrient exchange and oxygen (Bokhari & Bokhari, 2021). Hence patients are at risk of low oxygen saturation.

AVMs always occur during early development or shortly after birth. Also, they can occur in any part of the body. However, they are most common in the brain and spinal area (Schimmel et al., 2021). Interestingly, patients may live a normal life without symptoms. Some may be picked incidentally during examination for other pathologies, including chronic headaches and seizures. However, they tend to increase in size with time to cause symptoms. Large AVMs are at risk of rupture resulting in severe hemorrhage and hemodynamic instability.

Bleeding to the brain may lead to increased intracranial pressures (ICP). Increased ICP includes such features as headache, seizures, progressive loss of neurological dysfunction, loss of consciousness, and vomiting. Notably, other risk factors for AVM rupture include prior hemorrhage, deep AVM location, presence of an aneurysm, and exclusive deep venous drainage. In addition, stroke can also develop in the process. Stroke presents with limb weakness, problems in speech, visual problems, and loss of consciousness. Finally, fatal hemorrhage can lead to death.

Finally, patients with AVM should be educated on how t prevent complications. First, patients should adhere to follow-up in the hospital for periodic assessment and early identification of risks of hemorrhage. Secondly, patients should be aware of the deleterious effects of hypertension on AVM (Schimmel et al., 2021). Therefore, patients should avoid strenuous activity and lifting heavy objects to prevent rupture of vessels. Thirdly, patients should not take any anticoagulants due to the increased risk of bleeding due to these medications. Finally, patients should be educated about danger signs, including neurological deficit, loss of consciousness, repeated seizures, and worsening headache. These signs may require prompt care lest they cause general deterioration.


Bokhari, M. R., & Bokhari, S. R. A. (2021). Arteriovenous malformation of the brain. StatPearls Publishing.

Schimmel, K., Ali, M. K., Tan, S. Y., Teng, J., Do, H. M., Steinberg, G. K., Stevenson, D. A., & Spiekerkoetter, E. (2021). Arteriovenous malformations-current understanding of the pathogenesis with implications for treatment. International Journal of Molecular Sciences, 22(16), 9037.

NRS 641 Pathophysiology Discussion Topic 5 DQ 2

Management of AVM

AVM management involves complex procedures aimed at correcting the defect and improving patients` quality of life. The mainstay of management is surgery. Radiosurgery and endovascular embolization are common interventional procedures in unstable patients(Gupta & Tripp, 2022). However, there is a role of medical management in stable people using anticonvulsants for seizure control and analgesics for pain management. Phenytoin is the most common anticonvulsant used.

Phenytoin is a hydantoin derivative that controls seizures by blocking voltage-gated sodium channels leading to blockage of the high-frequency repetitive firing of action potentials (Gupta & Tripp, 2022).  Inhibition of the repetitive firing leads to slowing down of brain impulses leading to the cessation of seizures. Notably, phenytoin has a wide range of use in controlling generalized seizures with little neurological limit. It can be given orally or intravenously without disruption in its bioavailability. However, dosages should be titrated to avoid potential side effects.

Phenytoin causes various central nervous system side effects. They include drowsiness, confusion, slurred speech, difficulty in balance and coordination, and blurred vision (Kato et al., 2019). These adverse effects tend to impair individuals` judgment and function, hence they should not operate locomotives. In addition, patients can also present with gum swelling, body rashes, chest pain, palpitations, jaundice, and panic attacks while on phenytoin. Sadly, it can penetrate the placenta to cause teratogenic effects when taken during pregnancy. Therefore, its use during pregnancy should be determined upon evaluating the risks and benefits.

Various drug-drug interactions exist between phenytoin and other agents. Phenytoin is metabolized by the hepatic enzyme CYP3A4 to its inactive state (Kato et al., 2019). Therefore, it competes with various for the same metabolism pathway leading to antagonism and reduction in the efficacy of multiple agents. As a result, they are contraindicated. They include ergotamine, lovastatin, lumefantrine, atazanavir, apixaban, tolvaptan, sirolimus, and praziquantel among many others. In contrast, vigabatrin decreases the level of phenytoin levels and reduces efficacy. Finally, a prescription of phenytoin requires the understanding of the other existent interactions. This helps in improving efficacy while reducing side effects.


Gupta, M., & Tripp, J. (2022). Phenytoin.

Kato, Y., Dong, V. H., Chaddad, F., Takizawa, K., Izumo, T., Fukuda, H., Hara, T., Kikuta, K., Nakai, Y., Endo, T., Kurita, H., Xu, B., Beneš, V., Christian, R., Pavesi, G., Hodaie, M., Sharma, R. K., Agarwal, H., Mohan, K., & Liew, B. S. (2019). Expert Consensus on the management of Brain Arteriovenous Malformations. Asian Journal of Neurosurgery, 14(4), 1074–1081.

NRS 641 Topic 6 DQ 1.

Genitourinary System: Pyelonephritis.

Pyelonephritis is an infection of the kidneys. The common cause of the infection is gram-negative bacteria, with the commonest being Escherichia coli (Belyayeva & Jeong, 2021). Other agents include proteus and klebsiella. In addition, gram-positive bacteria such as Staphylococcus aureus and Enterococci also cause pyelonephritis.

Kidney infections are secondary to infection in other structural organs. Commonly, infections get into the urethra from the anus, from faces. The infectious agent then rises into the bladder, further spreading the infection to the kidneys and collecting ducts (Belyayeva & Jeong, 2021). However, bacteria can also spread through the hematogenous route, though uncommon in healthy individuals but cause more infections in immunocompromised people. Nevertheless, the infection’s development depends on both host factors and bacterial virulence.

The ascension of bacteria is favored by urine stasis that allows bacteria attachment aided by adhesins onto the urethral mucosa then spread to cause kidney inflammation and scarring of the renal parenchyma (Sabih & Leslie, 2022). Notably, stasis in urinary flow can be caused by either kidney stones or obstruction along the urethra. Furthermore, bladder outlet obstruction favors an environment that allows bacteria pooling and multiplication.

As a result of obstruction, there is reduced urine elimination with resultant reflux of urine into the kidneys to cause inflammation. The inflammation and scarring of kidneys lead to the presentation of symptomatology. They include flank pain, fever, nausea, burning urination, urgency, vomiting, and increased frequency of urination (Sabih & Leslie, 2022).

However, elderly patients may present with advanced features, including mental status deterioration, confusion, decompensated organ function, and generalized deterioration that may warrant admission. Consequently, a progressive kidney infection can lead to renal failure, kidney abscess, septic syndrome, septic shock, eventually death. These clinical features define the extent of body reaction to the infectious agent.

The prognosis of pyelonephritis is worse if not identified earlier. Complications such as renal failure and sepsis are life-threatening, leading to death. Therefore, early treatment is necessary. However, patients’ education is also an important consideration. Patients must be educated about the potential complications of pyelonephritis. As a result, patients should take their medications as prescribed to prevent antibiotic resistance (Umesha et al., 2018).

Furthermore, patients should take a lot of fluids to avoid dehydration. This is essential because dehydration favors stasis which favors bacterial growth. On the other hand, increased urine flow favors micro-organisms’ clearance, hence offering prevention. Finally, female patients should be instructed to practice front-back wiping to prevent the transmission of microorganisms from the anus to the urethra.


Belyayeva, M., & Jeong, J. M. (2021). Acute Pyelonephritis. StatPearls Publishing.

Sabih, A., & Leslie, S. W. (2022). Complicated Urinary Tract Infections. StatPearls Publishing.

Umesha, L., Shivaprasad, S. M., Rajiv, E. N., Kumar, M. M. S., Leelavathy, V., Sreedhara, C. G., & Niranjan, M. R. (2018). Acute pyelonephritis: A single-center experience. Indian Journal of Nephrology, 28(6), 454–461.

NRS 641 Topic 6 DQ 2

Management of Pyelonephritis

Treatment of pyelonephritis is complex and is dependent on the stage of patient presentation and patient factors. uncomplicated cases can be managed as an outpatient with oral medications. However, the complicated cases, including the severely ill, pregnant women, and those with comorbidities, are managed as in-patients using intravenous infusion. Notably, care aims to eliminate inflammation using anti-inflammatory and the elimination of micro-organisms like antibiotics (Chao & Farrah, 2019). However, the choice of antibiotics depends on the result of culture and sensitivity. Finally, surgery also has a role in patients with persistent fevers and deteriorating status despite initiation of medical therapy.

Various antibiotics are used for pyelonephritis management based on the results of the culture. Besides, ciprofloxacin is among the common fluoroquinolones prescribed as first-line for treating infections based on susceptibility. Ciprofloxacin and other fluoroquinolones act by inhibiting topoisomerase and DNA (deoxyribonucleic acid) gyrase enzymes, leading to inhibition of cutting and supercoiling of double-stranded DNA required for bacterial cell wall synthesis(Chao & Farrah, 2019). Therefore, they cause defective cell wall synthesis through inhibited DNA synthesis and bacterial growth that results in bactericidal. This agent is effective in suppressing bacterial multiplication that results in pyelonephritis.

Administration of ciprofloxacin should be monitored due to the risk associated with its use. There is a risk of tendinitis and tendon rupture in elderly patients >60 years or the immunocompromised (Gorsane et al., 2018). Liver and function functions must be assessed in patients on this medication. Other side effects include diarrhea, restlessness, arthralgia, headache, abdominal pain, memory loss, allergic reactions, nausea, vomiting, renal calculi, and rushes, among others. Therefore, this medication should be taken with care while assessing the adverse effects.

Furthermore, ciprofloxacin interacts with other agents based on its pharmacologic and pharmacodynamic properties. Pharmacodynamic antagonism exists when administered with BCG and typhoid live vaccine (Umesha et al., 2018). Hence absolute contraindication. Pharmacodynamics exist between ciprofloxacin and tretinoin. On the other hand, it increases the level of flibanserin by inhibiting the enzyme CYP3A4, thus limiting the metabolism of flibanserin (Umesha et al., 2018).

However, carbonyl iron and aluminum hydroxide inhibit the absorption of ciprofloxacin in the gastrointestinal leading to decreased levels with resultant low efficacy. These properties require a better understanding of both the pharmacokinetics and pharmacodynamic properties of various agents before administering agents to attain favorable patient outcomes without causing harm.


Chao, Y.-S., & Farrah, K. (2019). Fluoroquinolones for the treatment of urinary tract infection: A review of clinical effectiveness, cost-effectiveness, and guidelines.

Gorsane, I., Barrah, S., Barbouch, S., Kaaroud, H., Harzallah, A., & Ben Abdallah, T. (2018). Management of acute pyelonephritis. La Tunisie Medicale, 96(1), 42–47.

Umesha, L., Shivaprasad, S. M., Rajiv, E. N., Kumar, M. M. S., Leelavathy, V., Sreedhara, C. G., & Niranjan, M. R. (2018). Acute pyelonephritis: A single-center experience. Indian Journal of Nephrology, 28(6), 454–461.

NRS 641 Pathophysiology Discussion Topic 7 DQ 1

Neurological and musculoskeletal: Locked-in syndrome (LIS)

LIS is a complex neurological disorder caused by lesions that affect the ventral pons and caudal ventral midbrain while sparing the cerebral cortex. These lesions disrupt the neural functioning of the neural that passes through the ventral brainstem. Impairment of brain stem functions leads to paralysis of all voluntary muscles and loss of whole-body sensory while sparing the eye muscles (Das J et al., 2022). As a result, patients with LIS retain some functioning while losing others.

The retain functions include hearing, blinking, vertical eye movement, and cognition with no loss of consciousness. Sparing of pons tegmentum leads to preserved cognition. Interestingly, these patients can hear and reason out but fail to speak. On the other hand, the lost functions include quadriplegia, bulbar palsy leading to dysphagia and anarthria, difficulty maintaining the airway, apnea, vertigo, and hyperpnoea (Das J et al., 2022). Failure to identify the cause and offer early treatment can lead to patient suffering resulting in death.

Various causes are known to cause LIS. They include brain stem stroke from either hemorrhagic or ischemic stroke; infections such as pseudomonas pontine abscess and meningitis; traumatic brain injury; tumors such as astrocytoma; intracranial bleeding; occlusion of the middle and proximal basilar artery; demyelination caused by central pontine melanosis; multiple sclerosis, and medication overdose (Halan et al., 2021).  Any of these abnormalities can impair brainstem functioning leading to debilitating patient function. Therefore, the education of patients and their relatives is paramount to improving functioning.

Patients and caregivers must understand the complexities of LIS and related complications. As a result, basic patient care education should be provided. This includes periodic turning of the patient to prevent bedsores, appropriate feeding techniques using feeding tubes, adherence to prescribed medications, and timely intervention for any signs of worsening condition (Halan et al., 2021). Finally, patients can be trained to use the infrared eye movement sensor for communication with caregivers.


Das J, M., Anosike, K., & Asuncion, R. (2022). Locked-in Syndrome.

Halan, T., Ortiz, J. F., Reddy, D., Altamimi, A., Ajibowo, A. O., & Fabara, S. P. (2021). Locked-in syndrome: A systematic review of long-term management and prognosis. Cureus, 13(7), e16727.

NRS 641 Topic 7 DQ 2

Treatment of Locked-in Syndrome.

LIS is a complex neurological condition caused by various etiologies and is characterized by various systemic signs. No single medication has proved to cure LIS. Prompt identification of causative etiology is the mainstay of management. Infections can be treated by antibiotics, tumors can be excised surgically, and the use of neurogenerative compounds in demyelinating causes (Das et al., 2021). However, primary care of maintaining the airway by intubation, maintaining oxygen saturation, and monitoring circulation is the initial and vital step of treatment. 

Infections due to meningitis and pseudomonas brain abscess are the most common causes of reversible locked-in syndrome. Ceftriaxone is the most reliable and efficient medication for treating these infections. Ceftriaxone is a third-generation cephalosporin with broad-spectrum coverage. It acts selectively and irreversibly binds to transpeptidases to inhibit bacterial cell wall synthesis (Farr et al., 2021). It penetrates meninges easily and effectively kills disease-causing bacteria due to the defective cell wall synthesis process.

The pharmacokinetic properties define the effectiveness of the drug. It has low oral bioavailability hence given as an intramuscular or intravenous injection to increase absorption. It is 95% protein-bound with negligible metabolism (Griffiths et al., 2018).  Elimination is achieved through kidney excretion in urine and the remainder in feces. Therefore, any derangement in the kidney function limits elimination and favors toxicity, leading to urolithiasis and post-renal acute renal failure.

Monitoring of side effects is paramount during treatment. The known adverse effects include anemia, jaundice, diarrhea, blood clots, headache, dizziness, Steven-Johnson rash in the allergic patient, and stomach upset. Caution should be taken when administered in neonates as it can worsen hyperbilirubinemia that can result in kernicterus.

Finally, ceftriaxone interacts with other medications leading to serious adverse effects. The use of ceftriaxone and calcium-containing compounds is contraindicated due to the risk of fatal particulate precipitation in the lungs and kidneys (Griffiths et al., 2018). Furthermore, it increases the effects of anticoagulants such as warfarin, heparin, and fondaparinux leading to a decrease in prothrombin time. Last but not least, other antibiotics such as doxycycline, erythromycin, and chloramphenicol causes pharmacodynamic antagonism with ceftriaxone leading to reduced bactericidal effects.


Das, J. M., Anosike, K., & Asuncion, R. M. D. (2021). Locked-in Syndrome. StatPearls Publishing.

Farr, E., Altonji, K., & Harvey, R. L. (2021). Locked-in syndrome: Practical rehabilitation management. PM & R: The Journal of Injury, Function, and Rehabilitation, 13(12), 1418–1428.

Griffiths, M. J., McGill, F., & Solomon, T. (2018). Management of acute meningitis. Clinical Medicine (London, England), 18(2), 164–169.

NRS 641 Pathophysiology Discussion Topic 8 DQ 1

Endocrine: Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

SIADH is an endocrine abnormality characterized by continuous and inappropriate secretion of Antidiuretic Hormone (ADH) from the posterior pituitary gland and other sources, including lungs, due to small-cell lung cancer (Mentrasti et al., 2020). Other causes of SIADH include brain abscess, meningitis, medications such as carbamazepine and amitriptyline, atypical pneumonia, subarachnoid hemorrhage. Essentially, there is a loss of negative feedback from the hypothalamus to stop ADH release independent of serum osmolality. The excess ADH causes increased water reabsorption in the distal convoluted tubule with increased urinary sodium loss leading to dilution hyponatremia. The serum sodium levels decrease due to water overload resulting in hyponatremia. The level of hyponatremia determines the clinical manifestation.

Mild hyponatremia presents with acute symptoms such as dizziness and vertigo. In severe hyponatremia, more profound symptoms include loss of consciousness, generalized seizures, cognitive impairment, respiratory distress secondary to brain stem herniation, and other features of hypervolemia, including pulmonary edema, increased jugular venous pressure, and ascites (Mentrasti et al., 2020). Prompt identification of symptoms and making an early diagnosis is essential for a better outcome.

People with SIADH are at increased risk of fluid overload with diluted solutes. As a result, patients should be educated about management through restriction of fluid intake (Morris et al., 2018). Reduction in fluid intake reduces fluid overload and corrects sodium levels. Furthermore, patients should be cautioned against rapid correction of hyponatremia as they risk developing central pontine myelinolysis (CMP). Finally, patients should be educated against taking medications such as amitriptyline, selective serotonin receptor inhibitors, and carbamazepine which worsens SIADH.


Mentrasti, G., Scortichini, L., Torniai, M., Giampieri, R., Morgese, F., Rinaldi, S., & Berardi, R. (2020). Syndrome of inappropriate antidiuretic hormone secretion (SIADH): Optimal management. Therapeutics and Clinical Risk Management, 16, 663–672.

Morris, J. H., Bohm, N. M., Nemecek, B. D., Crawford, R., Kelley, D., Bhasin, B., Nietert, P. J., & Velez, J. C. Q. (2018). The rapidity of correction of hyponatremia due to syndrome of inappropriate secretion of antidiuretic hormone following tolvaptan. American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation, 71(6), 772–782.

NRS 641 Topic 8 DQ 2

Management of SIADH

Treatment of SIADH is non-specific, with management tailored towards the etiological process. Therefore, proper identification of etiological process and managing it is the standard care. However, the major goal of treatment is to correct sodium levels while preventing complications (Bartalis et al., 2021). According to Han et al. (2018), hyponatremia must never be corrected aggressively. The first line of treatment is fluid restriction, while the second line is increasing salt intake in combination with loop diuretics and oral sodium chloride. Vasopressin inhibitors such as conivaptan and tolvaptan can be used. Details of conivaptan are discussed hereafter.

Conivaptan is a selective inhibitor of the antidiuretic hormone through inhibiting its V 1A and V2 receptors (Han et al., 2018). This leads to restriction of water absorption at the renal collecting ducts with resultant loss of water through increased urination and subsequent restoration of normal serum sodium concentration. Notably, there is no electrolytes loss in the urine. It is indicated for the treatment of euvolemic and hypervolemic hypernatremia and is mainly given in hospital set-up through the intravascular route infused with normal saline. However, it should not be prescribed in people with known allergies to the product or those who can not pass urine.

Conivaptan has various known side effects that require monitoring. To begin with, conivaptan causes irregularities in potassium levels. It can lead to hypokalemia. As a result, doing serial kidney function tests is necessary during treatment. Features of hypokalemia include muscle weakness, muscle spasms, palpitations, fatigue, numbness, difficulty in breathing, changes in mood, and problems with digestions, including diarrhea and constipation (Han et al., 2018).

Other side effects include headache, nausea, vomiting, troubles in sleeping, thirst, dehydration, dry mouth, anemia, confusion, pruritus, pneumonia, and injection site reaction, including pain, erythema, and fever. In addition, due to increased water loss, this medication can lead to orthostatic hypotension. Therefore, patients on conivaptan should be warned against rapid rise from a lying or a sitting position to prevent falls that may cause trauma.

In addition, if signs of hypovolemia or hypotension persist, the medication should be stopped, and a complete reassessment should be done. Finally, rapid correction of hyponatremia leads to CMP. Features of CMP include dysphagia, mutism, dysarthria, seizures, coma, spastic quadriparesis, lethargy, and affective changes. Therefore, care should be taken when prescribing and using conivaptan due to serious death effects. Prescription alongside other agents should also be cautious due to interactions with other products.

Conivaptan has various levels of interactions ranging from minor to severe with other agents. Therefore, there are contraindications to prescription with other agents while others cause severe reactions. Conivaptan is contraindicated to be used with medications metabolized by CYP3A4 because it inhibits the enzyme CYP3A4 leading to an increase in the concentration of medications metabolized by CYPP3A4 (Bartalis et al., 2021).  

Examples of such medications include lopinavir, indinavir, isoniazid, chloramphenicol, clarithromycin, ergonovine, imatinib, and ketoconazole. Yet other serious effects can be seen when conivaptan is prescribed with amitriptyline, apomorphine, amlodipine, apixaban, bromocriptine, and carbamazepine. An alternative may be used, or other medications should be stopped while using conivaptan to prevent serious drug interactions.


  • Bartalis, E., Gergics, M., Tinusz, B., Földi, M., Kiss, S., Németh, D., Solymár, M., Szakács, Z., Hegyi, P., Mezösi, E., & Bajnok, L. (2021). Prevalence and prognostic significance of hyponatremia in patients with lung cancer: Systematic review and meta-analysis. Frontiers in Medicine, 8, 671951.
  • Han, S. W., Yi, J. H., Kang, K. P., Kim, H. Y., Kim, S. W., Choi, H. Y., Ha, S.-K., Kim, G.-H., Kim, Y. W., Jeong, K. H., Shin, S. K., & Kim, H.-J. (2018). Safety and efficacy of tolvaptan in Korean patients with hyponatremia caused by the syndrome of inappropriate antidiuretic hormone. Journal of Korean Medical Science, 33(15).