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Respond to these discussion posts:
1. Case Study: 26y/oF with varicella exposure; history of varicella at 8y/o
To explain adaptive immunity to a patient it’s important to discuss that when your body is exposed to a pathogen (such as the virus that causes chickenpox) that many times your immune cells will remember the virus and when exposed again will fight it off prior to infection. These cells that remember the virus are called B lymphocytes and will promptly respond to a viral infection that it identifies as a previous infection (NCI, n.d.). If the patient is unsure if they had chickenpox in the past, or they had a very mild case and they are afraid they are not still immune, titers can be drawn to determine if adaptive immunity is still present.
If she gets a varicella titer drawn, she will be able to conclusively determine her immunity to chickenpox as it will be negative (no evidence of the previous infection), equivocal (previous infection, but not enough antibodies to be protective), or positive (antibiotics considered to be in protective range) (What is a varicella titer, 2022). If the varicella titer shows negative or equivocal ranges she should consider varicella vaccination. It is indicated to get vaccinated after exposure within 3-5 days of being exposed if you have not had it before (CDC, 2021). Additional considerations for this patient are pregnancy risks of varicella during pregnancy which can cause congenital varicella syndrome. I’d discuss pregnancy risk and test for pregnancy. As varicella vaccination is NOT recommended during pregnancy or 30 days prior to pregnancy, I would recommend not to risk vaccination with a prior history of varicella infection at 8 years old as she more than likely retains her adaptive immunity.
If pregnancy is not concern my conclusion to her would be to have titers drawn if she is so inclined. If she is very nervous about the exposure, she can pursue vaccination so long as she is not pregnant or trying to become pregnant. And in the event, she does acquire a varicella infection, stock up on acetaminophen, calamine lotion, and colloidal oatmeal. As always NO NSAIDs for known viral infections. Monitor for signs and symptoms of viral illness, and report to the emergency department for any difficulty breathing. If a rash occurs, she should reach back out for a prescriiption for acyclovir or another antiviral.
While not entirely related, it worth mentioning is that people with a history of varicella infection are at risk for shingles infection. The varicella virus is a herpes virus that stays latent in nerve tissue after infection. Under certain circumstances, the virus can become reactivated as shingles. Shingles are caused by the same virus as chickenpox but present a little differently. Shingles will not occur due to chickenpox exposure but can spread varicella virus to others.
Centers for Disease Control and Prevention. (2021, April 28). Chickenpox vaccination: What everyone should know. Centers for Disease Control and Prevention. Retrieved June 14, 2022, from https://www.cdc.gov/vaccines/vpd/varicella/public/index.html#:~:text=You%20should%20get%20chickenpox%20vaccine,by%20minimum%20of%2028%20days.
NCI Dictionary of Cancer terms. National Cancer Institute. (n.d.). Retrieved June 14, 2022, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/adaptive-immunity
What is a varicella titer? e7 Health. (2022, December 6). Retrieved June 14, 2022, from https://www.e7health.com/post/248/what-is-a-varicella-titer/#:~:text=A%20varicella%20titer%2C%20also%20called,IgG%20antibodies)%20in%20the%20blood.
2. Case study to be discussed:
A 19-year-old college sophomore presents complaining of frequent diarrhea, abdominal cramping, and weight loss for 2 weeks. Upon further questioning, you learn that 6 weeks ago, he returned from an overseas summer trip to Africa. You suspect he has a parasitic GI infection.
If he asked you how it is possible he could have gotten such an infection weeks ago but not had symptoms until recently, how would you respond?
This depends deeply on the patient’s health literacy. Stepping back, it is important to explain that parasitic infections such as Giardia (giardiasis) can be in your system and you can never develop symptoms or be sick at all (CDC, 2021). For others that do develop symptoms, it takes one to three weeks for the parasites to incubate and worsen to the point of being symptomatic (many episodes of diarrhea, abdominal cramping, and weight loss)(CDC, 2021). If he has been experiencing these symptoms for two weeks, and he returned six weeks ago, this timeline for the incubation period makes sense.
b. What other illnesses might you consider that may be responsible for his symptoms?
Differential diagnoses are vast, but it is important to consider the following: cryptosporidiosis (also a parasitic infection), strongyloidiasis (caused by a roundworm), influenza, and generalized viral gastroenteritis (non-parasitic) (Dunn & Juergens, 2022). This illness is more than likely connected to travel if this individual is otherwise healthy and happy.
Clinical pearl: The CDC recommends testing all individuals with diarrhea lasting more than three days for giardiasis (CDC, 2021).
Centers for Disease Control and Prevention. (2021, February). General information. CDC. https://www.cdc.gov/parasites/giardia/general-info.html
Dunn, N., & Juergens, A. (2022, May). Home – books – NCBI. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK513239/
3. Lithium is used in the treatment of bipolar disorder. Many cellular processes are altered during lithium treatment, and although the mode of action is only theorized, it is effective in 60-80% of patients experiencing mania and hypomania. Lithium is a naturally occurring substance like sodium in its lack of metabolism. It is believed that lithium replaces sodium during depolarization in neuronal pathways thus stopping the transmission of electrical impulses and is also suspected of acting on the second messenger system postsynaptically to inhibit either the inositol monophosphates enzyme to modulate the G proteins or the messenger RNA to alter the protein kinase C (Woo & Robinson, 2020). Pharmacogenomic applications may be useful in identifying why lithium may work so well with some and also help to facilitate a personalized treatment plan. Variants were found on the genes regulating the glutamate system such as GADL1 and GRIA2 gene, those that are a mutually regulated target of lithium. This study also found a single nucleotide polymorphism discovered on SESTD1 that may explain lithium’s ability to permeate cell membranes and mediate autoimmune and renal effects (Vecera 2021). Although more studies do need to be done to better understand this, there is a suggestion that a person’s specific genome may contribute to how they respond to lithium therapy. Below is the link to this article.
After taking lithium, maximum blood levels occur within 0.5 – 3 hours and lithium has a half-life of 17-36 hours. Steady state is achieved in 5-7 days, with maximum efficiency taking 10-14 days. A normal dose of lithium will stay in a person’s system for about a week. The therapeutic index of lithium is very low and can have serious toxic side effects, therefore close monitoring is advised. Thyroid function needs to also be monitored. Lithium is renally eliminated and does not pass the liver. It is excreted by the kidneys, thus making kidney function a critical part of treatment. When sodium and fluids are depleted such as during severe vomiting, prolonged heavy sweating, NSAIDS and diuretic drug use, lithium levels are increased. When water intoxication happens, lithium levels are decreased (Whalen, 2019). A base line blood chemistry including creatinine, BUN and TSH levels should be obtained before treatment and this medication needs to use in caution with those patients also taking sodium depletion or diuretic medications. Because the index between therapeutic and toxic levels is narrow at the upper end, toxicity can occur even at therapeutic levels (0.6-1.5mEa/L). If toxicity happens, then lithium treatment needs to be discontinued or tapered down and treatment needs to be supportive to include hydration, possible dialysis and ECG monitoring to watch for arrhythmias. Depending on the severity of toxicity, monitoring may need to take place for a minimum of 24 hours (Woo & Robinson, 2020)
After a baseline blood test has been obtained, the following prescriiption is written as follows: Lithium 300mg three times a day by mouth for treatment of bipolar disorder. #90 no refills. Lithium blood level test to be taken on day fourteen, 12 hours after nighttime dose but before morning dose is taken. Follow up with provider for test results and possible dose adjustment thereafter. Patient will also need to have a lithium blood level test done 14 days after any future dosage changes as well as every 3-6months after stability is achieved (Woo & Robinson, 2020)
Vecera, C. M., Fries, G. R., Shahani, L. R., Soares, J. C., & Machado-Vieira, R. (2021). Pharmacogenomics of lithium response in bipolar disorder. Pharmaceuticals (Basel, Switzerland), 14(4). https://doi.org/10.3390/ph14040287
Whalen, K. (2019). Lippincott illustrated reviews: Pharmacology (7th ed.). Wolters Kluwer, Lippincott Publishing.
Woo, T.M., & Robinson, M.V. (2020). Pharmacotherapeutics for advanced practice nurse prescribers (5th ed.). F.A. Davis.
4. Carbamazepine is an anticonvulsant used to treat seizures and nerve pain (trigeminal neuralgia and diabetic neuropathy). It is also used to treat bipolar disorder. It works by reducing abnormal electrical activity in the brain. It is an antiepileptic drug in which pharmacogenomic information is relevant.
A severe cutaneous adverse reaction (SCAR) such as, Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms and acute generalized exanthematous pustulosis (AGEP), to a drug can cause a high risk of morbidity and mortality. Genetic factors can predispose a person to SCAR. According to Jhun et al.,” Since December 2007, the US FDA has included a black box warning in the carbamazepine drug label that recommends screening for HLA-B*15:02 prior to initiation of carbamazepine in individuals with Asian ancestry including South Asian Indians due to a strong association with this allele and SJS/TEN (pooled OR = 113.4)” (2019). More than 15% of the Asian population carry HLA-B*15:02. So, unless a patient carrier of HLA-B*15:02 has demonstrated to tolerate carbamazepine without SCAR for more than three months, this medication is not recommended for patients with genetic risk (Jhun et al., 2019).
The drug has a half-life of 25-65 hours on initial doses, 12-17 hours on repeating dosing. For extended release 35 to 40 hours. Due to autoinduction usually complete 3 to 5 weeks after initiation of a fixed carbamazepine regimen the half-life of the drug is considered variable. Following a dosing regimen of three times a day carbamazepine suspension affords steady-state plasma levels compared to carbamazepine tablets with a regimen dose of two times a day administering the same dose in mg. In the case of extended-release tablets following a twice a day dosage regimen, carbamazepine shows steady-state plasma levels in comparison with conventional tablets given four times a day administered at same dose in mg daily (Carbamazepine ER – FDA Prescribing Information, Side Effects and Uses, 2022).
Carbamazepine is metabolized in the liver by cytochrome P450 3A4 to active epoxide metabolite. Epoxide metabolite is metabolized by epoxide hydrolase to the trans-diol metabolite. The ratio of serum epoxide to carbamazepine concentrations may be higher in patients receiving polytherapy and in infants. Boys may clear carbamazepine faster so they will most likely require higher doses of the medication than girls of similar age and weight. It induces liver enzymes to increase metabolism and shorten half-life over time. It is excreted by urine 72% (1% to 3 % unchanged drug) and feces 28% (CarBAMazepine: Dosage, Mechanism/Onset of Action, Half-Life, 2020).
For a creatinine clearance of <10 decrease the usual dose by 25%. When on hemodialysis decrease usual dose by 25%, on dialysis days administer after dialysis. Caution advised with hepatic impairment but not specified (Tegretol Adult Dosing, 2022). "The first pass effect occurs when a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation" (Herman & Santos, 2022). The first pass effect is associated with the liver as it is the major site of drug metabolism. But it can also occur in lungs, vasculature, GI tract, and other metabolically active tissues. It is important in determining whether a drug can be orally administered. According to Herman & Santos, "If the first-pass effect is exceptionally prominent in a patient, the drug may require administration via a different route to bypass the first-pass effect" (2022). Prescriiption of initial dose for bipolar disorder John Doe DOB 06/14/1984 Carbamazepine 200 mg by mouth twice a day Disp: 60 (sixty) Take with food. Avoid grapefruit products. Avoid sunlight and tanning beds. Wear protective clothing and use sunscreen when outdoors (SPF 30 or higher). Avoid driving or hazardous activity. Will follow up in two weeks.
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