Pharmacology Concepts by Dr Mahtab Khan

A prescription for a 84 years old lady with symptoms of dementia confusion, insomnia and restlessness.
Citikeen 500 mg — Choline bitartrate
Esildon 1 mg — Estazolam
Memril 10 mg — Memantine HCl
Praximet 1 mg — Risperidone

For an 80-year-old woman, this combination needs very careful supervision by a physician, especially because several of these medicines affect the brain, memory, sleep, balance, and behavior.
Main Concerns in Elderly Patients
1) High Risk of Sedation & Falls
The most important interaction is:
Esildon (Estazolam) + Risperidone
Both can cause:
Drowsiness
Confusion
Dizziness
Unsteady walking
Falls/fractures
Excessive sleepiness
In an 80-year-old, even a low dose can significantly increase fall risk.
Drug-by-Drug Review
1. Choline Bitartrate (Citikeen 500 mg)
Usually used for:
Memory support
Cognitive weakness
Brain health
Common issues
Nausea
Sweating
Headache
Low evidence compared with prescription dementia drugs
Elderly suitability
Generally relatively safe, but benefits may be modest.
2. Estazolam 1 mg (Esildon)
This is a benzodiazepine sleeping tablet.
Used for:
Insomnia
Anxiety/sleep disturbance
Important Elderly Risks
In older adults it may cause:
Confusion
Memory worsening
Night falls
Daytime drowsiness
Dependence
Breathing suppression in frail patients
For 80-year-olds
Usually physicians try to:
Use the lowest possible dose
Use for short duration only
Avoid daily long-term use if possible
For many elderly patients, benzodiazepines are considered potentially inappropriate unless clearly needed.
3. Memantine 10 mg (Memril)
Used for:
Alzheimer’s disease
Dementia symptoms
Cognitive decline
Common side effects
Dizziness
Headache
Constipation
Confusion (sometimes)
Elderly suitability
Commonly used in older adults and often appropriate if dementia is diagnosed.
Typical dosing
Usually:
Started low
Gradually increased
Common maintenance:
10 mg twice daily OR adjusted depending on formulation and kidney function.
Kidney function is very important in elderly patients.
4. Risperidone 1 mg (Praximet)
Antipsychotic medicine used for:
Aggression
Hallucinations
Severe agitation
Behavioral symptoms in dementia
Major Elderly Warnings
In dementia patients, risperidone may increase:
Stroke risk
Sudden decline
Sedation
Falls
Parkinson-like symptoms
Low blood pressure
Dose concern
For frail elderly patients:
1 mg may be high as a starting dose depending on indication.
Many geriatric regimens start at:
0.25 mg
0.5 mg
unless symptoms are severe.
Important Interaction Summary
Combination
Concern
Estazolam + Risperidone
Severe sedation, falls, confusion
Risperidone + Memantine
Increased dizziness/confusion possible
Estazolam + Memantine
Increased cognitive slowing
All together
Fall risk, delirium, excessive sleepiness
Questions That Matter Before Judging Suitability
This combination may be reasonable only if the patient has conditions such as:
Alzheimer’s disease
Dementia with agitation
Severe insomnia
Night wandering
Hallucinations
Aggressive behavior
But it becomes risky if she has:
History of falls
Low blood pressure
Kidney disease
Parkinsonism
Stroke history
Severe weakness
Daytime confusion
Red Flag Symptoms — Seek Doctor Review Quickly
If she develops:
Excessive sleepiness
Sudden confusion
Difficulty walking
Tremors/stiffness
Facial drooping
Slurred speech
Repeated falls
Difficulty swallowing
Very low appetite
then the medicines need urgent reassessment.
Practical Geriatric Advice
For an 80-year-old:
Keep hydration good
Avoid sudden standing
Night bathroom lighting should be adequate
Monitor blood pressure
Review kidney function
Avoid self-adjusting doses
Reassess sleep medicines regularly
My Overall Assessment
Memantine: commonly appropriate in dementia.
Choline supplement: usually low risk.
Risperidone: should be used cautiously and at the lowest effective dose.
Estazolam: highest concern for long-term elderly safety.
The combination is not automatically wrong, but it definitely requires:
Close monitoring
Clear diagnosis
Periodic dose review
Fall-risk assessment

If you want, a Pharmacist may also help with:
�⁠A best timing schedule for these medicines

What are clinical targets for the management of Parkinson's Disease? Are there some new drugs discovered other than Levodopa?

Oxidative phosphorylation

News:
FDA Approves Upadacitinib for Moderately to Severely Active Ulcerative Colitis

Patients treated with upadacitinib achieved clinical remission of ulcerative colitis more frequently through weeks 8 and 52 versus the placebo group.

The FDA has approved upadacitinib (Rinvoq; AbbVie) for the treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to 1 or more tumor necrosis factor (TNF) blockers.

The action represents the first approval for upadacitinib in the field of gastroenterology. The approval was based on 3 randomized, double-blind, placebo-controlled phase 3 clinical trials. These included the U-ACHIEVE and U-ACCOMPLISH induction studies, in which upadacitinib was evaluated at 45 mg once daily for 8 weeks, followed by 15 mg or 30 mg once daily in the maintenance trial for 52 weeks.

The investigators found that patients treated with upadacitinib achieved clinical remission more frequently through weeks 8 and 52 versus the placebo group. The primary endpoint of the study was stool frequency subscore (SFS) ≤ 1 and not greater than baseline, re**al bleeding subscore (RBS) = 0, and endoscopy subscore (ES) of ≤ 1 without friability.

During the U-ACHIEVE and U-ACCOMPLISH induction trials at week 8, 26% and 33% of patients treated with upadacitinib 45 mg achieved clinical remission compared to 5% and 4% of patients administered placebo. Onset of response was observed as early as week 2, with a greater proportion of patients administered upadacitinib 45 mg once daily achieving clinical response, defined as a decrease of ≥1 point and ≥30 percent from baseline and a reduction in RBS of ≥1 or an absolute RBS ≤1 per the pmMS, compared to placebo.

Further, upadacitinib achieved all ranked secondary endpoints, including endoscopic improvement and histologic-endoscopic mucosal improvement, as well as corticosteroid-free clinical remission.

During the maintenance trial, 42% and 52% of patients administered upadacitinib 15 mg or 30 mg, respectively, achieved clinical remission at week 52 versus 12% of patients in the placebo group.

The study also found that 57% and 68% of patients administered upadacitinib 15 mg or 30 mg, respectively, achieved corticosteroid-free remission, defined as clinical remission (per mMS) and corticosteroid-free for ≥90 days immediately preceding week 52 in patients who achieved clinical remission at the end of the induction treatment, versus 22% of patients on placebo.

"Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding," said Maria T. Abreu, MD, Professor of Medicine, Professor of Microbiology and Immunology, University of Miami Miller School of Medicine and Director, Crohn's & Colitis Center, University of Miami Health System, in a press release. "In clinical trials, upadacitinib showed its ability to control symptoms for many patients."

Reference

RINVOQ® (upadacitinib) Receives FDA Approval for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis. AbbVie. [news release]. March 16, 2022.

RINVOQ® (upadacitinib) Receives FDA Approval for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis | AbbVie News Center March 16, 2022 RINVOQ® (upadacitinib) Receives FDA Approval for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis In clinical trials, RINVOQ (upadacitinib) achieved the primary endpoints of clinical remission (per modified Mayo Score [mMS]) at weeks 8 and 521-4  A great...

Antidote for Iron

WHO Recommends 2 New Drugs to Treat Patients With COVID-19
January 18, 2022
Ashley Gallagher, Assistant Editor
The World Health Organization issues a strong recommendation for baricitinib and a conditional one for sotrovimab.

A World Health Organization (WHO) group has issued a strong recommendation for the use of baricitinib to treat patients with COVID-19 and a conditional recommendation for the use of sotrovimab to treat the disease.

Baricitinib, a type of Janus kinase (JAK) inhibitor, is used to treat rheumatoid arthritis, but can also treat individuals with critical or severe COVID-19 in combination with corticosteroids, according to a WHO Guideline Development Group of International experts and published in The BMJ.

Their recommendation is based on moderate certainty evidence that baricitinib improves survival and reduces the need for ventilation, with no observed increase in adverse effects.

The WHO experts said that baricitinib has similar effects to other arthritis drugs called interleukin-6 (IL-6) inhibitors, so when both are available, they recommend choosing a treatment based on availability, clinician experience, and cost.

Using both drugs at the same time is not recommended.

The experts advise against the use of 2 other JAK inhibitors, ruxolitinib and tofacitinib, for individuals with critical or severe COVID-19, because low certainty evidence from small trials failed to show a benefit and suggests a possible increase in serious adverse effects with tofacitinib.

In the same guidelines update, the WHO experts also conditionally recommended the use of the monoclonal antibody sotrovimab for individuals with non-severe COVID-19 but only those who are at highest risk of hospitalization, reflecting trivial benefits in those at lower risks.

The WHO experts made a similar recommendation for casirivimab-imdevimab, another monoclonal antibody drug.

There is insufficient data to recommend 1 monoclonal antibody treatment over another, and the WHO experts acknowledged that their effectiveness against new variants, such as omicron, is still uncertain.

The guidelines for monoclonal antibodies will be updated when additional data become available, the WHO experts said.

The new recommendations are based on new evidence from 7 trials that include 4000 individuals with critical, non-severe, and severe COVID-19 infection.

These recommendations are part of a living guideline, developed by WHO and the methodical support of MAGIC Evidence Ecosystem Foundation, to provide guidance on the management of COVID-19 and help physicians make better decisions for patients.

Living guidelines are useful in fast-moving research areas, such as COVID-19, because they allow investigators to update previously peer-reviewed and vetted evidence summaries as new information becomes available.

The panel considers a combination of evidence assessing relative benefits, feasibility, harm, preferences, and values to make their recommendations.

The new guidance adds to previous recommendations for the use of conditional recommendations for the use of casirivimab-imdevimab, another monoclonal antibody treatment, in selected individuals; IL-6 receptor blockers and systemic corticosteroids for individuals with critical or severe COVID-19; and against the use of convalescent plasma, hydroxychloroquine, or ivermectin in individuals with COVID-19, regardless of disease severity.

Reference

WHO recommends two new drugs to treat patients with COVID-19. EurekAlert. News release. January 13, 2022. Accessed January 14, 2022.

WHO recommends two new drugs to treat patients with COVID-19 The drug baricitinib (a type of drug known as a Janus kinase (JAK) inhibitor, also used to treat rheumatoid arthritis) is strongly recommended for patients with severe or critical covid-19 in combination with corticosteroids, says a WHO Guideline Development Group of international experts in The BMJ...

Information

Rosuvastatin:

Indication: Rosuvastatin is used as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, non-HDL-C, and TG levels and to increase HDL-C for patients with primary hyperlipidemia and mixed dyslipidemia.

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