Tamsulosin (Urimax) In Female Patient: A Case of Recurrent UTI and Left Pelvic Calculi

Abstract

Tamsulosin hydrochloride is a selective ?1A-adrenergic receptor antagonist commonly used in the treatment of benign prostatic hyperplasia (BPH), a condition characterized by an enlarged prostate gland that can impede normal urinary flow in men. By selectively blocking ?1A receptors predominantly located in the smooth muscle of the prostate and bladder neck, tamsulosin relaxes these muscles, thereby improving urine flow and reducing symptoms of urinary obstruction. Administered orally, typically in extended-release formulations, tamsulosin is well-tolerated, with common side effects including dizziness, abnormal ejaculation, and rhinitis. It is metabolized primarily by the liver via cytochrome P450 enzymes and excreted in the urine. By relaxing the smooth muscles in the urethral and bladder neck, tamsulosin can be used off-label to treat voiding dysfunctions in females, such as LUTS (Lower urinary tract symptoms), BOO (Bladder outlet obstruction), or urinary retention. It should be used on an individual basis and is frequently saved for particular situations when there aren't many other options.

Keywords

Introduction

Tamsulosin was approved by the FDA in the April 15,1997. Tamsulosin hydrochloride is also known as Tamsulosin HCL, Harnal, Urimax, Flomax. MOLECULAR FORMULA = C₂₀H₂₉CLN₂₀O₅S MOLECULAR WEIGHT = 445.0g/mol IUPAC NAME = 5-[(2s)-2-[2-(2-ethoxyphenoxy) ethylamino] propyl]-2-methoxy-benzene-sulfonamide-hydrochloride. BRAND NAMES = Flomaxtra XL, Contiflo XL, Faramsil MR, Pamsvax XL, Tabphyn MR. MONOISOTOPIC MASS = 444.14857 Da, A TOPOLOGICAL POLAR SURFACE AREA = 108A² units.  Tamsulosin compound id canonicalized and it is a covalent hydrogen bond with a property of 3 in bond donor count & property of 7 in bond acceptor count. The complexity value of tamsulosin is 539.

Molecular structure of Tamsulosin hydrochloride  

Mechanism of action

Tamsulosin binds to specific adrenoreceptors and shows its antagonistic activity by relaxing the smooth muscles of prostate, thereby increasing the urinary out flow. It also used in treating benign prostatic hyperplasia, female voiding dysfunction and ureteral stones. Treats various voiding symptoms in females. Tamsulosin is a valuable treatment for specific conditions in women. It's primarily used to treat lower urinary tract symptoms (LUTS). According to studies, women with LUTS and bladder outlet obstruction may benefit greatly from even a small dosage of tamsulosin. Additionally, tamsulosin hydrochloride is prescribed for female patients who suffer from recurrent UTIs. This medication works by increasing urine outflow, which can help alleviate obstruction issues and prevent future infections ^[1-4].

Pharmacokinetics [ADME]

Tamsulosin is available as tablet and capsule, it is exclusively taken with oral route about a dosage of 0.4-0.8mg per day

Absorption

Oral route of tamsulosin is absorbed rapidly about 90%. The plasma concentration of tamsulosin is 3.1-5ng/ml and when taken along with food can increases the time of absorption and plasma concentration and the absorption is about 70% ^[5-8].

Distribution

Tamsulosin mostly bound to alpha-1 acid glycoprotein and it is 94-99% protein bounded ^[5-8].

Metabolism

Tamsulosin is metabolized in liver by cytochrome P450 3A4 and 2D6. It undergoes de-ethylation and oxidative deamination as well as hydroxylation for the production of M-1, AM-1, M-3, M-4 metabolites. These M-1, M-2, M-3, M-4 metabolites are again undergo glucuronidation reaction. Few metabolites M-1 and M-3 undergoes sulfate conjugation and there by excretion follows ^[5-8].

Elimination

Route of elimination of Tamsulosin hydrochloride is through kidneys, most part of the drug is eliminated in urine about 76%. Elimination half-life is 5-7 hrs ^[5-8].

Half-life 

Half-life of Tamsulosin is 14-15hrs. In patients it is 14hrs ^[8].

Pharmacodynamics

Tamsulosin is a selective alpha-1A and alpha-1B adrenoreceptor antagonist, which acts by relaxing the smooth muscles on the prostate and improving the urinary flow. Tamsulosin is a blocker of majorly alpha-1A, 1D adrenoreceptors. Binding and blocking of alpha-1D adrenoreceptors relaxes the detrusor muscles of urinary bladder which prevents various symptoms. Tamsulosin priorly binds to alpha-1A adrenoreceptor more than 3 times, when compared to that of alpha-1B receptor ^[9-11].

Dose

Tamsulosin usual dose is 0.4mg per day, can be increased till 0.8mg orally once daily for the patients do not show activity at 0.4mg dose. Tamsulosin must be given after 30minutes of a meal. The usual adult dose of Tamsulosin is 0.4mg in treating Benign prostatic hyperplasia. The dose adjustments are necessary in dealing with the patients with renal and liver dysfunctions.  Females with voiding dysfunction and suffering with subnormal uroflow are treated by using tamsulosin of 0.2mg every day for six weeks ^[12].

Adverse effects

Orthostatic hypotension, sleepiness, bradycardia, diarrhea, micturition syncope(fainting), light-headedness, abnormal ejaculation, sneezing or runny nose, body aches are the few common side effects caused due to Tamsulosin ^[13-15].

Toxicity

Oral lethal dose is about 650mg/kg. Overdose of Tamsulosin leads to excessive hypotension, decrease in heart rate and blood pressure. No studies performed on pregnant women neither the studies performed on the rats doesn’t show its harm on fetus. Tamsulosin shown infertility in male and female rats under their studies leading to impairment of ejaculation ^[16-18].

Interactions

Drug-Drug interaction

1) Ketoconazole + Tamsulosin (Moderate)

This combination majorly leads to serious effects like increasing the levels of tamsulosin in blood, decrease in blood pressure and ketoconazole inhibits the enzyme cytochromeP3A4, which is essential for the metabolism of Tamsulosin ^[19].

2) Tadalafil+ Tamsulosin (Moderate)

This combination can decrease the blood pressure and increase the risk of dizziness, lightheadedness ^[20].

3) Duloxetine+ Tamsulosin (Moderate)

This combination may decrease the blood pressure and effects tamsulosin action ^[21].

4) Empagliflozin + Tamsulosin (Moderate)

Metabolism of tamsulosin can be increase the risk of dehydration and causes low blood pressure ^[22].

6) Mirabegron + Tamsulosin (Moderate)

Combining Tamsulosin with Mirabegron can cause lowering the blood pressure and there by increasing heart rate ^[23].

Food-Drug interaction

Tamsulosin is taken after a meal, after 30 minutes of meal, when taken along with food leads to reduce in absorption and variations in plasma concentration ^[24].

CASE DISCUSSION

A patient of 38yrs old, female patient has admitted in the medical department on 30/12/2024 with the chief complaints of chills since 30 minutes, fever, rigors since 2 days. Patient has known history of diabetes type-2, hypertension, chronic anxiety disorder on regular treatment, left PVI calculus s/p stent on 20/12/2024 and removal on 27/12/2024 and left RIRS [Retrograde intrarenal surgery].

• Drug Hx (Psychiatric)
• T-Lorazepam 2mg
• T-Mirtaz 15mg
• T-Escitalopram 10mg
• T-Quetiapine 25mg
• T-Zolsoma 10mg

Attenders explain that the neck stiffness happens everyday after taking this medications and subsides by morning.

• Drug Hx (Diabetics)
• T- Gluconorm-G 1
• T- Gluconorm- 0.5

Now the patient has admitted for further treatment, On examination the patient is conscious and coherent and Temperature - 104 C, Pulse rate -111bpm, Blood pressure - 130/70mmHg, SPO2 - 94% @RA, GRBS - 140mg/dl.

On 30/12/2024, the patient’s

COMPLETE BLOOD PICTURE shows hemoglobin - 11 g/DL , PCV – 32vol%, Total RBC count – 3.6 millions/Cumm, Total WBC – 12110 Cells/ Cumm, Lymphocytes – 10. COMPLETE URINE EXAMINATION shows Protein – Positive (+), Blood – Positive (++), Pus cells – 4-5/hpf, Epithelial cells – 1-2/hpf, RBC 18-20/hpf. ELECTROLYTES shows Sodium – 134 mmol/L, Potassium – 3.3 mmol/L.  LIVER FUNCTION TESTS shows Direct bilirubin – 0.24 mg/dl, Alkaline phosphate – 135 U/L, Total protein – 6 g/dl, Albumin – 3.2 g/dl.  REAL TIME ULTRASOUND SCANNING OF ABDOMEN shows Cholelithiasis, Right ovarian cyst, Right pelvic caliculi. 

CT scan of KUB shows Contracted right kidney.

Based on this examination the patient was diagnosed with Urosepsis, Type-2 Diabetes, Hypertension, Anxiety disorder, Recurrent UTI. On 30/12/2024 patient was advised with INJ. PAN – 40mg OD, INJ.ZOFER – 4mg SOS, INJ.MAGNEX FORTE – 1.5gm BD, INJ.OPTINEURON – 1amp in 10NS OD, INJ-PCM – 1gm SOS( if temperature greater than 101 F), SYP-UTIJOY – 2 tbsp TD, T-LORAZEPAM 2mg OD, T- MIRTAZ – 15mg OD, T-ESCITALOPRAM – 10mg BD, T-QUETIAPINE- 25mg OD, T-ZOLSOMA – 10mg OD. Based on urologist opinion on 30/12/2024, the drug T-URIMAX 0.4mg OD has been advised and INJ. MAGNEX FORTE is changed to INJ. MEROPENUM – 1 gm TD. On 31/12/2024 patient was advised with INJ. PAN – 40mg OD, INJ.ZOFER – 4mg SOS, INJ.OPTINEURON – 1amp in 10NS OD, INJ-PCM – 1gm SOS( if temperature greater than 101 F), SYP-UTIJOY – 2 tbsp TD, T-LORAZEPAM 2mg OD, T- MIRTAZ – 15mg OD, T-ESCITALOPRAM – 10mg BD, T-QUETIAPINE- 25mg OD, T-ZOLSOMA – 10mg OD, T- URIMAX – 0.4 mg OD, SYP- DUPHALAC – 20ml HS, INJ.HAI – according to sliding scale, FOSFOPHYMICIN SACHET – 3gms STAT, T-PROVICET – 2mg STAT (constipation).

CONCLUSION

Tamsulosin hydrochloride (Urimax) is generally prescribed to males for relaxing smooth muscles of prostate glands, benign prostatic hyperplasia, chronic prostatitis, ureteral stones. Upon rare and severe condition urimax 0.2 mg can be prescribed in females. In this case female patient was advised with the dose of 0.4 mg T- URIMAX for 6 days, as she was suffering from recurrent UTI and left pelvic calculi.

ACKNOWLEDGMENTS

The authors would like to acknowledge the facilities provided by the Bharat Institutions- pharmacy in executing this article.

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