Tamsulosin hydrochloride

ntroduction, Chemical name, Chemical formula, Structure, Generic name, Trade name, Available forms, Classification, Uses, Mechanism of Action, Indications, Contraindications ,Route and Dosage, Pharmacodynamics, Pharmacokinetics, Adverse Effects, Toxicity, Drug Interactions, Nursing Implications

1. Drug Presentation TAMSULOSIN HYDROCHLORIDE Presented by : Dakshta MSc. (N) 1 st Year Date – 16 th Sept’2021

2. contents Introduction Chemical name Chemical formula Structure Generic name Trade name Available forms Classification Uses Mechanism of Action Indications Contraindications Route and Dosage Pharmacodynamics Pharmacokinetics Adverse Effects Toxicity Drug Interactions Nursing Implications

3. INTRODUCTION Tamsulosin is a selective alpha-1A and alpha-1D adrenoceptor antagonist that exerts its greatest effect in the prostate and bladder, where these receptors are most common. It is indicated for treating the signs and symptoms of benign prostatic hypertrophy. Antagonism of these receptors leads to relaxation of smooth muscle in the bladder trigone, sphincter and prostate, allowing for better urinary flow. Other alpha-1 adrenoceptor antagonists developed in the 1980s were less selective and more likely to act on the smooth muscle of blood vessels, resulting in hypotension. For eg. Prazosin and Terazosin. Tamsulosin was first approved by the FDA on April 15, 1997.

4. Chemical Name – 5-[(2 R )-2-[2-(2-ethoxyphenoxy) ethylamino ]propyl]-2-methoxybenzenesulfonamide;hydrochloride Chemical Formula – C 20 H 28 N 2 O 5 S Structure – Generic Name – Tamsulosin hydrochloride Trade Names – Flomax, Jalyn, Contiflo , Urimax , Dynapres

5. Available forms – 0.2 mg capsules 0.4 mg capsules

6. Classification Sympatholytics ( alpha and beta Blockers) Alpha blockers Non-selective Alpha-1 selective (Phenoxybenzamine, (Prazosin, Terazosin Phentolamine) Tamsulosin)

7. Uses of Alpha Blockers Hypertension – Prazosin, Terazosin Pheochromocytoma – diagnosis (Phentolamine) treatment (Phenoxybenzamine) BPH – Tamsulosin CHF – Prazosin Secondary Shock – Phenoxybenzamine, Prazosin PVD – Phenoxybenzamine, Prazosin

8. Mechanism of action Tamsulosin is a blocker of alpha-1A and alpha-1D adrenoceptors. About 70% of the alpha-1 adrenoceptors in the prostate are of the alpha-1A subtype. By blocking these adrenoceptors, smooth muscle in the prostate is relaxed and urinary flow is improved. The blocking of alpha-1D adrenoceptors relaxes the trigone smooth muscles of the bladder which prevents storage symptoms. The specificity of tamsulosin focuses the effects to the target area while minimizing effects in other areas.

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11. indications For symptoms of B enign prostatic hyperplasia. difficulty urinating (hesitation, dribbling, weak stream, and incomplete bladder emptying) painful urination urinary frequency and urgency. P rostatitis U reteral stones Urethral stricture

12. contraindications O rthostatic hypotension C ataract surgery Hypersensitivity to tamsulosin I n conjunction with another alpha 1A -adrenergic blocking agent L actation P ediatric patients Cautious use – Pregnancy (category B) History of Syncope and hypotension

13. ADMINISTRATION Oral route: Give 30 min after the meal each day. Instruct to swallow capsules whole; not to crush, chew, or open. If dose is interrupted for several days, reinitiate at the lowest dose, 0.4 mg. Store at 20°–25° C (68°–77° F). DOSAGE Adult Dose: PO  0.4 mg q.i.d . 30 min after a meal, may increase up to 0.8 mg q.i.d .

14. PHARMACODYNAMICS Tamsulosin is an alpha adrenoceptor blocker with specificity for the alpha-1A and alpha-1D subtypes, which are more common in the prostate and submaxillary tissue. The final subtype, alpha-1B, are most common in the aorta and spleen. Tamsulosin binds to alpha-1A receptors 3.9-38 times more selectively than alpha-1B and 3-20 times more selectively than alpha-1D. This selectivity allows for a significant effect on urinary flow with a reduced incidence of adverse reactions like orthostatic hypotension.

15. PHARMACOKINETICS Absorption Rapidly absorbed from GI tract. The maximum plasma concentration is 3.1-5.3ng/mL for a 0.4mg oral dose and 2.5-3.6ng/mL for a 0.8mg oral dose. >90% bioavailability.   Peak   4–5 hr. fasting 6–7 hr. fed Volume of Distribution 16L after intravenous administration. Widely distributed in body tissues, including kidney and prostate

16. Continued … Protein Binding Tamsulosin is 94%-99% protein bound, mostly to alpha-1-acid glycoprotein. Metabolism Tamsulosin is mostly metabolized in the liver by cytochrome P-450 (CYP) 3A4 and 2D6, with some metabolism by other CYPs. Route of Elimination 97% of an orally administered dose is recovered in studies, which 76% in the urine and 21% in the feces after 168 hours. 

17. Continued… Half Life The apparent half life is 14-15 hours. Clearance 2.88L/h.

18. Adverse effects Body as a Whole:  Asthenia, back or chest pain CNS:   Headache, Dizziness, insomnia CVS:   Orthostatic hypotension (especially with first dose) GI:   Diarrhea, Nausea Respiratory:   Rhinitis, pharyngitis, increased cough, sinusitis Urogenital:   Decreased libido, abnormal ejaculation   Special Senses:   Amblyopia.

19. TOXICITY Hypotension In the event of overdose, patients may experience hypotension and should lie down in a supine position to maintain blood pressure and heart rate.  If further measures are required intravenous fluids should be considered. If further progression is required, vasopressors may be used and renal function should be monitored. Dialysis is unlikely to assist in treating overdose because tamsulosin is extensively protein bound. C arcinogenic Tamsulosin is not mutagenic but may be carcinogenic at levels above the maximum recommended human dose. Fertility problems In men, tamsulosin is associated with abnormal ejaculation.

20. DRUG INTERACTIONS Acetaminophen - Acetaminophen may decrease the excretion rate of Tamsulosin which could result in a higher serum level. Acetazolamide – Acetazolamide may increase the excretion rate of Tamsulosin which could result in a lower serum level and potentially a reduction in efficacy . Chlorpropamide - The therapeutic efficacy of Chlorpropamide can be increased when used in combination with Tamsulosin. Cimetidine  may decrease clearance of tamsulosin. Sildenafil,   vardenafil,  and  tadalafil  may enhance hypotensive effects. Food Interactions Take after a meal. Take 30 minutes after the same meal each day to reduce plasma level variations.

21. Missed dose of tamsulosin If a dose of tamsulosin is missed, it should be taken immediately as long as it is not too close to bed time or to the usual time of taking next dose. In case it is the time for next dose, then usual schedule should be resumed missing that dose. It’s dose shouldn’t be doubled up to make up for the missed dose.

22. Nursing implications Assessment & Drug Effects Monitor for signs of orthostatic hypotension; take BP lying down, then upon standing. Report a systolic pressure drop of 15 mm Hg or more and a HR of 15 beats or more upon standing. Monitor patients on warfarin therapy closely. Patient & Family Education Make position changes slowly to minimize orthostatic hypotension. Report dizziness, vertigo, or fainting to physician. Exercise caution with hazardous activities until response to drug is known. Be aware that concurrent use of cimetidine may increase the orthostatic hypotension adverse effect of Tamsulosin. Advise patient that urinary symptoms (retention, dribbling, hesitancy, urgency) should improve, and to contact the physician if these symptoms continue to worsen. Instruct patient or family/caregivers to report other bothersome side effects such as severe or prolonged headache, nasal irritation, or problems with ejaculation.

23. Clinical trials The phase 4 clinical trials has been completed for Tamsulosin for it to be used safely for : the prevention of Post Operative Urinary Retention (POUR). the treatment of BPH, of Kidney and Ureteral stones. the treatment of Lower Urinary Tract Symptoms (LUTS).

24. RELATED RESEARCH ARTICLE A research was conducted by Yoshinori Nishino et al, published on 9 th March’ 2006 t o compare the efficacy of two α 1 - adrenoceptor antagonists, α 1 A -adrenoceptor-selective tamsulosin hydrochloride and α 1 D -adrenoceptor-selective naftopidil , in the treatment of lower urinary tract symptoms (LUTS) with benign prostatic hyperplasia (BPH). 34 patients with LUTS secondary to BPH were enrolled in a randomized crossover study. 17 patients were initially prescribed naftopidil 50 mg for 4 weeks, followed by tamsulosin 0.2 mg for 4 weeks (group A); another 17 were initially prescribed tamsulosin 0.2 mg, followed by naftopidil 50 mg (group B). It was concluded that , t he two agents provided similar efficacy in the treatment of LUTS with BPH. However, naftopidil was better than tamsulosin for nocturia. The disappearance of involuntary contraction and the greater increase in first-desire volume with naftopidil may be associated with the relief of nocturia. The α 1D -adrenoceptor antagonist is effective in alleviating both voiding and storage symptoms. The α 1D -adrenoceptor antagonist may be more effective than the α 1A -adrenoceptor antagonist in LUTS with BPH.

25. Summary In today’s drug presentation, we discussed all the characteristics and specifications of the drug TAMSULOSIN HYDROCHLORIDE. We covered its introduction, chemical name, chemical formula, structure, generic name, trade name, available forms, classification, uses, mechanism of action, indications, contraindications, route and dosage. Conclusion Tamsulosin hydrochloride is an Alpha 1 adrenergic receptor blocker drug which is routinely used in urology department for relieving the symptoms associated with BPH and other obstructive uropathies i.e. prostatitis, ureteral stones or urethral strictures.

26. bibliography KD Tripathi; Essentials of Medical Pharmacology 7 th Edition. New Delhi; Jaypee Publications, 2014, Pg no. 144-146. Williams and Wilkins; Nursing Drug Handbook 41 st Edition; Philadephia ; Walters Kluwer Publications, 2021, Pg no. 342-348. Wishart DS, Feunang YD, Guo AC, Wilson M. Drug Bank 5.0 : A major update to the Drug Bank database for 2018. Nucleic acids Res. 2017 Nov 8. Available from : https://go.drugbank.com/drugs/DB00706. Tamsulosin hydrochloride ; No date. Available from : https://www.robholland.com/Nursing/Drug_Guide/data/monographframes/T005. html.