Editing Functional: Pharmacological Management of LUTS (section)

== Other drugs ==

=== Desmopressin ===
* '''Mechanism of action:'''
** '''Analogue of the endogenous hormone''' '''vasopressin (also known as antidiuretic hormone).'''
*** Vasopressin
**** Functions (2):
****# Causes contraction of vascular smooth muscle
****# Stimulates water reabsorption from the collecting ducts
**** Release stimulated by:
***** Hyperosmolality
***** Hypovolemia
***** Stress
***** Nausea
***** Pregnancy
***** Hypoglycemia
***** Nicotine
***** Morphine
***** Other drugs
**** Release inhibited by:
***** Hypoosmolality
***** Hypervolemia
***** Ethanol
***** Phenytoin
* '''Pharmacology'''
** '''More powerful and longer-lasting antidiuretic action than vasopressin/anti-diuretic hormone''' due to selectivity for antidiuretic over vasopressor effects.
** '''Fast onset of action, with urine production decreasing within 30 minutes of oral administration'''
** Available in formulations for oral, parenteral, and nasal administration.
*** '''Because symptomatic hyponatremia with water intoxication,''' which is the only serious adverse event reported in children, '''occurred after intranasal or intravenous administration of desmopressin,''' the FDA and the European Medicines Agency (EMA) '''removed the indication for the treatment of primary nocturnal enuresis from all intranasal preparations of desmopressin.''' '''An oral lyophilisate formulation (MELT) requiring no concomitant fluid intake is currently available'''
* '''Efficacy'''
** '''Nocturia'''
*** '''Desmopressin is the most common vasopressin analogue used to treat nocturia in children and adults.'''
**** '''Decreased vasopressin levels are believed to be important in the pathophysiology of some forms of polyuria, specifically nocturnal polyuria.'''
*** '''Results in significant improvements in reducing nocturnal voids and increasing the hours of undisturbed sleep'''.
*** '''Generally well tolerated in all the studies on nocturia.'''
** '''Enuresis'''
*** In children, effective in reducing bedwetting. However, there was no effect after discontinuation of treatment, indicating that '''desmopressin suppresses the symptom of enuresis but does not cure the underlying cause.'''
**** In addition, not all children responded sufficiently to desmopressin monotherapy.
**** '''The combination of desmopressin and an enuresis alarm resulted in a greatly improved short-term success rate and decreased relapse rates'''
* '''Contraindications (drug monograph):'''
** '''Patients with type IIB or platelet-type (pseudo) Willerbrand disease, because of the risk of platelet aggregation and thrombocytopenia'''
** '''Any condition associated with impaired water excretion, such as:'''
*** '''Hyponatremia'''
*** '''Severe liver disease'''
*** '''[Hydro]nephrosis'''
*** '''Cardiac insufficiency'''
*** '''Chronic renal insufficiency'''
*** '''Congestive heart failure'''
*** '''Habitual or psychogenic polydypsia'''
** '''Any medical conditions which lead to sodium losing states such as:'''
*** '''Vomiting'''
*** '''Diarrhea'''
*** '''Bulimia'''
*** '''Anorexia nervosa'''
*** '''Adrenocortical insufficiency'''
*** '''Salt losing nephropathies'''
** '''Lactose intolerance/allergies'''
* '''Adverse events'''
** '''Hyponatremia'''
*** '''Can lead to a variety of adverse events ranging from mild headache, anorexia, nausea, and vomiting to loss of consciousness, seizures, and death'''
*** '''Usually occurs soon after treatment is initiated'''
*** '''Risk factors:'''
***# '''Increasing age'''
***# '''Female gender'''
***# '''Cardiac disease'''
***# '''Increasing 24-hour urine volume'''
* '''Dosing'''
** '''Females demonstrate increased sensitivity to demopression; recommended efficacious doses are 25 μg MELT for females and 50 to 100 μg MELT for males'''
** '''Prior to initiation, a serum sodium should be obtained at baseline, then again after initiation. Serum sodium should be assessed regularly, at least every 6 months with long-term desmopressin administration'''
** '''Initiation of desmopressin is currently not indicated for patients age ≥ 65''' (different than CUA guidelines, see below)
** '''2018 CUA MLUTS Guidelines'''
*** '''While the risk of hyponatremia is low in men with normal baseline serum sodium, sodium must be checked at baseline and 4–8 days as well as 30 days after initiation of treatment in (2):'''
***# '''All men taking desmopressin melts'''
***# '''Men ≥65 years taking 50 μg oral disintegrating tablet'''
**** Note that these guidelines are for male LUTS and therefore recommendations for females are not provided.

=== Phenazopyridine ===

* Trade name: Pyridium
* '''Mechanism of action'''
** Unknown
* '''Pharmacology'''
** Rapidly excreted in the urine
* '''Efficacy'''
** Considered a “grandfathered” drug that lacks both the safety and efficacy data required for Food and Drug Administration approval[https://pubmed.ncbi.nlm.nih.gov/31006341/]
*** Marketed prior to the Food, Drug, and Cosmetic Act of 1938
* '''Contraindications (2)[https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=165d01d4-a9f7-2293-e054-00144ff8d46c&type=pdf]'''
** Hypersensitivity
** Renal insufficiency
* '''Adverse events[https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=165d01d4-a9f7-2293-e054-00144ff8d46c&type=pdf]'''
** Most common
*** Headache
*** Rash
*** Pruritis
*** Skin or sclera discoloration
**** A yellowish tinge of the skin or sclera may indicate accumulation due to impaired renal excretion and the need to discontinue therapy
*** Urine discoloration
**** Patients should be informed that phenazopyridine produces a reddish-orange discoloration of the urine and may stain fabric.
*** GI disturbance
** Rare but serious: methylglobinemia, hemolytic anemia, thrombocytopenia, neutropenia, nephrotoxicity, and hepatotoxicity, usually at overdosage levels
* '''Dosing'''
** 200 mg three times daily after meals
** Duration of treatment
*** When used concomitantly with an antibacterial agent for the treatment of a urinary tract infection, the administration of Phenazopyridine HCl should not exceed 2 days.'''[https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=165d01d4-a9f7-2293-e054-00144ff8d46c&type=pdf]'''
***American Hospital Formulary Service states that therapy may be extended for up to 15 days in non-infectious scenarios[https://pubmed.ncbi.nlm.nih.gov/31006341/]
***Another study found no difference in adverse drug reactions among patients receiving phenazopyridine for >14 days compared to a matched comparator group[https://pubmed.ncbi.nlm.nih.gov/31006341/]
***

=== Dimethyl sulfoxide (DMSO) ===
* Has been used as an industrial solvent for many years
* '''Used in a 50% solution to improve symptoms in interstitial cystitis'''
* Has not been shown to be useful in the treatment of:
** Neurogenic detrusor overactivity
** Idiopathic detrusor overactivity
** Any patients with urgency or frequency but without interstitial cystitis

=== Baclofen ===
* Mechanism of action: depresses monosynaptic and polysynaptic excitation of motor neurons and interneurons in the spinal cord by activating GABAB receptors.
* Has been tried in idiopathic detrusor overactivity but with poor efficacy

=== Cyclooxygenase inhibitors ===
* Although there are theoretic mechanisms by which prostaglandin synthesis inhibitors could affect filling and storage symptoms, clinical evidence for this is scarce. The interest in the use of selective COX-2 inhibitors was tempered by concerns about long-term cardiovascular toxicity with these drugs.

=== Calcium antagonists ===
* Activation of detrusor muscle seems to require influx of extracellular Ca2+ through Ca2+ channels as well as via mobilization of intracellular Ca2+. The influx of extracellular calcium can be blocked by calcium antagonists, blocking L-type Ca2+ channels, and theoretically this would be an attractive way of inhibiting DO and regulating detrusor smooth muscle tone. Although these in vitro data suggest a possible role for calcium channel inhibitors, in the treatment of DO and incontinence, only limited clinical studies are available

=== Potassium channel openers ===
* Potassium channels contribute to the membrane potential of smooth muscle cells and hence to the regulation of smooth muscle tone. Despite promising preclinical efficacy data, potassium channel openers at present are not a therapeutic option and may never become one owing to a lack of selectivity for bladder over cardiovascular tissues