@@ Line 121: / Line 121: @@
 ** '''May have negative effects on cognitive function, particularly in the elderly population but also in children'''
 *Estimated cost per month: 10$ USD[https://www.goodrx.com/]
+====== Tolterodine (Detrol) ======
+* '''Metabolism: extensively metabolized by the liver (cytochrome P450) into its major active metabolite 5-HMT'''
+** '''5-HMT has''' '''a similar pharmacologic profile as the mother compound and significantly contributes to the therapeutic effect of tolterodine.'''
+**'''5-HMT is metabolized in the liver, but a significant part of 5-HMT is excreted renally without additional metabolism'''
+* '''Selectivity:''' tissue selective (has selectivity for the bladder compared with the salivary gland) but no selectivity for muscarinic receptor subtypes.
+* Dosing: Available in immediate release and extended release formulations. The extended release form seems to have advantages over the immediate release form in terms of both efficacy and tolerability
+* Outcomes: significant improvement in frequency and incontinence episodes
+* Adverse events:
+** No effect on QT interval
+** '''Low incidence of cognitive effects''' (relatively low lipophilicity of tolterodine and even lesser one of 5-HMT imply limited propensity to penetrate into the CNS)
+*Estimated cost per month: 35$ USD[https://www.goodrx.com/]
+====== Fesoterodine (Toviaz) ======
+* '''Metabolism: an orally active prodrug that is converted to the active metabolite 5-hydroxymethyl tolterodine (5-HMT)'''
+** All of the effects of fesoterodine are thought to be mediated via 5-HMT.
+* Selectivity: no selectivity for muscarinic receptor subtypes
+* '''Dosing: Recommended doses are 4 and 8 mg/day,''' with the 8-mg dose having a greater effect at the expense of a higher rate of dry mouth.
+** The suggested starting dose, 4 mg/day, can be used in patients with moderately impaired renal or hepatic function because of the '''combination of renal excretion and hepatic metabolism of 5-HMT'''
+* Adverse events:
+** Most common side effects are dry mouth, headache, and constipation
+** No effect on QT interval
+*Estimated cost per month: 50$ USD[https://www.goodrx.com/]
 ====== Darifenacin (Enablex) ======
@@ Line 142: / Line 165: @@
 ** '''No effect on cognitive function''' or heart rate. 30-mg dose may increase QT interval
 *Estimated cost per month: 30$ USD[https://www.goodrx.com/]
-====== Fesoterodine (Toviaz) ======
-* '''Metabolism: an orally active prodrug that is converted to the active metabolite 5-hydroxymethyl tolterodine (5-HMT)'''
-** All of the effects of fesoterodine are thought to be mediated via 5-HMT.
-** '''5-HMT is metabolized in the liver, but a significant part of 5-HMT is excreted renally without additional metabolism'''
-* Selectivity: no selectivity for muscarinic receptor subtypes
-* '''Dosing: Recommended doses are 4 and 8 mg/day,''' with the 8-mg dose having a greater effect at the expense of a higher rate of dry mouth.
-** The suggested starting dose, 4 mg/day, can be used in patients with moderately impaired renal or hepatic function because of the '''combination of renal excretion and hepatic metabolism of 5-HMT'''
-* Adverse events:
-** Most common side effects are dry mouth, headache, and constipation
-** No effect on QT interval
-*Estimated cost per month: 50$ USD[https://www.goodrx.com/]
-====== Tolterodine (Detrol) ======
-* '''Metabolism: extensively metabolized by the liver (cytochrome P450) into its major active metabolite 5-HMT'''
-** '''5-HMT has''' '''a similar pharmacologic profile as the mother compound and significantly contributes to the therapeutic effect of tolterodine.'''
-* '''Selectivity:''' tissue selective (has selectivity for the bladder compared with the salivary gland) but no selectivity for muscarinic receptor subtypes.
-* Dosing: Available in immediate release and extended release formulations. The extended release form seems to have advantages over the immediate release form in terms of both efficacy and tolerability
-* Outcomes: significant improvement in frequency and incontinence episodes
-* Adverse events:
-** No effect on QT interval
-** '''Low incidence of cognitive effects''' (relatively low lipophilicity of tolterodine and even lesser one of 5-HMT imply limited propensity to penetrate into the CNS)
-*Estimated cost per month: 35$ USD[https://www.goodrx.com/]
 *
 ====== Tropsium (Trosec) ======
-* '''Metabolism: mainly eliminated unchanged in the urine; not metabolized by the cytochrome P450 enzyme'''
+* '''<span style="color:#ff0000">Metabolism: mainly eliminated unchanged in the urine; not metabolized by the cytochrome P450 enzyme</span>'''
 ** Darifenacin, solifenacin, fesoterodine, tolterodine, and oxybutynin, are all actively metabolized in the liver by the cytochrome P450 enzyme system. Trospium chloride is not metabolized to any significant degree in the liver
 * '''Selectivity:''' no selectivity for muscarinic receptor subtypes.
@@ Line 202: / Line 202: @@
 ==== β3-adrenoreceptor agonists ====
-* '''3 β-ARs subtypes (β1, β2, and β3) have been identified in the detrusor and urothelium.'''
+* '''<span style="color:#ff0000">3 β-ARs subtypes (β1, β2, and β3) have been identified in the detrusor and urothelium.</span>'''
 ** Stimulation of β2- and β3-adrenergic receptors results in the direct relaxation of the detrusor smooth muscle
-** '''β3-adrenergic receptor is the most highly expressed subtype''' among α- and β-adrenoceptor subtypes at the mRNA level in human bladder
+** '''<span style="color:#ff0000">β3-adrenergic receptor is the most highly expressed subtype</span>''' among α- and β-adrenoceptor subtypes at the mRNA level in human bladder
 ===== Mechanism of action =====
 * '''Stimulates β3-adrenoceptor causing activation of adenylyl cyclase with the subsequent formation of cAMP, resulting in detrusor relaxation'''
-** Recall that in erectile physiology, actvation of guanyl cyclase results in increased cGMP, resulting in arterial wall smooth muscle relaxation
+** Recall that in erectile physiology, activation of guanyl cyclase results in increased cGMP, resulting in arterial wall smooth muscle relaxation
 * '''Inhibits filling induced activity in both mechanosensitive Aδ and C-fiber primary bladder afferents,''' at least in an animal model.
 ===== Mirabegron =====
-* '''Metabolism'''
-** Rapidly absorbed
+====== Metabolism ======
-** '''Metabolized in the liver via multiple pathways, mainly by cytochrome P450'''
+* Rapidly absorbed
-*** '''Subject to clinically relevant drug-drug interactions;''' should be used with caution in patients who are taking ketoconazole or other potent CYP3A4 inhibitors.
+* '''Metabolized in the liver via multiple pathways, mainly by cytochrome P450'''
-*** Metabolites are inactive
+** '''Subject to clinically relevant drug-drug interactions;''' should be used with caution in patients who are taking ketoconazole or other potent CYP3A4 inhibitors.
-* '''Outcomes:'''
+** Metabolites are inactive
-** '''Increases bladder capacity, improves frequency, urgency, incontinence episodes'''
-** '''Does not adversely affect flow rate, detrusor pressure at maximum flow rate, bladder contractile index, or residual volume'''
+====== Outcomes ======
-* '''Contraindications''' (drug monograph) '''(3):'''
+* '''Increases bladder capacity, improves frequency, urgency, incontinence episodes'''
-*# '''Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg.'''
+* '''Does not adversely affect flow rate, detrusor pressure at maximum flow rate, bladder contractile index, or residual volume'''
-*# '''Pregnancy'''
-*# '''Hypersensitivity'''
+====== Contraindications(3):[https://www.astellas.com/ca/system/files/pdf/Myrbetriq_PM_EN.pdf §] ======
-* '''Dosage'''
+# '''<span style="color:#ff0000">Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg.</span>'''
-** '''Starting dose of 25 mg and increasing to 50 mg, if needed, is recommended.'''
+# '''<span style="color:#ff0000">Pregnancy</span>'''
-** '''Lowest dose is also recommended for renal and hepatic impairment'''
+# '''<span style="color:#ff0000">Hypersensitivity</span>'''
-* '''Adverse events'''
-** '''Common side effects''' (drug monograph)''':'''
+====== Dosage ======
-*** '''Hypertension'''
+* '''Starting dose of 25 mg and increasing to 50 mg, if needed, is recommended.'''
-**** The mean increase (compared with placebo) in systolic and diastolic blood pressure after therapeutic doses of mirabegron once daily was ≈0.5-1 mm Hg and was reversible on discontinuation of treatment.
+* '''Lowest dose is also recommended for renal and hepatic impairment'''
-**** In the clinical efficacy and safety studies, the change from baseline in mean pulse rate for mirabegron 50 mg was ≈1 beat/min and reversible on discontinuation of treatment.
-*** '''Headache, dizziness'''
+====== <span style="color:#ff0000">Adverse events[https://www.astellas.com/ca/system/files/pdf/Myrbetriq_PM_EN.pdf §]</span> ======
-*** '''UTI'''
+* '''<span style="color:#ff0000">≥1% (5)</span>'''
-*** '''Constipation,''' '''dry eyes, blurry vision'''
+*# '''<span style="color:#ff0000">Hypertension</span>'''
-*** '''Does not cause increase QT interval'''
+*#* The mean increase (compared with placebo) in systolic and diastolic blood pressure after therapeutic doses of mirabegron once daily was ≈0.5-1 mm Hg and was reversible on discontinuation of treatment.
-** '''Even if the cardiovascular effects of mirabegron observed in clinical studies have been minimal and clinically not relevant, effects on HR and blood pressure need to be monitored when the drug is prescribed'''
+*#* In the clinical efficacy and safety studies, the change from baseline in mean pulse rate for mirabegron 50 mg was ≈1 beat/min and reversible on discontinuation of treatment.
+*# '''<span style="color:#ff0000">Tachycardia</span>'''
+*#'''<span style="color:#ff0000">Nasopharyngitis</span>'''
+*#'''<span style="color:#ff0000">Urinary tract infection</span>'''
+*#'''<span style="color:#ff0000">Headache</span>'''
+*#'''<span style="color:#ff0000">Constipation</span>'''
+*'''Does not cause increase QT interval'''
+* '''Effects on HR and blood pressure need to be monitored when the drug is prescribed''', even if the cardiovascular effects of mirabegron observed in clinical studies have been minimal and clinically not relevant
 ==== Toxins ====
@@ Line 243: / Line 250: @@
 * '''A neurotoxin produced by''' '''gram-positive Clostridium botulinum'''
 * '''7 subtypes; subtype A has the longest duration of action, making it the most relevant clinically.'''
-** Subtype A is available in 4 different forms''': onabotulinumtoxinA''' (onabotA), abobotulinumtoxinA (abobotA), and incobotulinumtoxinA (incobotA) for '''Botox''', Dysport, and Xeomin, respectively.
+** Subtype A is available in different forms''':'''
-*** Although the toxin is the same, it is wrapped by different proteins that modify the relative potency of each brand.
+***'''OnabotulinumtoxinA''' (onabotA) - '''Botox'''
-*** Most of the information available about intravesical application of BoNTA derives from the use of onabotA (Botox).
+***'''AbobotulinumtoxinA''' (abobotA) - '''Dysport'''
+***IncobotulinumtoxinA (incobotA) - Xeomin
+**** Although the toxin is the same, it is wrapped by different proteins that modify the relative potency of each brand.
+**** Most of the information available about intravesical application of BoNTA derives from the use of onabotA (Botox).
+****Dysport associated with higher rates of need for clean intermittent self-catheterization
 ** Clinical dose conversion studies for the LUT do not exist.
-* '''Mechanisms of action (4):'''
+* '''<span style="color:#ff0000">Mechanisms of action (4):'''
-*# '''Inhibits release of acetylcholine from pre-synaptic cholinergic motor nerve endings by cleaving SNAP 25 and rendering the SNARE complex inactive, resulting in muscle paralysis'''
+*# '''<span style="color:#ff0000">Inhibits release of acetylcholine from pre-synaptic cholinergic motor nerve endings by cleaving SNAP 25 and rendering the SNARE complex inactive, resulting in muscle paralysis'''
 *#* '''Acts on both striated muscle and smooth muscle'''
 *#** '''Striated muscle paralysis recovers within 2-4 months'''
-*# '''Terminal axonal degeneration due to accumulation of neurotransmitter-containing synaptic vesicles'''
+*# '''<span style="color:#ff0000">Terminal axonal degeneration due to accumulation of neurotransmitter-containing synaptic vesicles'''
-*# '''Inhibits the release of other neurotransmitters including ATP and neuropeptides such as substance P'''
+*# '''<span style="color:#ff0000">Inhibits the release of other neurotransmitters including ATP and neuropeptides such as substance P'''
-*# '''Reduces afferent activity from bladder'''
+*# '''<span style="color:#ff0000">Reduces afferent activity from bladder'''
 * Efficacy
 ** RCTs have documented the clinical effects of onabotulinumtoxinA both in neurogenic detrusor overactivity and idiopathic detrusor overactivity, wherein the drug decreases incontinence episodes, frequency, and urgency and improves QoL.
 ** '''Shown to be effective in patients with OAB.'''
 *** '''Successful OAB treatment with BoNTA does not appear to be related to the existence of DO.''' No differences in outcomes were found between those with and those without baseline DO
-* '''Contraindications (4):'''
+* '''<span style="color:#ff0000">Dosing: FDA-approved dose of 200U for neurogenic OAB</span>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649594/ §][https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739988/ §]'''
-*# '''Active UTI'''
+**'''<span style="color:#ff0000">Not FDA-approved in non-neurogenic OAB patients, 100U typically used</span>'''
-*# '''Acute urinary retention'''
+*'''<span style="color:#ff0000">Contraindications (4):</span>'''
-*# '''Unwillingness or inability to self-catheterize'''
+*# '''<span style="color:#ff0000">Active urinary tract infection</span>'''
-*# '''Hypersensitivity'''
+*# '''<span style="color:#ff0000">Acute urinary retention</span>'''
-* '''Adverse events:'''
+*# '''<span style="color:#ff0000">Unwillingness or inability to self-catheterize</span>'''
-** '''Most common: bladder pain and urinary infections. Hematuria, usually mild, may also occur'''
+*# '''<span style="color:#ff0000">Hypersensitivity</span>'''
-** '''Most serious: paralysis of the striated musculature caused by circulatory leakage of the toxin'''
+* '''<span style="color:#ff0000">Adverse events:</span>'''
-*** Has never been reported.
+**'''<span style="color:#ff0000">Most common (3):</span>'''
-**** '''Caution should be used in treating high-risk patients, including:'''
+**#'''<span style="color:#ff0000">Bladder pain</span>'''
-****# '''Children'''
+**#'''<span style="color:#ff0000">Gross hematuria (usually mild)</span>'''
-****# '''Patients with low pulmonary reserve'''
+**# '''<span style="color:#ff0000">Urinary tract infection</span>'''
-****# '''Patients with myasthenia gravis'''
+**'''<span style="color:#ff0000">Most serious (2):</span>'''
-*** '''Transient muscle weakness''' was reported with abobotA application
+**#'''<span style="color:#ff0000">Urinary retention and a transient necessity to perform CIC (≈5%)</span>'''
-** '''Most feared in patients with voluntary voiding: urinary retention and a transient necessity to perform CIC.'''
+**#*<span style="color:#ff0000">'''Patient must be able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary'''
-*** '''The proportion of patients who initiate CIC at any time during treatment cycle 1 was 6.1%''' versus none in the placebo group; for over half the patients who initiated CIC, the duration of CIC was 6 weeks or less.
+**#*'''The proportion of patients who initiate CIC at any time during treatment cycle 1 was 6.1%''' versus none in the placebo group; for over half the patients who initiated CIC, the duration of CIC was 6 weeks or less.
+**#'''Paralysis of the striated musculature caused by circulatory leakage of the toxin'''
+**#* '''Has never been reported.'''
+**#** '''Caution should be used in treating high-risk patients, including:'''
+**#**# '''Children'''
+**#**# '''Patients with low pulmonary reserve'''
+**#**# '''Patients with myasthenia gravis'''
+**#* '''Transient muscle weakness''' was reported with abobotA application
+**'''<span style="color:#ff0000">Other:</span>'''
+**#'''<span style="color:#ff0000">Dry mouth</span>'''
+**#'''<span style="color:#ff0000">Dysphagia</span>'''
+**#'''<span style="color:#ff0000">Impaired vision</span>'''
+**# '''<span style="color:#ff0000">Eyelid weakness</span>'''
+**#'''<span style="color:#ff0000">Arm weakness</span>'''
+**#'''<span style="color:#ff0000">Leg weakness</span>'''
+**# '''<span style="color:#ff0000">Torso weakness</span>'''
 ** '''Aminoglycosides should be avoided during BoNTA treatment because they might block motor plates and therefore enhance BoNTA effect'''
@@ Line 329: / Line 355: @@
 ** And progesterone '''increases the frequency of incontinence in those incontinent at baseline'''
 ** Alone or with progestin increases the risk of de novo UI in postmenopausal women
-* '''Local (vaginal) estrogen'''
+* '''<span style="color:#ff0000">Local (vaginal) estrogen</span>'''
-** '''May improve OAB symptoms in postmenopausal women by treating urogenital atrophy'''
+** '''<span style="color:#ff0000">May improve OAB symptoms in postmenopausal women by treating urogenital atrophy</span>'''
 *** The vaginal route improves dryness, pruritus, and dyspareunia and provides a greater improvement in physical findings than oral administration.
 ** '''Estrogen when given alone does not appear to be an effective treatment for SUI in the woman'''
@@ Line 345: / Line 371: @@
 ===== Mechanism of action =====
 *'''<span style="color:#ff0000">Capable of reducing smooth muscle tone in the bladder outlet in both men and women and in the prostatic muscle.</span>'''
-** Facilitate urine release in conditions of functionally increased urethral resistance, such as with BOO secondary to prostatic enlargement., and bladder neck dysfunction
+** Facilitate urine release in conditions of functionally increased urethral resistance, such as with BOO secondary to prostatic enlargement and bladder neck dysfunction
 * '''<span style="color:#ff0000">Urethral tone and intraurethral pressure are influenced by α-adrenergic receptors</span>'''
 ** Hypogastric nerve stimulation and α-adrenergic agonists raise intraurethral pressure, which is blocked by α1-adrenergic antagonists.
@@ Line 391: / Line 417: @@
 #* '''<span style="color:#ff0000">Most often reported with silodosin and tamsulosin.</span>'''
 #** '''<span style="color:#ff0000">Silodosin is associated with higher rates of ejaculatory dysfunction (14%)</span> compared to tamsulosin (2%).''' However, only 1.3% of silodosin-treated patients discontinued treatment because of this adverse event.
+===== Contraindications =====
+* '''Absolute (1)[https://www.ncbi.nlm.nih.gov/books/NBK556066/ §]'''
+** '''Hypersensitivity to alpha-blockers or any other component of the drug formulation'''
+* '''<span style="color:#ff0000">Caution (4):</span>'''
+*# '''<span style="color:#ff0000">Planned cataract surgery[https://pubmed.ncbi.nlm.nih.gov/34384237/ ★]</span>'''
+*#* Can complicate cataract surgery by inducing sudden iris prolapse and pupil constriction during the surgery, known as "intraoperative floppy iris syndrome[https://www.ncbi.nlm.nih.gov/books/NBK556066/ §]
+*#** Tamsulosin has the highest risk for IFIS (40x that of alfusozin), but all alpha blockers increase the risk of IFIS to some degree.[https://pubmed.ncbi.nlm.nih.gov/34384237/ §]
+*#** For every 255 men receiving tamsulosin in the immediate preoperative cataract surgical period, one serious complication (e.g., retinal detachment, lost lens or lens fragment, endophthalmitis) would result.[https://pubmed.ncbi.nlm.nih.gov/34384237/ §]
+*#* '''<span style="color:#ff0000">When initiating alpha blocker therapy, patients with planned cataract surgery should be informed of the associated risk of intraoperative floppy iris syndrome risk and be advised to discuss these risks with their ophthalmologists, ideally with delay of medication initiation until after planned procedures.[https://pubmed.ncbi.nlm.nih.gov/34384237/ ★]'''
+*#* '''Discontinuation of tamsulosin 4 to 7 days prior to cataract surgery is routine practice, but it does not completely eliminate intraoperative floppy iris syndrome risk.[https://pubmed.ncbi.nlm.nih.gov/34384237/ ★]'''
+*# '''<span style="color:#ff0000">Patients on several antihypertensives, or with orthostatic hypotension[https://pubmed.ncbi.nlm.nih.gov/34384237/ ★]</span>'''
+*#* '''When treating patients on several antihypertensives, or with orthostatic hypotension, it is best to select an alpha blocker that exhibits minimal impact on blood pressure (eg, the highly selective alpha 1a blocker silodosin)[https://pubmed.ncbi.nlm.nih.gov/34384237/ §]'''
+*#'''<span style="color:#ff0000">Concomitant use of a PDE5[https://pubmed.ncbi.nlm.nih.gov/34384237/ ★]</span>'''
+*#*'''<span style="color:#ff0000">The hypotensive effects of terazosin and doxazosin can be potentiated by concomitant use of a PDE5, such as sildenafil or vardenafil.[https://pubmed.ncbi.nlm.nih.gov/34384237/ ★]</span>'''
+*#*'''Tamsulosin at a dose of 0.4 mg/day, however, does not appear to significantly potentiate the hypotensive effects of sildenafil.[https://pubmed.ncbi.nlm.nih.gov/34384237/ §]'''
+*#*'''Regardless, patients utilizing both these medications should be counselled appropriately regarding the risk for drops in blood pressure and symptoms associated with this.[https://pubmed.ncbi.nlm.nih.gov/34384237/ §]'''
+*#'''<span style="color:#ff0000">With tamsulosin, caution may be required in patients with serious sulfonamide allergy[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831305/ §]</span>'''
 === Decreasing Outlet Resistance at a Site of Anatomic Obstruction ===
@@ Line 419: / Line 464: @@
 *** During the 12 months of treatment, the '''maximal urinary-flow rates increased''' progressively in both finasteride-treated groups, but not in the group given placebo
 *** During the first six months, the median size of the prostate decreased progressively in both finasteride-treated groups, after which it did not change significantly, and it was significantly smaller in both finasteride-treated groups than in the placebo group at all times. After 12 months of treatment, the '''prostate had shrunk by 19 percent from base line''' in the group given 5 mg of finasteride, by 18 percent in the group given 1 mg of finasteride, and by 3 percent in the group given placebo
-** Gormley, Glenn J., et al."The effect of finasteride in men with benign prostatic hyperplasia." ''New England Journal of Medicine'' 327.17 (1992): 1185-1191.
+** [https://pubmed.ncbi.nlm.nih.gov/1383816/ Gormley, Glenn J., et al."The effect of finasteride in men with benign prostatic hyperplasia." ''New England Journal of Medicine'' 327.17 (1992): 1185-1191.]
 ===== Adverse events =====
@@ Line 435: / Line 480: @@
 # '''Reduced risk of BPH-related surgical intervention'''
 === Decreasing Outlet Resistance at the Level of the Striated Sphincter ===
-* '''There is no class of pharmacologic agents that will selectively relax the striated musculature of the pelvic floor. However, injection of botulinum toxin into the striated sphincter has been used with some clinical success, especially in patients with neurologic striated sphincter dyssynergia'''. The potential for spread to nearby structures is greater than with intravesical therapy, and distant effects can also occur, but these are rare
+* '''No class of pharmacologic agents that will selectively relax the striated musculature of the pelvic floor.'''
+*'''Injection of botulinum toxin into the striated sphincter has been used with some clinical success, especially in patients with neurologic striated sphincter dyssynergia'''.
-=== Phosphodiesterase inhibitors ===
+**The potential for spread to nearby structures is greater than with intravesical therapy, and distant effects can also occur, but these are rare
-* '''Mechanism''': drugs acting through the nitric oxide (NO)/cGMP system, such as PDE5 inhibitors, can '''relax the smooth muscle of the bladder outflow region''' '''and may improve urinary bladder blood perfusion'''
-* '''As monotherapy, PDE5 inhibitors significantly improve IPSS and International Index of Erectile Function (IIEF) scores, but not Qmax, when compared with placebo.'''
-** '''PDE inhibitors seem to improve subjective measurements but not objective ones, eg. Qmax'''
-** '''The mechanism behind the beneficial effect of the PDE inhibitors on LUTS and OAB and their site(s) of action largely remain to be elucidated.'''
-** Combination of PDE5 inhibitors and α-blockers led to significant improvements of the IPSS and IIEF scores as well as Qmax when compared with the use of α-blockers alone.
-* As of the time of Campbell’s writing, only tadalafil has been approved for the treatment of LUTS caused by benign prostatic obstruction (BPO)
-* There is insufficient information is available on the combination of PDE5 inhibitors with other LUTS medications such as 5α-reductase inhibitors.
 === Increasing Intravesical Pressure and Bladder Contractility ===
-* '''There is currently no effective drug for the treatment of detrusor underactivity or underactive bladder'''
+* '''Currently no effective drug for the treatment of detrusor underactivity or underactive bladder'''
 * '''Parasympathomimetic agents'''
 ** ACh, which stimulates bladder contraction, cannot be used for therapeutic purposes because of its action at both muscarinic and nicotinic receptors and it is rapidly hydrolyzed by cholinesterases.
 ** Many ACh-like drugs exist, but only bethanechol chloride exhibits a relatively selective in vitro action on the urinary bladder and gut with little or no nicotinic action.
-*** '''Bethanechol is cholinesterase resistant and causes an in vitro contraction of smooth muscle from all areas of the bladder. However, there is little evidence of its efficacy.'''
+*** '''Bethanechol'''
+****'''Cholinesterase resistant'''
+****'''Causes an in vitro contraction of smooth muscle from all areas of the bladder.'''
+****'''Little evidence of its efficacy'''
 **** At least in a "denervated" bladder, an oral dose of 200 mg is required to produce the same urodynamic effects as a subcutaneous dose of 5 mg.
 * Prostaglandins
@@ Line 462: / Line 503: @@
 **# Potentiation of acetylcholine (but not ATP) release from cholinergic nerve terminals through prejunctional prostanoid receptors.
 ** Initial reports of the use of intravesical prostanoids producing lasting favorable clinical effects have not been confirmed.
+=== Phosphodiesterase Inhibitors ===
+* '''Mechanism''': drugs acting through the nitric oxide (NO)/cGMP system, such as PDE5 inhibitors, can '''relax the smooth muscle of the bladder outflow region and may improve urinary bladder blood perfusion'''
+* '''<span style="color:#ff0000">As monotherapy, PDE5 inhibitors significantly improve IPSS and International Index of Erectile Function (IIEF) scores, but not Qmax, when compared with placebo.</span>'''
+** '''PDE inhibitors seem to improve subjective measurements but not objective ones, eg. Qmax'''
+** '''The mechanism behind the beneficial effect of the PDE inhibitors on LUTS and OAB and their site(s) of action largely remain to be elucidated.'''
+** Combination of PDE5 inhibitors and α-blockers led to significant improvements of the IPSS and IIEF scores as well as Qmax when compared with the use of α-blockers alone.
+* As of the time of Campbell’s writing, only tadalafil has been approved for the treatment of LUTS caused by benign prostatic obstruction (BPO)
+* There is insufficient information is available on the combination of PDE5 inhibitors with other LUTS medications such as 5α-reductase inhibitors.
 === Phytotherapy ===
-* '''Saw palmetto'''
-** RCT
+==== Saw palmetto ====
-*** 225 men age >49 with moderate-to-severe symptoms of benign prostatic hyperplasia
+* RCT
-*** Randomized to to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo.
+** 225 men age >49 with moderate-to-severe symptoms of benign prostatic hyperplasia
-*** Primary outcome: changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate.
+** Randomized to to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo.
-*** Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects.
+** Primary outcome: changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate.
-*** Results
+** Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects.
-**** '''No significant difference between the saw palmetto and placebo groups in the change in AUASI scores, maximal urinary flow rate, prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen'''
+** Results
-*** Bent, Stephen, et al."Saw palmetto for benign prostatic hyperplasia." New England Journal of Medicine 354.6 (2006): 557-566.
+*** '''No significant difference between the saw palmetto and placebo groups in the change in AUASI scores, maximal urinary flow rate, prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen'''
+** [https://pubmed.ncbi.nlm.nih.gov/16467543/ Bent, Stephen, et al."Saw palmetto for benign prostatic hyperplasia." New England Journal of Medicine 354.6 (2006): 557-566.]
 == Other drugs ==
-* '''Desmopressin'''
+=== Desmopressin ===
-** '''Mechanism of action:'''
+* '''Mechanism of action:'''
-*** '''Analogue of the endogenous hormone''' '''vasopressin (also known as antidiuretic hormone).'''
+** '''Analogue of the endogenous hormone''' '''vasopressin (also known as antidiuretic hormone).'''
-**** Vasopressin
+*** Vasopressin
-***** Functions (2):
+**** Functions (2):
-*****# Causes contraction of vascular smooth muscle
+****# Causes contraction of vascular smooth muscle
-*****# Stimulates water reabsorption from the collecting ducts
+****# Stimulates water reabsorption from the collecting ducts
-***** Release stimulated by:
+**** Release stimulated by:
-****** Hyperosmolality
+***** Hyperosmolality
-****** Hypovolemia
+***** Hypovolemia
-****** Stress
+***** Stress
-****** Nausea
+***** Nausea
-****** Pregnancy
+***** Pregnancy
-****** Hypoglycemia
+***** Hypoglycemia
-****** Nicotine
+***** Nicotine
-****** Morphine
+***** Morphine
-****** Other drugs
+***** Other drugs
-***** Release inhibited by:
+**** Release inhibited by:
-****** Hypoosmolality
+***** Hypoosmolality
-****** Hypervolemia
+***** Hypervolemia
-****** Ethanol
+***** Ethanol
-****** Phenytoin
+***** Phenytoin
-** '''Pharmacology'''
+* '''Pharmacology'''
-*** '''More powerful and longer-lasting antidiuretic action than vasopressin/anti-diuretic hormone''' due to selectivity for antidiuretic over vasopressor effects.
+** '''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'''
+** '''Fast onset of action, with urine production decreasing within 30 minutes of oral administration'''
-*** Available in formulations for oral, parenteral, and nasal 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'''
+*** '''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'''
+* '''Efficacy'''
-*** '''Nocturia'''
+** '''Nocturia'''
-**** '''Desmopressin is the most common vasopressin analogue used to treat nocturia in children and adults.'''
+*** '''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.'''
+**** '''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'''.
+*** '''Results in significant improvements in reducing nocturnal voids and increasing the hours of undisturbed sleep'''.
-**** '''Generally well tolerated in all the studies on nocturia.'''
+*** '''Generally well tolerated in all the studies on nocturia.'''
-*** '''Enuresis'''
+** '''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 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.
+**** 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'''
+**** '''The combination of desmopressin and an enuresis alarm resulted in a greatly improved short-term success rate and decreased relapse rates'''
-** '''Contraindications (drug monograph):'''
+* '''Contraindications (drug monograph):'''
-*** '''Patients with type IIB or platelet-type (pseudo) Willerbrand disease, because of the risk of platelet aggregation and thrombocytopenia'''
+** '''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:'''
+** '''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'''
+*** '''Severe liver disease'''
-**** '''Usually occurs soon after treatment is initiated'''
+*** '''[Hydro]nephrosis'''
-**** '''Risk factors:'''
+*** '''Cardiac insufficiency'''
-****# '''Increasing age'''
+*** '''Chronic renal insufficiency'''
-****# '''Female gender'''
+*** '''Congestive heart failure'''
-****# '''Cardiac disease'''
+*** '''Habitual or psychogenic polydypsia'''
-****# '''Increasing 24-hour urine volume'''
+** '''Any medical conditions which lead to sodium losing states such as:'''
-** '''Dosing'''
+*** '''Vomiting'''
-*** '''Females demonstrate increased sensitivity to demopression; recommended efficacious doses are 25 μg MELT for females and 50 to 100 μg MELT for males'''
+*** '''Diarrhea'''
-*** '''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'''
+*** '''Bulimia'''
-*** '''Initiation of desmopressin is currently not indicated for patients age ≥ 65''' (different than CUA guidelines, see below)
+*** '''Anorexia nervosa'''
-*** '''2018 CUA MLUTS Guidelines'''
+*** '''Adrenocortical insufficiency'''
-**** '''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):'''
+*** '''Salt losing nephropathies'''
-****# '''All men taking desmopressin melts'''
+** '''Lactose intolerance/allergies'''
-****# '''Men ≥65 years taking 50 μg oral disintegrating tablet'''
+* '''Adverse events'''
-***** Note that these guidelines are for male LUTS and therefore recommendations for females are not provided.
+** '''Hyponatremia'''
-* '''Dimethyl sulfoxide (DMSO)'''
+*** '''Can lead to a variety of adverse events ranging from mild headache, anorexia, nausea, and vomiting to loss of consciousness, seizures, and death'''
-** Has been used as an industrial solvent for many years
+*** '''Usually occurs soon after treatment is initiated'''
-** '''Used in a 50% solution to improve symptoms in interstitial cystitis'''
+*** '''Risk factors:'''
-** Has not been shown to be useful in the treatment of:
+***# '''Increasing age'''
-*** Neurogenic detrusor overactivity
+***# '''Female gender'''
-*** Idiopathic detrusor overactivity
+***# '''Cardiac disease'''
-*** Any patients with urgency or frequency but without interstitial cystitis
+***# '''Increasing 24-hour urine volume'''
-* '''Baclofen'''
+* '''Dosing'''
-** Mechanism of action: depresses monosynaptic and polysynaptic excitation of motor neurons and interneurons in the spinal cord by activating GABAB receptors.
+** '''Females demonstrate increased sensitivity to demopression; recommended efficacious doses are 25 μg MELT for females and 50 to 100 μg MELT for males'''
-** Has been tried in idiopathic detrusor overactivity but with poor efficacy
+** '''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'''
-* Cyclooxygenase inhibitors
+** '''Initiation of desmopressin is currently not indicated for patients age ≥ 65''' (different than CUA guidelines, see below)
-** 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.
+** '''2018 CUA MLUTS Guidelines'''
-* Calcium antagonists
+*** '''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):'''
-** 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
+***# '''All men taking desmopressin melts'''
-* Potassium channel openers
+***# '''Men ≥65 years taking 50 μg oral disintegrating tablet'''
-** 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
+**** 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
 == Combinations ==
-* '''Alpha-blockers and 5-ARIs'''
+=== Alpha-blockers and 5-ARIs ===
-** '''MTOPS'''§
+* '''<span style="color:#ff00ff">MTOPS</span>'''§
-*** '''Population: 3047 men age ≥ 50 with IPSS 8-30, PSA ≤ 10 ng/mL, Qmax ≥4 but ≤15 ml/s with minimum voided volume ≥125 ml'''
+** '''Population: 3047 men age ≥ 50 with IPSS 8-30, PSA ≤ 10 ng/mL, Qmax ≥4 but ≤15 ml/s with minimum voided volume ≥125 ml'''
-**** '''Mean prostate volume: 36mL'''
+*** '''Mean prostate volume: 36mL'''
-**** '''Mean PSA: 2.4ng/mL'''
+*** '''Mean PSA: 2.4ng/mL'''
-*** '''Randomized to placebo, doxazosin, finasteride, or combination therapy'''
+** '''Randomized to placebo, doxazosin, finasteride, or combination therapy'''
-*** '''Primary outcome: overall clinical progression, defined as the first occurrence of:'''
+** '''Primary outcome: overall clinical progression, defined as the first occurrence of:'''
-***# '''≥ 4 points increase from baseline AUA symptom score'''
+**# '''≥ 4 points increase from baseline AUA symptom score'''
-***# '''Acute urinary retention'''
+**# '''Acute urinary retention'''
-***# '''Renal insufficiency'''
+**# '''Renal insufficiency'''
-***# '''Recurrent UTI'''
+**# '''Recurrent UTI'''
-***# '''Urinary incontinence'''
+**# '''Urinary incontinence'''
-*** Secondary outcomes: changes over time in the AUA symptom score and the maximal urinary flow rate
+** Secondary outcomes: changes over time in the AUA symptom score and the maximal urinary flow rate
-*** '''Results:'''
+** '''Results:'''
-**** '''Mean follow-up: 4.5 years'''
+*** '''Mean follow-up: 4.5 years'''
-**** '''Rate of overall clinical progression:'''
+*** '''Rate of overall clinical progression:'''
-***** Placebo 4.5 per 100 person-years
+**** Placebo 4.5 per 100 person-years
-***** '''Doxazosin''': 2.7 per 100 person-years '''(P<0.001)'''
+**** '''Doxazosin''': 2.7 per 100 person-years '''(P<0.001)'''
-***** '''Finasteride''': 2.9 per 100 person-years '''(P=0.002)'''
+**** '''Finasteride''': 2.9 per 100 person-years '''(P=0.002)'''
-***** '''No difference between doxazosin alone vs. finasteride alone'''
+**** '''No difference between doxazosin alone vs. finasteride alone'''
-***** '''Combination therapy: 1.5 per 100 person-years (P<0.001), a significantly greater reduction than doxazosin alone (P<0.001) or finasteride alone (P<0.001)'''
+**** '''Combination therapy: 1.5 per 100 person-years (P<0.001), a significantly greater reduction than doxazosin alone (P<0.001) or finasteride alone (P<0.001)'''
-** '''CombAT'''§
+* '''<span style="color:#ff00ff">CombAT</span>'''§
-*** '''Population: 4844 men age ≥ 50''' with a clinical diagnosis of BPH, '''IPSS ≥ 12,''' '''prostate volume ≥ 30g''', PSA 1.5-10 ng/ml, Qmax >5 but ≤15 ml/s with minimum voided volume ≥125 ml
+** '''Population: 4844 men age ≥ 50''' with a clinical diagnosis of BPH, '''IPSS ≥ 12,''' '''prostate volume ≥ 30g''', PSA 1.5-10 ng/ml, Qmax >5 but ≤15 ml/s with minimum voided volume ≥125 ml
-**** '''Mean prostate volume: 55mL (larger than MTOPS)'''
+*** '''Mean prostate volume: 55mL (larger than MTOPS)'''
-**** '''Mean PSA: 4.0ng/mL (higher than MTOPS)'''
+*** '''Mean PSA: 4.0ng/mL (higher than MTOPS)'''
-*** '''Randomized to daily tamsulosin, dutasteride, or a combination of both (no placebo)'''
+** '''Randomized to daily tamsulosin, dutasteride, or a combination of both (no placebo)'''
-*** '''Primary end point: time to first AUR or BPH-related surgery'''
+** '''Primary end point: time to first AUR or BPH-related surgery'''
-*** Secondary end points included BPH clinical progression, symptoms, Q(max), prostate volume, safety, and tolerability
+** Secondary end points included BPH clinical progression, symptoms, Q(max), prostate volume, safety, and tolerability
-**** BPH clinical progression defined as one of the following: symptom deterioration by International Prostate Symptom Score ≥4 points on two consecutive visits; BPH-related AUR; BPH-related urinary incontinence; recurrent BPH-related urinary tract infection or urosepsis; BPH-related renal insufficiency
+*** BPH clinical progression defined as one of the following: symptom deterioration by International Prostate Symptom Score ≥4 points on two consecutive visits; BPH-related AUR; BPH-related urinary incontinence; recurrent BPH-related urinary tract infection or urosepsis; BPH-related renal insufficiency
-*** '''Results''':
+** '''Results''':
-**** '''Combination therapy was significantly better than tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery'''
+*** '''Combination therapy was significantly better than tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery'''
-**** '''Combination therapy was significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression'''
+*** '''Combination therapy was significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression'''
-**** '''Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr.'''
+*** '''Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr.'''
-** '''Summary of evidence for combination alpha-blockers and 5-ARIs from these trials:'''
+* '''Summary of evidence for combination alpha-blockers and 5-ARIs from these trials:'''
-*** '''Combination better reduces risk of clinical progression and symptoms benefit at 4 years'''
+** '''Combination better reduces risk of clinical progression and symptoms benefit at 4 years'''
-*** '''Monotherapy with 5-ARI and alpha-blockers are equally effective in risk of overall clinical progression'''
+** '''Monotherapy with 5-ARI and alpha-blockers are equally effective in risk of overall clinical progression'''
-*** '''5-ARI reduces risk of AUR or BPH-related surgery, addition of tamsulosin does not increase benefit'''
+** '''5-ARI reduces risk of AUR or BPH-related surgery, addition of tamsulosin does not increase benefit'''
-* '''Alpha-blockers and anti-cholinergics'''
-** Several RCTs have demonstrated that the '''combination treatment of anti-cholinergics and α1-blockers was more effective at reducing male LUTS''' '''than α1-blockers alone in men with OAB and coexisting bladder outlet obstruction'''
+=== Alpha-blockers and anti-cholinergics ===
-** '''α1-blockers and anti-cholinergics may have an additional synergistic effect on the bladder in the neurogenic population'''. This suggests that targeting multiple receptors may maximize the effectiveness of pharmacologic treatment of neurogenic bladder and should be considered in patients in whom treatment with antimuscarinics alone fails
+* Several RCTs have demonstrated that the '''combination treatment of anti-cholinergics and α1-blockers was more effective at reducing male LUTS''' '''than α1-blockers alone in men with OAB and coexisting bladder outlet obstruction'''
-* '''Beta-3-agonist and anti-cholinergics''':
+* '''α1-blockers and anti-cholinergics may have an additional synergistic effect on the bladder in the neurogenic population'''. This suggests that targeting multiple receptors may maximize the effectiveness of pharmacologic treatment of neurogenic bladder and should be considered in patients in whom treatment with antimuscarinics alone fails
-** '''Mirabegron combination therapy with solifenacin''' '''demonstrated greater efficacy than solifenacin''' alone on voided volume and micturition frequency.
-*** The enhanced efficacy with the combination was of a magnitude that is probably similar to the enhanced '''efficacy one might expect from uptitrating the dose of the anti-cholinergic'''. However, the '''combination was not associated with the adverse effects one would expect to encounter with higher doses of antimuscarinics.'''
+=== Beta-3-agonist and anti-cholinergics ===
-* '''Combining anti-cholinergics'''
+* '''Mirabegron combination therapy with solifenacin''' '''demonstrated greater efficacy than solifenacin''' alone on voided volume and micturition frequency.
-** '''Needs further investigation''' to verify its efficacy as a non-invasive alternative for patients in whom anti-cholinergic monotherapy fails.
+** The enhanced efficacy with the combination was of a magnitude that is probably similar to the enhanced '''efficacy one might expect from uptitrating the dose of the anti-cholinergic'''. However, the '''combination was not associated with the adverse effects one would expect to encounter with higher doses of antimuscarinics.'''
-* '''Anti-cholinergics and 5-ARIs'''
-** '''Anti-cholinergics are safe and effective in selected patients with OAB and BPO when used in combination with 5-ARIs'''
+=== Combining anti-cholinergics ===
+* '''Needs further investigation''' to verify its efficacy as a non-invasive alternative for patients in whom anti-cholinergic monotherapy fails.
+=== Anti-cholinergics and 5-ARIs ===
+* '''Anti-cholinergics are safe and effective in selected patients with OAB and BPO when used in combination with 5-ARIs'''
 == Questions ==

Functional: Pharmacological Management of LUTS: Difference between revisions