Bladder, Incontinence and Drugs Flashcards
Stimulation of Muscarinic M3 receptor of the bladder causes?
Bladder contraction
Stimulation of Muscarinic Nicotinic receptor of the bladder causes?
Contraction of the external sphincter’s striated smooth muscle
Sympathetic stimulation of B3 adrenergic receptors of the bladder detrusor muscle cause?
Relaxation of the bladder smooth muscle
Sympathetic stimulation of alpha-1 adrenergic receptors of the urethral smooth muscle cause?
Contraction of urethral smooth muscle
Definition Card:
The uncontrolled leakage of urine, which can be continuous or intermittent, is called?
Incontinence
Definition Card:
Sudden and unexpected experience of immediate need to void
Urgency
Definition Card:
Awakening to void at night
Nocturia
Definition Card:
Daytime frequency is defined by urinating how many times per day?
8 or more
Definition Card:
Difficulty in the initiation of voiding
Hesitancy
Definition Card:
Application of abdominal pressure (Valsalva maneuver) to initiate and maintain voiding
Straining
Definition Card:
the discomfort or burning sensation with voiding
Dysuria
Most commonly prescribed antimuscarinic drugs used for the tx of urinary incontinence?
- Tolterodine
2. Oxybutynin
How does the adverse CNS effects of Trospium compare to the other anticholonergic drugs?
Trospium has less adverse CNS effects
- Because it does not cross the BBB
Describe the receptor specificity for darifenacin? Is it more clinically useful?
Greater M3 selectivity
- clinical studies have not recorded a substantially better profile for this
drug in clinical use, as compared to the other, non-selective, drugs.
Unique metabolism of Trospium?
All of the Anticholinergic are CYP3A4 metabolized except for Trospium
Route of administration of the anticholinergics?
All oral
- Tolterodine and Oxybutynin are available in extended release forms due to their shorter half-lives compared to the others
- Oxybutynin is also available transdermally
What is the major side effect that causes patients to withdraw from taking their anticholinergic incontinence medication?
Dry mouth (xerostomia)
Contraindications for Anticholinergics for incontinence
especially in elderly taking many medications
- Glaucoma
- Urinary and gastric obstruction
- Need for mental alertness (Operating machinery?)
- Alzheimer’s type dementia
Adverse effects of anti-cholinergics used for incontinence
- blurred vision
- Dry mouth (xerostomia)
- CV effects: Palpitations, tachycardia, prolonged QT interval
- Drowsiness
- GI effects: Constipation and alters absorption of other drugs
- Facial flushing
- Urinary retention, especially in BPH
When would botox be useful to tx urinary incontinence?
In patients who responded to anticholinergic drugs but couldn’t tolerate the adverse effects
- Not as much in those who were unresponsive to the anticholinergics
Function of botox in regards to its use in preventing incontinence
- Inhibits the afferent cholinergic impulses (via inhibition of vessicular release of excitatory neurotransmitters)
- Causes a phenotypic change within the urothelial tissue to ablate the excitatory effect of local chemical mediators that signal via the cholinergic system to make the bladder hyper-responsive in the first instance.
Mirabegron
- classification?
- use?
- MOA?
Beta-3 Adrenergic AGONIST
- used to tx: Incontinence, urgency, and frequency
-MOA: Binds B3 and causes relaxation of the detrusor muscle
MOA and use of Phenylephrine?
Alpha-1 adrenergic AGONIST
- used to treat stress incontinence (urine loss w/ couching, sneezing, or laughing)
-Alpha-1 stimulation causes profound constriction of urethral smooth muscle
Metabolism of sympathomimetic drugs used to treat incontinence
Mirabegron
- undergoes extensive metabolic metabolism
- (CYP3A4»_space; CYP2D6)
Elimination of sympathomimetic drugs used to treat incontinence?
Urinary
- May need to dose adjust with renal dysfunction!
Side effects of sympathomimetic drugs used to treat incontinence?
- HTN
- Tachycardia/arrhythmia
- Anxiety, Restlessness, insomnia
Use and MOA of methionine?
An adjunctive agent in the treatment of urinary incontinence to reduce odor emanating from the leaked urine.
- creates ammonia-free urine by acidifying urine pH
Adverse effects of Methionine?
Drowsiness, nausea, and vomiting
Use of Bovine Collagen?
Incontinence die to intrinsic sphincter deficiency
- for PTs failing other therapies for > 12 months
MOA of Bovine collagen?
Forms a soft network of fibers increasing the tissue bulk around the urethral lumen
Adverse rxns of Bovine collagen? (6)
- Urinary retention
- Hematuria
- Worsening incontinence
- erythema
- Urticaria
- Abscess formation
What drugs are used to tx urinary retention?
- Bethanechol- direct muscarinic agonist and
- Neostigmine - acetylcholinesterase inhibitor
- both ORAL (several times daily due to short T1/2)
Adverse effects of Bethanechol? (5)
- CV: Lightheadedness, synscope
- GI: Diarrhea, stomach cramps
- Neurologic: Dizziness
- Opthalmic: Excessive tear production
- Renal: Urgency
Adverse effects of Neostigmine? (4)
- AV block, Brady-arrhythmia
- Cardiac Arrest, Cardiac dysrhythmia
- Hypotension, Syncope
- Tachycardia
Adverse effect of opiates?
Urinary retention
- mainly with epidural/intrathecal
- Cholinomimetics (Bethanechol and neostigmine) may be useful to reverse this adverse effect
Alpha-1 Blockers used to tx BPH?
“Sins”
- Prazosin (short acting)
- Alfuzosin (short acting)
- Terazosin (Long acting)
- Doxazosin (Long acting)
- Tamsulosin (partially selective)
- Silodosin (partially selective)
PDE-5 inhibitor used to tx BPH?
Tadalifil (Cialis)
5-alpha reductase inhibitors used to tx BPH?
- Finasteride
2. Dutasteride
Site of action of Alpha-1 blockers to tx BPH?
Alpha-1a = lower GU tract, whereas alpha-1d = detrussor muscle of the urinary bladder.
MOA of Alpha-1 blockers to tx BPH?
alpha-1 blockers cause relaxation of the smooth
muscle in the prostatic and penile urethra,
- thereby permitting easier urination
Common side effects of Alpha-1 Blockers?
- Orthostatic hypotension
- syncope
- Xerostomia
- Nausea
- Asthenia (lethargy)
- headache
- insomnia
- drowsiness (somnolence)
ADME of Alpha-1 Blockers?
- Oral (once daily)
- CYP metabolism
- Prazosin (effect varies patient to patient-dose titrate)
What are the partially active Alpha-1a Blockers and what are the additional side effects?
Tamsulosin and Sildosin
- Diminished effects on CV function
- Increased sexual (ejaculation) dysfunction
MOA of PDE-5 inhibitor used to tx BPH?
PDE5 inhibitors decrease the breakdown of cGMP by inhibition of PDE5
=> prolonged high levels of cGMP necessary for erections or for flow of urine from the urinary bladder.
Adverse effects and contraindications of Tadalifil (Cialis)
AE:
- Nasopharyngitis
- Upper Res. Tract Infection (URTIs)
- Hearing and Vision loss
- Contras: Concurrent organic NITRATES
1. Profound Hypotension
2. Exacerbated by Alcohol consumption
MOA of 5-alpha-reductase inhibitors?
5-alpha-reductase (competitive) inhibitors reduce the dihydrotestosterone-driven proliferation of the prostate
- provide relief for urinary evacuation by reducing the
prostate from pressing on and constricting urine flow along the urethra. - Finasteride inhibits Type 2
- Dutasteride inhibits Both Types 1 and 2
Route of administration and metabolism of 5-alpha-reductase inhibitors?
Orally (once daily)
- CYP3A4 hepatic metabolism
Adverse effects and Contras for 5-alpha-reductase inhibitors?
AE:
- Ejaculatory dysfunction
- ED
- Decreased libido
- Gynecomastia
- Decreases PSA levels (prob if using to monitor for cancer)
- Contra: Pegnancy (category X)
What is Beta-sitosterol? Use?
Herbal used for BPH
- provide symptomatic relief, while not
significantly shrinking the prostate size.
What is Saw-Palmetto? Use?
Herbal
- not enough evidence to support its use for BPH
