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Reproductive > PHARM: Urinary Incontinence or Retention > Flashcards

PHARM: Urinary Incontinence or Retention Flashcards

1
Q

What type of axons are responsible for bladder stimulation?

A

Parasympathetic postganglionic axons

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2
Q

What nerve carries the parasympathetic postganglionic axons responsible for bladder stimulation?

A

pelvic nerve

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3
Q

What is released by the parasympathetic postganglionic axons that stimulate the bladder?

A

acetylcholine and ATP (at bladder)

NO (at urethra)

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4
Q

What is the target of the parasympathetic postganglionic axons that stimulate the bladder?

A

M3 muscarinic receptors in the bladder smooth muscle (leads to SM contraction)

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5
Q

What is released by parasympathetic postganglionic axons at urethral smooth muscle?

A

NO (to relax smooth muscle for urine to flow through)

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6
Q

What type of axons are responsible for bladder relaxation?

A

Sympathetic postganglionic neurons

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7
Q

What nerve carries the sympathetic postganglionic axons responsible for bladder relaxation?

A

hypogastric nerve

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8
Q

What is released by the sympathetic postganglionic axons responsible for bladder relaxation?

A

norepinephrine

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9
Q

What is the target/action of the sympathetic postganglionic axons responsible for bladder relaxation?

A

β3 adrenergic receptors to relax bladder smooth muscle

α1 adrenergic receptors to contract urethral smooth muscle.

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10
Q

What type of nerves are responsible for contraction of the external sphincter striated muscle?

A

somatic axons (voluntary)

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11
Q

What nerve carries the somatic axons to the external sphincter striated muscle?

A

pudendal nerve

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12
Q

What is released by the somatic nerves responsible for contraction of the external sphincter striated muscle?

A

Ach

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13
Q

What is the target (receptor) of the somatic nerves responsible for contraction of the external sphincter striated muscle?

A

nicotinic cholinergic receptors

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14
Q

In the urine storage reflex, what does the distention of the bladder cause?

A

low-level vesical afferent firing

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15
Q

What is the consequent of the low-level vesical afferent firing in the urine storage reflex?

A

stimulation of the sympathetic outflow in the hypogastric nerve to the bladder outlet (the bladder base and the urethra) and the pudendal outflow to the external urethral sphincter.

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16
Q

What is the name of the “reflex” that causes urinary continence?

A

guarding reflex

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17
Q

What may lead to increase striated urethral sphincter activity (so that you do not have urine outflow in the urine storage reflex?)

A

pontine storage center

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18
Q

What nerve carries the intense bladder-afferent firing during voiding?

A

pelvic nerve

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19
Q

What is the role of the pelvic nerve during voiding reflex?

A

activates spinobulbospinal reflex pathways that pass through the pontine micturition centre

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20
Q

What does the spinobulbospinal reflex result in?

A

stimulates the parasympathetic outflow to the bladder and to the urethral smooth muscle and inhibits the sympathetic and pudendal outflow to the urethral outlet.

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21
Q

Where might the ascending afferent input from the spinal cord might pass through before reaching the pontine micturition centre?

A

periaqueductal grey (PAG)

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22
Q

Conscious bladder sensations and the mechanisms that underlie the switch from storage to voiding involve what structures?

A

cerebral circuits above the PAG.

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23
Q

What underlies urge incontinence?

A

detrusor overactivity

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24
Q

What underlies stress incontinence?

A

outlet incompetence

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25
What drug class is used for urge incontinence?
Antimuscarinics
26
What drug class is used for stress incontinence?
Alpha-agonists
27
What is the first line treatment for bladder incontinence?
noninvasive approaches like behavioral therapy (patient education, fluid management, bladder retraining, pelvic floor exercises, biofeedback and timed bladder emptying).
28
List the anti-cholinergics used for bladder incontinence?
``` Darifenacin Fesoterodine Oxybutynin Solifenacin Tolterodine Trospium ```
29
Which anti-cholinergic can be used as a patch?
oxybutynin
30
What is the target of anti-cholinergics?
BLOCK the M2 and M3 receptors
31
What is the role of M2 receptors?
opposes the beta-adrenergic receptor (which works to relax the bladder so no urination occurs), leading to contraction as an indirect effect
32
What is the role of M3 receptors?
has a direct effect in contracting the smooth muscle of the urinary bladder
33
MOA: Inhibits vesicular release of excitatory Ach and axonal expression of other SNARE-complex dependent proteins in urothelium/sub-urotehlium mediating intrinsic or spinal reflexes thought to cause detrusor overactivity
Botulinum Toxin
34
List the sympatheticomimetics used for urinary incontinence.
Mirabegron Pseudoephedrine Ephedra, Ma Huang
35
What is the MOA of the sympatheticomimetics?
Mimics NE (activates beta-3 adrenergic receptors to relax bladder SM and activates alpha-1 adrenergic receptors to contract urothelial SM
36
MOA: Creates ammonia-free urine (controls odor, dermatitis, and ulceration due to leaked out urine in patients) by acifidying urine pH
Methionine
37
MOA: Injected into submucosal tissue of urethra or bladder neck and forms a soft, cohesive network of fibers increasing tissue bulk around the urethral lumen
Bovine Collagen Implant
38
What are some peripheral effects of anti-cholinergics?
dry mouth (oral not as bad in ER), mydriasis, constipation, urinary retention, tachycardia
39
What are some central effects of anti-cholinergics?
sedation, confusion/delirium, hallucinations, Severe cognitive impairment, sleep disruptions.
40
TOXICITY: HTN (monitor), tachycardia
Mirabegron
41
TOXICITY: HTN, A-fib, tachyarrhythmia, insomnia, anxiety, nervous, restless; MAOI interaction
pseudoephedrine
42
TOXICITY: HTN, CHF, MI, tachyarrhythmia, insomnia, symptoms of CNS sitmulation; MAOI interaction
Ephedra, Ma Huang
43
TOXICITY: Drowsiness, nausea, vomiting
Methionine
44
TOXICITY: Urinary retention, hematuria, injection site rxn, worsening incontinence, erythema, urticaria, abscess formation; Interactions with immunosuppressive therapy and corticosteroids
Bovine collagen implant
45
Which anti-cholinergic has > M3 selectivity, but is not better than others?
darifenacin
46
Which anti-cholinergic is rapidly metabolized to 5-hydroxymethyl-tolterodine?
fesoterodine
47
Which anti-cholinergics are available in extended release (ER) formats is to counter their otherwise short duration of clinical effect?
oxybutynin | tolterodine
48
Which anti-cholinergic has the longest half-life (45-68 hr)?
solifenacin
49
Which anti-cholinergic has the LEAST severe central side effects? Why?
``` trospium Quaternary amine (does not cross BBB) ```
50
Which anti-cholinergic does NOT undergo hepatic metabolism because poor bioavailability?
trospium
51
What therapy for urinary incontinence is delivered by carefully placed injections into the urothelial wall ?
botulinum toxin
52
What drug used for urinary incontinence is a Beta-3 agonist?
mirabegron (increases bladder capacity by relaxing detrusor SM)
53
What drug used for urinary incontinence is a direct and indirect alpha > beta agonist?
pseudoephedrine
54
What drug used for urinary incontinence is an indirect non-selective alpha and beta agonist?
ephedra, ma huang
55
Which drug's half life depends on urinary pH?
pseudoephedrine
56
How does the metabolism of mirabegron differ from the other sympatheticomimetics?
it is extensively CYP metabolized while the other two have minimal metabolism
57
What drug for urinary incontinence must be taken with food or with milk/other liquid?
methionine
58
What therapy is ONLY used in patients who have failed other therapies for >12 months and have incontinence due to intrinsic sphincter deficiency?
bovine collagen implant
59
What are the contraindications for anti-muscarinic drugs?
* Angle closure or narrow-angle glaucoma * Urinary or gastric obstruction * Need for mental alertness * Alzheimer’s type dementia (worsen already existing cholinergic effect)
60
What should you monitor in a patient receiving anti-muscarinics?
``` Urinary retention (especially in BPH) CV effects (palpitations, tachycardia, prolonged QT) GI effects (mild constipation to severe obstruction) ```
61
Describe the patient profile most likely to respond to botox.
Botox is more effective in patients who responded to anticholinergic drugs but couldn’t tolerate the adverse effects, as opposed to those patients who were unresponsive to the anticholinergics altogether.
62
Other than inhibiting the afferent cholinergic impulses, what is the MOA of botox?
causes a phenotypic change within the urothelial tissue (integrating stretch receptors) 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
63
How do opiates cause urinary retention?
inhibiting parasympathetic outflow and detrusor activation (via opiate receptor effects upon voiding responses arising from centers in the CNS)
64
What mediates opiates' effect on the bladder?
mu and delta receptors in the sacral cord
65
What is the Direct Muscarinic Agonist used for urinary retention?
bethanechol
66
What is the Ach inhibitor used for urinary retention?
neostigmine
67
What are the opiod antagonists used for urinary retention?
methylnaltrexone | naltrexone
68
Neostigmine inhibits Ach and augments its effects at what receptors?
muscarinic and nicotinic receptors
69
Can bethanechol cross the BBB? Where does it act?
NO, urinary bladder and GI
70
TOXICITY: CV (lightheadedness, syncope), GI (diarrhea, cramps), dizziness, excessive tear production, miosis, urgent desire to urinate
bethanechol
71
TOXICITY: AV block, bradycardia, cardiac arrest, cardiac dysrhythmia, hypotension, syncope, tachycardia
Neostigmine
72
What is the major side effect seen with opiod antagonists?
Reversal of analgesia may accompany reversal of detrusor relaxation
73
What drug for urinary retention is NOT inactivated by cholinesterases?
bethanechol
74
How is neostigmine inactivated?
inactivated by cholinesterases and hepatic microsomal enzymes
75
True or false: bethanechol and neostigmine have long half-lives.
FALSE; Short half-lives (need administration multiple times a day)
76
Do all opiods produce urinary retention?
no- intrathecal admin (into spine) is major

Reproductive (21 decks)

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