ED
Define erectile dysfunction? Risk factors?
persistent failure (>3 months) to achieve a penile erection to allow for satisfactory sexual intercourse
increase risk with age, medical conditions
What PDE5 inhibitors are available?
What is urinary incontinence? Which branch of the nervous system is usually not working properly?
involuntary leakage of urine
parasympathetic-causes urination
What is first line for UI and what is the MOA?
antimuscarinic agents, antagonize muscarinic receptors and suppress premature detrusor contractions and enhance bladder storage
Do these drugs cross the BBB? What can affect that ability to cross?
All are lipophilic and cross BBB except when they are charged
BBB permeability increases w/ age, all drugs can potentially cross the BBB in elderly pts
What medications can induce ED?
SSRIs, antipsychotics, anticonvulsants, anti-HTN (thiazides, beta blockers except nebivolol), statins
What is the MOA of PDE5 inhibitors? What is still needed for an erection to occur?
compete for cGMP binding on PDE5
lack direct effect on corpus cavernosum smooth muscle relaxation so need sexual stimulation
Anatomy lesson: what are the detrusor muscle, internal urethral sphincter, and the external urethral sphincter?
Detrusor: bundles of smooth muscle located within the walls of the bladder
internal: smooth muscle that involuntarily contracts or relaxes
external: skeletal muscle that voluntarily open and closes the urethra to void urine
What are the antimuscarinic agents?
oxybutynin, tolterodine, fesoterodine, darifenacin, solifenacin, trospium chloride
What is significant about oxybutynin? What additional AEs can it have? What formulation is offered to allow it to be more tolerable?
highest incidence of AEs, especially xerostomia
causes orthostatic hypotension, sedation, weight gain
transdermal patch allows it to bypass first pass effect and gives it more tolerable AE profile
What is required for a male pt to experience a normal erection?
vascular functions (arterial blood flow increases and erection is prolonged by a decrease in venous outflow), nervous system functions, and hormonal functions
must be psychologically receptive to sexual stimuli
What can affect bioavailability of PDE5 inhibitors and which specific ones are affected?
food with high fat content can decrease rate of absorption
Sildenafil and vardenafil
What are some non pharm therapies for UI?
behavioral interventions, external neuromodulation, anti incontinence devices, supportive interventions
What are the adverse effects of antimuscarinic agents?
anti-DUMBELLS
DUMBELLS: diarrhea, urination, miosis, bradycardia, bronchoconstriction, emesis, lacrimation, lethargy, salivation
What are important counseling points about trospium chloride (Sanctura)?
food reduces bioavailability drastically, take on empty stomach
anticholinergic AEs more common in pts >75 years old
What molecule induces vascular relaxation and promotes erection? How? What is it opposed by, which mediate vascular contraction?
Nitric oxide
increased production of cGMP, which induces relaxation of smooth muscle
endothelin 1 and Rho kinase
invasive therapy that produces erection secondary to drug induced increased arterial inflow and decreased venous outflow, do not need sexual stimulation
Alprostadil (causes vasodilation directly on arterial smooth muscle), phentolamine (nonselective alpha adrenergic blocking agent, used in combo with papaverine), papaverine (nonspecific PDE5 inhibitor that decreased catabolism of cAMP, causes smooth muscle relaxation)
do not use in pts who might have conditions predisposing to priapism
What are some drugs that can induce UI?
diuretics, alcohol, caffeine, cholinesterase inhibitors, anticholinergics, narcotic analgesics, psychotropic drugs, alpha adrenergic blockers and agonist, ACE inhibitor, BBB
What 2 non traditional drugs can be used to treat UI? MOAs?
botox: prevents ACh release from presynaptic membrane, temporarily paralyzing the muscle
duloxetine: increased circulating levels of NE and serotonin by blocking the reuptake, facilitate the bladder to sympathetic reflex pathway
What is unique about solifenacin and darifenacin in regard to selectivity? What are the AEs?
show some preference for M3 receptors
AEs: dry mouth, constipation, blurred vision
What are the 3 mechanisms that ED may result from? What is organic ED vs psychogenic ED? Stimulation of what branch of the nervous system causes erection?
failure to initiate, failure to fill (arteriogenic), failure to store adequate blood volume within the lacunar network
single or combination abnormality
organic: vascular, neurologic, or hormonal etiologies
psychogenic: do not respond to stimuli
parasympathetic
What are common AEs of PDE5 inhibitors? What is contraindicated alongside their use? When is medical attention required?
HA, flushing, dyspepsia, congestion, back pain, blurred vision and a blue-green tinting of vision, hearing loss, increased risk of melanoma
use with nitrates is contraindicated, potentiate the hypotensive effects and produce dangerously low BP
priapism, erection lasting longer than 4 hrs can run the risk of ischemic damage
Define stress UI, urge UI (what drugs can induce this?), overflow UI, functional incontinence.
SUI: decreased or inadequate urethral closure forces, muscular tissues surrounding the urethra are compromised
UUI: leakage associated with urgency, a compelling desire to void, diuretics, alcohol, and Ach inhibitors can induce
OUI: overfilled and distended bladder that is unable to empty, detrusor muscle becoming weakened (most commonly seen in long term chronic bladder outlet obstruction in men, BPH)
Functional: cognitive or mobility deficits, not caused by bladder or urethra specific factors
What are the beta 3 adrenergic receptor agonists? What are their AEs? Contraindications?
Mirabegron (Myrbetriq): activation of beta 3 leads to detrusor muscle relaxation and increased bladder capacity, prevents voiding. AEs: HTN, nasopharyngitis, UTI, HA. CI: HTN
Vibegron: newly approved. AEs: hot flashes, GI, HA, URTI, nasopharyngitis
What are the indications for tolterodine and fesoterodine? What are the common AEs? Who should avoid these drugs?
for symptoms of urinary frequency, urgency or urge incontinence
AEs: dry mouth, dyspepsia, HA, constipation, dry eyes (fesoterodine caused more AEs than tolterodine ER)
patients with severe hepatic impairment should avoid both of these