erectile dysfunction Flashcards
explain the physiology of an erection
- arterial flow into the penis increases while venous outflow decreases
- activation of parasympathetic system by ACh –> cause smooth muscle relaxation
- path one: ACh increases formation of NO –> increases activity of guanylate cyclase –> increases cGMP ie. muscle relaxant
- path two: ACh and PG E increases adenyl cyclase –> increase cAMP
- smooth muscle relaxation and vasodilation –> more blood inflow
- corpora cavernosa fills up with blood
- swelling causes a compression of the venules against the tubica albuginea
explain the physiology of detumescence
- activation of sympathetic nervous system as cGMP gets deactivated by PDE5 enzyme leading to vasoconstriction
- sympathetic nervous system activated as smooth muscle contracts due to activation of alpha2 adrenergic receptors of arteriole leading to reduction in blood flow
how would you explain what is ED
a persistent (>6m) inability to achieve or maintain an erection of sufficient duration or firmness to complete satisfactory intercourse
what are the etiology of ED
organic
- vascular (arteriosclerosis, peripheral vascular disease, HTN, DM), nervous (spinal cord trauma or disorder, trauma, cns tumor, stroke) or hormonal (hypogonadism, hyperprolactinemia which suppresses testosterone production) systems compromised
- medication induced
psychogenic
- due to thoughts or feelings rather than physical pathology
- malaise, loss of attraction, stress, performance anxiety, mental disorders, sedation
mixed
others
- smoking
- excessive alcohol
- ilicit drug use
- obesity
what are the medications that can cause ED
- anticholinergics (TCAs, first gen antihistamine, phenothiazines) –> decrease ACh activity
- SSRIs –> increase 5HT which decreases testosterone
- DA antagonist –> DA related to sexual arousal or stimulation
- CNS depressants (BZPs, ASM) –> suppress perception of psychic stimulus
- BP drugs (methyldopa, BB except Nebivolol, thiazides) –> decrease penile blood flow
what are the s/sx and complications of ED
- inability to achieve an erection
- anger
- depression
- embarrassment
- disharmony in a r/s
- loss of interest in sexual activities
- performance anxiety
- low self esteem
what is the key assessment criteria for patients presenting with ED
evaluate for CVD as ED might be an early sx of unidentified comorbid CVD
what are the non-pharmacological management strategies for ED
- address modifiable risk factors (smoking, alcohol, weight control, BP/lipids/glucose control)
- psychotherapy
- vacuum erection device
- penile implant
what are the pharmacological management of ED
PDE5i
- tadalafil
- sildenafil
- vardenafil
- avanafil
testosterone replacement
- yohimbine
- alprostadil
what is the moa of PDE5i for ED
- inhibit PDE5 to induce catbolism of cGMP –> enhance activity of cGMP –> induce smooth muscle relaxation –> erection
what is the place in therapy for ED (s/e, ddi, dose adjustments etc)
- first line agent
- cause and enhance erection only after sexual stimulation
- s/e includes HA, flushing, rhinitis, back and muscle pain, dizziness, hypotension, prolonged erections, sudden hearing loss (with tinnitus), ocular problems (photosensitivity, NAION)
- ddi with nitrates (potentially fatal hypotension), multiple antihypertensives, alcohol, cyp3A4 inhibitors (increases conc of PDE5i)
- dose adjustments for ≥65yo, concomitant alpha blockers, renal failure, cyp3A4 inhibitors
what are the different s/e between PDE5i
- tadalafil assoc with muscle pain due to affinity for PDE11
- sildenafil assoc w retina problems due to affinity for PDE6
- vardenafil assoc w QTc prolongation and retina problems due to affinity for PDE6
what are the spacing intervals between nitrates and PDE5i
- 12h for avanafil
- 24h for sildenafil and vardenafil
- 48h for tadalafil (due to long half life of 36hr)
when should the dose of PDE5i be reduced
- age ≥65yo
- renal failure
- concom alpha antagonist
- cyp3A4 inhibitors
what is the moa of testosterone replacement
to restore serum testosterone to normal range
