Erectile Dysfunction Flashcards
Define erectile dysfunction (ED)
The persistent/recurrent inability to achieve or maintain an erection of sufficient rigidity to permit satisfactory sexual activity for at least 3 months
Define sexual dysfunction
More encompassing
May include ED, +/or diminished libido, premature or delayed ejaculation, orgasm, or priapism
- broad terminology (encompasses erectile dysfunction)
How does an erection occur overall?
Complex interaction between the vascular, hormonal, neurological, and psychological systems
Describe the physiology of an erection
When stimulated, acetylcholine produces an erection through multiple pathways which ultimately increase the levels of cGMP, cAMP and nitric oxide.
This results in smooth muscle relaxation which increases arterial blood flow, allowing the corpora to fill with blood.
Flacid State: Flow of blood into and out of the corpora is equal
Erect State - Flow in of blood > FLow out of the corproa
How does erectile dysfunction occur?
Any abnormality in the vascular, hormonal, neurologic, or psychogenic system
Describe the prevalence of the causes of erectile dysfunction?
~ 80% of ED cases related to organic disease
Vascular
hormonal
or neurologic causes
<10% of ED cases are due to psychogenic factors
up to 25% of ED cases are medication-induced
Describe the impact of ED. What should a pharmacist investigate if new onset ED?
Can be distressing for the person and their partner(s)
80% of the time – due to disease causes
There are many drug causes
– Concern when New onset
What are the risk factors for erectile dysfunction?
Age
Lifestyle: Tobacco, Obesity, Sedentary
Medical Conditions e.g. CVD, Diabetes
Medications
Describe the epidemiology of erectile dysfunction
Incidence is low in men <40yo, increases with age
What are the vascular causes of erectile dysfunction?
Disease states that compromise vascular flow to the corpora cavernosum can cause ED
The most common cause(s) of ED
Associated medical conditions:
Diabetes
Atherosclerosis
Hypertension
Renal Disease
Liver Disease
Excessive cigarette smoking
Radiation (causing vascular damage)
Impaired blood flow to the corpora and can be associated with numerous medical conditions
Describe the relationship between ED and CAD
Blood vessels in penis are small so may be showing signs of atherosclerosis
Describe the relationship between ED, PDE5i’s and diabetes
Describe the neurological relationship of ED
Sexual arousal causes nerve impulses to travel from the brain via the spinal cord to the genital region
Conditions that impair nerve conduction to the brain:
Spinal cord injury
Stroke
Pelvic trauma, prostate surgery
Conditions that impair nerve conduction to the penile vasculature:
Parkinsons, Alzheimer’s, multiple sclerosis, epilepsy
Diabetic neuropathy, alcoholic neuropathy
Impaired nerve function in the brain and in the penis
Describe the hormonal causes of ED
Describe the psychogenic causes of ED and the treatment
When is psychogenic causes of ED more common? Response?
More common in younger indivdiuals
Response here is often better – No dmage to te parts needed to cause an erection
Describe the causees of drug induced ED and the mechanisms for which it occurs?
Diagnosis of ED depends on evelauation of
Goals of TX ED
Non-RX TX ED and benefit
Can be managed; often cannot be cured
Counselling if psychological factors
1st LIne tegrapy for ED
Describe the MOA of PDE5 Inhibitors. Is this all that is required for an erection?
Type-5 enzyme is more common in the corpora
Sexual stimulation is still required to maintain an erection
Effeicacy of PDE5 Inhibitors and Trial
Similar for all 3: success rates from 60-70%
Efficacy is improved with education
1st dose can be efficacious, but can see improved success with successive doses
Should be tried 6 to 8 times before judging their success
Non-response in 4-6 tries under optimal conditions at max dose
Effect is dose related (80% of effect at low dose; further 20% at high dose)
Failure with one PDE5I does not rule out a trial of another
Comapre the PDE5 Inhibitors
Sildenafil Education
Takes 60 minutes to peak
Lasts for only about 4 hours (up to 12)
High fat meal delays the onset
Vardenafil education
Takes 60 minutes to peak
Lasts for only about 4 hours
High fat meal decreases absorption
No renal dose adjustment
ODT tablet available
TAdalafil Education
Takes 120 minutes to peak
Lasts up to 36 hours (“weekender drug”)
Food has no impact
Can daily dose or use prn
Metabolism of PDE% Inhibitors
All metabolized via CYP 3A4 (major pathway)
Sildenafil & vardenafil: also 2C9 (minor pathway)
Drug Inetractions PDE5 Inhibiutors
Nitrates –> severe hypotension! (contraindicated!)
The vasodilator actions of nitrates (po, sl, transdermal) are profoundly amplified with concomitant use of PDE5 Inhibitors and this could be fatal
CYP 3A4 inducers and inhibitors (use with caution)
Examples: Ketoconazole, protease inhibitors, erythromycin, grapefruit juice, etc.
Non-selective α1-blockers (particularly terazosin/doxazosin): may experience further hypotensive effects–recommended to space dosing by 4-6hrs if used these together
Antihypertensives?? – OK as long as BP is fine
Nitrates and PDE5 Waiting
Reality – Long acting nitro patch – cannot not use them at all
PRN nitro spray – Can use PDE5 inhibitors – Cannot use nitro spray after
(Tadalafil 48 h, sildenafil/vardenafil 24 h)
Experience chest pain that does not go away at rest for 5 mins – Hospital
Caution of PDE5
Sexual activity increases the chances of experiencing ischemic events and myocardial infarction
Avoid use in those at high risk of CV events (e.g. unstable angina, class IV HF, recent stroke/MI, high risk arrhytmias, uncontrolled HTN)
Adverse EFfects PDE inhibitors
Overall well-tolerated
Most common: headache (14%), flushing (4-12%), dyspepsia (4-7%), dizziness, rash, rhinitis/nasal congestion (4%)
Others:
Back and muscle pain (inhibition of PDE11 in skeletal muscle): tadalafil (2-5%)
Hypotension (inhibition of PDE1): sildenafil and vardenafil > tadalafil
8-10mmHG SBP and 5-8 DBP within an hour – lasts a few hours
Color visual changes (inhibition of PDE6 in the retina):
Blurred vision, ↑ light sensitivity
Loss of blue – green differentiation (up to 2-3%; dose-related; Sildenafil > vardenafil > tadalafil)
Seerious Adverse EFfects
Serious but rare:
Sudden unilateral hearing loss: post-marketing reports
NAION (nonarteritic anterior ischemic optic neuropathy)- sudden, unilateral, vision loss
Post-marketing reports (<0.01%)
Those at risk of NAION should be evaluated by an eye doc first
QT prolongation with vardenafil
Priapism
Chest pain
Alprostadil MOA
Stimulates ↑’d production of cAMP and causes smooth muscle relaxation of tissues in the corpora & restricts venous outflow
Alprostadil Products
Intracavernosal injection: Caverject®
Intraurethral insert: MUSE®
Alprostadil Dose, Onset and Efficcay of Options
Alprostadil Admin and Caution
Inject 10-30min pre-sex
If erection lasts >1hr, decrease dose
If erection lasts >4hrs, seek help
Alprostadil Adverse Effects. Caution with medictaions?
C.I. Alprostadil
C.I in those with a predisposition to priapism – Had it before, sickle cell disease,
Other agents for ED. Are they common?
o Papaverine use limited by adverse effects
o Phentolamine use limited by adverse effects
Otehr therapies for ED
Surgery - can be an option: effective but Risks
Testosterone should not be sued for erecetile dysfuntion on its own – can be sued in patients with low testosterone and erectile dysfunction
Non-Rx Deveices for ED Advatages and disadvatages?
Female Sexual Dysfucntion Prevalence
~ 40% of women had sexual concerns
Low desire
Orgasmic disorder
Sexual pain
May be due to physical (medical conditions and medications), hormonal, or psychological conditions
Female Sexual Dysfucntion TX
treatment options are much more limited
PDE5i’s: not effective, could maybe possible ↓ SSRI AEs
Topical estrogen
May enhance lubrication, decrease dyspareunia
Testosterone: controversial
Female Sexual Dysfucntion TX Med
