Erectile Dysfunction

Question 1

Define erectile dysfunction (ED)

Answer 1

The persistent/recurrent inability to achieve or maintain an erection of sufficient rigidity to permit satisfactory sexual activity for at least 3 months

Question 2

Define sexual dysfunction

Answer 2

More encompassing

May include ED, +/or diminished libido, premature or delayed ejaculation, orgasm, or priapism

• broad terminology (encompasses erectile dysfunction)

Question 3

How does an erection occur overall?

Answer 3

Complex interaction between the vascular, hormonal, neurological, and psychological systems

Question 4

Describe the physiology of an erection

Answer 4

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

Question 5

How does erectile dysfunction occur?

Answer 5

Any abnormality in the vascular, hormonal, neurologic, or psychogenic system

Question 6

Describe the prevalence of the causes of erectile dysfunction?

Answer 6

~ 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

Question 7

Describe the impact of ED. What should a pharmacist investigate if new onset ED?

Answer 7

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

Question 8

What are the risk factors for erectile dysfunction?

Answer 8

Age
Lifestyle: Tobacco, Obesity, Sedentary
Medical Conditions e.g. CVD, Diabetes
Medications

Question 9

Describe the epidemiology of erectile dysfunction

Answer 9

Incidence is low in men <40yo, increases with age

Question 10

What are the vascular causes of erectile dysfunction?

Answer 10

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

Question 11

Describe the relationship between ED and CAD

Answer 11

Blood vessels in penis are small so may be showing signs of atherosclerosis

Question 12

Describe the relationship between ED, PDE5i’s and diabetes

Answer 12

Question 13

Describe the neurological relationship of ED

Answer 13

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

Question 14

Describe the hormonal causes of ED

Answer 14

Question 15

Describe the psychogenic causes of ED and the treatment

Answer 15

Question 16

When is psychogenic causes of ED more common? Response?

Answer 16

More common in younger indivdiuals
Response here is often better – No dmage to te parts needed to cause an erection

Question 17

Describe the causees of drug induced ED and the mechanisms for which it occurs?

Answer 17

Question 18

Diagnosis of ED depends on evelauation of

Answer 18

Question 19

Goals of TX ED

Answer 19

Question 20

Non-RX TX ED and benefit

Answer 20

Can be managed; often cannot be cured
Counselling if psychological factors

Question 21

1st LIne tegrapy for ED

Answer 21

Question 22

Describe the MOA of PDE5 Inhibitors. Is this all that is required for an erection?

Answer 22

Type-5 enzyme is more common in the corpora

Sexual stimulation is still required to maintain an erection

Question 23

Effeicacy of PDE5 Inhibitors and Trial

Answer 23

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

Question 24

Comapre the PDE5 Inhibitors

Answer 24

Question 25

Sildenafil Education

Answer 25

Takes 60 minutes to peak Lasts for only about 4 hours (up to 12) High fat meal delays the onset

Question 26

Vardenafil education

Answer 26

Takes 60 minutes to peak  Lasts for only about 4 hours  High fat meal decreases absorption  No renal dose adjustment  ODT tablet available

Question 27

TAdalafil Education

Answer 27

Takes 120 minutes to peak  Lasts up to 36 hours (“weekender drug”)  Food has no impact  Can daily dose or use prn

Question 28

Metabolism of PDE% Inhibitors

Answer 28

All metabolized via CYP 3A4 (major pathway) Sildenafil & vardenafil: also 2C9 (minor pathway)

Question 29

Drug Inetractions PDE5 Inhibiutors

Answer 29

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

Question 30

Nitrates and PDE5 Waiting

Answer 30

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

Question 31

Caution of PDE5

Answer 31

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)

Question 32

Adverse EFfects PDE inhibitors

Answer 32

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)

Question 33

Seerious Adverse EFfects

Answer 33

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

Question 34

Alprostadil MOA

Answer 34

Stimulates ↑’d production of cAMP and causes smooth muscle relaxation of tissues in the corpora & restricts venous outflow

Question 35

Alprostadil Products

Answer 35

Intracavernosal injection: Caverject® Intraurethral insert: MUSE®

Question 36

Alprostadil Dose, Onset and Efficcay of Options

Answer 36

Question 37

Alprostadil Admin and Caution

Answer 37

Inject 10-30min pre-sex If erection lasts >1hr, decrease dose If erection lasts >4hrs, seek help

Question 38

Alprostadil Adverse Effects. Caution with medictaions?

Answer 38

Question 39

C.I. Alprostadil

Answer 39

C.I in those with a predisposition to priapism – Had it before, sickle cell disease,

Question 40

Other agents for ED. Are they common?

Answer 40

o Papaverine use limited by adverse effects o Phentolamine use limited by adverse effects

Question 41

Otehr therapies for ED

Answer 41

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

Question 42

Non-Rx Deveices for ED Advatages and disadvatages?

Answer 42

Question 43

Female Sexual Dysfucntion Prevalence

Answer 43

~ 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

Question 44

Female Sexual Dysfucntion TX

Answer 44

treatment options are much more limited PDE5i’s: not effective, could maybe possible ↓ SSRI AEs Topical estrogen May enhance lubrication, decrease dyspareunia Testosterone: controversial

Question 45

Female Sexual Dysfucntion TX Med

Answer 45