PHARMACOLOGICAL APPROACH

in
ERECTILE DYSFUNCTION

Rozaimah Zain-Hamid

Department of Pharmacology
Faculty of Medicine
Universitas Islam Sumatera Utara
 ERECTILE DYSFUNCTION
(ED)

Previously known as impotence

The consistent inability to achieve

and/or maintain an erection adequate
for satisfactory sexual intercourse

Zain-Hamid, R Faculty of Medicine UISU.

 PENILE ANATOMY
3 cylindrical erectile bodies 2 paired corpora
cavernosa and corpus spongiosum
surrounding the urethra
Corpora cavernosa separated by common
medial septum: perforated elastic tissue
allows for shared circulation
Erectile tissue lattice of vascular lacunar
sinusoids,surrounded by smooth muscle
Penile skin loosely adherent and flexible to
permit expansion
Zain-Hamid, R Faculty of Medicine UISU.
Penile Anatomy

Zain-Hamid, R Faculty of Medicine UISU.

 PENILE VASCULATURE
ARTERIAL SUPPLY:
Cavernosal arteries run down centre
of each corpus cavernosum, giving off
multiple helicine arteries which open
directly into lacunar spaces.
VENOUS DRAINAGE:
Subtunical venules compressed
during erection
 PHYSIOLOGY OF ERECTIONS

SEXUAL STIMULATION

DECREASED PERIPHERAL RESISTANCE

INCREASED ARTERIAL BLOOD FLOW

RAISED INTRACAVERNOSAL PRESSURE

RELAXATION OF VASCULAR SMOOTH MUSCLE

LACUNAR ENGORGEMENT AND ERECTION

Zain-Hamid, R Faculty of Medicine UISU.
Physiology of erection

Zain-Hamid, R Faculty of Medicine UISU.

Requirements for erectile function

Central nervous system

Dopamine (apomorphine)
Parasympathetic nervous system
Relaxation of penile smooth muscle
passage of blood into penis
Relaxation mediated by nitric oxide
(NO) activates cGMP

Zain-Hamid, R Faculty of Medicine UISU.

 Evaluation of Erectile Dysfunction

Predictors for ED: DM, HTN, smoking, dyslipidemia, CV

disease, med use
Screen for cardiovascular disease

Medicines:
antidepressants, spironolactone,
sympathetic blockers (clonidine, methyldopa), thiazides,
ketoconazole, cimetidine (not other H2 blockers)

Consider neurological factors

(CVA, prostate Ca, pelvic trauma)
Zain-Hamid, R Faculty of Medicine UISU.
CAUSES OF ERECTILE DYSFUNCTION

Organic
Psychogenic

Often combination of both

Zain-Hamid, R Faculty of Medicine UISU.

 ORGANIC CAUSES
OF ERECTILE DYSFUNCTION

Vasculogenic
Neurogenic
Endocrine
Drug-related

Zain-Hamid, R Faculty of Medicine UISU.

 Causes of erectile dysfunction
Aging
Psychological Depression, anxiety
Neurological Cerebral, spinal, peripheral neuropathy,
pudendal nerve
Hormonal Hypogonadism, prolactin, thyroid,
Cushing syndrome
Vascular Atherosclerosis, venous incompetence
Medications Antihypertensives, antidepressants,
estrogen, anti-androgens
Habits Cannabis, alcohol, narcotics, tobacco
Other Diabetes, renal, hypertension, COPD

Zain-Hamid, R Faculty of Medicine UISU.

ERECTILE DYSFUNCTION
DRUG - RELATED CAUSES

SUBSTANCE ABUSE
Alcohol
Smoking
Cannabis

Zain-Hamid, R Faculty of Medicine UISU.

ERECTILE DYSFUNCTION
DRUG - RELATED CAUSES

PRESCRIPTION DRUGS
Thiazide diuretics
Antihypertensives
Cardiac drugs
Antidepressants
Tranquilisers
H2 agonists
Anticholinergics
Zain-Hamid, R Faculty of Medicine UISU.
 TREATMENT
OF ORGANIC ERECTILE DYSFUNCTION

Drug therapy
Medical devices
Surgery

Zain-Hamid, R Faculty of Medicine UISU.

ERECTILE DYSFUNCTION

DRUG THERAPY

Oral agents
Intracavernosal injections
Intra-urethral pellets
Topical gels (experimental)
Nasal spray

Zain-Hamid, R Faculty of Medicine UISU.

Current Treatment of Erectile Dysfunction

1st line therapies: phosphodiesterase inhibitors

(sildenafil, vardenafil, tadalafil)

2nd line: penile self-injectable drugs,

intraurethral alprostadil, vacuum devices

3rd line: penile prosthesis (malleable

rods and inflatable prostheses)
Psychotherapy alone
or in combination with the above
Obesity - weight loss andZain-Hamid,
physical activity
R Faculty of Medicine UISU.
Phosphodiesterase-5 Inhibitors

Zain-Hamid, R Faculty of Medicine UISU.

Formation of Nitric Oxide

Zain-Hamid, R Faculty of Medicine UISU.

 Phosphodiesterase-5 Inhibitors

Sildenafil- longest safety record

Contraindicated with use of nitrates

Caution with alpha-blockers

Visual effects

Rare nonarteritic anterior ischemic

optic neuropathy (NAION)
Zain-Hamid, R Faculty of Medicine UISU.
 Phosphodiesterase-5 Inhibitors

sildenafil (viagra), vardenafil (levitra) ,

tadalafil (cialis )

All proven to be effective in restoring

erectile function
No head to head studies

Tadalafil - longer duration of action (36

vs. 4 hrs),
quicker onset (16 vs. 30 minutes),
less affected by high fat meals
Zain-Hamid, R Faculty of Medicine UISU.
 ERECTILE DYSFUNCTION

PDE5 Inhibitors

Enhance and potentiate corporal smooth
muscle relaxation
Active sexual stimulation necessary
1 hour prior to planned intercourse
Effective 70 - 90%
Intact neurovascular bundle necessary
not good post RRP
Expensive

Zain-Hamid, R Faculty of Medicine UISU.

 ERECTILE DYSFUNCTION

PDE 5 Inhibitors

SIDE EFFECTS
Headache
Facial flushing
Visual disturbances: color perception
(inhibition of PDE6 in retina, Viagra only)
Dyspepsia
Nasal congestion/ stuffiness
C/I:nitrate Rx hypotension
Zain-Hamid, R Faculty of Medicine UISU.
 ERECTILE DYSFUNCTION

PDE 5 Inhibitors

Dose Duration Food
of Action
Sildenafil 50 100 mg 4 - 6 hrs Not within 2
hrs

Tadalafil 20 mg 24 - 36 hrs No
Weekender restriction

Vardenafil 20 mg 4 6 hrs Not within 2

hrs

Zain-Hamid, R Faculty of Medicine UISU.

 Sildenafil
82% vs 24% (placebo) effective
Best response in psychogenic
Best 1 hr before sexual activity
Headache, flushing, dyspepsia, rhinitis
Affected by diet
hypotensive effect of nitrates
dose: >65, renal, hepatic insufficiency
Interactions: erythromycin, cimetidine,
ketoconazole (cyto P450)
Zain-Hamid, R Faculty of Medicine UISU.
% with improved erections Efficacy of Sildenafil

90 85 82
68
61 57

31

0
PsychogenicSpinalHypertensionTURP Diabetes Radical
injury prostate

Zain-Hamid, R Faculty of Medicine UISU.

 Tadalafil

Peak 2h, half life 17.5h

16min-36h activity duration
No dietary restrictions
Reduces requirement for planned
sexual activity

Zain-Hamid, R Faculty of Medicine UISU.

 Vardenafil

More potent than other agents

Peak 40 min,
Half life 4.4-4.8 hours
No colour vision changes

Zain-Hamid, R Faculty of Medicine UISU.

 Side-effects of
phosphodiesterase-5 Inhibitors

Potentially cause hypotension

No increase in MI
Avoid if nitrates possible
Use short-acting if stable IHD

Zain-Hamid, R Faculty of Medicine UISU.

 Other agents

- blockers
Phentolamine: mild benefit
Yohimbine
Used for ED for years, marginal benefit

Zain-Hamid, R Faculty of Medicine UISU.

 Other agents
Dopamine agonists

Apomorphine SL
Approved in Europe, South America
Dopamine agonist, works on CNS
Dose 2 4 mg S/L 10 20 prior to
sexual activity
Nitrate interaction

Zain-Hamid, R Faculty of Medicine UISU.

 Other agents

Apomorphine (Uprima)

Onset of action 10
Duration of action 30
Effective 55 60%
S/E nausea (40%), vomiting (11%),
dizziness (20%), somnolence (10%),
sweatiness (18%), hypotension (4%)
Zain-Hamid, R Faculty of Medicine UISU.
 Yohimbine

Blocks presynaptic alpha-2-adrenergic

receptors

Increases cholinergic tone,

decreases sympathetic tone

Best results when restricted to men

with psychogenic erectile dysfunction

Not recommended by AUA

Zain-Hamid, R Faculty of Medicine UISU.
 Testosterone
Deficiency results in impotence in experimental
animals and men; resolves once testosterone
levels are normalized*

Acts through psychogenic channels

to enhance libido

Necessary for maintenance of nitric oxide

synthase levels

1/3 of men with DM have subnormal testosterone

*Bancroft, J, Wu, FC. Changes in erectile responsiveness during androgenic
replacement therapy. Arch Sex Behav 1983; 12:59.

Zain-Hamid, R Faculty of Medicine UISU.

 ERECTILE DYSFUNCTION

INTRA-URETHRAL PELLETS
PROSTAGLANDIN E1
(Medicate Urethral System for Erection / MUSE)

Easy administration
Dose titration necessary
Patient education required
Moist urethra .. void prior to pellet insertion
Onset of response ~20
Erection lasting 30 - 60
50 - 60% successful
Zain-Hamid, R Faculty of Medicine UISU.
 ERECTILE DYSFUNCTION

PROSTAGLANDIN E1

Rapid onset of response
(5 - 15 after injection)
No sexual stimulation required
At right dose, erection for 30 - 45
Discreet use possible
Cost factor
Zain-Hamid, R Faculty of Medicine UISU.
 PROSTAGLANDIN E1

Dose-response effect,
titration required
Patient education re technique
80% successful

SIDE EFFECTS
Pain
Priapism
Corporal fibrosis
Zain-Hamid, R Faculty of Medicine UISU.
 ERECTILE DYSFUNCTION:
INTRACAVERNOSAL INJECTIONS

Prostaglandin E1 (Caverject)
Papaverine
Cocktails

MODE of ACTION
Cavernosal smooth muscle relaxation

Zain-Hamid, R Faculty of Medicine UISU.

Zain-Hamid, R Faculty of Medicine UISU.
 ERECTILE DYSFUNCTION

INTRA-URETHRAL PELLETS
PROSTAGLANDIN E1 (MUSE)

SIDE EFFECTS:
Local pain, urethral burning
Vaso-vagal episodes
Minor urethral bleeding

Zain-Hamid, R Faculty of Medicine UISU.

 Conclusions
Organic causes of erectile dysfunction (ED) :
vasculogenic, neurogenic, endocrine,
drug-related

Treatment of ED:
drug therapy, medical devices, surgery

1st line therapies for ED:

phosphodiesterase inhibitors
(sildenafil, vardenafil, tadalafil)

Zain-Hamid, R Faculty of Medicine UISU.

Thank
You