[farmaco] P3 Disfunção erétil final

Esta é uma pré-visualização de arquivo. Entre para ver o arquivo original

*
Disfunção erétil
André Schenka
*
Introdução
*
Disfunção erétil
Dificuldade em obter ou manter uma ereção suficiente para uma relação sexual
Conceito subjetivo
Evitar o termo “impotência”
Não inclui: disfunções de libido ou ejaculatórias
*
Epidemiologia e etiologia
Idade (): 40% aos 40 anos!
Envelhecimento
Doenças crônicas
Uso de medicamentos
Estilo de vida
*
Anatomia
*
FISIOLOGIA
*
Controle neural:
Simpático x Parassimpático
FLACIDEZ
Tônus simpático
NE-receptores α2
Contração musculatura lisa
*
Controle neural:
Simpático x Parassimpático
FLACIDEZ
Contração musculatura lisa
Equilíbrio entre entrada e saída de sangue 
*
Controle neural:
Simpático x Parassimpático
EREÇÃO
Tônus parassimpático
Ach (M)  NO (endotelial)
Fibras neurais NANC: NO
ML: NO  GMPc Ca2+
Relaxamento musculatura lisa
*
Controle neural:
Simpático x Parassimpático
EREÇÃO
Relaxamento musculatura lisa
influxo  efluxo
fluxo arterial
Dilatação sinusoidal (P)
Compressão veias subtunicais
tamanho e rigidez
*
Controle neural:
Simpático x Parassimpático
EREÇÃO (outros mediadores)
VIP, PG E1 e E2
VIP/PG  AMPc Ca2+
Relaxamento musculatura lisa
influxo  efluxo
fluxo arterial
Dilatação sinusoidal (P)
Compressão veias subtunicais
tamanho e rigidez
*
Controle neural:
Simpático x Parassimpático
DETUMESCÊNCIA
Descarga simpática pós-ejaculação
Contração muculatura lisa:
redução de influxo
descompressão sinusoidal
Aumento de efluxo
*
Óxido nítrico (NO)
Principal mediador da ereção
Produzido a partir de L-arginina
Reação catalizada pela NOS (NO sintase):
nNOS (neural)
eNOS (endotelial)
iNOS (induzível: sistema imune e CV)
*
Testosterona
Ação central:
Libido
Ação periférica:
Estabilização dos níveis de NOS
Manutenção da anatomia peniana
“Andropausa”
*
Ereção: fenômeno neurovascular
*
Disfunção erétil
Orgânica (80%)
Psicogênica
Mista
*
Causas de DE orgânica
*
*
Causas de DE orgânica
*
DE psicogênica
Ausência de resposta a estímulo psíquico
Causas comuns:
Ansiedade (estímulo simpático)
Relacionamentos desgastados
Baixa libido
Distúrbios psiquiátricos (Depressão, esquizofrenia) 
*
DE mista
Orgânica + psicogênica
30% dos casos de DE orgânica
*
Quadro clínico & diagnóstico
*
Avaliação diagnóstica
Componentes:
Histório clínica completa (incluindo aspectos sexuais e psicossociais)
Exame físico direcionado
Exames laboratoriais (glicemia, testosterona, perfil lipídico, …)
Objetivos:
Descartar natureza psicogênica
Identificar causas e FR orgânicos
Identificar contraindicações ao uso de certos fármacos
*
Avaliação diagnóstica
The International Index of Erectile Dysfunction (IIED) – gravidade
15 questões:
Função erétil
Libido
Função orgásmica
Satisfação sexual
Satisfação geral
Escore < 26 em função erétil  algum grau de DE
*
*
Tratamento
*
Objetivos
Obtenção de ereções suficientes para a relação sexual e melhora da qualidade de vida
Prevenir: depressão, baixa auto-estima, alterações da auto-imagem, problemas conjugais
Efeitos colaterais mínimos
Administração conveniente
Pouca ou nenhuma interação medicamentosa
*
Abordagem geral
Determinar: orgânica ou psico ou ambas
Identificar doenças causadoras, FR, medicamentos
Discutir as opções com o paciente
Iniciar com a opção menos invasiva
Individualizar (preferências, resposta, via de adm, custo, tolerância, segurança)
*
Tratamento não farmacológico
Modificações de estilo de vida
(+): dieta, exercício físico, perda de peso.
(-): tabagismo, etilismo, drogas ilícitas.
Psicoterapia
Psicogênica ou mista.
Participação da parceira(o). Não invasiva. Tempo/custo.
Dispositivos de ereção à vácuo
Pressão negativa: turgescência. Manutenção: anel elástico (não ultrapassar <30 min).
Muito eficaz. Pode ser associado a outras modalidades.
Lento (~30 min), dor, dificuldade de ejaculação. Anemia falciforme: priapismo.
*
*
Tratamento não farmacológico
Próteses:
Inseridas cirurgicamente dentro do CC
Tipos:
Semi-rígidas maleáveis (dobrável)
Infláveis (bomba de transferência de líquidos no escroto)
Última linha de tratamento
Menor satisfação da(o) parceira(o)
Riscos: infecção, mau funcionamento
Vida útil: 7-10anos
*
*
Opções farmacológicas
*
Inibidores da fosfodiesterase 5
Representantes:
Sildenafil (Viagra®)
Tadalafil (Cialis®)
Vardenafil (Levitra®)
Lodenafil (Helleva®)
Mecanismo de ação:
Inibe a quebra de GMPc pela PDE5
GMPc: relaxamento m. lisa (ereção)
*
*
Inibidores da fosfodiesterase 5
Condições para o bom funcionamento:
Estímulo sexual
Capacidade de resposta sexual (SNC/P)
Integridade do sistema NO/GMPc
São facilitadores, não iniciadores
*
Inibidores da fosfodiesterase 5
Primeira linha:
Alta eficiência
Fácil adm, manipulação de doses
Raros EC graves
*
Inibidores da fosfodiesterase 5
Comparação entre os representantes:
Eficiência ~ (resposta 50-80% - dose/etiolog.)
 efeito: prostatectomia radial, DM, doenças vasculares
Principal diferença: tempo de duração
Sildenafil/vardenafil: meia-vida= 3-4h
Taladafil: meia-vida= 18h (> espontaneidade, EC, interações)
*
Inibidores da fosfodiesterase 5
Efeitos adversos:
Cefaléia
Rubor facial
Congestão nasal
Dispepsia
Priapismo (raro)
Dificuldade de distinguir azul de verde (reação cruzada com PDE6 na retina)
NAION (neuropatia óptica isquêmica não arterítica)
Hipotensão (pode ser potencializada com nitratos)
*
Inibidores da fosfodiesterase 5
Uso em pacientes com doenças cardiovasculares:
Relatos de eventos cardiovasculares…
Atividade sexual (esforço  angina)
Hipotensão (vasodilatação NO mediada)
QT (vardenafil)  arritmias
Contra-indicações absolutas:
Pacientes em uso de nitratos (ou que possa necessitar)
Pacientes em uso de alfa-bloq
*
Alprostadil
Análogo de prostaglandina E1
AMPc
Injeção intracavernosa (+ eficaz)
Caverject® or Edex® 
Supositório intrauretral
MUSE®, medicated urethral system for erection
Segunda linha (invasivo)
*
Alprostadil
EC: dor, priapismo, pequenos sangramentos, fibrose
Contraindicações:
Parceira grávida (OK se condom)
Inconvenientes:
Adm
Falta de espontaneidade
*
*
Outras drogas injetáveis
Geralmente associadas ao alprostadil
Papaverina:
Inibidor PDE não seletivo
 
Fentolamina:
Antagonista de receptor alfa-adrenérgico
*
Yohimbine
Alcalóide (casca da árvore africana yohimbe)
Inibidor seletivo alfa-2 no cérebro
Efeito sobre libido
Dados limitados sobre eficácia
EC: náusea, irritabilidade, cefaléia, ansiedade, taquicardia, hipertensão
*
Suplementação de testosterona
Só eficaz em pacientes com níveis comprovadamente baixos de testo
No hipogonadismo, corrige:
Libido
Fadiga
Sarcopenia (perda muscular)
Alterações do sono
Depressão
*
Suplementação de testosterona
Vias de administração:
VO
IM (menor custo, maior eficácia):
A cada 2-4sem.
Oscilações de concentração (e humor).
Transdérmica: adesivos, gel
Bucal
*
Suplementação de testosterona
EC:
Ginecomastia
Policitemia
Acne
retenção de Na+: hipertensão, edema, piora de ICC
Contraindicações: HNP, câncer de próstata
*
Obrigado.
schenka@hotmail.com
*
Erectile dysfunction (ED) is defined as the inability to
achieve or maintain an erection sufficient for sexual intercourse.
The definition is very subjective due to differences in
desired or needed rigidity in patients of different ages and in
different types of relationships. Patients may refer to their dysfunction
as impotence, but the National Institutes of Health
Consensus Development Conference recommends that
the
term “erectile dysfunction” replace the term impotence due to
confusion with other forms of sexual dysfunction and the
negative connotation associated with the term impotence.1
Patients may also develop libido or ejaculatory disorders, but
these are not considered erectile dysfunction.
*
ED becomes increasingly frequent as men age. According to
data from the Massachusetts Male Aging Study the prevalence
of ED of any degree is 40% among 40-year-old men and 70%
among 70-year-old men.2 The increase in incidence could be
due to physiologic changes that occur with aging, the onset of
chronic disease states associated with ED, increased medication
use, lifestyle factors, or a combination of the above.
*
The penis consists of three components, two dorsolateral corpora
cavernosa and a ventral corpus spongiosum that surrounds
the penile urethra and distally forms the glans penis.
The corpora cavernosa consist of blood-filled sinusoidal or
lacunar spaces, which are lined with endothelial cells, supported
by trabecular smooth muscle, and surrounded by a
thick fibrous sheath called the tunica albuginea. The cavernosal
arteries, which are branches of the penile artery, penetrate
the tunica albuginea and supply blood flow to the penis.
*
Sympathetic and parasympathetic nerves innervate the
penis. In the flaccid state, α2-adrenergic receptors mediate
tonic contraction of the arterial and corporal smooth muscles.
This maintains high penile arterial resistance and a balance
exists between blood flow into and out of the corpora. With
sexual stimulation, nerve impulses from the brain travel down
the spinal cord to the thoracolumbar ganglia.3 A decrease in
sympathetic tone and an increase in parasympathetic activity
then occurs, causing a net increase in blood flow into the erectile
tissue. Erections may also occur as a result of a sacral nerve
reflex arc while patients are sleeping (nocturnal erections).
*
Sympathetic and parasympathetic nerves innervate the
penis. In the flaccid state, α2-adrenergic receptors mediate
tonic contraction of the arterial and corporal smooth muscles.
This maintains high penile arterial resistance and a balance
exists between blood flow into and out of the corpora. With
sexual stimulation, nerve impulses from the brain travel down
the spinal cord to the thoracolumbar ganglia.3 A decrease in
sympathetic tone and an increase in parasympathetic activity
then occurs, causing a net increase in blood flow into the erectile
tissue. Erections may also occur as a result of a sacral nerve
reflex arc while patients are sleeping (nocturnal erections).
*
Acetylcholine-mediated parasympathetic activity leads to
production of the non-adrenergic–non-cholinergic transmitter
nitric oxide. By enhancing the activity of guanylate cyclase, nitric
oxide increases the production of cyclic guanosine monophosphate
(cGMP).Vasoactive peptide and prostaglandins E1 and E2
stimulate increased production of cAMP. Both cyclic adenosine
monophosphate (cAMP) and cGMP ultimately lead to a
decrease in calcium concentration within smooth muscle cells
of the penile arteries and the sinusoidal spaces, leading to
smooth muscle relaxation and increased blood flow. As the
sinusoidal spaces become engorged, intracavernosal pressure
increases, subtunical venules are compressed, and the penis
becomes rigid and elongated (Fig. 48–1).
*
Acetylcholine-mediated parasympathetic activity leads to
production of the non-adrenergic–non-cholinergic transmitter
nitric oxide. By enhancing the activity of guanylate cyclase, nitric
oxide increases the production of cyclic guanosine monophosphate
(cGMP).Vasoactive peptide and prostaglandins E1 and E2
stimulate increased production of cAMP. Both cyclic adenosine
monophosphate (cAMP) and cGMP ultimately lead to a
decrease in calcium concentration within smooth muscle cells
of the penile arteries and the sinusoidal spaces, leading to
smooth muscle relaxation and increased blood flow. As the
sinusoidal spaces become engorged, intracavernosal pressure
increases, subtunical venules are compressed, and the penis
becomes rigid and elongated (Fig. 48–1).
*
Acetylcholine-mediated parasympathetic activity leads to
production of the non-adrenergic–non-cholinergic transmitter
nitric oxide. By enhancing the activity of guanylate cyclase, nitric
oxide increases the production of cyclic guanosine monophosphate
(cGMP).Vasoactive peptide and prostaglandins E1 and E2
stimulate increased production of cAMP. Both cyclic adenosine
monophosphate (cAMP) and cGMP ultimately lead to a
decrease in calcium concentration within smooth muscle cells
of the penile arteries and the sinusoidal spaces, leading to
smooth muscle relaxation and increased blood flow. As the
sinusoidal spaces become engorged, intracavernosal pressure
increases, subtunical venules are compressed, and the penis
becomes rigid and elongated (Fig. 48–1).
*
Detumescence occurs with sympathetic discharge after
ejaculation. Sympathetic activity induces smooth muscle contraction
of arterioles and vascular spaces leading to a reduction
in blood inflow, decompression of the sinusoidal spaces, and
enhanced outflow.
*
Testosterone also plays a significant albeit complex role in
erectile function. Testosterone is responsible for much of a
man’s libido. With low serum concentrations, libido declines.
Additionally, testosterone helps with stabilization of intracavernosal
levels of nitric oxide synthase, the enzyme responsible for
triggering the nitric oxide cascade. Interestingly, some patients
with low or borderline low serum concentrations of testosterone
will have normal erectile function, while some with normal
levels will have dysfunction.
*
Normal penile erections are complex events that require the
full function of the vascular, neurologic, and hormonal systems.
Anything that affects the function of these systems may lead to
ED.
*
❶ ED can be classified as organic, psychogenic, or a mixture
of these. Organic dysfunction includes abnormalities in the three
systems responsible for a normal erection or may be medicationinduced
(Tables 48–1 and 48–2). Note that many of the risk
factors for ED are the same as risk factors for cardiovascular
disease. In many patients, ED is the first indication of the
endothelial dysfunction associated with cardiovascular disease.4
The presence of ED risk factors leads to the assumption that the
patient has organic dysfunction.Most commonly, medical conditions
that impair arterial flow into or out of the erectile tissue
or affect the innervation will be strongly associated with ED.
Patients with diabetes mellitus have exceptionally high rates of
ED as a result of vascular disease and neuropathy.
*
❶ ED can be classified as organic, psychogenic, or a mixture
of these. Organic dysfunction includes abnormalities in the three
systems responsible for a normal erection or may be medicationinduced
(Tables 48–1 and 48–2). Note that many of the risk
factors for ED are the same as risk factors for cardiovascular
disease. In many patients, ED is the first indication of the
endothelial dysfunction associated with cardiovascular disease.4
The presence of ED risk factors leads to the assumption that the
patient has organic dysfunction.Most commonly, medical conditions
that impair arterial flow into or out of the erectile tissue
or affect the innervation will be strongly associated with ED.
Patients with diabetes mellitus have exceptionally high rates of
ED as a result of vascular disease and neuropathy.
*
❶ ED can be classified as organic, psychogenic, or a mixture
of these. Organic dysfunction includes abnormalities in the three
systems responsible for a normal erection or may be medicationinduced
(Tables 48–1 and 48–2). Note that many of the risk
factors for ED are the same as risk factors for cardiovascular
disease. In many patients, ED is the first indication of the
endothelial dysfunction associated
with cardiovascular disease.4
The presence of ED risk factors leads to the assumption that the
patient has organic dysfunction.Most commonly, medical conditions
that impair arterial flow into or out of the erectile tissue
or affect the innervation will be strongly associated with ED.
Patients with diabetes mellitus have exceptionally high rates of
ED as a result of vascular disease and neuropathy.
*
Psychogenic dysfunction occurs if a patient does not
respond to psychic arousal. It occurs in up to 30% of all
cases of ED. Common causes include performance anxiety,
strained relationships, lack of sexual arousability, and overt
psychiatric disorders such as depression and schizophrenia.5
It is postulated that the anxious or nervous man will have
excessive stimulation of the sympathetic system, leading to
smooth muscle contraction of arterioles and vascular spaces
within erectile tissue.6 ❶ Many patients may initially have
organic dysfunction, but develop a psychogenic component as
they try to cope with their inability to achieve an erection. It
has been estimated that up to 80% of ED cases have an
organic cause, with many having a psychogenic component
as well.1
*
The evaluation of a patient presenting with ED should consist
of a thorough medical history including sexual and psychosocial
issues to determine if the dysfunction is psychogenic. In addition, a
directed physical exam and laboratory tests should be performed
such as total and free serum testosterone, serum glucose, a
fasting lipid panel, and a thyroid panel.9 Identification of
concomitant disease states is important for determining first
line therapy. Some medical conditions and their associated
medications contraindicate the use of some ED therapies or may
lead to drug interactions. It is also necessary to assess the patient’s
ability to safely perform intercourse and to review lifestyle factors
such as smoking, alcohol consumption, and regular exercise.
The International Index of Erectile Dysfunction (IIED) is the
most widely used questionnaire to assess the severity of ED.10 It
consists of 15 questions with 5 domains: erectile function, libido,
orgasmic function, sexual satisfaction, and overall satisfaction.
The erectile function domain has a maximum score of 30 with a
score of less than 26 indicating some degree of ED.
*
The evaluation of a patient presenting with ED should consist
of a thorough medical history including sexual and psychosocial
issues to determine if the dysfunction is psychogenic. In addition, a
directed physical exam and laboratory tests should be performed
such as total and free serum testosterone, serum glucose, a
fasting lipid panel, and a thyroid panel.9 Identification of
concomitant disease states is important for determining first
line therapy. Some medical conditions and their associated
medications contraindicate the use of some ED therapies or may
lead to drug interactions. It is also necessary to assess the patient’s
ability to safely perform intercourse and to review lifestyle factors
such as smoking, alcohol consumption, and regular exercise.
The International Index of Erectile Dysfunction (IIED) is the
most widely used questionnaire to assess the severity of ED.10 It
consists of 15 questions with 5 domains: erectile function, libido,
orgasmic function, sexual satisfaction, and overall satisfaction.
The erectile function domain has a maximum score of 30 with a
score of less than 26 indicating some degree of ED.
*
Desired Outcomes
ED is not a life-threatening condition, but left untreated it can be
associated with depression, loss of self-esteem, poor self-image,
and marital discord.11 The primary goal of therapy is achievement
of erections suitable for intercourse and improvement in
patient quality of life.Additionally, the ideal therapy should have
minimal side effects, be convenient to administer, have a quick
onset of action, and have few or no drug interactions.7
*
General Approach to Treatment
After determining if the ED is organic or psychogenic, the
initial step in management is to identify associated disease
states and lifestyle activities that adversely affect erectile function
and treat them optimally. Medications suspected to
cause or worsen ED should also be discontinued if possible.
❹ A wide range of treatment options are now available for
men with ED. These include medical devices, pharmacologic
treatments, lifestyle modifications, surgery, and psychotherapy.
❺ When determining the best treatment for an individual, the
role of the clinician is to inform the patient and his partner of
all available options while understanding his medical history,
desires, and goals. Most often treatment is initiated with the
least invasive option and then treatment progresses to more
invasive options if needed. Ultimately, the choice of therapy
should be individualized, taking into account patient and
partner preferences, concomitant disease states, response,
administration, cost, tolerability, and safety. Common drug
treatment regimens for ED are listed in Table 48–3.
*
Nonpharmacologic Therapy
Lifestyle Modifications
Lifestyle modifications should always be addressed in the
management of ED. A healthy diet, increase in regular physical
activity, and weight loss are associated with higher IIED
scores and an improvement in erectile function.12 The clinician
should recommend smoking cessation, reduction in
excessive alcohol intake, and discontinuation of the use of
illicit drugs.
Psychotherapy
Psychotherapy is an appropriate treatment approach for
patients with psychogenic or mixed dysfunction. It should
address immediate causes of dysfunction, and if possible the
partner should attend sessions as well. Effectiveness is not well
documented for organic dysfunction unless combined with
other therapies. Advantages include non-invasiveness and partner
participation, while disadvantages include increased cost
and time commitment.
Vacuum Erection Devices
Vacuum erection devices (VEDs) induce erections by creating
a vacuum around the penis; the negative pressure draws blood
into the penis by passively dilating arteries and engorging the
corpora cavernosa. The erection is maintained with a constriction
band placed at the base of the penis to reduce venous
outflow (Fig. 48–2). They may be used as often as desired, but
it is recommended that the constriction band not be in place
longer than 30 minutes at a time.
❻VEDs are one of the most effective treatment modalities for
ED. They have a success rate of greater than 90% in obtaining an
erection sufficient for coitus and are considered a first-line noninvasive
therapy.13 Rigidity may be improved by using a double
pump technique in which the vacuum is applied for a couple
of minutes, removed, then reapplied for another few minutes.
Higher efficacy rates can also be achieved by combining VEDs
with other therapies.
Onset of action is slow at around 30 minutes, which limits
spontaneity. In addition, patients and partners may complain
of a cold, lifeless, discolored penis that has a hinge-like feel.
Painful ejaculation or inability to ejaculate are additional
adverse effects. VEDs are contraindicated in persons with
sickle cell disease and should be used with caution in patients
on oral anticoagulants or who have bleeding disorders due to
the increased possibility of priapism.
*
Prostheses
Penile prostheses are semi-rigid malleable or inflatable rods,
which are inserted surgically into the corpus cavernosa to allow
erections (Fig. 48–2). The malleable rods are rigid at all times,
but may be bent into position by the patient when desired.
The inflatable prostheses remain flaccid until the pump within
the scrotum moves fluid from a reservoir to the cylinders within
the penis. Detumescence is achieved when the fluid is then
transferred back to the reservoir by activating a release button.
Because prostheses are the most invasive treatment
available,
they are only considered in patients who do not respond
to medications or external devices, or those who have significant
adverse effects from other therapies. Patient satisfaction
rates can be as high as 80% to 90% with partner satisfaction
rates just slightly lower.9 The primary risks of insertion of
prostheses are infection and device failure, although these
only happen in 2% to 3% and 2% to 14% of patients, respectively.
Higher infection rates have been reported in uncontrolled
diabetic patients, paraplegics, and patients undergoing
reimplantation or penile reconstruction.14,15 Most prostheses
can be expected to last from 7 to 10 years.16
*
Phosphodiesterase Type 5 Inhibitors
Sildenafil (Viagra®), tadalafil (Cialis®), and vardenafil
(Levitra®) act by selectively inhibiting phosphodiesterase
(PDE) type 5, an enzyme that breaks down cGMP. By inhibiting
the breakdown of cGMP, smooth muscle relaxation isinduced, leading to an erection (Fig. 48–1). However, the PDE
inhibitors are only effective in the presence of sexual stimulation
to drive the nitric oxide/cGMP system, making them facilitators
of an erection, not initiators. Patients must be informed
of the need for sexual stimulation to induce an erection, as it
will not occur spontaneously.
❼ Effectiveness of the three available phosphodiesterase
inhibitors is essentially comparable, but differences exist in duration
of action, and to a small degree, incidence of side effects and drug
interactions (Table 48–4). Studies directly comparing the side
effects and efficacy of the drugs in this class have not been published.
In addition, trials for vardenafil and tadalafil excluded
subjects who did not respond to sildenafil. Review of available
data for each individual agent shows a 50% to 80% response rate
depending on the dose of agent used and the etiology of dysfunction.
Patients with radical prostatectomy tend to have lower
response rates.6 Response rates are also lower in patients with diabetes,
severe nerve damage, or severe vascular disease.17 The PDE
inhibitors are considered first-line therapies due to high efficacy
rates, convenience of dosing, and minimal severe adverse effects.
The most dramatic difference between the three agents is
tadalafil’s extended duration of action, earning it the nickname
“the weekender drug.” While sildenafil and vardenafil
have average half-lives of 3 to 4 hours, tadalafil’s half life is
approximately 18 hours.18 The extended half-life allows for
more spontaneous sexual activity over a couple of days, but
may increase the duration of adverse effects and liklihood of
drug interactions or sildenafil.
The most common side effects experienced with PDE
inhibitors include headache, facial flushing, nasal congestion,
dyspepsia, and rarely priapism. Vardenafil and sildenafil may
also cause difficulty in discriminating blue from green, bluish
tones in vision, or difficulty seeing in dim light due to crossreactivity
with PDE 6 in the retina. There has also been a
recent change in the labeling for all PDE inhibitors warning
about non-arteritic ischemic optic neuropathy (NAION) in a
small number of patients. This is a condition in which blood
flow is blocked to the optic nerve. If patients experience sudden
or decreased vision loss they should call a health care
provider immediately.
Concern exists about the safety of using PDE inhibitors in
patients with cardiovascular disease. Because of the numerous
adverse cardiovascular events reported after the release of
sildenafil, a management approach was developed to give recommendations
for the use of PDE inhibitors in patients with
cardiovascular disease19 (Table 48–5). In addition to the inherent
risk of renewing sexual activity, PDE inhibitors can lead to
significant hypotension. Patients taking organic nitrates are
the most at risk, as they potentiate the drop in blood pressure.
All three PDE inhibitors are absolutely contraindicated in
patients taking any form of nitrate, whether scheduled or sublingual
for acute situations. Caution should be used when
using a PDE inhibitor in patients taking α-blockers due to an
increased risk of hypotension. In addition, the labeling for
vardenafil contains a precautionary statement about the possibility
of QT prolongation with the use of the drug. Other
drug interactions and cautions vary slightly between agents
and are described in Table 48–4.
The introduction of the oral PDE inhibitors has dramatically
changed the treatment of ED.Direct-to-consumer advertising
has informed patients of the availability of oral drugs
for treatment. However, patients must be fully informed of
side effects, drug interactions, mechanism of action, and dosing
before being prescribed the medication. In addition, they
need to understand the need for sexual stimulation to achieve
the desired result and that a single trial is not adequate. It is
estimated that six to eight attempts with a medication and
specific dose may be needed before successful intercourse
results.20
*
Phosphodiesterase Type 5 Inhibitors
Sildenafil (Viagra®), tadalafil (Cialis®), and vardenafil
(Levitra®) act by selectively inhibiting phosphodiesterase
(PDE) type 5, an enzyme that breaks down cGMP. By inhibiting
the breakdown of cGMP, smooth muscle relaxation isinduced, leading to an erection (Fig. 48–1). However, the PDE
inhibitors are only effective in the presence of sexual stimulation
to drive the nitric oxide/cGMP system, making them facilitators
of an erection, not initiators. Patients must be informed
of the need for sexual stimulation to induce an erection, as it
will not occur spontaneously.
❼ Effectiveness of the three available phosphodiesterase
inhibitors is essentially comparable, but differences exist in duration
of action, and to a small degree, incidence of side effects and drug
interactions (Table 48–4). Studies directly comparing the side
effects and efficacy of the drugs in this class have not been published.
In addition, trials for vardenafil and tadalafil excluded
subjects who did not respond to sildenafil. Review of available
data for each individual agent shows a 50% to 80% response rate
depending on the dose of agent used and the etiology of dysfunction.
Patients with radical prostatectomy tend to have lower
response rates.6 Response rates are also lower in patients with diabetes,
severe nerve damage, or severe vascular disease.17 The PDE
inhibitors are considered first-line therapies due to high efficacy
rates, convenience of dosing, and minimal severe adverse effects.
The most dramatic difference between the three agents is
tadalafil’s extended duration of action, earning it the nickname
“the weekender drug.” While sildenafil and vardenafil
have average half-lives of 3 to 4 hours, tadalafil’s half life is
approximately 18 hours.18 The extended half-life allows for
more spontaneous sexual activity over a couple of days, but
may increase the duration of adverse effects and liklihood of
drug interactions or sildenafil.
The most common side effects experienced with PDE
inhibitors include headache, facial flushing, nasal congestion,
dyspepsia, and rarely priapism. Vardenafil and sildenafil may
also cause difficulty in discriminating blue from green, bluish
tones in vision, or difficulty seeing in dim light due to crossreactivity
with PDE 6 in the retina. There has also been a
recent change in the labeling for all PDE inhibitors warning
about non-arteritic ischemic optic neuropathy (NAION) in a
small number of patients. This is a condition in which blood
flow is blocked to the optic nerve. If patients experience sudden
or decreased vision loss they should call a health care
provider immediately.
Concern exists about the safety of using PDE inhibitors in
patients with cardiovascular disease. Because of the numerous
adverse cardiovascular events reported after the release of
sildenafil, a management approach was developed to give
recommendations
for the use of PDE inhibitors in patients with
cardiovascular disease19 (Table 48–5). In addition to the inherent
risk of renewing sexual activity, PDE inhibitors can lead to
significant hypotension. Patients taking organic nitrates are
the most at risk, as they potentiate the drop in blood pressure.
All three PDE inhibitors are absolutely contraindicated in
patients taking any form of nitrate, whether scheduled or sublingual
for acute situations. Caution should be used when
using a PDE inhibitor in patients taking α-blockers due to an
increased risk of hypotension. In addition, the labeling for
vardenafil contains a precautionary statement about the possibility
of QT prolongation with the use of the drug. Other
drug interactions and cautions vary slightly between agents
and are described in Table 48–4.
The introduction of the oral PDE inhibitors has dramatically
changed the treatment of ED.Direct-to-consumer advertising
has informed patients of the availability of oral drugs
for treatment. However, patients must be fully informed of
side effects, drug interactions, mechanism of action, and dosing
before being prescribed the medication. In addition, they
need to understand the need for sexual stimulation to achieve
the desired result and that a single trial is not adequate. It is
estimated that six to eight attempts with a medication and
specific dose may be needed before successful intercourse
results.20
*
Phosphodiesterase Type 5 Inhibitors
Sildenafil (Viagra®), tadalafil (Cialis®), and vardenafil
(Levitra®) act by selectively inhibiting phosphodiesterase
(PDE) type 5, an enzyme that breaks down cGMP. By inhibiting
the breakdown of cGMP, smooth muscle relaxation isinduced, leading to an erection (Fig. 48–1). However, the PDE
inhibitors are only effective in the presence of sexual stimulation
to drive the nitric oxide/cGMP system, making them facilitators
of an erection, not initiators. Patients must be informed
of the need for sexual stimulation to induce an erection, as it
will not occur spontaneously.
❼ Effectiveness of the three available phosphodiesterase
inhibitors is essentially comparable, but differences exist in duration
of action, and to a small degree, incidence of side effects and drug
interactions (Table 48–4). Studies directly comparing the side
effects and efficacy of the drugs in this class have not been published.
In addition, trials for vardenafil and tadalafil excluded
subjects who did not respond to sildenafil. Review of available
data for each individual agent shows a 50% to 80% response rate
depending on the dose of agent used and the etiology of dysfunction.
Patients with radical prostatectomy tend to have lower
response rates.6 Response rates are also lower in patients with diabetes,
severe nerve damage, or severe vascular disease.17 The PDE
inhibitors are considered first-line therapies due to high efficacy
rates, convenience of dosing, and minimal severe adverse effects.
The most dramatic difference between the three agents is
tadalafil’s extended duration of action, earning it the nickname
“the weekender drug.” While sildenafil and vardenafil
have average half-lives of 3 to 4 hours, tadalafil’s half life is
approximately 18 hours.18 The extended half-life allows for
more spontaneous sexual activity over a couple of days, but
may increase the duration of adverse effects and liklihood of
drug interactions or sildenafil.
The most common side effects experienced with PDE
inhibitors include headache, facial flushing, nasal congestion,
dyspepsia, and rarely priapism. Vardenafil and sildenafil may
also cause difficulty in discriminating blue from green, bluish
tones in vision, or difficulty seeing in dim light due to crossreactivity
with PDE 6 in the retina. There has also been a
recent change in the labeling for all PDE inhibitors warning
about non-arteritic ischemic optic neuropathy (NAION) in a
small number of patients. This is a condition in which blood
flow is blocked to the optic nerve. If patients experience sudden
or decreased vision loss they should call a health care
provider immediately.
Concern exists about the safety of using PDE inhibitors in
patients with cardiovascular disease. Because of the numerous
adverse cardiovascular events reported after the release of
sildenafil, a management approach was developed to give recommendations
for the use of PDE inhibitors in patients with
cardiovascular disease19 (Table 48–5). In addition to the inherent
risk of renewing sexual activity, PDE inhibitors can lead to
significant hypotension. Patients taking organic nitrates are
the most at risk, as they potentiate the drop in blood pressure.
All three PDE inhibitors are absolutely contraindicated in
patients taking any form of nitrate, whether scheduled or sublingual
for acute situations. Caution should be used when
using a PDE inhibitor in patients taking α-blockers due to an
increased risk of hypotension. In addition, the labeling for
vardenafil contains a precautionary statement about the possibility
of QT prolongation with the use of the drug. Other
drug interactions and cautions vary slightly between agents
and are described in Table 48–4.
The introduction of the oral PDE inhibitors has dramatically
changed the treatment of ED.Direct-to-consumer advertising
has informed patients of the availability of oral drugs
for treatment. However, patients must be fully informed of
side effects, drug interactions, mechanism of action, and dosing
before being prescribed the medication. In addition, they
need to understand the need for sexual stimulation to achieve
the desired result and that a single trial is not adequate. It is
estimated that six to eight attempts with a medication and
specific dose may be needed before successful intercourse
results.20
*
Phosphodiesterase Type 5 Inhibitors
Sildenafil (Viagra®), tadalafil (Cialis®), and vardenafil
(Levitra®) act by selectively inhibiting phosphodiesterase
(PDE) type 5, an enzyme that breaks down cGMP. By inhibiting
the breakdown of cGMP, smooth muscle relaxation isinduced, leading to an erection (Fig. 48–1). However, the PDE
inhibitors are only effective in the presence of sexual stimulation
to drive the nitric oxide/cGMP system, making them facilitators
of an erection, not initiators. Patients must be informed
of the need for sexual stimulation to induce an erection, as it
will not occur spontaneously.
❼ Effectiveness of the three available phosphodiesterase
inhibitors is essentially comparable, but differences exist in duration
of action, and to a small degree, incidence of side effects and drug
interactions (Table 48–4). Studies directly comparing the side
effects and efficacy of the drugs in this class have not been published.
In addition, trials for vardenafil and tadalafil excluded
subjects who did not respond to sildenafil. Review of available
data for each individual agent shows a 50% to 80% response rate
depending on the dose of agent used and the etiology of dysfunction.
Patients with radical prostatectomy tend to have lower
response rates.6 Response rates are also lower in patients with diabetes,
severe nerve damage, or severe vascular disease.17 The PDE
inhibitors are considered first-line therapies due to high efficacy
rates, convenience of dosing, and minimal severe adverse effects.
The most dramatic difference between the three agents is
tadalafil’s extended duration of action, earning it the nickname
“the weekender drug.” While sildenafil and vardenafil
have average half-lives of 3 to 4 hours, tadalafil’s half life is
approximately 18 hours.18 The extended half-life allows for
more spontaneous sexual activity over a couple of days, but
may increase the duration of adverse effects and liklihood of
drug interactions or sildenafil.
The most common side effects experienced with PDE
inhibitors include headache, facial flushing, nasal congestion,
dyspepsia, and rarely priapism.
Vardenafil and sildenafil may
also cause difficulty in discriminating blue from green, bluish
tones in vision, or difficulty seeing in dim light due to crossreactivity
with PDE 6 in the retina. There has also been a
recent change in the labeling for all PDE inhibitors warning
about non-arteritic ischemic optic neuropathy (NAION) in a
small number of patients. This is a condition in which blood
flow is blocked to the optic nerve. If patients experience sudden
or decreased vision loss they should call a health care
provider immediately.
Concern exists about the safety of using PDE inhibitors in
patients with cardiovascular disease. Because of the numerous
adverse cardiovascular events reported after the release of
sildenafil, a management approach was developed to give recommendations
for the use of PDE inhibitors in patients with
cardiovascular disease19 (Table 48–5). In addition to the inherent
risk of renewing sexual activity, PDE inhibitors can lead to
significant hypotension. Patients taking organic nitrates are
the most at risk, as they potentiate the drop in blood pressure.
All three PDE inhibitors are absolutely contraindicated in
patients taking any form of nitrate, whether scheduled or sublingual
for acute situations. Caution should be used when
using a PDE inhibitor in patients taking α-blockers due to an
increased risk of hypotension. In addition, the labeling for
vardenafil contains a precautionary statement about the possibility
of QT prolongation with the use of the drug. Other
drug interactions and cautions vary slightly between agents
and are described in Table 48–4.
The introduction of the oral PDE inhibitors has dramatically
changed the treatment of ED.Direct-to-consumer advertising
has informed patients of the availability of oral drugs
for treatment. However, patients must be fully informed of
side effects, drug interactions, mechanism of action, and dosing
before being prescribed the medication. In addition, they
need to understand the need for sexual stimulation to achieve
the desired result and that a single trial is not adequate. It is
estimated that six to eight attempts with a medication and
specific dose may be needed before successful intercourse
results.20
*
The most common side effects experienced with PDE
inhibitors include headache, facial flushing, nasal congestion,
dyspepsia, and rarely priapism. Vardenafil and sildenafil may
also cause difficulty in discriminating blue from green, bluish
tones in vision, or difficulty seeing in dim light due to crossreactivity
with PDE 6 in the retina. There has also been a
recent change in the labeling for all PDE inhibitors warning
about non-arteritic ischemic optic neuropathy (NAION) in a
small number of patients. This is a condition in which blood
flow is blocked to the optic nerve. If patients experience sudden
or decreased vision loss they should call a health care
provider immediately.
Concern exists about the safety of using PDE inhibitors in
patients with cardiovascular disease. Because of the numerous
adverse cardiovascular events reported after the release of
sildenafil, a management approach was developed to give recommendations
for the use of PDE inhibitors in patients with
cardiovascular disease19 (Table 48–5). In addition to the inherent
risk of renewing sexual activity, PDE inhibitors can lead to
significant hypotension. Patients taking organic nitrates are
the most at risk, as they potentiate the drop in blood pressure.
All three PDE inhibitors are absolutely contraindicated in
patients taking any form of nitrate, whether scheduled or sublingual
for acute situations. Caution should be used when
using a PDE inhibitor in patients taking α-blockers due to an
increased risk of hypotension. In addition, the labeling for
vardenafil contains a precautionary statement about the possibility
of QT prolongation with the use of the drug. Other
drug interactions and cautions vary slightly between agents
and are described in Table 48–4.
The introduction of the oral PDE inhibitors has dramatically
changed the treatment of ED.Direct-to-consumer advertising
has informed patients of the availability of oral drugs
for treatment. However, patients must be fully informed of
side effects, drug interactions, mechanism of action, and dosing
before being prescribed the medication. In addition, they
need to understand the need for sexual stimulation to achieve
the desired result and that a single trial is not adequate. It is
estimated that six to eight attempts with a medication and
specific dose may be needed before successful intercourse
results.20
*
Concern exists about the safety of using PDE inhibitors in
patients with cardiovascular disease. Because of the numerous
adverse cardiovascular events reported after the release of
sildenafil, a management approach was developed to give recommendations
for the use of PDE inhibitors in patients with
cardiovascular disease19 (Table 48–5). In addition to the inherent
risk of renewing sexual activity, PDE inhibitors can lead to
significant hypotension. Patients taking organic nitrates are
the most at risk, as they potentiate the drop in blood pressure.
All three PDE inhibitors are absolutely contraindicated in
patients taking any form of nitrate, whether scheduled or sublingual
for acute situations. Caution should be used when
using a PDE inhibitor in patients taking α-blockers due to an
increased risk of hypotension. In addition, the labeling for
vardenafil contains a precautionary statement about the possibility
of QT prolongation with the use of the drug. Other
drug interactions and cautions vary slightly between agents
and are described in Table 48–4.
The introduction of the oral PDE inhibitors has dramatically
changed the treatment of ED.Direct-to-consumer advertising
has informed patients of the availability of oral drugs
for treatment. However, patients must be fully informed of
side effects, drug interactions, mechanism of action, and dosing
before being prescribed the medication. In addition, they
need to understand the need for sexual stimulation to achieve
the desired result and that a single trial is not adequate. It is
estimated that six to eight attempts with a medication and
specific dose may be needed before successful intercourse
results.20
*
Alprostadil
Alprostadil is a prostaglandin E1 analog that induces an erection
by stimulating adenyl cyclase, which leads to an increase
in smooth muscle relaxation, rapid arterial inflow, and
increased penile rigidity. Alprostadil is available as an intracavernosal
injection (Caverject® or Edex®) or a transurethral
suppository (MUSE®, medicated urethral system for erection),
but the injectable form is more effective (Fig. 48–3).
Both forms of alprostadil are considered more invasive than
oral medications or VEDs, and are therefore second-line
therapies.8
MUSE consists of a urethral pellet of alprostadil with an
applicator. Onset of action is within 5 to 10 minutes and it is
effective for 30 to 60 minutes. Initial dose titration should
occur in a physician’s office to ensure correct dose and prevent
adverse events. Although effectiveness rates in clinical trials
have been as high as 65%,21 its success in practice has been
lower. Aching in the penis, testicles, legs, and perineum,
warmth or burning sensation in the urethra, minor urethral
bleeding or spotting, priapism, and lightheadedness are all
possible adverse effects. In addition, partners may experience
vaginal burning or itching. Disadvantages include lower effectiveness,
high cost, adverse effects, complicated insertion technique,
and a contraindication against use with a pregnant
partner unless using a condom.
Alprostadil injected into the corpus cavernosum is the more
effective form and is the only Food and Drug Administration
(FDA)-approved agent for injection. The onset of action is
*
Aching in the penis, testicles, legs, and perineum,
warmth
or burning sensation in the urethra, minor urethral
bleeding or spotting, priapism, and lightheadedness are all
possible adverse effects. In addition, partners may experience
vaginal burning or itching. Disadvantages include lower effectiveness,
high cost, adverse effects, complicated insertion technique,
and a contraindication against use with a pregnant
partner unless using a condom.
Alprostadil injected into the corpus cavernosum is the more
effective form and is the only Food and Drug Administration
(FDA)-approved agent for injection. The onset of action is
similar to transurethral alprostadil, but duration varies with
dose and must be titrated in a physician’s office to achieve an
erection lasting no more than 1 hour. Injections should be
done into one side of the penis directly into the corpus cavernosum,
and then the penis should be massaged to distribute
the drug. Because of cross-circulation, both corpora will
become erect when massaging. Education is extremely important
with intracavernosal injections. Patients must be adequately
informed of technique, expectations, side effects, and
when to seek help.❻ Intracavernosal injections are effective in
up to 90% of patients, but side effects, lack of spontaneity, and
fear of needles limit their widespread use as first-line therapy,
and therefore this therapy is most appropriate for patients in
long-term stable relationships. Adverse effects include pain
with injection, bleeding or bruising at the injection site,
fibrosis, or priapism. Use with caution in patients with sickle
cell disease, those on anticoagulants, or those who have
bleeding disorders, due to an increased risk of priapism and
bleeding.
*
Papaverine and phentolamine are non–FDA-approved agents
used for intracavernosal injection. Papaverine is a non-selective
PDE inhibitor that induces an erection by relaxing smooth
muscle and increasing blood flow. Phentolamine is a competitive
α-adrenergic receptor antagonist that increases arterial
inflow by opposing arterial constriction. Both drugs are rarely
used alone, and are most often mixed in various concentrations
with alprostadil for increased effectiveness and in an
effort to reduce adverse effects with smaller doses of each
medication. Patients typically must see a specialist for use of
these medications in mixtures, as they are the most likely to
compound them and adjust dosages.
*
Yohimbine is an indole alkaloid produced in the bark of
yohimbe trees. It selectively inhibits α2-adrenergic receptors
in the brain that are associated with libido and penile erection.
Since there is only limited data supporting its efficacy, yohimbine
is not a recommended treatment for any form of ED.22
Adverse effects of the drug include nausea, irritability,
headaches, anxiety, tachycardia, and hypertension.
*
Testosterone Supplementation
❽ Androgens are important for general sexual function and
libido, but testosterone supplementation is only effective in
patients with documented low serum testosterone levels. In
patients with hypogonadism, testosterone replacement is the
initial treatment of choice, as it corrects decreased libido,
fatigue, muscle loss, sleep disturbances, and depressed mood.
Improvements in ED may occur, but they should not be
expected to occur in all patients.23 The initial trial should be
for 3 months. At that time, re-evaluation and the addition of
another ED therapy is warranted. Routes of administration
include oral, intramuscular, topical patches or gel, and a
buccal tablet.
Injectable esters of testosterone offer the most inexpensive
and effective replacement option. Testosterone cypionate and
enanthate have the longest duration of action and are therefore
the preferred agents. There are several drawbacks associated
with parenteral testosterone including the need to administer
deep intramuscular injections every 2 to 4 weeks. In addition,
levels of hormone are well above physiologic values within the
first few days. Concentrations then decline and eventually dip
below physiologic levels just before the next dose. These
extreme changes in concentration lead to mood swings and a
reduced sense of well-being.23
Treatment with topical products is attractive to patients
due to convenience, but they tend to be more expensive than
*
Routes of administration
include oral, intramuscular, topical patches or gel, and a
buccal tablet.
Injectable esters of testosterone offer the most inexpensive
and effective replacement option. Testosterone cypionate and
enanthate have the longest duration of action and are therefore
the preferred agents. There are several drawbacks associated
with parenteral testosterone including the need to administer
deep intramuscular injections every 2 to 4 weeks. In addition,
levels of hormone are well above physiologic values within the
first few days. Concentrations then decline and eventually dip
below physiologic levels just before the next dose. These
extreme changes in concentration lead to mood swings and a
reduced sense of well-being.23
Treatment with topical products is attractive to patients
due to convenience, but they tend to be more expensive than
Testosterone patches and gels are administered
daily and result in serum levels within the physiological range
during the 24-hour dosing period.23 Most patients prefer the
non-scrotal patch or the gel since the scrotal patch requires
shaving of the area, and the patch has a tendency to fall off.
Care must be taken with the use of the gel to wash hands thoroughly
after use and avoid baths or showers within 5 to 6 hours
of application. The most common side effects of topical testosterone
are dermatologic reactions caused by the absorption
enhancers.
Oral testosterone products are also available for supplementation.
Unfortunately, testosterone has poor oral bioavailability
and undergoes extensive first-pass metabolism. Alkylated derivatives
such as methyltestosterone and fluoxymesterone have
been formulated to compensate for these problems, but this
modification makes them considerably more hepatotoxic. This
adverse effect makes oral replacement undesirable and this route
of administration should not be used.
An alternative to the oral route is the buccal mucoadhesive
system. The Striant® buccal system adheres to the inside of the
mouth and the testosterone is absorbed through the oral
mucosa and delivered to the systemic circulation. There is no
first-pass effect, as the liver is bypassed by this route of administration.
Patients apply a 30-mg tablet to the upper gum twice
daily. The cost is similar to that of the patch or gel. Side effects
unique to this dosage form include oral irritation, bitter taste,
and gum edema.
*
General side effects of testosterone include gynecomastia,
dyslipidemia, polycythemia, and acne. Weight gain,
hypertension, edema, and exacerbations of congestive heart
failure also occur due to sodium retention. Before initiating
testosterone, the patient should undergo evaluation for benign
prostatic hypertrophy and prostate cancer. Routine followup
includes yearly prostate-specific antigen, digital rectal exam,
hemoglobin, and liver function in addition to assessment of
response.