Download Clinical Therapeutics Lecture #6 Drugs for Sexual Dysfunction Drug

Clinical Therapeutics Lecture #6 Drugs for Sexual Dysfunction
Drug Induced Erectile Dysfunction
Example
ADR
Diuretic
Decreases libido
Spironolactone
Breast Swelling
Centrally acting
antihypertensives
Example
Tricyclic antidepressants
Impotence
Psychotropic
Decreases libido
Trazadone
ADR
Decreased Libido
Priapism
Impotence
Clonidine
Studied in low doses to create
an erection, You do not want to
go too far, too much, too long
Methyldopa
Prolonged
Painful
Erection
Alpha 1 blockers
Beta blockers
Retrograde
Ejaculation
MAO inhibitors
Decreased Libido
PTZ antipsychotics
Decreased Ejaculation
Impotence
Labetalol
Inhibited
Ejaculation
Decreased Libido
Decreased Libido
Decreased Ejaculation
SSRIs
Anorgasmia
Selective Serotonin Receptor
Also recreational for males to
last longer and for treatmen
of premature ejaculation
Inhibitor
These can be a promlem in
females not achieving
orgasm.
Cimetidine,
Decreased Libido
This is an H2 blocker
Gynecomastica
Some Drugs Create
Awesome Knockers
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Lithium
Impotence
Clinical Therapeutics Lecture #6 Drugs for Sexual Dysfunction
MALES Study
“Men’s Attitudes to Life Events and Sexuality”
MSAM – 7 Study
Multinational Survey of Aging Male
Determined that 16% of men are effected by Erectile Dysfunction
Highest incidence of ED: USA
Lowest incidence of ED: Spain
This study did correlate the incidence of ED with Lower Urinary Tract
Symptoms and BPH independent of
Increased Age
HTN
DM
Ischemic Heart Disease
Hypercholesterolemia
And Depression
It showed that there is increased prevalence of ED with:
Increased Age
HTN
DM
Ischemic Heart Disease
Hypercholesterolemia
Depression
The IPSS or International Prostate Symptom Score proved that there is
an increased correlation between BPH, LUTS and ED
Criticism:
This study did not correlate the incidence of ED with Lower Urinary
Tract Symptoms and Benign Prostaic Hyperplasia
Pathophysiology of ED
MCC: Vascular, a combination between venus and arteriole insufficiency, venoarteriole insufficiency, leads to a cascade of events which reduce blood flow
Venoarteriole insufficiency may also cause Poor trapping of penile blood which would prevent the penis from erecting
Drug Induced ED, drugs may also cause the Vascular Problems
Intra-Penile Nitric oxide level impairment
Hormonal conditions such as Decreased Testosterone Levels or High Prolactin Levels can lead to ED
Neurologic Injuries such as a Pituitary or Hypothalamus tumor causing hypogonadism
Performance Anxiety and Relationship Issues lead to stress and anxiety which lead to a heightened sympathetic tone, Increases Sympathetic Nervous System. The SNS
constricts the arterioles and inbibits vascular relaxation thereby preventing erection. The cure is Viagra and the others.
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Clinical Therapeutics Lecture #6 Drugs for Sexual Dysfunction
Diagnosis of ED
Co-morbid Risk Factors: Increasing Age, HTN, DM, Ischemic Heart Disease, Hypercholesterolemia, Depression, BPH, Lower Urinary Tract Symptoms
Lifestyle Risk Factors: Smoking can decrease Intra-Penile Nitric Oxide Levels, Alcohol Use, illicit drug use, Obesity
Use of Prescription Drugs/Herbs: Refer to Chart
Discuss with Patient: Severity, Nature and Onset of ED, his experience of libido, ejaculation and orgasm, determine any Underlying Psychological and Social Issues
Treatment of ED
Treatment is based on the cause of the ED, the needs of the patient and his partner.
Treatment varies with respect to patient’s age and PMHx and any comorbid conditions and adverse DDI’s.
Must consider psychological and lifestyle issues in all cases.
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Clinical Therapeutics Lecture #6 Drugs for Sexual Dysfunction
Drugs for ED
Class
Example
PDE 5 Inhibitors
Phospho Diesterase
Enzyme 5 Inhibitors
st
1 generation Sildenafil (Viagra)
end in –afil 1st gen
10x more affinity for
PDE 5 than for PDE 6
nd
2 generation Vardebafil (Levitra)
longer duration of 2nd gen
action
end in - afil 15x more affinity for
PDE 5 than for PDE 6
Tadalafil (Cialis)
2nd gen
700x more affinity for
PDE 5 than for PDE 6
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MOA
Indications
ADR
Comments
Regulate smooth muscle tone
11 isoenzymes of PDE (1-11)
All have a role in regulating
smooth muscle tone and
therefore affect many
physiologic processes.
PDE5 causes a decline in
cGMP. cGMP is necessary for
vasodilation and erection.
PDE5 inhibitors increase
cGMP leading to vasodilation
and erection
Contraindicated in:
Concurrent use of nitrates
and alpha-1 blockers
Nitrates vasodilate and
these drugs vasodilate,
together they would cause
profound vasodilation.
Flushing, Headache
Nasal Congestion
Dyspepsia, Dizziness
Transient Hypotension
Cardiac Effects
Back Pain – Mainly Cialis
VISION PROBLEMS –
Mainly VIAGRA – more
affinity to PDE 6 which
alters blood flow to the
retina
Precaution – Underlying CVD
DDi
All are CYP450 substrates
Alcohol
Clinical Therapeutics Lecture #6 Drugs for Sexual Dysfunction
Comparison between Viagra, Levitra and Cialis
**Sexual Stimulation is Required for Response to Treatment** ie: if you take Cialis, you won’t walk around with an erection for 36 hours. Only when sexually stimulated.
All drugs should be taken in anticipation to sex, however, Cialis is approved in a low dose maintenance dose that can be taken once / day
Drug
ContraIndications
Warnings /
Precautions
Onset of
Action
Duration
of Action
Nitrates, alpha-1
blocker
(Except Flomax)
Flomax is a
specific alpha 1
blocker for BPH,
therefore it
won’t have
peripheral
dilation of blood
vessels
Vardenafil Nitrates, alpha-1
(Levitra)
blockers
All alpha-1
blockers
contraindicated
CVD, can cause
Priapism
30 – 60
minutes
4 hours
All 3 drugs cause
Priapism
Prolonged
Painful
Erection
longest
onset of
action
CVD, hepatic
disease, can
cause Priapism
25 – 30
minutes
Tadalafil
(Cialis)
CVD, hepatic
disease, renal
disease, can
cause Priapism
15 – 60
minutes
Sildenafil
(Viagra)
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Nitrates, alpha-1
blocker
(Except Flomax)
see exception
above with
Viagra
shortest
onset of
action
4–5
hours
Up to 36
hours
Longest
duration
of action
Dose
ADR
DDi’s
25, 50 or 100mg
PRN
(MDD = QD)
Once / day
Flushing,
Headache, nasal
congestion,
priapism, vision
problems
CYP3A4 substrate,
therefore if taken w/
a CYP450 Enzyme
Inhibitor, they will
cause increased
erection, increased
vasodilation, lower
blood pressure
5, 51 or 20mg
PRN
(MDD = QD)
Once / day
Flushing,
Headache, nasal
congestion,
priapism
5, 51 or 20mg
PRN
(MDD = QD) or
2.5 – 5.0mg QD
this is the low
dose
maintenance
dose
Flushing,
Headache, nasal
congestion,
priapism, back
pain
Nitrates – cause
vasodilation
HTN drugs such as
Beta blockers,
calcium channel
blockers, all reduce
blood pressure
alcohol
Meals
Take with or
without
Advantages
Most clinical
trials
Most clinical
experience
Take with or
Quicker
without but
onset than
absorption may Viagra
be reduced
with high fat
meals
Take with or
without
Longest
Duration of
Action
Clinical Therapeutics Lecture #6 Drugs for Sexual Dysfunction
Hormonal Therapy
Testosterone replacement therapy is used to treat ED due to Hypogonadism, where Testosterone is low or where Prolactin is Increased.
Testosterone enanthate or cypionate IM injection every 2 to 3 weeks
Testosterone Scrotal Patches (Testoderm) QD in the am, the Scrotal Patch has the best absorption
Testosterone Non-Scrotal Patch (Androderm), QD in the pm, can be on the back, abdomen, upper arm, absorption is not so good, but location is preferred
Testosterone Gel (Androgel), QD in the am, Do not apply to genitals.
Clominphene (Clomid) – stimulates gonadotropin release
Dopamine agonists – decrease Prolactin production: Bromocriptine
Dopamine Receptor Agonist – Apomorphine (Spontane): in phase 3 trials, MOA: D1 & D2 receptor agonist, Penile Erection may be induced by stimulation of D1 & D2
receptors, Sub Lingual route of administration preferred, ADR: tolerance, nausea, syncope
Intercavernosal Agents
Drugs injected directly into the corpus cavernosum of the penis, these drugs were used prior to Viagra
Alprostadil: Was the Agent of Choice prior to Viagra; MOA: causes vasodilation directly at the vascular and ductus arteriosus smooth muscle smooth muscle
Available as: (Caverject) – injection or (Muse) – intraurethral pellet or (Alprox) – topical crème
ADR: penile pain, urethral burning, testicular pain, and in the female: vaginal burning and itching
Other agents include: Papaverine and Phentoloamine
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Clinical Therapeutics Lecture #6 Drugs for Sexual Dysfunction
Non-Intercavernosal Agents
Organic Nitrates: (topical) – Vasodilator, Nitroglycerine ointment, can pass onto female partner, Headaches in both male and female
Forskolin (plant derivative) Vasodilator
Yohimbine: (topical or oral) Natural Alpha-2 blocker
Trazadone (oral) Anti-depressant, Has a Side Effect of Priapism
Pomegranite Juice: small study showed efficacy
Non-Pharmacological Treatment
Less Side Effect Profile, Safe, Effective, May cause some scarring
Vacuum devices, Erectaid, Catalyst, VED pump, Cylinders that when pumped cause a vacuum, causes blood to flow to penis
Venous Flow Controllers: Vacuumless, they trap blood in the penis, silicone rubber ring or tube: (Actis): Not to be used longer than 30 minutes. Contraindicated in
patients w/ underlying bleeding conditions or patients on anticoagulants
Penile Implants: Hydraulic implant w/in penis: Limitations, irreversible, permanent damage of erectile tissue. Complications: Infection
Vascular Surgery, Revascularization, Venous Ligation
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Clinical Therapeutics Lecture #6 Drugs for Sexual Dysfunction
Female Sexual Dysfunction
Hypoactive Sexual Desire Disorder –Sexual Anhedonia, Decreased or absent pleasure in sex activity, Caused by depression or drugs
Sexual Arousal Disorder - Persistent or recurrent inability to attain or maintain the lubrication – swelling response of sexual excitement until completion of sexual
activity. Causes: Psychological behavioural: lack of knowledge, anxiety, fear of intimacy, or Physical Causes: Endometriosis, hypothyroidism, MD, Drugs, Hysterectomy,
Increased age: menopause, a woman should be able to achieve orgasm thru age 60.
Female Orgasmic Disorder – Persistent of recurrent delay or absence of orgasm after a normal excitement phase of sexual activity that is assessed as adequaett in focus
intensity and duration, Causes: Similar to Sexual Arousal Disorder, SSRI’s Selective Serotonin Receptor Inhibitors – proven to prevent orgasm in females.
Dyspareunia – Painful coitus or interrupted coitus
Vaginismus – A conditioned involuntary contraction (spasm) of the lower vaginal muscles resulting from a woman’s unconscious desire to prevent penetration. Causes: a
learned response, fear of pregnancy, being controlled by a man, rape, abuse
Treatment of Female Sexual Dysfunction
PDE 5 Inhibitors – Viagra and others
Herbal products: Avlimil, Zestra arousal oil, Sensua
EROS Therapy Device – Handheld medical device, Increases blood flow to clitoris and external genitalia
Estrogen – Oral, Injectable and topical. Useful in post menopausal women or in female hypogonadism
Testosterone – Investigational for female sexual dysfunction, Injectable or topical, Avoid oral formas due to high incidence of liver toxicity
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