Lecture 27: Pharmacologic Approaches to the Treatment of Sexual Dysfunction Flashcards
What are the types of disturbances in male sexual function?
- loss of libidio
- Impotence
- Ejaculatory failure
All three present at same time
What is the neural control of male sexual function?
Derives in the forebrain limbic system
To generate sexual drive
That in turn is chronically stimulated by the effects of circulating androgens
What are the characteristics of impotence?
Failure to attain an erection of sufficient strength to carry out sexual intercourse
25% of the time
Occurs to 50% of population over 50yo
What are the neuronal networks required for normal erectile function?
- Central (limbic system): initiating events involve combination of tactile, visual, auditory and imaginitve stimuli
-increase in parasympathetic outflow
AND
-inhibition of sympathetic outflow - Local parasympathetic arc
-local tactile stimuli
-penis-spinal cord-penis
Masturbation = visual/imaginary stimuli + tactile stimuli (hand lmaooo)
What is the sequence of events for normal erectile function?
- Stimulation, arousal
- relaxation of helicine arteries in corpora cavernosa
-increase blood flow - relaxation of smooth muscle of trabeculae of corpus cavernosa
Increase blood flow - venous drainage is impeded as a result of compression of engorged corpora cavernosa to maintain erection
- sacral efferents are responsible for ejaculation
What is the bulbocavernosus reflex test?
Stroking the posterior shaft of the penis to elicit an erectile response LOL
What is the cellular mechanism of erectile response?
- The changes in blood flow are mediated by release of NO from post synaptic parasympathetic neurons and endothelial cell
- The readily diffusible NO stimulates guanylate cyclase in the trabecular and arterial smooth muscle cells increasing their content of cyclic GMP which in turn relaxes the cells
What is the significance of guanylate cyclase stimulation by NO?
Guanylate cyclase stimulation increases cyclic GMP which relaxes the cell and leads to erection
What are drugs that lead to impotence?
- alcohol, nicotine, narcotics, stimulants
- androgens
- antihypertensives
- anticholinergic
- antihistamines
- disulfuram
- SSRIs
- Estrogens
What are common causes of impotence?
- Prostatectomy
- Diabetes, hypothyroidism
- Vascular disease (CVD stroke)
- Chemotherapy and radiotherapy
- neurological disease (MS) and trauma
- Liver + renal failure
What is NPT testing?
Nocturnal penile tumescence testing
Put electrode on dick while they sleep…because average erections in sleep is 16 lmaooo
What is Tumescensce?
Quality or state of being tumescent or SWOLLEN
How do you test if ED is caused by vascular problems?
Intracorporeal injection of vasodilators can be used to evaluate if erectile dysfunction has a vascular cause…
What is significance of cyclic GMP in erectile response?
Cyclic GMP allows cells to relax and for blood to fill
What does diabetes lead to?
Diabetes leads to KNIVES Kidney Nerves Infection Vascular Eyes Skin
How do you treat impotence?
- counseling if psychogenic
- surgery if local genital abnormality
- adjust drug regimen – if drug inducd
- testosterone
- vacuum device (penis pump lmaoo)
- surgical therapy with penile implants
- vasodilators
- papaverine
- PGE1 analog
- alprostadil
- oral PDE 5 inhibitors
What breaks down cyclic GMP?
Phosphodiesterase (PDE) 5
What is the significance of phosphodiesterase (PDE) 5?
This breaks down cyclic GMP
More phosphodiesterase, the less erectile ability
So ED drugs inhibit phosphodiesterase
So how do we keep cyclic GMP high penile tissue to promote erection?
Give Phosphodiesterase inhibitors
What are the pharmacokinetics of phosphodiesterase inhibitors in people with hepatic disease?
You get 100% increase of PDE inhibitor in blood because liver is where it is broken down
What are phosphodiesterase inhibitors?
- Sildenafil (Viagra)
- Vardenafil (Levitra)
- Tadalafil (Cialis)
Work by MAINTAINING vasodilatory response
You need to initiate boner
What are drugs that are contraindicated with phosphodiesterase inhibitors?
- Macrolide antibiotics (erythromycin, clarithromycin)
- Antifungal agents (ketoconazole, itraconazole)
- Protease inhibitors (indinavir, ritonavir)
- Cimetidine (Tagamet)
What is priapism?
When erect patients does not return to flaccid state
Common in people who use phosphodieseterase inhibitors
What is the pharmacodynamics of phosphodiesterase inhibitors?
- Vasodilation
- can be used for cystic fibrosis and BPH potentially
Lack of specificity of effect
-sperm motility
-esophogeal motility
-change in color vision in retina
What populations use Viagra?
Cardiovascular disease
Diabetics
Elderly
What is a common contraindication?
Nitrates for chest pain + Viagra
Nitrates also vasodilate and can lead to hypotension and MI
What are the adverse effects of viagara?
- Vasodilation
- headache
- flushing
- rhinitis
- Cardiovascular
- hypotension and tachycardia
- platelet inhibition
- Gastrointestinal
- dyspepsia due to relaxation of lower esophageal sphincter (LOS) pressure
- Visual abnormalities
- blue green color tinged vision, increased light perception and blurred vision
- rhodopsin is broken down by PDE
- sildenafila nd vardenafil are weak inhibitors of PDE6
- not seen with tadalafil
What are caveats for PDE5 inhibitor efficacy?
- initial stimulatory response is necessary for clinical response to be seen
- PDE 5 inhibitors inhibit cGMP catabolism and thereby maintain the erectile response
What are the characteristics of female sexual dysfunction?
- historically treated by psychiatrists and sex therapists
- increasingly addressed by urologists, gynecologists and internists
-recognized as a medical condition
-increasing number of associated medical conditions
-diminished pelvic and vaginal blood flow
-trauma-related aversion to sex - Focus on medical, cultural and relational reasons
-dysfunction and dissatisfaction
IN ADDITION
Female sexual dysfunction is classified by APA as a mental disorder
-loss of sexual drive or arousal
-discomfort during intercourse (pain)
-inability to achieve orgasm (anorgasmia)
What are causes of female dysfunction?
- alcohol
- anxiety
- depression
- stress
- inadequate stimulation
- trauma
- drug
What treatment is available to female sexual dysfunction?
- educational
- behavioral and sex therapy
- anatomy arousal and response
- Hormone replacement therapy
- estrogen and sometimes testosterone
- Vascular treatment
- PDE5 inhibitors (SSRI induced dysfunction)
- Eros therapy (handheld device to increase clit blood flow)
- L-arginine topical treatment (Viagel, sensual)
- substrate for NO synthesis
- underevaluation
