Control of Erection and Male
Sexual Function It is necessary to establish a basic understanding of normal sexual function prior to the discussion of potential mechanisms for drug-induced pathology.
Normal male sexual function requires
(1) an intact libido,
(2) the ability to achieve and maintain penile erection,
(3) ejaculation, and
(4) detumes- cence.
The major anatomic structures of the penis that are involved in erectile function include the paired corpora cavernosa and the single corpus spongiosum that encloses the urethra. The tunica albuginea, a collagenous sheath, individually sur- rounds each corpus. The microarchitecture of the corpora is composed of a mass of smooth muscle which contains a network of endothelial-lined lacunar spaces. Penile tumescence leading to erection depends on the increased flow of blood into the lacunar network after complete relaxation of the arteries and corporal smooth muscle. Subse quent compression of the trabecular smooth muscle against the fibroelastic tunica albuginea causes a passive closure of the emissary veins and accu- mulation of blood in the corpora. In the presence of a full erection and a competent valve mechanism, the corpora become noncompressible cylin- ders from which blood cannot escape. The central nervous system exerts an important influence by either stimulating or antagoniz- ing spinal pathways that mediate erectile function and ejaculation. These interactions are mediated by a combination of central and peripheral innervation. Canadian pharmacy viagra – cheap ed medications online.
Sensory nerves that originate from receptors in the penile skin and glans converge to form the dorsal nerve of the penis, which travels to the S2S4 dorsal root ganglia via the pudendal nerve. Parasympathetic nerve fibers to the penis arise from neurons in the intermediolateral columns of S2S4 sacral spinal segments. Sympa thetic innervation originates from the T-11 to the L-2 spinal segments and descends through the hypogastric plexus. Neural input to smooth mus- cle tone is crucial to the initiation and maint nance of an erection. There is also an intricate interaction between the corporal smooth muscle cell and its overlying endothelial cell lining. Nitric oxide, which induces vascular relax- ation, promotes erection and is opposed by endothelin1 (ET1), which mediates vascular contraction. Nitric oxide is synthesized from larginine by nitric oxide synthase (NOS), and is released from the nonadrenergic, noncho- linergic (NANC) autonomic nerve supply to act postjunctionally on smooth muscle cells. Nitric oxide increases the production of cyclic 3¢,5¢guanosine monophosphate (cyclic GMP), which interacts with protein kinase G and decreases intracellular calcium, causing relax- ation of the smooth muscle. Cyclic GMP is grad- ually broken down by phosphodiesterase type 5 (PDE5). Inhibitors of PDE5, such as the oral medication sildenafil, maintain erections by reducing the breakdown of cyclic GMP.
However, if nitric oxide is not produced at a basal level, the addition of PDE5 inhibitor is not effective, as the drug facilitates but does not initiate the initial enzyme cascade. In addition to nitric oxide, vasoactive prostaglandins (PGE1 , PGF2a) are synthesized within the cavernosal tissue and increase cyclic AMP levels, also leading to the relaxation of cavernosal smooth muscle cells. Ejaculation is stimulated by the sympathetic nervous system, which results in contraction of the epididymis, vas deferens, seminal vesicles, and prostate, causing seminal fluid to enter the urethra. Seminal fluid emission is followed by rhythmic contractions of the bulbocavernosus and ischiocavernosus muscles, leading to ejacu- lation. Detumescence is mediated by norepinephrine released from the sympathetic nerves, the release of ET1 from the vascular surface, and contraction of smooth muscle induced by the activation of postsynaptic a-adrenergic receptors. These events increase venous out- flow and restore the flaccid state. Venous leak can cause premature detumescence and is thought to be caused by insufficient relaxation of the corporal smooth muscle.
Erectile dysfunction (ED) may result from three basic mechanisms:
(1) failure to initiate (psychogenic, endocrinologic, or neurogenic);
(2) failure to fill (arteriogenic); or
(3) failure to store (venoocclusive dysfunction) adequate blood volume within the lacunar network.
The inability to initiate an erection may have psychogenic, vasculogenic, endocrinologic, or neuro- genic etiologies. These categories are not mutually exclusive, and multiple factors contribute to ED in many patients. ED has also beencommonly associated with prescription and non- prescription medications. The remainder of this chapter focuses on the literature and the hypoth- esized mechanisms of dysfunction surrounding this relatively common clinical entity is contributing to the sexual addition, physicians should tion to the presence of othe (i.e., the patient’s psychosoc exist outside of the disease drug in question. The final s addresses management strat ment of druginduced ED.