Canadian Medical News

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.