Phosphodiesterase 5 inhibitors cause:
NO is released either at non-adrenergic non-cholinergic nerve terminals (nitrergic) on the cavernous smooth muscle cell or on the endothelial cell lining of the sinusoids. Through membrane-bound G proteins, NO activates guanylate cyclase, which induces cleavage of guanosine triphosphate to 3′,5′-cyclic guanosine monophosphate (3′,5′-cGMP). The smooth muscle-relaxing effects of NO are mediated by this second messenger (cGMP). Cyclic GMP activates protein kinase G, which phosphorylates proteins at the so-called maxi-potassium channels. This results in an outflow of potassium ions into the extracellular space with subsequent hyperpolarisation, with inhibition of voltage-dependent calcium channels and therefore a decrease in intracellular calcium ion concentrations. The intracellular decline in calcium ions suppresses the activity of myosin light chain kinase and thus increases the intracellular content of dephosphorylated myosin light chain, which enables the smooth muscle cell to relax. The enzyme phosphodiesterase type 5 inactivates cGMP and thereby reduces relaxation. By inhibiting this enzyme, PDE5 inhibitors promote smooth muscle relaxation in the corpus cavernosum by increasing the cGMP concentration.
Regarding Balanitis xerotica obliterans (lichen sclerosus et atrophicus):
Extra genital disease can occur, though in contrast to women, perianal disease is uncommon in men; 28% patients with penile carcinoma have histological changes of lichen sclerosis. The condition occurs in all ages.
Regarding alprostadil pharmacotherapy in ED:
Prostaglandin E1 causes direct relaxation of cavernosal smooth muscle and antagonises the action of norepinephrine. These dual effects may explain its efficacy in inducing erections. The Alprostadil Study Group reported a 2% incidence of penile fibrosis. Pain is the major problem associated with alprostadil injection, with an incidence of 16% to 40% and a clear dose dependency. Alprostadil has a higher rate of penile pain compared to papaverine. Prolonged erection occurred in 5% of the men in the Alprostadil Study Group.
Which of the following is NOT a risk of intracavernosal injection of vasoactive agents?
Intracavernosal injection of vasoactive agents carries the risk of fibrosis, penile pain, prolonged erection, priapism and hematoma at the injection site. Fibrosis of the corpus cavernosum is a particular concern with papaverine.
Which answer is CORRECT regarding ED and diabetes mellitus?
In diabetics, the incidence of ED is estimated to range from 35% to 50%. The cause of ED in diabetes mellitus is multifactorial. Anejaculation and retrograde ejaculation can occur in diabetic patients due to autonomic neuropathy.
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