Phosphodiesterase type congestion

Long-term treatment with inhibitors of phosphodiesterase type III is associated with increased mortality in congestive heart failure (SEDA-17, 217). 

Pimobendan is an inhibitor of phosphodiesterase type III with calcium sensitizing properties in the myocardium. It has been associated with a worrisome albeit non-significant increase in mortality in patients with chronic congestive heart failure (1). 

Katz SD. Potential role of type 5 phosphodiesterase inhibition in the treatment of congestive heart failure. Congest Heart Fail 2003 9 9-1 5. 

Some PHOSPHODIESTERASE INHIBITORS (e.g. cnoximone and milrinone) are valuable, and some exert most of their effect on the myocardium (those acting at a heart-specific subtype of this enzyme (type III phosphodiesterase) to raise the intracellular concentration of cAMP) and may be used as positive INOTROPIC AGENTS in the short-term treatment of severe congestive heart failure. 

Inhibitors of a heart-specific subtype (type III) phosphodiesterase, which are positive inotropics, may be used in the short-term treatment of severe congestive cardiac failure, e.g. amrinone, enoximone and milrinone. However, developments of oral formulations of drugs of this type have been halted by the results of the PROMISE trial (Prospective Randomised Milrinone Survival Evaluation trial) which documented a paradoxical increase in mortality in class IV heart failure patients randomised to receive milrinone. However, some benzimidazole derivatives with class III phosphodiesterase inhibitor actions seem to be beneficial in heart failure. The agent vesnarinone is an orally active compound that may act as a class III phosphodiesterase inhibitor but appears to be a vasodilator with multiple mechanisms. See HEART FAUURE TREATMENT INOTROPIC AGENTS. 

Most adverse effects of the phosphodiesterase inhibitors are nfild or moderate and self-limited, rarely reqniring treatment discontinuation. In usual doses the most common adverse effects are headache, facial flushing, dyspepsia, nasal congestion, and dizziness, all of which result from inhibition of phosphodiesterase isoenzyme type 5 in extragenital tissues. ... 

---