Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Smooth muscle antispasmodic, including for the gastrointestinal and urogenital system.
ATC code: A03AD01.

Papaverine is a direct-acting and non-specific smooth muscle relaxant causing an effect on the blood vessels (vasodilator action) and other smooth muscle systems. Papaverine can also depress conduction in the heart muscle and prolong the diastolic period.
The cerebral blood flow is increased in most cases, and this effect has a short duration. The peripheral vasodilator effect is of variable intensity and probably depends on the development stage of artery and arteriole wall sclerosis, and therefore is probably inversely proportional to the severity of the vascular pathology. Papaverine is effective in the symptomatic treatment or prevention of spasms.
Papaverine blocks, to a certain extent, the flow of Ca++ ions across the cell membrane, which explains the anti-tachyarrhythmic activity. The intensity of this blockage may vary from one vascular site to another as well as from one individual to another.
It is clear that the wide range of pharmacological activities makes papaverine useful in a great variety of vessel and/or visceral conditions. The effect is evident in most cases, with a short duration, and non-curative.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
After injection, papaverine hydrochloride is rapidly distributed in the organism.
The half-life time is 90-130 minutes and the apparent volume of distribution is 0.99-1.52 L/kg.
The substance is highly bound to plasma proteins (87%). After intravenous administration of a 1 mg/kg dose, a blood level of 1 mg/L is reached in 5 minutes.

Metabolism
Ninety percent of papaverine hydrochloride is metabolized in the liver in a few hours. The initial step of metabolism is demethylation to 6-hydroxypapaverine or 4-hydroxypapaverine and, in turn, their phenolic group is affected by the glucurono- or sulfoconjugation. It should be noted that 4-hydroxypapaverine also has a clinically significant phosphodiesterase inhibitory activity.

Elimination
Elimination is carried out by the renal route as unmetabolized papaverine (less than 1% is found unchanged in the urine) and as metabolites (more than 50%). The rest is eliminated by the bile.