Pathways

Perindopril is angiotensin-converting enzyme (ACE) inhibitor for the conversion of angiotensin I into angiotensin II. Angiotensin II is a critical circulating peptide hormone that has powerful vasoconstrictive effects and increases blood pressure. Perindopril is used to treat hypertension, high blood pressure, congestive heart failure, and chronic renal failure as it decreases blood pressure. Perindopril is converted into perindoprilat through the liver after being ingested which travels in the blood to inhibit ACE which is from the lungs. Angiotensin has many vasoconstrictive effects by binding to angiotensin II type 1 receptor (AT1) in blood vessels, kidneys, hypothalamus, and posterior pituitary. In blood vessels, AT1 receptors cause vasoconstriction in the tunica media layer of smooth muscle surrounding blood vessels increasing blood pressure. Less angiotensin II that is circulating lowers the constriction of these blood vessels. AT1 receptors in the kidney are responsible for the production of aldosterone which increases salt and water retention which increases blood volume. Less angiotensin II reduces aldosterone production allowing water retention to not increase. AT1 receptors in the hypothalamus are on astrocytes which inhibit the excitatory amino acid transporter 3 from up-taking glutamate back into astrocytes. Glutamate is responsible for the activation of NMDA receptors on paraventricular nucleus neurons (PVN neurons) that lead to thirst sensation. Since angiotensin II levels are lowered, the inhibition of the uptake transporter is not limited decreasing the amount of glutamate activating NMDA on PVN neurons that make the individual crave drinking less. This lowers the blood volume as well. Lastly, the AT1 receptors on posterior pituitary gland are responsible for the release of vasopressin. Vasopressin is an anti-diuretic hormone that cases water reabsorption in the kidney as well as causing smooth muscle contraction in blood vessels increasing blood pressure. Less angiotensin II activating vasopressin release inhibits blood pressure from increasing. Overall, Perindopril inhibits the conversion of angiotensin I into angiotensin II, a powerful vasoconstrictor and mediator of high blood pressure so decreasing levels of angiotensin will help reduce blood pressure from climbing in individuals.

Benazepril, brand name Lotensin, belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors and is used primarily to lower high blood pressure (hypertension). This drug can also be used in the treatment of congestive heart failure and type II diabetes. Benazepril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form benazeprilat via cleavage of its ester group by the liver. Angiotensin-converting enzyme (ACE) is a component of the body's renin–angiotensin–aldosterone system (RAAS) and cleaves inactive angiotensin I into the active vasoconstrictor angiotensin II. ACE (or kininase II) also degrades the potent vasodilator bradykinin. Consequently, ACE inhibitors decrease angiotensin II concentrations and increase bradykinin concentrations resulting in blood vessel dilation and thereby lowering blood pressure.

Perphenazine is a piperazinyl phenothiazine first generation antipsychotic that acts on the central nervous system, and has a greater behavioral potency than other phenothiazine derivatives whose side chains do not contain a piperazine moiety. Binds to the dopamine D1 and dopamine D2 receptors and inhibits their activity. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone and vomiting centre. Perphenazine also binds the alpha adrenergic receptor. This receptor's action is mediated by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.