PM 719 Pharmacology II Lecture Notes (LN) - Vasoactive Peptides PDF

**PM 719 Pharmacology II Lecture Notes (LN)** Chap 17 Vasoactive Peptides Peptides are small proteins. They can range from a few hundred amino acids down to five amino acids or less. This chapter will cover the bioactive peptides which have clinical importance. **Angiotensin-Renin System** Cov...

**PM 719 Pharmacology II Lecture Notes (LN)** Chap 17 Vasoactive Peptides Peptides are small proteins. They can range from a few hundred amino acids down to five amino acids or less. This chapter will cover the bioactive peptides which have clinical importance. **Angiotensin-Renin System** Covered in previous chapters many times already but very important, worth repeating. (Did I say important?) Renin: released into circulation by the kidney in response to lowered blood pressure. Many drugs used to lower blood pressure cause release of renin also. Angiotensinogen from the liver is cleaved to the smaller Angiotensin I peptide by the Angiotensin I is cleaved into smaller Angiotensin II (or Angio II) by the enzyme found in endothelial cells named angiotensin converting enzyme (ACE). Angiotensin Converting Enzyme (ACE): converts Angio I into Angio II, a potent vasoconstrictor, more potent than epinephrine. **Angiotensin II** Directly contracts vascular smooth muscle to increase blood pressure (BP) Also stimulates release of NE which causes vasoconstriction and elevation of BP Angio II stimulates the adrenal medulla to release aldosterone which causes sodium and water retention, increased blood volume and increased BP Angio II receptors are G-protein coupled receptors on cell surfaces of a wide variety of cells Angio II binds to Angio II receptors on vascular smooth muscle and causes vaso- constriction, increase in BP **Renin Inhibitor Drugs:** beta blockers (**propranolol**) inhibit the release of renin from the kidney **aliskerin** the drug is a direct inhibitor of renin **ACE Inhibitors:** Inhibit the conversion of Angio I to Angio II **Captopril** and **enalapril**, all end in "pril", covered in previous chapters. Never use in pregnancy, all may cause a serious cough, change to another class of drugs. **Angiotensin Receptor Blockers:** **Losartan**, **valsartan**, all end in "sartan." Covered in previous chapters. Never use in pregnancy, cough incidence still possible but lower frequency compared to ACE Inhibitors Drugs are competitive antagonists at Angio II receptors, block actions and prevent vasoconstriction **Renin Inhibitor:** **Aliskiren,** inhibits the enzyme renin and lowers the production of Angio II Never use in pregnancy, used to control BP in any hypertensive patient. **Kinins** Potent vasodilator peptides. Kallikreins: enzymes found in the blood and in tissues that form kininogen substrate Kininogen: the substrate that kallikrein converts into kinins, substrate found in plasma and other body fluids the two major kinins in humans are **bradykinin and kallidin** **Kallidin & Bradykinin** formed in the plasma or tissues half-life is \< 15 seconds both produce marked vasodilation in a wide variety of vascular beds arterial smooth muscle is dilated, veins are contracted Kinin receptors are G-protein coupled receptors found on a wide range of tissues Bradykinin can produce the four classic symptoms of inflammation, redness, local heat, swelling, and pain kallikrelin enzyme kininogen kinin peptides (bradykinin and kallidin) found in plasma and tissues kinin in cardiovascular system causes vasodilation and a drop in BP kinin also causes inflammation (redness, local heat, swelling, pain) **Icatibant** bradykinin receptor antagonist, must be given sc **Vasopressin (antidiuretic hormone, ADH)** acts on the kidney to reabsorb water, increase blood volume, increase BP **tolvaptan** and **conivaptin** covered in another chapter (see Diuretics Chapter 15) **Natriuretic Peptides** how the body lowers BP (one of the major ways) atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) produced in a variety of tissues ANP increases urine output and increases sodium excretion ANP also inhibits release of renin and aldosterone ANP agonist = **carperitide** BNP agonist = **nesiritide** both are a recombinant forms of the natural peptide both produce vasodilation, natriuresis, inhibition of renin-angiotensin system The remaining items in this chapter are of interest but have limited clinical application. Only the most important or widely used items are covered. The Required Drugs Are in **Bold along with all drugs listed in this Lecture Note above:** Kinin Inhibitor **icatibant** blocks the action of kinin which induces pain and inflammation and angioedema Vasopressin Agonist **vasopressin** induces vasoconstriction in shock Antagonist **conivaptan** vasodilation in hypertension Natriuretic Peptides **nesiritide** vasodilation, water loss Drugs required but covered in previous chapters: Angiotensin-Converting enzyme Inhibitor drugs (**ACE Inhibitors**) ("pril" drugs) Angiotensin Receptor Blockers (**the receptor blockers**) ("sartan" drugs) Renin Inhibitor (only one **aliskieren**) (Kirin beer?)