Lecture 3 Flashcards
What is the SNS for?
Fight or Flight. The blood flow goes to your heart, skeletal muscles, brain and the lungs. It increases activity of cardiovascular system (Increase in CO, rate and force of contraction of heart, increase in BP).
How does RAAS (renin-angiotensin-aldosterone system) work synergistically with SNS?
Alters the vascular tone (contraction of smooth muscles around blood vessels). Control natriuresis (excretion of sodium in the urine - increase blood volume in a smaller area).
What are the main components of RAAS?
R - Renin. It is a proteolytic enzyme produced in the kidney and released in response to SNS. Noradrenaline is released in the kidneys, binds on to Beta-1 adrenoreceptors in the juxtaglomerular cells - promotes release of rein. Renin then converts angiotensinogen to angiotensin 1, via cleaving off amino acids.
A - Angiotensin1. Angiotensin 1 has little natural activity, but is converted into angiotensin 2. It is a potent vasoconstrictor.
Describe smooth muscle contraction in terms of angiotensin?
Agonists act on different receptors (GPCR). There is an increase in calcium levels intracellular.
Describe RAAS in overview/summary?
Renal SNA and beta-agonists. Drop in renal percussion pressure will activate RAAS (tell the body to retain fluid). Once angiotensin 2 binds to AT1 receptors. There is vascular growth (hyperplasia and hypertrophy), there is vasoconstriction (this is through directly and indirectly) and there is salt retention (aldosterone secretion and tubular sodium reabsorption).
Describe angiotensin 3 and 4?
Cleave off one amino acid and 2 becomes 3, cleave off 2 and it becomes 4. 3 will promote aldosterone secretion (sodium reabsorption, thirst). 4 will bind to it’s own distinct receptor to cause effects, including inhibition of clot clearance.
Describe aldosterone?
Released int response to variety factors (angiotensin 2 and 3 and elevates protein levels). The receptors in the collecting tubule’s in the kidney’s, once bound to will increase apical sodium channels and basolateral Na+/K+ transporters. Promote reabsorption of sodium from the urine, thus resorbing water as well.
Identify drug targets in RAAS?
ACE - cause a breakdown in the system, preventing the production of Angiotensin 2.
Beta Antagonists - prevent the release of Renin.
Describe ACE Inhibitors (ACE-I)?
Inhibits the conversion of angiotensin 1 to 2. It is a competitive inhibitor of ACE e.g. cilazipril.
Describe the dual effect of ACE-Is?
Because ACE (kininase 2) is involved in the breakdown of bradykinin, a ACE-I will increase bradykinin level. The adverse effects of this is:
1) Dry Cough.
2) Angioedema.
Describe ACE-I induced angioedema?
Increased levels of bradykinin will cause vasodilation, increased vascular permeability and sensitisation of pain. Angioedma is swelling of: lips, larynx and pharynx. This will block the airways. To stop this effect, stop giving the drug OR can give drug to inhibit the effects of bradykinin.
Describe angiotensin receptor antagonists/blockers (ARBs)?
These are competitive antagonists at AT-1 receptors. They block angiotensin 2 from binding to the receptor. Don’t get vascular growth, vasoconstriction or salt retention.
What is a better inhibitor for RAAS?
Generally ACE-I are more effective, however more likely to display adverse effects. Often start on ACE-I, then ARB can be used as a substitute. Or you can use both which is dangerous (high levels of potassium in the blood or damage the kidneys).
Describe aldosterone antagonists?
Blocks the mineralocorticoid receptor and will inhibit Aldosterone from binding, thus stopping sodium reabsorption.
Describe calcium channel blockers?
Main action is to decrease contractility of the muscle. They do this by blocking the calcium channel, so decreasing the calcium concentration. This will cause the relaxation of the blood vessel, which will cause an increase in diameter, which will cause a decrease in blood pressure.
