Lecture 9 - ACE inhibitors Flashcards
What does renin do?
It cleaves angiotensinogen to angiotensin I. This means that angiotensin I is able to convert to angiotensin II via ACE, angiotensin II has many effects.
Why is renin released?
- Loss of blood volume.
- Decrease in blood pressure (haemorrhage or dehydration) - baroreceptors see this in the carotid sinus.
- Decrease in NaCl concentration - this will stimulate the macula densa to signal the JGA cells.
What does angiotensin II do to arterioles?
Vasoconstriction occurs where there is arteriolar constriction, the blood flow is constricted and there is an increase in vascular resistance, this increases blood pressure.
What does angiotensin II do to glomerular arterioles?
It causes an increase in calcium intracellularly on the smooth muscle of efferent arteriole causing vasoconstriction. This causes an increase in glomerular hydrostatic pressure (back flow of blood to the renal corpuscle) which causes an increase in GFR to normal levels.
What does angiotensin II do in terms of aldosterone?
It causes aldosterone to be released by binding to the adrenal cortex. Aldosterone binds to the mineralocorticoid receptors on DCT and Collecting Ducts (kidneys) causing them to increase the amount of ENaC channels. This increases the reabsorption of Na (sodium) and consequently water, it also causes potassium to be excreted. Which increases the blood volume and blood pressure.
What does angiotensin II do in terms of ADH?
It causes ADH to be released from the post.pituitary so that it can bind to the collecting ducts in the kidneys causing aquaporin 2 channels to be inserted on the collecting duct membranes. This causes an increase in water reabsorption. This causes an increase in blood pressure/blood volume.
What does angiotensin II do in terms of atrial natriuretic peptide (ANP)?
If there are high levels of angiotensin II it will cause ANP to be released (this typically due to an increase in blood pressure and volume caused by angiotensin II). ANP will cause dilation of the afferent arteriole, this will cause an increase in glomerular hydrostatic pressure which increases GFR. Therefore there will be a decrease in renin released and eventually decrease in angiotensin II and its effects, thus decrease in water reabsorbed.
What happens if there is continual high angiotensin II levels?
- Hypertension.
- Involved in congestive heart failure progression.
- Adverse cardiovascular effects - cardiac hypertrophy, atherosclerosis, plaque rupture, pro-inflammation.
List the ACE inhibitor drugs?
- Cilazapril.
- Catopril.
- Enalapril.
- Lisinopril.
- Ramipril.
What is the mechanism of action of ACE inhibitors?
It binds to ACE, stopping ACE from converting angiotensin I to angiotensin II. Thus, stopping all the angiotensin II effects e.g. increase in blood pressure.
What are ACE inhibitors used for?
- Hypertension - ACEi are first line therapy and synergistic with diuretics.
- Congestive cardiac failure - part of multiple treatments.
What is cilazapril used for?
- Hypertension.
2. Heart failure.
Why do patients not take cilazapril?
They do not take it if they have the following:
- Hypersensitive to ACEi (can get angioedema).
- Pregnant.
- On diuretics.
- Renal impairment (GFR <10).
- Aortic stenosis.
- Collagen vascular disease.
- Atherosclerosis.
- On drugs that increase potassium serum conc.
- On concomitant NSAIDs.
What are the adverse effects of cilazapril?
- Nausea.
- Vomiting.
- Diarrhoea.
- Hypotension (decrease in BP).
- Dry cough.
- Headache.
- Fatigue.
- Hyperkalaemia.
- Angina.
- Tachycardia.
- Angioedema.
- Flushing.
- SOB - dyspnoea.
- Fever.
- Impotence.
List the angiotensin II antagonists (ARBs)?
- Candesartan.
- Losartan.
- Valsartan.
- Irbesartan.
- Eprosartan.
