Lecture 20 - Control Of Blood Pressure : Pharmacology And The Role Of The Kidney Flashcards
What is the cause of 90% of hypertension cases
It is unknown
If the cause of hypertension is unknown what type of hypertension is it
Primary/essential hypertension
Hypertension that can be traced to a known condition is usually associated with
Renal disease or endocrine disturbances
Hypertension that can be traced to a condition is known as what type of hypertension
Secondary hypertension
What are the consequences of chronic hypertension
Abnormal thickening of the left wall of the ventricle and narrowing of the lumen in resistance vessels
What is chronic hypertension a risk factor for
Heart failure, stroke, renal failure and myocardial infarction
How can hypertension be managed
Through lifestyle modification
What lifestyle modifications can be made to manage hypertension
The loss of additional weight, increase aerobic exercise, reduced alcohol intake, low salt diet and no smoking
What drugs are used in the treatment of hypertension
ACE inhibitors or AT1 receptor blockers (ARBs), beta-blockers, calcium channel blockers and diuretics
What is the stepwise treatment for hypertension in under 55 and non-black
Step 1 - ACE inhibitors
Step 2 - ACE inhibitors and calcium channel blockers
Step 3 - ACE inhibitors, calcium channel blockers and diuretics
Step 4 - Consider adding alpha-blockers, beta-blockers or spironolactone or additional diuretics
What is the stepwise treatment for hypertension for over 55 and black
Step 1 - Calcium channel blockers
Step 2 - ACE inhibitors and calcium channel blockers
Step 3 - ACE inhibitors, calcium channel blockers and diuretics
Step 4 - Consider adding alpha-blockers, beta-blockers or spironolactone or additional diuretics
What do B-blockers act as
Competitive antagonists of B-adrenoceptors
What effects do B-blockers have
A reduced cardiac output, reduced MABP, reduced renin release from the kidneys and a CNS action that reduces sympathetic activity
In what patients are B-blockers useful
Patients with angina or following a myocardial infarction
What are the adverse effects of B-blockers
Bronchospasm, aggravation of cardiac failure, bradycardia, hypoglycaemia, fatigue and cold extremities
What does the RAAS system play a major role in
The regulation of sodium excretion and vascular tone
What activates the RAAS
A drop in blood pressure
Describe the RAAS
A drop in blood pressure is detected by the kidneys which causes the stimulation of the granular cells to release renin. Renin interacts with angiotensinogen, produced by the liver, and converts it to angiotensin I. Ang I then travels to the lungs where angiotensin converting enzyme (ACE) converts it to angiotensin II. Ang II travels to the adrenal gland and causes the release of aldosterone. Aldosterone travels to the kidney and causes an increase in sodium chloride and water retention which causes an increase in blood pressure
What cells are found within the juxaglomerular apparatus
Macula densa, granular cells and mesanglial cells
What is the function of macula densa
To detect the sodium chloride concentration in the blood
What is the function of granular cells
To produce renin
What innervates the granular cells
The sympathetic nervous system
What effect does RAAS have on congestive heart failure
A failing heart has a decreased CO and BP, the lowered BP causes the stimulation of RAAS and this increases the salt and water retention which causes the heart to fail
Where are ACE-membrane bound enzymes found
On the surface of endothelial cells
What is the function of the ACE-membrane bound enzymes
To convert inactive angiotensin I to angiotensin II
What does angiotensin II inactivate
Bradykin
Function of ACE inhibitors
They block the conversion of angiotensin I to angiotensin II
Example of an ACE inhibitor
Lisinopril
What is the function of AT1 receptor antagonists
To block the agonist action of angiotensin II at AT1 receptors in a competitive manner
What do ACE inhibitors cause
Venous dilation so reduced preload, arteriolar dilation so reduced after load and TPR, which decreases the arterial blood pressure and cardiac load
What do ACE inhibitors reduce the release of
Aldosterone
What does a reduction in the production of aldosterone cause
An increase in the loss of Na+ and H2O
What are the adverse effects of ACE inhibitors
A dry cough and can also cause hypotension
What are the properties of ARBs
Similar to ACE inhibitors
What conditions should ACE inhibitors and ARBs contraindicated in
Pregnancy and bilateral renal artery stenosis
What are the clinical uses of ACE inhibitors and ARBs
Hypertension, cardiac failure and following a myocardial infarction
What is the benefit of using ACE inhibitors and ARBs in hypertension
Reduced TRP and MABP and the possible suppression of proliferation of smooth muscle cells in the media of resistance vessels
What is cardiac failure associated with
The inappropriate activation of the RAAS
What do ACE inhibitors do
They decrease vascular resistance improving perfusion, increase secretion of Na+ and H2O and cause regression of left ventricular hypertrophy
What do diuretics act on
The kidneys
What is the function of diuretics
To increase excretion of Na, Cl and H2O and exert additional indirect relaxant effects on the vasculature
What are the major classes of diuretics
Thiazides and loop agents
Thiazides
Inhibit NaCl reabsorption in the distal tubule by blocking the Na+/Cl- co-transporter
Example of a thiazide
Bendroflumethiazide
What are thiazides widely used in
Heart failure, hypertension and additionally in severe resistant oedema
What do thiazides reduce
MABP
What does the loss of Na+ and H2O cause
Contracts blood volume and initially reduces the cardiac output
Loop agents
They inhibit the the NaCl reabsorption in the thick ascending loop of henle by blocking the Na+/Cl-/K+ co-transporter
What do thiazides and loop agents cause an undesirable loss of
K+
How is the loss of K+ corrected
By co-administering a potassium sparing diuretic or K+ supplements
Example of loop agent
Furosemide
Loop agents are used to reduce the salt and water overload associated with
Acute pulmonary oedema and chronic heart failure
How is the salt and water overload corrected
As a result of an absorption of extracellular fluid contributing to oedema in capillaries as a consequence of diuretic-induced reduction of blood volume
