Diuretics Flashcards
What happens to water if we block Na resorption into the blood?
More water leaves in the urine
What does higher blood volume cause?
Higher blood pressure
How much volume is filtered in Bowman’s capsule?
20%
How much fluid filtered in Bowman’s capsule gets resorbed?
> 19%
How much plasma entering the kidney get sent back into circulation and how much gets excreted?
> 99% back into circulation
What is the site of action for diuretics?
Nephron
What does Carbonic anhydrase do?
Facilitates Na reabsorption and H20 retention
Osmotic diuretics
A type of diuretic that inhibits reabsorption of water and sodium
Pharmacologically inert substances that are given intravenously
Increase osmolarity of blood and renal filtrate
Where do osmotic diuretics act?
Proximal convoluted tubule and
Proximal straight tubule
Loop diuretics
Act on the ascending loop of Henle
Primarily used in meds that treat hypertension and edema often due to congestive heart failure and renal insufficiency
More effective in patients with impaired kidney function
What is the site of action of loop diuretics
Thick ascending loop of Henle
What is the mechanism of how Loop Diuretics work?
Should be excreted in the lumen
Inhibits Na, K, 2Cl transporter –> this significantly increases the excretion of Na, K, and Cl
Osmotic gradient for water resorption is also decreased –> Increasing water excretion
Ca and Mg are excreted as well
What site do Thiazide diuretics act on?
Distal convoluted tubule
What is the mechanism of how Thiazide diurtics work?
Secreted by Proximal tubules but work in the distal convoluted tubules
Inhibit Na-Cl symporter from the lumen to tubular cells –> this increases Na and Cl excretion (and water)
K+ sparing diuretics site of aciton
Collecting tubule
Potassium sparing diuretics
Do not promote the secretion of potassium in the urine
Used as adjunctive therapy (together with other drugs) in the treatment of hypertension and management of congestive heart failure
Used with other drugs that would otherwise tend to lower K levels
Potassium sparing diuretics mechanism of aciton
Competitive antagonist that either compete with aldosterone for intracellular cytoplasmic receptor sites
or
Directly block sodium channels
These cause for a lack of stimulation of Na-K exchange sites in the collection tubules, preventing Na reabsorption and K secretion
What is blood pressure the measurement of?
The force applied to artery walls
Systolic
When the ventricles contract
Diastolic
When ventricles are relaxed
Mean Arterial Pressure
MAP = CO x TPR
Cardiac Output
Stroke volume x HR
What is responsible for short term BP regulation
Sympathetic nervous system
What is responsible for long term BP regulation
Renal system
Baroflex regulation of blood pressure
Baroreceptors send blood pressure information to the medulla
Sympathetic nerves adjust the catcholamines to regulate vasoconstriciton, heart beat, and CO
How does the kidney sense blood pressure?
Juxtaglomerular cells have baroreceptors, sense low renal blood blow, and secrete renin
Renin
Enzyme resonsible for Angiotensinogen to be converted to Angiotensin I
Angiotensinogen
Produced by the liver
Converted to Angiotensin I by Renin
Angiotensin I is converted to Angiotensin II by Angiotensin converting enzyme (ACE)
Angiotensin II
Mediates direct and indirect vasoconstriction, sodium reabsorption and water retention
Can also produce structural remodeling
Promotes aldosterone release from the adrenal cortex
Which Angiotensin II receptor is the site of drugs to treat hypertension?
AT1 receptor
What drugs can be used to treat hypertension?
Diuretics
Sympathoplegic agents
Direct vasodilators
Block Angiotensin II production or activity
Sympathoplegic agents
Act on CNS
Reduce release of epinephrine from sympathetic nerve endings
Block selective adrenoreceptors
Sympathoplegic agent side effects
Sedation, depression, sleep disturbances
Static hypotension
Selective side effects
What is the mechanism of Sympathoplegic agents acting on the CNS
Activate a2 receptors in the CNS
Diminishing central sympathetic outflow, and reducing cardiac output
How do Sympathoplegic act to block selective adrenoreceptors
They block B2 receptors to diminish CO and Renin produciton
They can also block a1 receptors to block voasoconstriction (can cause Na and water retention - need a diuretic)
What mechanisms can Direct vasodilators work?
1) Nitric oxide pro-drugs or drugs that promote NO release form the endothelium
2) Reduce Ca influx to vascular smooth muscle
3) Hyperpolarization of vascular smooth muscle (by openign K channels)
4) Activation of dopamine receptors
How can direct vasodilators reduce Ca influx to vascular smooth muscle cells?
Block L-type Ca channels
Used in treatment of angina, hypertension, and arrythmias
Drugs that cause Hyperpolarization of vascular smooth muscle mechanism
Activates K channels causing hyperpolarization of smooth muscle cells
Diminishes Ca levels and contraction
Direct vasodilators activating dopamine receptors
Produce effects similar to B2 adrenergic receptor agonists on bronchial smooth muscle
Used in emergency and post-op treatment
How can hypertension drugs block angiotensin II production activity?
1) ACE inhibitors
2) Competitive antagonists of angiotensin receptors
3) Renin inhibitors
4) Aldosterone inhibitors
ACE inhibitors
Prevent Angiotensin I from becoming Angiotensin II
Also degrades bradykinin, which is a vasoconstrictor, so they also promote vasodilation
Competitive antagonists of angiotensin receptors
Block AT1 receptor
