PHARM - Drugs for the Treatment of Hypertension - Week 4 Flashcards
What do diuretic drugs do?
Decreases plasma volume, which decreases TPR.
In what way do diuretics affect cardiac output (4)?
Lowers stroke volume by lowering preload.
This is done by lowering intravascular volume by affecting Na+/H2O retention
Name three factors that affect Na+/H2O retention, and the effect they have.
Sympathetic system - increase
Aldosterone - increase
ADH - increase
When are diuretics used in a hypertnesion treatment therapy?
Early strategy for hypertension management - after Na+ balance by dietary salt restriction.
What kind of drug is viable as a diuretic, and does this class have other effects?
Orally active thiazide diuretics - have antihypertensive effects alone, and enhance efficacy of all other hypertensive drugs.
What is the primary effect of a diuretic?
Decreases reabsorption of Na+ and Cl- from filtrate, increasing water loss, and increasing excretion of salt.
It decreases blood volume and therefore BP.
Where on a nephron do thiazide diuretics act?
Distal convoluted tubule.
Briefly describe in 2 steps the mechanism of Na+ reabsorption in the distal convoluted tubule, and how thiazides act here.
Na+ is absorbed apically by Na+/Cl- co-transporter (C3) down its concentration gradient.
It is pumped out basolaterally by Na+/K+-ATPase.
Thiazides inhibit C3, increasing Na+ secretion.
How do thiazides affect K+?
K+ loss may be significant because K+ excretion is regulated by Na+ reabsorption.
Name 4 adverse effects of thiazides, and their mechanisms.
- Uric acid retention (gout) - uric acid excretion is decreased because thiazides compete for tubular secretion mechanisms
- Impaired glucose tolerance - activation of Katp channels in pancreatic islet cells, inhibiting insulin secretion
- Allergic reaction
- Hypokalaemia (decreased K+)
In what case does K+ loss with diuretics cause problems?
If thiazides are co-administered with:
-cardiac glycosides/antidysrhythmic drugs whose toxicity is increased by low plasma K+
How does Na+ reabsorption affect K+ secretion?
Na+ reabsorption increases driving force for K+ secretion.
K+ loss increases when more Na+ reaches the collecting duct.
What effect do ACE inhibitors and AT1 receptor antagonists have on blood pressure, and how?
They decrease blood pressure by decreasing total peripheral resistance.
What is renin and what is its action?
An enzyme made and secreted by the kidney.
It converts angiotensinogen to angiotensin I.
What is angiotensinogen, and where is it made and secreted?
A globulin made and secreted by the liver.
What is ACE, where is it found (2), and what does it do?
An enzyme found 40% in lung endothelium, and 60% elsewhere.
It converts angiotensin I to angiotensin II.
What effect does angiotensin II have at the adrenal cortex?
Aldosterone production
What effect does angiotensin II have at the renal proximal tubule?
Increases NaCl reabsorption
What effect does angiotensin II have at the renal efferent arterioles?
Vasoconstriction to maintain GFR
What effect does angiotensin II have at systemic arterioles?
Vasoconstriction, increasing TPR
What effect does angiotensin II have at the hypothalamus?
Thirst, and increased ADH
What effect does aldosterone have?
Increased renal NaCl reabsorption
How many receptors for angiotensin II are there?
Where are they found (9)?
2 - AT1 and AT2
AT1 - vascular smooth muscle, myocardial tissue, adrenal cortex, kidney, and the brain
AT2 - adrenal medulla, kidney, brain, and foetus
By which angiotensin II receptor are most of its known actions mediated by?
AT1
