Lecture 8 - Drugs Used to treat high blood pressure II Flashcards
What is the agonist effect of alpha 1 receptor? What is the antagonist effect of the alpha 1 receptor?
Agonist: vasoconstriction
Antagonist: vasodilation
What is the agonist effect of beta 1 receptor? What is the antagonist effect of the beta 1 receptor?
Agonist: promotes contraction in the heart
Antagonist: dilation in the heart
What is the agonist effect of beta 2 receptor? What is the antagonist effect of the beta 2 receptor?
Agonist: promotes dilation in vascular smooth muscle
Antagonist: constrictes airway of vascular smooth muscle
Increased intracellular Ca2+ is the main signal for smooth muscle ____. It can arise from plasma membrane Ca2+ channels or activation of Gq-coupled cascade such as alpha 1.
contraction
What drug is commonly used for anti-hypertensive purposes which blocks the voltage sensitive calcium channels, blocking a way you could generate a calcium signal?
Amlodipine
What is RAAS?
- Renin angiotensin aldosterone system
What 3 functions does RAAS control?
- blood volume
- salt balance
- blood pressure
What is ARBs and ACEIs?
ARB: Angiotensin receptor blockers
ACEI: Angiotensin converting enzyme inhibitor
What enzyme is secreted by the kidneys that processes angiotensinogen to Angiotensin I ( AT1)?
Renin
What is the function of ACE and where it does it happen?
- converts AT1 to AT2
- happens in the circulation in the lungs
Is AT1 or AT2 a powerful vasoactive peptide that causes vascular smooth muscle control and aldosterone release from teh adrenal cortex?
AT2
How is the RAAS pathway stimulated?
if your blood pressure is reduced; triggers your kidneys to release renin.
AT2 will restore blood pressure by acting directly on ____ and aldosterone will restore blood pressure by acting directly on ____ triggering changes in our water and salt balance.
Blood vessels; kidneys
AT2 causes vaso____ and aldosterone release at the same time; can’t do it individually.
constriction
Which steroid hormone promotes reabsorption of Na+ and H20 in the kidney (preserved blood volume and increases blood pressure)?
aldosterone
Memorize the following pathway on the purple side
Renin is secreted by the kidney in response to ____ blood pressure by the stimulation of adrenergic stimulation.
low
Renin release is stimulated by ____ receptors
Beta 1
ACE or ARB exists primarily as a membrane bound protein in the pulmonary capillary endothelium?
ACE
Angiotensin II effects are primarily mediated by the ATII receptor usually called the ____ receptor
AT1 receptor; also known as AT2 type 1 receptor
AT1 receptors are GCPRs, coupled to the ____ signaling cascade.
Gq
In adrenal cortex, Ca2+ signals trigger synthesis/release of ____ (steroid hormone; lipid soluble)
aldosterone
Does aldosterone have a intracellular or extracellular signaling pathway?
intracellular
What are the key transcriptionsal targets in the nephron?
- Na+/K+ pump
- Epithelial Na+ channel (ENaC)
- NCC (Na+/Cl- symporter)
Receptors for aldsoterone are found in the ____ convoluted tubule; when they are active, they promote trancription of target genes (the 3 target genes in the nephron)
distal
Is captopril an ACE, aldosterone antagonist, or ARB (AT1 blocker)?
ACE
What drug acts as an enzyme inhibitor and binds to ACE to prevent the cleavage of ATI to AT, as a consequence, it reduces all of the downstream RAAS signals (ATII and aldosterone?
Captopril
What are the side effects of Captopril?
- Most common is dry cough; ACE is responsible for the breakdown of a inflammatory mediator called Bradykinin (peptide hormone), ACE cleaves bradykinin and breaks it down.
In you ____ ACE, you have excess amounts of Bradykinin, triggering cough in patients.
inhibit
Is Losartan an ACE, aldosterone antagonist, or ARB (AT1 blocker)?
AT1 blocker (ARB)
Losartan and other ARBs have a vaso____ effect. They inhibit powerful vaso____ effects of ATII.
dilatory; constrictive
ARB’s inhibit vasoconstrictive effects of AT2 by ____ the GCPRs in vascular muscle and ____ the production of aldosterone.
inhibiting; inhibits
In vascular smooth muscle, AT1 receptors mediate vaso____.
constriction
Is spironolactone an ACE, aldosterone antagonist, or ARB (AT1 blocker)?
Aldosterone antagonist
Spironolactone acts as a ____ antagonist for aldosterone
competitive
Aldosterone antagonists have what kind of effects?
- acts as a diuretic by inhibiting aldosterone effect (i.e., no reabsorption of sodium or water)
RELATIVE RISK REDUCTION OF MAJOR CARDIOVASCULAR EVENTS: 1 – (13209/137319)/(14068/128259) = ~12%
ABSOLUTE RISK REDUCTION = (14068/128259) – (13209/137319) = 1.3%
NNT = 74
RELATIVE RISK REDUCTION OF ALL CAUSE MORTALITY: 1-(9775/138298)/(9998/129700) = ~8%
ABSOLUTE RISK REDUCTION = (9998/129700) – (9775/138298) = 0.64%
NNT = 156
It is common to use anti-hypertensice drugs in combination therapy because they can have ____ effects on blood pressure.
additive
