3.A-Hormone Pathways Flashcards
What are the major hormones relating to blood pressure?
RAAS
sympathetic hormones (NE and epinephrine)
vasopressin (ADH)
peptide vasodilators (VIP, kinins, natriuretic peptides)
nitric oxide
Which tissues are influenced by epinephrine and norepinephrine?
heart (B1 receptors)
brains/CNS (a1 and a2 receptors)
lungs (B2 receptors)
kidney (B1 receptors)
blood vessels (a1 and B2 receptors)
Which drugs interfere with sympathetic nervous system actions?
beta-receptor antagonists
alpha-receptor antagonists
alpha-receptor agonists
(B2 agonists and a1 agonists augment SNS)
What happens when B1 receptors are activated in cardiac myocytes?
increased intracellular cAMP causing increased intracellular Ca which increases cardiac contractility and rate of contractions
What happens when B2 receptors are activated in smooth muscle cells of blood vessels?
increased intracellular cAMP causing decreased intracellular Ca which relaxes smooth muscle of the blood vessels (vasodilation)
Which receptors are blocked by beta-blockers?
B1
B2
a1
What do all beta-blockers end in?
-lol
What are the most common uses of B1 selective blockers?
high blood pressure (exact mechanism not clear)
high heart rate (tachycardia, tachyarrythmias)
cardiac workload/cardiac demand (angina)
cardiac damage (HF or heart attack)
Why are beta blockers used for cardiac damage?
if theres been damage to cardiac muscle, adrenaline can potentially worsen the damage so beta blockers act as a shield against the harmful effects of adrenaline
What are some B1 selective blockers?
bisoprolol
metoprolol
atenolol
acebutolol
esmolol
What are some non-selective beta-blockers?
nadolol
pindolol
propanolol
timolol
In addition to the effects that you would see through B1 antagonism, what are the effects of non-selective beta blockers?
smooth muscle:
-inhibition of B2 receptors in blood vessels, inhibiting
vasodilation
lung:
-inhibition of B2 receptors in airways
Are non-selective beta-blocker used for cardiac conditions? Why or why not?
rarely used for CV conditions anymore
theres very little benefit of non-selective beta-blockers over B1 selective blockers, also some tolerability issues
True or false: the selectivity between B1 and B2 is absolute
false
if you push the dose of a B1 receptor blocker, that agent will be become less selective
What are the non-selective beta and alpha blockers?
carvedilol
labetalol
What are the actions of non-selective beta and alpha blockers?
non-selective B1 and B2 inhibition
a1 receptor inhibition (vasodilatory effect)
True or false: there is a greater fall in blood pressure expected with non-selective beta and alpha blockers compared to other beta blockers
true
What are cautions with the use of beta-blockers?
reduced blood pressure
reduced cardiac output
bradycardia (decreased HR)
heart block (AV block)
increased K
exacerbate circulation problems via B2 blockade (cold extremities)
theoretical interaction with respiratory medications
slight blood sugar increase possible
What are the cautions in diabetics who are using beta-blockers?
reduced recognition of hypoglycemia
slight increase in blood sugar from vasoconstriction and reduced insulin release
What is the mechanism of action of alpha-receptor antagonists?
inhibit vasoconstriction that is induced by the SNS
After alpha-receptor antagonists have induced their action, what is often seen?
increases in HR, CO, and RAAS from the baroreceptor activation
True or false: alpha-receptor antagonists are mainly used for BP control
false
mainly used for BPH
What do all alpha-receptor antagonists end in?
-osin
What are some alpha-receptor antagonists?
alfuzosin
doxazosin
prazosin
silodosin
tamsulosin
terazosin
How do alpha-2 agonists work?
also called centrally-acting antihypertensives
lowering BP by affecting the brain
the a2 receptor is located on the pre-synaptic terminal and stimulation shuts down further release of messengers into the SNS nerve fiber
What is the result of alpha-2 agonists?
decreased circulating NE and decreased SNS nerve transmission
lowers BP and HR
What are side effects of alpha-2 agonists?
sedation
dry mouth (anti-cholinergic properties)
What are two examples of alpha-2 agonists?
clonidine
methyldopa
What are examples of endogenous peptide vasodilators?
vasoactive intestinal peptide (VIP)
kinins (bradykinin)
atrial natriuretic peptide (ANP)
brain natriuretic peptide (BNP)
How do endogenous peptide vasodilators have relevance to drugs?
kinins, ANP, and BNP are all broken down by an enzyme called neprilysin
What is an example of a neprilysin inhibitor? What is its partner drug?
sacubitril
valsartan
What is sacubitril exclusively used for?
heart failure
no major effect on BP
What is the action of nitric oxide?
a paracrine hormone synthesized by endothelial cells to signal smooth muscle cells to relax (vasodilation)
Differentiate between paracrine, endocrine, and autocrine.
paracrine: affects cells in vicinity
autocrine: affects cell in which it is made
endocrine: secreted in blood for systemic effects
How does relaxation result from nitric oxide?
activation of cGMP results in decreased cytoplasmic Ca which results in relaxation (vasodilation)
What is the most common nitrate?
nitroglycerin
Why is nitroglycerin not used for hypertension?
it causes vasodilation to veins thus little effect on BP
True or false: nitrates are prodrugs that are converted to nitric oxide in the circulation
true
If someone is using salbutamol and then they are prescribed either a non-selective beta-blocker (ex: propanolol) or a non-selective beta and alpha blocker (ex: carvedilol), what should warn this person about?
advise the patient to watch for a decreased response from their salbutamol
-non-selective beta blockers will inhibit B2 receptors in the
lung while the salbutamol is trying to activate the B2
receptors
What is the effect of sacubitril on blood pressure?
no major effect on blood pressure
What are the triggers of nitric oxide production in endothelial cells?
ACh
bradykinin
shear stress
