B-antagonist lecture Flashcards
activation of what increases body’s readiness for strenuous activity & stress? (“fight or flight)
sympathetic nervous system (SNS)
effects of SNS activation
> : arterial pressure, HR, cardiac output, blood flow to muscles & heart, RR, oxygen consumption, blood glucose, glycolosis, mental activity
<: blood flow to GIT & kidneys
main effectors of SNS
norepinephrine & epinephrine
Norepinephrine (NE)
synthesized in sympathic nerve terminals & CNS as a neurotransmitter
epinephrine (Epi)
synthesized in adrenal medula (Chomaffin cells) as a hormone & in CNS (adrenergic neurons) as a neurotransmitter
synthesis of NE & epi starts with
Tyrosine
Tyr-> DOPA->domapine->NE->epi
what happens to the release of NE when beta 2 is stimulated?
increase release of NE
what happens to the release of NE when alpha 2 is stimulated?
stop release of NE
where are alpha 1 receptors found?
post synaptic
blood vessels, skin, pulmonary, kidney
where are alpha 2 receptors found?
presynaptic
where are Beta1 receptors found?
myocardium, JG cells in kidneys
where are beta2 receptors found?
smooth muscles (can be pre & post-synaptic) SMC of arteruikes, bronchial SMC, skeletal muscle, liver, ciliary muscle of eye
where are beta 3 receptors found?
adipose tissue -> lypolysis
what kind of receptors are adrenoceptors(Alpha & Beta)?
GPCRs
what is alpha 1 coupled to?
Gq-> >inositol triphosphate, DAG & Ca
what is alpha 2 coupled to?
Gi-> < adenylyl cyclase-> < cAMP
what are all beta coupled to?
Gs-> >adenylyl cyclase-> . cAMP
alpha 1 receptors cause
vasoconstriction
contribute to Na reabsorption
beta 1 receptors cause
chrono-dromo-iono-tropic effects
stimulate renin releaase
beta 2 receptors cause
vasodilation, bronchodilation, > secretion, glycogenolysis & gluconeogenesis
in the eye-> relxation & > intraocular pressure
1st generation beta blockers are
non-selctive B1 & B2 antagonists
2nd generation beta blockers are
selective B1 antagonists
3rd generation beta blockers are
non-selective & selective antagonists with additional effects
beta blocker effect on normal HR or BP at rest
little effect; profound effect when SNS is high (HTN, stress, exercise)
short term effect of non-selective B-blockers
< CO-> sympathetic activation-> > NE/Epi->activation of alpha receptors in vessels-> > PR ( B2 is blocked so no vasodilation)
long term effect of non-selective B-blockers
PR returns to initial value & CO continues to lower
reduction in BP in HTN with beta-blockers due to
- reduction of cardiac output (B1)
- inhibition of renin release from JG cells (B1)
- from B2- < NE
- w/ selective Beta-1-> vasodilation through B2
beta-blockers commonly used in the treatment of
HTN, angina, cardiac arrhythmias, MI, glaucoma, migraine prophylaxis
intrinsic sympathomimetic activity
partial agonist
some beta-blockers bind to receptors but can also slightly stimulate them
beta-blocker structures are all derived from
NE & Epi structure
main adverse cardio effects of beta-blockers
induce or worsen HF, induce arrhythmias in pts with AV conduction defects, worsen peripheral vascular disease, may cause sexual dysfunction
abrupt discontinuation of beta-blockers can cuase
angina pectoris (myocadial ischemia) & increase risk of death
main adverse pulmonary effects of beta-blockers
may worsen asthma or COPD
bronchospasm
main adverse CNS effects
sedation. sleep disturbances & depression
main adverse metabolic & endocrine effects
mask hypoglycemia-induced tachycardia in DM, may increase TG since lipolysis is inhibited
- chronotropic effect
decreased HR
- ionotropic effect
decreased contraction force-> decreased CO
- dromotropic effect
decreased cardiac rhythm & automaticity
