Exam 4 - Lecture 42-43, Adrenergic Agonists I + II Flashcards
a1 antagonist signaling
block Gaq -> no Ca increase -> smooth muscle dilation
a2 antagonist signaling
blocks Gai -> increase Ca2 + cAMP production -> increase transmitter release and smooth muscle relaxation
b antagonists signaling
blocks Gas -> no increase cAMP -> decrease heart muscle contraction, decrease renin secretion
a1 receptor antagonist commonly used..
for vascular relaxation effects, inhibit vasoconstriction and cause vasodilation
b receptors…
decrease HR contractility, conductor velocity and relaxation rate
little vascular effect, but can have small degree of vasoconstriction
contraindicated in patients with sinus sickness
cause inhibition of renin release form kidneys
a antagonists used to…
control BP during surgery and in treatment of pheochromocytomas
a1 selective antagonists
are used in primary hypertension and BPH major depressive disorder, PTSD
a2 selective antagonists
have limited clinical usefulness; limited benefit in male ED
b antagonists are useful in…
variety of clinical conditions and are firmly established in treatment of hypertension, ischemic heart disease, arrhythmias, endocrinology and neurologic disorders, glaucoma, and other conditions
Angina pectoris
severe pain in chest, due to inadequate blood supply to heart.
beta blockers decrease contractility, cardiac work and oxygen demand
Myocardial infarction
beta blockers used as secondary prevention, reducing infarct size, risk of ventricular fibrillation and decrease overall risk of death
beta blocker reduce HR,BP and contractility
Arrhythmia/Dysrhythmias
abnormalities in cardiac muscle contractions or normal rhythm of the rate of rate heart beat.
Beta blockers may stop the dysrhythmia, primarily used to slow down heart rate during dysrhythmia.
beta blocker reduce HR,BP and contractility
Congestive heart failure
cardiac output is insufficient to meet metabolic demand leading to fluid build up around the heart.
Beta blockers block harmful activation of the SNS or renin-angiotensin system
beta blocker reduce HR,BP and contractility
hypertension
treatment with beta blockers useful for reducing cardiac output, reduction of renin release form kidney, and decrease of sympathetic activity
beta blocker reduce HR,BP and contractility
Pheochromocytoma
tumor in medulla of adrenal gland which produces large amounts of catecholamines
localized using CT scan or MRI with MIBG
Benign prostatic hypertrophy
enlarged prostate gland leading to decreased urine output
a antagonist used to relax prostate and bladder smooth muscle, but do not decrease the size of prostate
glaucoma
disease of optic nerve causing cupping of optic disc leading to loss of vision
Beta blockers used to decrease intraocular pressure
Thyrotoxicosis
“thyroid storm” increased thyroid hormone production and secretions resulting in increased heart rate, tremors, and nervousness
nonselective beta blockers treat increase HR and tremors
Anxiety
non specific beta blockers treat symptoms
PTSD
a antagonist and B blockers clinically used to alleviate symptoms
Migraine prophylaxis
beta blockers = prophylactic treatments of migraines
alpha non-selective
phenoxybenzamine
Phentolamine
a1 selective
-osin’s
indoramin
urapidil
a2 selective
yohimbine
beta non selective (first gen)
nadolol penbutolol pindolol propranolol timolol sotalol levobunolol metipranolol
b1 selective (second gen)
acebutolol atenolol bisoprolol esmolol metoprolol
best for heart
beta non selective (3rd gen)
carteolol
carvedilol
bucindolol
labetalol
b1 selective (3rd gen)
betaxolol
celiprolol
nebivolol
Phentolamine
Non-selective Alpha antagonist
Indications: Hypertensive emergency; treat and diagnose pheochromocytoma; reversal of anesthesia
Side effect: hypotension, orthostatic hypotension, reflex tachycardia, priapism; nasal congestion
Contraindications: angina/coronary artery disease, MI, hypotension
Prazosin
Prototypic for a1 antagonists
Indications: Monotherapy for mild hypertension or with other drugs for moderate to severe hypertension BPH
side effects: slight risk of pancreatitis, dizziness, headache, lethargy, 1st dose can cause sever hypotension
Pregnancy category: C but avoided
Terazosin
close structural analog to prazosin, but less potent
Indications: benign prostatic hyperplasia, hypertension
Mechanism: similar to prazosin
Side effects: similar to prazosin
Doxazosin
close analog to prazosin
Indications: Benign prostatic hyperplasia; ureteric stone; neurogenic bladder and ED diagnosis
Mechanism: non-subtype-selective a1 antagonist
side effects: nausea, cardiovascular edema, priapism may occur leading to permanent impotence
Contraindications: Do not use with PDE5 inhibitor for risks of hypotension
tamsulosin
Indications: BPH; ureteric stone; neurogenic bladder
Mechanism: selective a1 receptor antagonist
Side effects: failure to jizz; orthostatic hypertension; dizziness, vertigo, somnolence; maybe back pain, rhinitis, or pharyngitis
Contraindications hepatic or renal impairment; advise surgeons before cataract surgey
Yohimbine
a2 antagonists, mainly used in research
Indications: no FDA approved; natural product for impotence in males
Contraindications: psych patients, history of ulcers, renal or liver disease, tyramine contains foods, pregnancy, antidepressant, chronic inflammation of sex organs of prostate gland
Pregnancy Category X
Beta blockers properties
little effect on heart when person at rest, but big effect when sympathetic control of heart is dominant (exercise or stress)
block chronotropic and inotropic actions of catecholamines
block exercise-induced increases in HR and contractility, but cardiac output is less effected due to an increased stroke volume
1st gen beta is non selective
blocks both b1 and b2
many side effects
2nd generation are cardiac selective
most affects heart but will decrease cardiac output
3rd gen shows additional effects
ISA
membrane stabilizing effects
some drugs have additional mechanism of vasodilation
ISA
intrinsic sympathomimetic activity
mimic effects of E and NE causing very slight increase in BP and HR
Propranolol
prototypic B receptor antagonist
Indications: Hypertension, angina, essential tremors, prevention of MI, migraine prophylaxis
Lacks: ISA
Side effects: cold extremities, anorexia, nausea, vomiting, insomnia, wheezing
Monitor: asthma symptoms and blood glucose
Contraindications: low blood pressure (<50/30), sinus bradycardia w/o pacemaker
** Highly Lipophilic, crosses BBB **
Nadolol
Indications: angina, hypertension, ff label migraine prophylaxis and parkinsonian tremors
Use caution/adjust doses in patients with renal failure
Long acting antagonist with B1=B2 affinities
Timolol
Indications: Intraocular hypertension and glaucoma
Contraindications: OU admin can lead to systemic effects in patients with asthma or CHF, use caution with cimetidine due to increase plasma levels of timolol
Pregnancy category C, can cross placenta resulting in bradycardia and cardiac arrhythmia
Pindolol
Indications: angina, hypertension
Mechanism: nonselective b antagonist, with ISA with membrane stabilizing activity and low lipid solubility
Use caution in patients with renal failure, excreted from kidney
Side effects: decreased sex drive, sleep problems, tired feeling, anxiety, nervousness, dizziness, drowsiness
Pregnancy category B - no proven risk humans
Metoprolol
Indications: angina, CHF, hypertension
Mechanism: b1 selective antagonist, devoid of ISA and membrane stabilizing activity
Contraindications: acute MI in patients with HR <45bpm, systolic BP <100 mmHG or in moderate to sever HF, severe bradycardia or sick sinus syndrome
Side effects: diarrhea, fatigue, headache or depression; drug may mask symptoms of hypoglycemia
Pregnancy category C, safe breast feeding
Acebutolol
Indications: Hypertension, ventricular arrhythmias
Mechanism: B1 selective antagonis 2nd gen, ISA and membrane-stabilizing activity
Side effect: dizziness, headache, fatigue…monitor asthma and blood glucose
contraindications: cardiogenic shock, overt cardiac failure, sever bradycardia, 2nd/3rd degree heart block
Pregnancy class: B
Bisoprolol
Indications: hypertension
b1 selective antagonist 2nd gen), lacks both ISA and membrane stabilizing activity
Side effect: dizziness, bradycardia, hypotension and fatigue….monitor: asthma and blood glucose
Contraindications: cardiogenic shock, overeat cardiac failure; severe bradycardia, 2nd/3rd degree hear block
Pregnancy Class: C
Atenolol
Indications: Hypertension, coronary heart disease, arrhythmias, angina
Mechanism: B1 selective antagonist that is devoid of ISA and membrane stabilizing activity
contraindications: cardiogenic shock, overt cardiac failure; severe bradycardia, 2nd/3rd degree hear block
Pregnancy class: D
How do 3rd gen B Blockers lower BP?
through peripheral vasodilation, enhancing hypotension, increasing peripheral blood flow and/or decreasing after load
Labetalol
Indications: hypertension
Mechanism: mixed a1 and non-selective b antagonist….membrane stabilizing effects and ISA effects
Side effects: orthostatic hypotension, tingling of skin, dizziness, nasal congestion, bronchospasm
Contraindications: bronchial asthma, overt cardiac failure; COPD; hypotension
Pregnancy class: C
Carvedilol
Indications: hypertension; HF, impaired left ventricular function
Mechanism: mixed a1 and non-selective B antagonist; has antioxidant and antiflammatory effects, at high dose Ca channel-blocking activity. No ISA but has membrane stabilizing activity. Reno-protective, favorable effects in patients with diabetes or metabolic syndrome
Side effects: weight gain, diarrhea, dizziness, ED
Contraindications: use caution with drugs that affect liver oxidation; similar to metoprolol
Pregnancy class: not assigned, considered safe but conflicting data
