Adrenergic Agonists and Antagonists Flashcards
Effects of stimulating Alpha 1 receptors?
- vasoconstriction
- increased peripheral resistance
- increased BP
- mydriasis (pupil dilation)
- increased closure of bladder sphincter
Effects of stimulating Alpha 2 receptors?
- inhibits NE release
- inhibits ACh release
- inhibits insulin release
Effects of stimulating beta 1 receptors?
- tachycardia (increased HR)
- increased lipolysis
- increased heart contractility
- increased release of renin
Effects of stimulating beta 2 receptors?
- vasodilation
- decreased peripheral resistance
- bronchodilation
- increased glycogenolysis
- increased release of glucagon
- uterine dilation
Selegiline?
- MOA inhibitor
- prevents degradation of NE
Cocaine?
- NET inhibitor
- prevents uptake of NE, prolongs stimulation
Tyramine and Amphetamine?
- similar structure to NE
- they are uptaken into presynaptic cell and deplete NE out of vesicle
- increase NE stimulation
Entacapone?
- COMT inhibitor
- prevents degradation of NE
Why do catecholamines have a short duration of action?
- OH groups on C3 and C4 make them reactive and easily degraded by COMT and MOA
- cannot be taken orally because MOA and COMT have a lot of enzymes in GI tract
- more polar so cannot cross BBB
Mechanism of alpha 1 receptors?
- Gq protein coupled
- phospholipase C generates IP3 and DAG
- increases Calcium inside the cell
- smooth muscle contraction, vasoconstriction
Norepinephrine?
- alpha agonist
- stimulates all receptors, but mainly alpha 1 at low doses
Effects:
- vasoconstriction
- increases peripheral resistance
- increases BP
- reflex bradycardia due to high BP
Clinical use:
- shock (IV slow drip)
- rapid onset, short duration
- monitor closely for high BP
ADR:
- increased BP (hypertension)
- reflex bradycardia
- nasal dryness
- blurred vision (pupils dilated)
- tissue necrosis (IV infiltration, use alpha antagonist)
Phenylephrine?
-selective alpha 1 agonist
Effects:
- increased BP
- vasoconstriction
Clinical use:
- nasal decongestant
- drops for mydriasis (pupil dilation)
- relieve redness for eyes
ADR:
- increased BP, cardiac failure, arrhythmia
- reflex bradycardia
- infiltration necrosis
- rebound nasal congestion (don’t use long term)
Naphazoline and Oxymetazoline?
- non selective alpha agonist
- relief of redness of eyes from swimming, cold, or allergy
Clonidine?
-selective alpha 2 agonist
Effects:
- stimulates alpha 2 in CNS to decreases sympathetic outflow to periphery
- reduce NE
- blood vessel dilation
- reduced BP
Clinical use:
- hypertension
- withdrawal from opiates, tobacco, benzodiazepines
ADR:
- lethargy, sedation
- constipation
- dry mouth
- rebound hypertension, taper slowly
Mechanism of beta 1 receptor activation?
- Gq protein coupled
- adenylyl cyclase activated to increase cAMP
- increased calcium
- increases HR and contractility
Mechanism of beta 2 receptor activation?
- increase cAMP
- inactivate myosin LC kinase
- dissociation of actin and myosin
- smooth muscle relaxation
Isoproterenol?
-nonselective beta agonist
Effects:
- stimulates heart
- relaxes smooth muscle
Clinical use:
- longer half life than Epi (metabolized by COMT, not MAO)
- treat heart block, bradycardia, ventricular arrhythmia
- do not use to treat asthma (stimulates heart as well as dilating blood vessels)
ADR:
- tachycardia
- headache
- flushing
- ischemia
- arrhythmia in CHD patients
Dobutamine?
-selective beta 1 agonist
Effects:
-increase HR and contractility of heart
Clinical use:
-parenterally for acute CHS as inotropic drug
ADR:
- ventricular arrhythmia
- tolerance after prolonged use
Albuterol and Terbutaline?
-selective beta 2 agonist, use lower dose
Effects:
- relaxes smooth muscle
- bronchodilation
- uterine dilation
- vasodilation
Clinical use:
- parenterally, short acting (3-6 hours)
- relieve acute bronchospasm in asthma via inhaler
- inhibits uterine contractions in premature labor (terbutaline)
- Salmeterol and Formoterol are long acting, combined with steroid for asthma
ADR:
- tremor
- tachycardia
- higher does cause beta 1 stimulation
Epinephrine?
-stimulates all adrenergic receptors (higher affinity for beta 2 at lower dose)
Clinical use:
- rapid onset and brief duration
- asthma
- anaphylaxis shock (epipen)
- angioedema
- cardiac arrest, bradycardia, heart block in ER
ADR:
- ventricular arrhythmias
- headache
- restlessness
Effect of NE on HR, BP, and peripheral resistance?
- stimulates alpha 1, vasoconstriction
- increases PR significantly
- SBP and DBP increases, increasing MAP
- MAP activates baroreceptors to reduce HR
Effect of Epi on HR, BP, and peripheral resistance?
- Epi stimulates all receptors
- net effect of is blood vessel dilation
- reduces PR slightly, due to vasoconstriction of alpha 1
- DBP decreases
- HR and contractility increases
- CO and SBP increases
- MAP has no change due to decreases in DBP and increases is SBP
Effect of Isoproterenol on HR, BP, and peripheral resistance?
- stimulates beta receptors nonselectively
- blood vessel dilation
- decreases PR significantly
- DBP decreases significantly
- SBP increases slightly
- MAP decreases
- less stimulation of baroreceptors
- HR increases significantly
Trimethaphan?
- blocks autonomic ganglion
- when given before phenylephrine, baroreceptor stimulation is not complete
- phenylephrine will increase BP due to vasoconstriction
- HR won’t change due to baroreflex block by trimethaphan
Dopamine?
Effects:
- low dose causes vasodilation in kidney and GI to generate more urine and maintain kidney function
- medium dose- Beta 1 increased HR
- high dose- alpha 1 vasoconstriction
Clinical use:
- circulatory shock
- acute heart failure
- Epi and NE would vasoconstriction the kidneys, shutting them down
ADR:
- tachycardia
- angina pain
- arrhythmias
- headache
Fenoldopam?
- selective peripheral Dopamine 1 antagonist (D1)
- raid vasodilator for treating severe hypertension
Ephedrine and Pseudoephedrine?
- stimulates alpha and beta receptors in CNS
- mixed acting
Clinical use:
- use as nasal decongestant
- increase BP
Phentolamine?
- reversible (competitive) nonselective alpha antagonist or blocker
- short acting
Clinical use:
- diagnose and treat pheochromocytoma (tumor in adrenal gland that increases BP)
- used to treat hypertension
ADR:
- reflex tachycardia
- postural hypotension
- sexual dysfunction
- Epi reversal
Phenoxybenzamine?
- irreversible (noncompetitive) nonselective alpha blocker or antagonist
- long acting
Clinical use:
-management of pheochromocytoma (adrenal tumor)
ADR:
- reflex tachycardia
- postural hypotension
- sexual dysfunction
- Epi reversal
Prazosin?
-selective alpha 1 blocker
Effects:
- blocks alpha 1 and prevents NE from stimulating vasoconstriction
- blood vessel is more dilated
Clinical use:
- treat benign prostate hyperplasia
- reduces urinary hesitancy
- allows relaxation and ease of passing urine
ADR:
- postural hypotension (feel dizzy when stand up), give at bed time
- head ache, dizziness, nasal congestion, blurred vision
- reflex tachycardia
- sexual dysfunction
- Epi reversal- if alpha blocker is given before, Epi becomes a beta stimulator only, reduces PR and MAP
Adverse effects of beta blockers?
- Asthma and COPD
- diabetic difficulties (hypoglycemia)
- abrupt withdrawal due to receptor up regulation
Propanolol?
- nonselective beta blocker
- membrane stabilizing ability
- most lipid soluble beta blocker
Clinical use:
- used to treat arrhythmia
- do not give to patients with asthma or COPD
- may influence diabetics insulin dose
Timolol and Nadolol?
- more potent nonselective beta blocker than propranolol
- no membrane stabilizing ability
Clinical use:
- Nadolol long duration of action, use for hypertension, angina, migraine
- Timolol treats open angle glaucoma (topical), hypertension, migraine
Pindolol?
- non selective beta blocker
- intrinsic sympathetic activity
Clinical use:
-use as antihypertensive in people with diminished cardiac reserve (beta 1 stimulation is low, need to stimulate heart to respond for more CO)
Metoprolol and Atenolol?
- selective beta 1 blockers
- Metoprolol has membrane stabilizing effects
Clinical use:
- hypertension
- angina
- acute MI
- heart failure
- tachycardia
Esmolol?
- selective beta 1 blocker
- very short half life, given via IV
Clinical use:
- hypertensive crisis
- acute SVT
Nebivolol?
- selective beta 1 blocker
- can stimulate NO release causing vasodilation
Clinical use:
-use for hypertension
Acebutolol?
- selective beta 1 blocker
- half life is 3 hours
- active metabolite is Diacetolol (half life 8-12 hours)
- has membrane stabilizing effect
- has intrinsic sympathetic effect
Clinical use:
-ventricular arrhythmias
Labetalol and Carvedilol?
-alpha 1 and nonselective beta blockers
Effects:
- decreases PR and CO
- balanced approach to inhibiting sympathetic system
Clinical use:
- Labetalol (IV) used for hypertension, hypertensive emergencies, and pheochromocytoma (blocks alpha 1 reducing CO)
- Carvedilol is used for heart failure, it reduces lipid oxidation, reduces vascular wall thickening
ADR:
- combo of alpha and beta blocks
- hepatic injury
Reserpine?
- adrenergic neuronal blocker
- depletes serotonin and dopamine in CNS
- inhibits Dopamine from being transported into vesicles
Clinical use:
- hypertension
- outdated use for antipsychosis
ADR:
- hypotension
- reflex tachycardia
- increased GI
- CNS depression
Guanethidine?
- adrenergic neuronal blocker
- reduces fusion of vesicle to nerve terminal, reduces NE release
Clinical use:
-hypertension
ADR:
- hypotension
- reflex tachycardia
- increased GI
- CNS depression
