Adrenergic Drugs Flashcards
What is the prototypical agonist of alpha 2 receptors?
Clonidine
What are the prototypical agonists and antagonists of alpha 1 receptors?
Phenylephrine
Prazosin
What are prototypical agonists and antagonists of beta 1 receptors?
Dobutamine
Metoprolol
What are prototypical agonist of beta 2 receptors?
Terbutaline
Albuterol
What are the important receptors that define responses of cardiovascular system to catecholamines?
Alpha 1 and beta 2 receptors in blood vessels
Beta 1 receptors in heart
Phenylephrine - cardiovascular system
Very selective alpha 1 agonist
Given IV Causes marked arterial vasoconstriction –> peripheral resistance up –> BP up –> HR decreased –> CO down –> peripheral BF down
Parenterally or topically for effects on vascular smooth muscle
Relatively short acting
Clonidine - cardiovascular system
Selective alpha 2 agonist
Oral or transdermal admin
Given IV can cause elevation of BP
Orally reduces peripheral resistance when patients upright and reduces HR and SV in supine - activation of receptors in lower brainstem
Reduces plasma concentrations of NE, and sometimes renin and aldo
Dobutamine - cardiovascular system
Relatively selective beta 1 agonist
Peripheral resistance unchanged
CO increased and BP rises
Cost of increased oxygen consumption
Isoproterenol - cardiovascular system
Non selective beta agonist
IV admin - positive chronotropic and inotropic on heart, agent in bradycardia or heart block
Vasodilation due to beta 2 activity
CO increased
Mean and diastolic pressure fall but systolic may stay of even rise
Epinephrine - cardiovascular system
Low doses - effect on beta receptor predominate
Higher doses - alpha 1 responses come in and alpha 1 and beta 1 responses dominate - BPs elevated
Vasoconstriction (alpha1) useful for vascular collapse and reduce edema of pulmonary epithelium, bronchodilation, used in cardiac arrest, to prolong action of anesthetics, and topical hemostasis
Norepinephrine - cardiovascular system
Agonist of everything but beta 2
Systolic and diastolic BP increase
CO may be maintained or decrease
Used as press or agent when necessary with pos inotropic effect in treatment of shock
Dopamine - cardiovascular system
Short half life, IV admin
Lowest doses - activates d1 dopaminergic receptors in renal and mesenteric vascular beds
Cause vasodilation and increased blood flow - valuable when renal perfusion compromised
Doses increase - beta 1 activated
Still higher doses - activates alpha 1 causing vasoconstriction and reduced CO - generally undesirable
How do adrenergic drugs affect respiratory smooth muscle?
Beta 2 agonists are powerful bronchodilators
Albuterol and terbutaline selective beta 2 agonists
Salmeterol - longer acting
How do adrenergic drugs affect uterine smooth muscle?
Alpha 1 agonists cause uterine contractions
Beta 2 agonists cause relaxation
Ritodrine
Beta 2 agonist used to treat premature labor
Terbutaline can be substituted
First admin IV then oral
Pregnancies between 20-34/36 weeks
Cardiovascular and metabolic side effects abound
What are the metabolic effects of adrenergic drugs?
Catecholamines and related agonists cause hyperglycemia
Phenylephrine and other alpha 1 agonists - general
Local vasoconstriction - limits distribution of anesthetics and prolongs action
Nasal decongestion - shrinks mucous membranes, topical or oral, possible rebound hyperemia
Ophthalmic - mydriatic agent, controls hyperemia of conjunctiva
Paroxysmal atrial tachycardia - raise BP and slow heart via vagal effect, outmoded
Hypotensive states - chronic orthostatic hypotension, shock
How do adrenergic drugs act in shock?
Hypovolumic - symp system activated, pos inotropic agent useful if heart must keep up with infused fluids, sometimes vasodilators useful
Cardiogenic - reduce ventricular after load with vasodilators, use of positive inotropic agents but dangerous
Hyper dynamic - fall in peripheral vascular resistance
Anaphylactic - treated with Epi, beta 2 agonist will relieve bronchial constriction
Septic - depends on situation
Clonidine - general
Orally effective, transdermal patches available
Half life about 12 hrs can be prolonged in renal failure
Adverse = may elevate BP, dry mouth, bradycardia, postural hypotension, withdrawal syndrome
Uses = anti hypertensive, blunt sympathetic reflexes from vasodilators, opioid withdrawal, potentiation of anesthesia, hot flashes in menopause
Body thinks you have more Epi and signals to stop release
Dobutamine - general
Half life 2 min
Given IV for short term treatment of cardiac decompensation
Excessive may cause increased PVR, HR, and cardiac automaticity
Beta 2 agonists (albuterol, terbutaline, salmeterol, ritodrine) - general
Should be poorly absorbed by GI tract or extensively metabolized by liver in case not all inhaled and some swallowed
Albuterol and terbutaline - bronchodilation in 30 min, effective 3-6 hrs, orally or s.c.(terbutaline only) or inhalation
Salmeterol - effective 12 hrs but delayed onset of action
How do indirectly acting sympathomimetic amines work?
Cause release of NE from sympathetic neurons
Less effective after repeated admins because store depleted = tachyphylaxis
Similar responses to NE but slower onset and longer duration
Mixed acting can also act directly on receptors
Tyramine
Prototype of indirectly acting sympathomimetic
Not used as drug, found in food
Ephedrine
Mixed acting sympathomimetic amine
Orally effective
Used for asthma and as CNS stimulant
Alpha and beta agonist as well as indirect actions
Amphetamine
Indirectly acting sympathomimetic amine
Orally active, long lasting, lipid soluble, metabolically blocked
Cardiovascular - BP up, HR reflexively slowed, cardiac arrhythmias
CNS - stimulant due to release of dopa and NE, can be fatal OD
suppress appetite but tolerance develops quickly
Can be used for narcolepsy or ADHD
Methylphenidate
Sympathomimetic amine
CNS stimulant
Similar effects to amphetamine
Used widely for ADHD
Dosage should be highly individualized, drug holidays when possible
Adverse = insomnia, anorexia, weight loss
How are adrenergic drugs used on obesity?
Amphetamine like substance effective short term, never long
Phentermine and fenfluramine = fen-phen - popular in 90s but shown to cause valvular heart disease
Few drugs approved for long term management
Methyldopa
Interferes with adrenergic nerve function
Prodrug - Converted to methylNE by same enzyme than does dopa –> NE
Accumulates in secretory vesicles of adrenergic neurons and is released upon nerve simulation
False neurotransmitter - alpha 2 agonist, acts like clonidine
Orally active - short half life but 24 hr duration
Adverse = sedation, dry mouth, stuffiness, depression, hepatic toxicity, sometimes hemolytic anemia
Reserpine
Binds to and inactivates certain neuronal storage vesicles blocking ability to transport or store
Eventual result complete depletion of all peripheral catecholamines and serotonin
Some advantage - can lower BP at doses sig. below side effect dose
Inexpensive and long duration of action
General properties of alpha adrenergic antagonists
Vasodilation –> decreased PVR and BP
Compensatory - immediate tachycardia and slow fluid retention
Pressor effect of Epi converted to vasodepessor = Epi reversal
May block ejaculation and cause stuffiness
Enhanced sympathetic outflow –> vasoconstriction and cardiac stimulation
Phenoxybenzamine
Nonselective alpha blocker
Alkylates alpha receptors irreversibly - blockade develops slowly and lasts long
Inhibits catecholamine uptake into sympathetic neurons
Major medical use = management of pheochromocytoma
Adverse = postural hypotension, fluid retention, inhibition of ejaculation
Prazosin and Tamsulosin
Selective alpha 1 blockers
Decreased PVR and venous return –> BP down
Little tachycardia
Tamsulosin - more specific for a than b, for bladder smooth muscle than vascular
Oral admin - P (short half life, metabolized in liver), T (longer half life, metabolized in liver)
Adverse - sometimes early hypotension and syncope
Use - primary systemic HT (not T), short term effect in CHF, BPH
What are the pharmacological properties of beta blockers?
Slow HR and decrease force of contraction, particularly during exercise or stress
Decrease CO and increase PVR but PVR eventually returns to initial value
Slow pacemaking
Block catecholamine stimulated renin secretion
Avoid in patients at risk for bronchoconstriction
Propranolol
Nonselective beta blocker
Lipophilic, Completely absorbed, extensive first pass metabolism
Variable plasma concentrations
Enters CNS
Half life 4 hrs but once a day dosing possible
Metoprolol
Beta 1 selective blocker
Short half life
Extensive metabolized
Genetic differences in rate of metabolism - plasma concentrations vary among individuals
Atenolol
Beta 1 selective blocker
Longer half life than metoprolol
More limited penetration of brain
Carvedilol
Racemic mixture - one isomer Nonselective beta blocker, both isomers alpha 1 blockers
Metabolized at different rates
Antioxidant
New studies for use in treatment of CHF
What are the untoward effects of beta blockers?
Life threatening bradyarrhythmias in patients with conduction defects
Rebound on abrupt discontinuation
Increased airway resistance
CNS effects - sleep disturbances and depression
Decreased exercise tolerance
May worsen peripheral vascular disease symptoms
What are 12 therapeutic uses of beta blockers?
- First line for HT - more effective in younger, can be used in combo (with diuretics, reduce reflex tachycardia with vasodilators)
- Angina - decrease effects of catecholamines on myocardial oxy use, blunt increase in HR during exercise
- *useful in supra ventricular and ventricular arrhythmias
- Early admin after myocardial infractions lowers death rate
- Heart failure only when HT, ischemia, or arrhythmias play role - otherwise can make it worse because failing heart needs symp
- Hypertrophic obstructive cardiomyopathy - relieve angina and arrhythmias, short term use pending surgery
- Acute dissecting aortic aneurysm - short term, pending surgery
- Hyperthyroidism - thyroid stimulates synthesis of beta receptors
- Prophylaxis of migraine
- Acute panic syndrome - relieve manifestations of anxiety
- Open angle glaucoma
- Pheochromocytoma
