Adrenergic Drugs

Question 0

What is the prototypical agonist of alpha 2 receptors?

Answer 0

Clonidine

Question 1

What are the prototypical agonists and antagonists of alpha 1 receptors?

Answer 1

Phenylephrine

Prazosin

Question 2

What are prototypical agonists and antagonists of beta 1 receptors?

Answer 2

Dobutamine

Metoprolol

Question 3

What are prototypical agonist of beta 2 receptors?

Answer 3

Terbutaline

Albuterol

Question 4

What are the important receptors that define responses of cardiovascular system to catecholamines?

Answer 4

Alpha 1 and beta 2 receptors in blood vessels

Beta 1 receptors in heart

Question 5

Phenylephrine - cardiovascular system

Answer 5

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

Question 6

Clonidine - cardiovascular system

Answer 6

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

Question 7

Dobutamine - cardiovascular system

Answer 7

Relatively selective beta 1 agonist
Peripheral resistance unchanged
CO increased and BP rises
Cost of increased oxygen consumption

Question 8

Isoproterenol - cardiovascular system

Answer 8

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

Question 9

Epinephrine - cardiovascular system

Answer 9

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

Question 10

Norepinephrine - cardiovascular system

Answer 10

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

Question 11

Dopamine - cardiovascular system

Answer 11

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

Question 12

How do adrenergic drugs affect respiratory smooth muscle?

Answer 12

Beta 2 agonists are powerful bronchodilators
Albuterol and terbutaline selective beta 2 agonists
Salmeterol - longer acting

Question 13

How do adrenergic drugs affect uterine smooth muscle?

Answer 13

Alpha 1 agonists cause uterine contractions

Beta 2 agonists cause relaxation

Question 14

Ritodrine

Answer 14

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

Question 15

What are the metabolic effects of adrenergic drugs?

Answer 15

Catecholamines and related agonists cause hyperglycemia

Question 16

Phenylephrine and other alpha 1 agonists - general

Answer 16

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

Question 17

How do adrenergic drugs act in shock?

Answer 17

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

Question 18

Clonidine - general

Answer 18

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

Question 19

Dobutamine - general

Answer 19

Half life 2 min
Given IV for short term treatment of cardiac decompensation
Excessive may cause increased PVR, HR, and cardiac automaticity

Question 20

Beta 2 agonists (albuterol, terbutaline, salmeterol, ritodrine) - general

Answer 20

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

Question 21

How do indirectly acting sympathomimetic amines work?

Answer 21

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

Question 22

Tyramine

Answer 22

Prototype of indirectly acting sympathomimetic

Not used as drug, found in food

Question 23

Ephedrine

Answer 23

Mixed acting sympathomimetic amine
Orally effective
Used for asthma and as CNS stimulant
Alpha and beta agonist as well as indirect actions

Question 24

Amphetamine

Answer 24

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

Question 25

Methylphenidate

Answer 25

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

Question 26

How are adrenergic drugs used on obesity?

Answer 26

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

Question 27

Methyldopa

Answer 27

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

Question 28

Reserpine

Answer 28

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

Question 29

General properties of alpha adrenergic antagonists

Answer 29

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

Question 30

Phenoxybenzamine

Answer 30

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

Question 31

Prazosin and Tamsulosin

Answer 31

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

Question 32

What are the pharmacological properties of beta blockers?

Answer 32

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

Question 33

Propranolol

Answer 33

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

Question 34

Metoprolol

Answer 34

Beta 1 selective blocker Short half life Extensive metabolized Genetic differences in rate of metabolism - plasma concentrations vary among individuals

Question 35

Atenolol

Answer 35

Beta 1 selective blocker Longer half life than metoprolol More limited penetration of brain

Question 36

Carvedilol

Answer 36

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

Question 37

What are the untoward effects of beta blockers?

Answer 37

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

Question 38

What are 12 therapeutic uses of beta blockers?

Answer 38

1. First line for HT - more effective in younger, can be used in combo (with diuretics, reduce reflex tachycardia with vasodilators) 2. Angina - decrease effects of catecholamines on myocardial oxy use, blunt increase in HR during exercise 3. *useful in supra ventricular and ventricular arrhythmias 4. Early admin after myocardial infractions lowers death rate 5. Heart failure only when HT, ischemia, or arrhythmias play role - otherwise can make it worse because failing heart needs symp 6. Hypertrophic obstructive cardiomyopathy - relieve angina and arrhythmias, short term use pending surgery 7. Acute dissecting aortic aneurysm - short term, pending surgery 8. Hyperthyroidism - thyroid stimulates synthesis of beta receptors 9. Prophylaxis of migraine 10. Acute panic syndrome - relieve manifestations of anxiety 11. Open angle glaucoma 12. Pheochromocytoma