adrenergic agonists and sympathomimetic agents

Question 1

epinephrine heart

Answer 1

positive chronotropic effect
positive inotropic effect
increased conduction in atria, A-V nodes & purkinje fibers
increased oxygen consumption
the work of the heart is increased substantially

Question 2

epinephrine blood vessels

Answer 2

Epinephrine stimulates both
a1vasoconstriction
b2vasodilation
Epinephrine is more potent at b2than a1
NE = Epi at b1; Epi>NE at a1, Epi&raquo_space;NE at b2
At high doses, a1vasoconstriction predominates

Distribution and density of a& breceptors differs in different vascular beds
skeletal muscleboth b2 and a1 present
dose-dependent vasodilation (b2) or vasoconstriction (a1)
coronariesvasodilation due to both b2 and metabolic
(NO, adenosine)
kidney, skin, mucosa, primarily a1vasoconstriction
mesenteric beds,both b2 and a1, density varies
cerebralunchanged
pulmonaryvasoconstriction a1

Question 3

epinephrine smooth muscle

Answer 3

Bronchial relaxation b2
GI-relaxation; slight decrease in muscle tone
Bladder
relax detrusor b2
contract sphincter a1
Spleen contraction
Eye -mydriasis, lowers IOP
Uterus -relax (b2)during last month of pregnancy

Question 4

epinephrine glands

Answer 4

Lacrimation (a1 secretion)
Sweating (palms) and piloerection (a1)
Salivation -scant, mucous secretion
Pancreas -blocks insulin release(a2 inhibit > b2 stimulate)

Question 5

epinephrine metabolic effects

Answer 5

Calorigenic effect
Glycogenolysis and gluconeogenesis by liver (a1, b2)
Lipolysis -increased free fatty acids(a1, b1, b2,b3) (a2inhibit)

Question 6

epinephrine clinical uses

Answer 6

Anaphylaxis (drug of choice)
bronchodilation b2
vasoconstriction a1
maintains BP, prevents spread of antigen
inhibits release of histamine and other allergic mediators from mast cells (b2)

Anaphylactic Shock
Epi (usually s.c. injection) is the drug of choice
bronchodilation
vasoconstriction
reduced edema
reduce spread of antigen
reduced release of inflammatory mediators
counteracts hypotension

Asthma (pediatrics)
Racemic Epi delivered by nebulizer is used for bronchodilation
Glaucoma –rarely used
Infiltration with local anesthetics for vasoconstriction to keep anesthetic local
Cardiac resuscitation
Topical hemostatic
arterioles and capillaries
ineffective for large blood vessels

Question 7

epinephrine adverse effects

Answer 7

Arrythmias
especially with certain gaseous anesthetic agents
Cerebral hemorrhage from elevated blood pressure when given high dose i.v.
Tissue necrosis from vasoconstriction at site of injection
CNS -fear, anxiety, headache

Question 8

epi contraindications

Answer 8

Hypertension
Shock (hypovolemic) -further compromised blood flow
Hyperthyroidism
Angina pectoris -increases O2demand
Asthmatics with degenerative heart disease

Question 9

norepinephrine

Answer 9

Natural sympathetic and CNS neurotransmitter
Agonist at a1, a2, b1receptors
very weak (low potency) at b2receptors
Heart:
direct: positive inotropic and chronotropic (b1)
indirect: reflex bradycardia (blocked by atropine)
net effect: increase force; decreased rate
slow, forceful heartbeat
Blood vessels: a1-mediated vasoconstriction; BP

Administration: IV infusion to maintain blood pressure during spinal anesthesia or hypotensive shock.
Side Effects: anxiety, slow forceful heart beat; headache

Question 10

Isoproternol

Answer 10

Synthetic catecholamine
Potent agonist at all breceptors; no aeffects
Heart b1increased heart rate and force
Blood vessels:
b2vasodilation in skeletal muscle & mesentery
decreased diastolic BP
increased systolic BP
no change or decreased mean BP

Smooth muscle: relaxes bronchial and uterine
Metabolic: increases free fatty acids
stimulates insulin release & glycogenolysis
Clinical Uses: can be used (not 1st choice) in cardiac arrest, MI, cardiogenic shock to increase cardiac output
Side Effects: tachycardia, headache, flushing, arrhythmias, anginal pain

Question 11

Dopamine

Answer 11

Important neurotransmitter in CNS
CNS receptors: D1, D2, D3, D4, D5
Peripheral receptors: D1, b1, a
Pharmacological effects
blood vessels: vasodilates renal& mesenteric(D1receptors) increase blood flow to kidney
heart: mild increase in rate & force (partial agonist b1)
blood vessels: high doses cause vasoconstriction & increased BP (a1)

Question 12

Dopamine clinical uses

Answer 12

Clinical Uses:
Cardiogenic Shock
Increases cardiac output and enhances perfusion of kidney
Must monitor BP carefully because higher infusion rate or dose causes vasoconstriction and decreased tissue perfusion
Sometimes used in chronic CHF

Question 13

Dobutamine

Answer 13

b1-selective agonist
actually complicated b1agonist, a1 agonist/antagonist
Clinically mostly b1-effects
positive inotropic & some increase in rate
Cardia output increases
little vascular effect
Clinical Use: MI, CHF, cardiogenic shock
Adverse effects: may increase size of infarct
potential arrhythmias

Question 14

phenylephrine

Answer 14

a1 agonist prototype
Effects:
vasoconstriction
increase peripheral resistance; increase BP
increased blood pressure causes reflex bradycardia (blocked by atropine)

Uses: to maintain BP in hypotensive states
spinal anesthesia
paroxysmal atrial tachycardia
induces baroreceptor reflex slowing of rate
Nasal decongestant
Glaucoma: decreases IOP
deceases aqueous humor production
Infiltration with local anesthetic (usually epi)

Question 15

other a1 agonists

Answer 15

Methoxamine (Vasoxyl)
Midodrine (Pro Amatine)

Mixed Acting Alpha agonists
Mephentermine (Wyamine sulfate)
Metaraminol (Aramine)

Question 16

albuterol

Answer 16

relatively selective b2 (10x)
bronchodilation
used for treated bronchospams in asthma
aerosol delivery -restricts to lungs, decreases systemic absorption and side effects
p.o. -sometimes used, more side effects when oral
Side effects:
muscle tremors, tachycardia (b1 and reflex), anxiety, restlessness, headache, hypoglycemia, hypokalemia

Question 17

other b2 selective agonist

Answer 17

Metaproterenol (Metaprel, Alupent)
Terbutaline (Brethine)
inhaled, PO or SC -asthma; delay delivery
Isoetharine (generic)
Ritodrine (Yutopar)
i.v.; relax uterine muscle; delay premature delivery
Salmeterol(Serevent)
long-acting bronchodilator for nighttime asthma
Formoterol(Foradil) –like salmeterol
Bitolterol (Tornalate) -prodrug; asthma

Question 18

tyramine

Answer 18

indirect acting sympathomimetic

Tyramine is found in high levels in certain foods: beer, red wine, cheese.
Normally rapidly degraded by MAO in GI tract and liver
Patients taking MAO inhibitor (for depression) get high level of tyramine
Tyramine displaces NE from nerve terminal -causes hypertensive crisis, MI, stroke.

Question 19

cocaine

Answer 19

Indirect acting sympathomimetic

Cocaine, tricyclic antidepressants (TCAs), and SNRIs competitively block NE reuptake into nerve terminal
NE levels in synapse higher for longer periods

Question 20

ephedrine

Answer 20

Mixed acting agonist (direct and indirect)
direct: b-receptor agonist
indirect: releases NE
Not substrate for COMT or MAO
orally active and long-acting
CNS -stimulant
CV -mild increase force and rate, weak vasoconstriction
Lungs -mild bronchodilation
Uses: pressor agent, bronchospasm, nasal decongestant