Test 1-DIRECT acting sympathomimetics

Question 1

CATECHOLAMINES:

Answer 1

Catecholamines are technically endogenous substances that serve as hormones and neurotransmitters. The list below includes some endogenous catecholamines and synthetic catecholamine analogues (isoproterenol, dobutamine). These drugs should be considered together and compared/ contrasted.
Like the endogenous ligand actions will end through uptake and then enzymatic breakdown (eg. by MAO)

Question 2

Catecholamines are generally well absorbed after

Answer 2

Catecholamines are generally well absorbed after injection but are rapidly metabolized in the GI tract after oral administration (low oral bioavailability). They are also generally used in emergent situations where oral use is generally inappropriate.

Question 3

Do most catecholamines cross the BBB?

Answer 3

Most catecholamines do not cross the BBB and so effects are going to be seen on peripheral organ systems.

Question 4

Epinephrine

Answer 4

Epinephrine (Adrenalin®)

• Activates all adrenergic receptors (alpha-1, alpha-2, beta-1, beta-2, and beta-3)
• Available as solution for injection 1:1000 (1mg/mL) in ampules or vials
• Can be given IV, IM, SC, intratracheal but generally NOT given PO

Question 5

What are the indications to give Epinephrine?

Answer 5

Indications:
o Typically used in situations where a vasopressor is needed –  Cardiac arrest
 Anaphylaxis or anaphylactoid reactions
 Situations in which significant vasoconstriction and positive inotropy are needed

Question 6

What are the cautions for Epinephrine?

Answer 6

Cautions:
o Contraindicated in some forms of glaucoma, shock due to causes other than anaphylaxis,
some cardiac diseases and any situation where vasoconstriction is contraindicated.
o Avoid with other drugs that sensitize the heart to catecholamines (some anesthetics)
o Avoid with tachycardia, tachyarrhythmias or high risk of them developing

Question 7

Norepinephrine

Answer 7

• Agonist at alpha receptors primarily, beta-1 receptors (at higher doses), minimal beta-2
• Injectable formulations available, given IV
• At doses similar to epinephrine it will tend to increase the mean blood pressure more (more
  potent vasoconstriction because of lack of beta-2 effects)
  o Because of this can cause a baroreceptor response (reflex vagal bradycardia) at lower
  doses than you’d expect with epinephrine.
• Cautions as for epinephrine, also avoid extravasation (potential for tissue damage)

Question 8

Dopamine

Answer 8

Precursor to NE, acts directly & indirectly on alpha and beta-1 receptors, and dopamine receptors.

• Available as solutions for injection (as with other catecholamines it would have poor oral bioavailability), has a very short half-life. Given as an IV infusion
• Cautions as for epinephrine, as with norepinephrine avoid extravasation (tissue damage)

Question 9

At low dose Dopamine

Answer 9

At low doses it will act predominately on peripheral dopamine receptors, causing dilation of vascular beds (particularly renal, mesenteric, coronary, and intracerebral)

Question 10

At moderate dose Dopamine

Answer 10

At moderate doses it will also activate beta-1 receptors, causing positive inotropic and then chronotropic effects on the heart

Question 11

At very high doses Dopamine

Answer 11

At very high doses it will also activate alpha-1 receptors and cause release of NE, leading to vasoconstriction

Question 12

SYNTHETIC CATECHOLAMINES:

Answer 12

Dobutamine and Isoproterenol

Question 13

Dobutamine

Answer 13

• Synthetic beta-1 agonist, with weak beta-2 and alpha-1 activity (tend to cancel each other out)
• Available as an injectable solution (various concentrations), very short half-life (minutes)

Question 14

What kind of inotrope is dobutamine?

Answer 14

Generally used as a positive inotrope (more inotropic effect than chronotropic effect)
o May increase cardiac blood flow and oxygen demand

Question 15

What are the cautions of Dobutamine?

Answer 15

Catuions: Similar to epinephrine, caution with increased myocardial oxygen demand (ie after
myocardial infarction).

Question 16

Isoproterenol

Answer 16

synthetic nonselective beta-1 and beta-2 agonist (not commonly used anymore)
- Available as an injectable solution (1:5000 or 0.2mg/mL)

Question 17

What can Isoproternol treat?

Answer 17

• May be used to treat bradyarrhythmias or acute bronchoconstriction
  o Will increase inotropy, chronotropy but also increases myocardial oxygen consumption and decreases peripheral vascular resistance. Will cause some bronchiolar relaxation. (More commonly parasympatholytics (eg. atropine) will be used to treat bradyarrhythmias) and more selective beta-2 agonists to treat bronchoconstriction)

Question 18

Cautions of Isoproternol?

Answer 18

Cautions: Can cause tachycardia and lead to tachyarrhythmias