Test 1- DIRECT ACTING BETA ANTAGONISTS (“BETA BLOCKERS”)

Question 1

DIRECT ACTING BETA ANTAGONISTS (“BETA BLOCKERS”)

Answer 1

As a group the beta-adrenergic antagonists can be considered similar in that they will generally decrease cardiac rate and/or contractility. They are primarily used to treat tachycardias. The degree of beta-2 antagonism (i.e. whether selective or non-selective) varies between different beta-blockers.

Question 2

Propanolol

Answer 2

Non-selective beta-antagonist (may actually be an inverse agonist).
- Causes bradycardia through decreased firing of the sinoatrial (SA) node, decreased
atrioventricular (AV) node conduction, decreased cardiac output and myocardial oxygen demand. Can increase airway resistance. Also has membrane stabilizing effects (on neurons and muscle) which may provide additional benefit.
- Available as oral or injectable formulation

Question 3

Does Propanolol have a high or low bioavailability?

Answer 3

Undergoes significant first-pass effect (oral bioavailability ~2-27%) but still can be used orally.
Most excretion in the urine as metabolites, T1/2 1-2hrs.

Question 4

What does Propanolol treat?

Answer 4

Clinically used to treat tachyarrhythmias (supraventricular), such as in adjunctive therapy in feline
hyperthyroidism or treatment of methylxanthine (chocolate) toxicosis.

Question 5

What are the cautions of propanolol

Answer 5

Cautions:
o Can cause bradycardia, hypotension, bronchospasm (beta-2 blockade)
o Contraindicated with overt heart failure, sinus bradycardia, heart block or bronchospastic
lung disease.
o Receptor desensitization and upregulation can occur (more reported in humans)
o Caution if hepatic or renal disease, hypoglycemia (can mask signs, also can alter glucose
levels), digitalis treatment (additive cardiac effects).

Question 6

Timolol

Answer 6

Timolol (Timoptic® ophthalmic): Will be discussed with ophthalmic medications.

Question 7

Metoprolol

Answer 7

Beta-1 selective antagonist
- Has been used in the treatment of methylxanthine (chocolate) toxicity as propanolol may delay
renal excretion of the toxin somewhat. It is also longer acting than other beta-blockers.

Question 8

Atenolol

Answer 8

• Beta-1 selective antagonist
• Available as oral tablets
• Does not cross the BBB as much as propanolol, requires minimal liver metabolism (about half is
  excreted unchanged in the urine and half in the feces). Half-life is longer than propanolol.
  Beta-1 selectivity means less effect on beta-2 receptors in the lungs, so this may be a better choice
  in patients with bronchial disease (eg. asthma)

Question 9

Esmolol

Answer 9

• Beta-1 selective antagonist
• Injectable, does not cross the BBB, has very short duration of action (~20 mins)
• Lacks membrane-stabilizing effects of propanolol. Consider in situations where the short duration
  would be of benefit (eg. testing response to beta-blocker therapy).

Question 10

Sotalol

Answer 10

• Class III anti-arrhythmic and non-selective beta blocker (less potent beta blocker than propanolol)
• Sotalol acts as an anti-arrhythmic by prolonging the duration of cardiac action potentials and
  refractory period thus, unlike the other beta-blockers, it is used to manage ventricular tachyarrhythmias.

Question 11

Carvedilol

Answer 11

Non-selective Beta-1 antagonist with selective alpha-1 blocking activity.

Question 12

Reserpine

Answer 12

Clinically relevant INDIRECT acting sympatholytics- ONLY ONE- Indirect acting sympatholytics will generally alter synthesis, storage or release of norepinephrine. Of these the only drug to remember is;

• Indirect acting sympatholytic
• Blocks vesicular monamine transporters thus reducing norepinephrine uptake into vesicles and
  leading to reduced storage of NE and mediator depletion. It is used as a calming agent for equines in situations such as long-term stall rest.