1. Beta receptors:

• Arterioles

2. Alpha receptors:

• precapillary sphincters
• venules
• capacitance veins

Phenoxybenzamine: irreversible, non-selective alpha-1 and alpha-2 blocker

Phentolamine: reversible alpha-1 and alpha-2 blocker

Yohimbine: reversible alpha-2 blocker

"osins": reversible alpha-1 blockers

1. If you block beta or stimulate alpha-2 receptors you decrease sympathetic tone (decreased cAMP levels, HR and contractility)

2. If you block alpha-2 receptors you increase sympathetic tone.

3. If you stimulate alpha-2 receptors (clonidine/dexmedetomidine) you decrease sympathetic tone.

Prazosin competes with Nepi at alpha-1 receptors (alpha-1 blockade) causing:

• a reduction in afterload (via alpha-1 receptors on precapillary sphincters)
• a reduction in preload (via alpha-1 receptors in veins) causing orthostatic hypotension

1. To reduce spinal induced hypotension

2. Maintain intravascular volume after the onset of sympathetic blockade

1. Beta adrenergic agonists increase serum glucose levels.

2. Beta adrenergic antagonists decrease serum glucose levels

3. Alpha-2 receptors decrease insulin secretion, leaving more glucose in the blood.

4.  Beta-2 receptors increase insulin secretion and extract glucose from blood for storage (opposite alpha-2 receptors).

What do you expect from a combo of:

• propranolol and isoproterenol?
• epinephrine and propranolol?
• Norepinephrine and phentolamine?

Propranolol: beta-1 and beta-2 blocker

isoproterenol: synthetic catecholamine that stimulates b-1 and b-2

epinephrine: alpha and beta agonist

phentolamine: blocks alpha effects

Norepinephrine: alpha and beta agonist

1. propranolol and isopreterenol: propranolol will block the actions of isoproterenol preventing cardiac stimulation (such as decreased MAP adn diastolic pressure)

2. epinephrine and propranolol: alpha effects

3. norepinephrine and phentolamine: beta stimulation

Signs and symptoms:

1. exaggerated effects of thyroid hormone

2. induced hypermetabolism

3. stimulation of adrenergic nervous system

4. enhancement of effects of catecholamines

Drugs to treat:

1. non-selective beta blockers to block or minimize sympathomimetic symptoms

• Propranolol

Labetolol: alpha and non-selective beta adrenergic receptor blocking agent. More potent at beta than alpha adrenergic receptors.

1. non-selective antagonist at beta-adrenergic receptors

2. competative antagonist of post synaptic alpha-1 adrenergic receptors.

Carvedilol: Non-selective potent antagonist of beta-1 and beta-2 adrenergic receptors. Potent alpha-1 adrenergic antagonist.

1. Unique b/c it can selectively block alpha-1 receptors while acting as non-selective beta adrenergic blocker.

Cardioselective beta-1 blockers:

• acebutolol
• atenolol
• esmolol
• metoprlol

(non-selective beta blockers (that block both beta-1 and beta-2) can lead to severe exacerbation of bronchospasm in patients with asthma.

*The only place you find beta-1 receptors are in the heart and kidneys*

1. Which beta blockers have "intrinsic sympathetic activity"?

2. What does that signify?

3. What are the clinical indications for these medications?

Intrinsic sympathetic activity (ISA) is the ability of a beta blocker to exert partial agonism at the adrenergic receptor while blocking endogenous catecholamines from binding to receptor.

• competative binding to receptor --> antagonist activity
• partial interaction at receptor's activation site --> agonist activity

1. Acebutolol - moderate effects

2. Pindolol - high effects

Patients that would benefit from agonist activity but have pre-existing problems with: bradycardia, CHF compromised pulmonary function, or withdrawl of beta-adrenergic antagonist therapy.

1. resperdine: antihypertensive and antipsychotic agent

• vesicular monoamine transporter responsible for transporting free Nepi, 5HT and dopamine into presynaptic nerve vesicles for later release.
  
• Unprotected (not in vesicles) neurotransmitter can be metabolized by MAO

Guanethidine: antihypertensive drug

• reducing release of catecholamines such as Nepi
• transported across the sympathetic nerve membrane the same way Nepi is
  
• competes with Nepi and replaces it inside the vesicles --> depleting available stores of Nepi