Beta-receptors located in arterioles.

Alpha-receptors located in precapillary sphincters, venules and capacitance veins.

Phenoxybenzamine = irreversible, non-selective alpha-1 and alpha-2 blocker.

Phentolamine = reversible alpha-1 and alpha-2 blocker. It does not "cause epinephrine reversal". It blocks the alpha but not beta effects of EPI.It can trigger arrhythmias and angina and is not used in patients with decreased coronary perfusion

Yohimbine is a direct acting reversible alpha-2 blocker.

"osins" = reversible alpha-1 blockers.

tamsulosin = Flomax (used for BPH)

Important to know that if you block beta or stimulate alpha-2 receptors then you decrease sympathetic tone (eg, cAMP levels, HR, and contractility will decrease).

If you block alpha-2 receptors you increase sympathetic tone. If you stimulate alpha-2 receptors (for example with clonidine or dexmedetomidine) you decrease sympathetic tone. This is not intuitive so make sure you understand this, it will be on test.

All are alpha adrenergic blockers that block endogenous catecholamines that have a strong effect on blood pressure.

Phenoxybenzamine is non-selective and links to both a1 and a2 receptors. The block is irreversible, body has to make new adrenoceptors to overcome the drug. This takes about a day so the effects last about 24 hours for a single dose. It can be a few hours between administration and block because drug has to transform to active form. Causes postural hypotension. Blocks peripheral blood vessels from catecholamines which causes decreased peripheral resistance leading to reflex tachycardia. In heart, it blocks a2 receptors which increases cardiac output and causes more norepinephrine to be released which causes B receptors to increase cardiac output.

Prazosin, Doxazosin, Terazosin and Tamsulosin (the osins) are a1 receptor blockers. Prazosin, Terazosin and Doxazosin are useful in treating hypertension.  All decrease vascular resistance and lower arterial blood pressure by relaxing the arterial and venous smooth muscle. Tamsulosin is the least effective on blood pressure. Tamsulosin is more potent inhibitor of a1 receptors on the smooth muscles of the prostate and is used to treat BPH. There is minimal changes in cardiac output, renal blood flow and GFR with their use. The first dose causes exaggerated orthostatic hypotension(Note that this is similar to orthostatic hypotension associated with spinal and epidural anesthesia - JM).

Alpha-1 blockade reduces afterload (via alpha-1 receptors on precapillary sphincters)and also reduces preload (via alpha-1 receptors in veins). The reduced preload causes orthostatic hypotension.

To reduce spinal induced hypotension and maintain intravascular volume after the onset of a sympathetic blockade.

Spinal and epidural anesthesia may cause blockade of motor, sensory and sympathetic nerves. 

Sympathetic nerves act to maintain venous tone (alpha-receptors are located on venules and capacitance veins). 

Sympathetic blockade (either by spinal/epidural or even alpha-1 blocker drugs) causes venodilation and hypotension. 

If you do a spinal on a patient you will often see CVP and PA pressures decrease. This is why we administer a fluid bolus prior to administering spinal or epidural anesthesia.

How do beta-adrenergic agonists and antagonists affect serum glucose levels?

Describe the role of alpha-2 and beta-receptors in control of serum glucose levels.

Beta-adrenergic agonists increase serum glucose levels. Beta-adrenergic antagonists decrease serum glucose levels. 

Alpha 2 receptors decrease insulin secretion and leave more glucose in the blood. 

Beta 2 receptors increase insulin secretion and extract glucose from the blood for storage. (Opposite of Alpha 2 receptor)

What are the trade names of the following drugs:

1. Acebutolol

2. Pindolol

3. Metoprolol

4. Propranolol

5. Timolol

6. Labetalol

7. Carvedilol

8. Nadolol

1. Sectral

2. Visken

3. Lopressor or Toprol

4. Inderal

5. Timoptic

6. Normodyne or Trandate

7. Coreg

8. Corgard

These are just FYI may not be on the test.

What would you expect from a combination of propranolol and isoproterenol?

From epinephrine and propranolol?

From norepinephrine and phentolamine?

Propranolol and Isoproterenol-Propranolol is a B1 and B2 blocker. Isoproterenol is a synthetic catecholamine that stimulates B1 and B2. Since all beta blockers can block the actions of Isoproterenol on the cardiovascular system, there won't be the normal cardiac stimulation or the reduction of mean arterial pressure and diastolic pressure that is usually seen with Isoproterenol. 

Epinephrine and Propranolol-Epinephrine is a alpha and beta agonist. Propranolol is a non specific beta blocker. The combination would cause alpha effect (vasoconstriction). 

Norepinephrine and Phentolamine-Norepinephrine has alpha and beta agonist effects. Phentolamine blocks alpha effects. The result would be beta stimulation

Labetalol is a combined alpha and non-selective beta adrenoceptor blocking agent. It is a non-selective antagonist at beta-adrenoceptors and is a competitive antagonist of postsynaptic alpha-1 adrenoceptors. It is more potent at beta that alpha adrenoceptors. 

Carvedilol is a non-selective potent antagonist of beta 1 and beta 2 adrenoceptors as well as a potent alpha 1 arenoceptor antagonist.

Thyroid storm is a decompensated state due to severly exaggerated effects of thyroid hormone-induced hypermetabolism and stimulation of the adrenergic nervous system and enhancement fo the effects of catecholamines. 

Non-selective beta blockers such as propranolol are given to aid in blocking or minimizing sympathomimetic symptoms. 

Which beta-blockers have "intrensic sympathetic activity"? 

What does that signify?

What are the clinical indications for these medications?

Intrinsic sympathetic activity (ISA) is the ability of a beta-blocker to stimulate beta-adrenergic receptors weakly while also providing beta-blockade. This means it has competitive binding to the receptors producing antagonist activity and partial interaction at the receptor's activation site producing the agonist activity.

Two beta-blockers with ISA that exert this partial agonism at the adrenergic receptors while blocking endogenous catecholamines from binding to receptors are:

1. Acebutolol

2. Pindolol

The clinical indications for these medications pertain to those patients who have clinical indications which would benefit from agonist activity but have problems with bradycardia and/or mild congestive heart failure and or compromised pulmonary function. These medications would also benefit the patient who is undergoing withdrawal of beta-adrenergic antagonist therapy.

The safest beta-blockers to use for asthmatic patients are the cardioselective beta-1 blockers since non-selective beta-blockers (blocking both beta-1 and

 beta-2) can lead to severe excaberations of bronchospasm in patients with asthma.

Selective beta-1 antagonists do not appear to pose a threat with those with mild to moderate asthma.

Some familiar selective beta-blockers are acebutolol, atenolol, esmolol, metoprolol and.

See Figure 6.16 on page 80. Note the only place you find beta-1 receptors is in heart and kidneys.

Briefly discuss the pharmacology of reserpine and guanethidine.

1. Reserpine - a antihypertensive and antipsychotic drug
Works by blocking vesicular monamine transporters which are responsible for transporting free norepinephrine, serotonin (5-hydroxytryptamine) and dopamine into presynaptic nerve vesicles for later release. The now unprotected neurotransmitters are metabolized by MAO and never reach their intended targets.

2. Guanethidine - a antihypertensive drug
Works by reducing the release of catecholamines such as norepinephrine. Guanethidine is transported across the sympathetic nerve membrane the same way norepinephrine is transported (via norepinephrine transporter). Once Guanethidine is inside the presynaptic nerve fiber, it will compete with norepinephrine and will eventually replace the neurotransmitter inside the vesicles, slowly depleting the available stores of norepinephrine.

See figure 6.3 page 67. Note that reserpine blocks step 2, guanethidine blocks step 3.