20. What is the treatment of choice
for anaphylactic shock?
Epinephrine
Why?
It is the only drug that addresses the
most serious manifestations:
• β1 increases cardiac output
• β2 relaxes constricted bronchioles
• α1 constricts capillaries
This is the starting point. Important to remember that they also work in the CNS.
Heart muscle as an example; other important organs are blood vessels, bronchial smooth muscle, urinary bladder, eye, uterus, and kidney. He made the point that sympathetic and parasympathetic influences are usually opposite to each other.
Exception to the dual innervation generality. Important because the primary determinant of blood pressure is peripheral vascular resistance.
Why is this important? (Parkinson’s disease)
Actually, of minor importance with regard to regulation of catecholamine activity. Nevertheless, MAO inhibitors will be important later on.
The major mechanism for inactivation of norepinephrine activity in the synapse. We will revisit this system later. Cocaine is a NE reuptake inhibitor, any some of the antidepressants are reuptake inhibitors.
These drugs are not important at this point, though all will come up again later. This is mainly to illustrate some of the mechanisms that various drugs employ to interact with the sympathetic nervous system.
In the gut, both alpha and beta receptors cause relaxation. In the heart, beta 1 is excitatory (heart rate, conduction velocity, force of contraction).
Different from NE inactivation. In this case enzymatic degradation is important. Anticholinesterase drugs are important.
Preview of the next 8 slides. These are all drugs to know.
Also used for the treatment of xerostomia (dry mouth). Stimulates salivation. Why are they not used for bronchial asthma, et al.?
These are muscarinic receptor antagonists. Side effects are important; antimuscarinic effects come up with other drugs. The five subtypes of muscarinic receptors probably explain the differences in susceptibility of various functions to these drugs.
Which one depends upon how long the agent remains bound to the cholinesterase, thereby inactivating it. eye - miosis, decrease in intraocular pressure GI - stimulates secretions and augments motor activity; used to treat paralytic ileus. Urinary tract - contract detrusor muscle, relax sphincters, i.e., promotes urination. Skeletal muscle - stimulates contraction.
Atropine blocks muscarinic receptors, but has no effect on nicotinic receptors, so mechanical support of respiration may still be necessary.
Paralytic ileus is spasm in the GI tract, often postoperatively. Severe constitpation. Myasthenia gravis is an autoimmune disease directed against nicotinic receptors. Must control muscarinic side effects (atropine).
Remember that pancuronium is a competitive nicotinic receptor antagonist. Tubocurarine also in the competitive group, and one that he said to remember. Remember (1) mechanism of action, (2) duration of action, and (3) side effects.
Reflexes must be considered in addition to the drug effects.
Massive release of histamine leads to vasodilation and a fall in blood pressure, and release of leukotrienes leads to bronchiolar contriction.
“ Selective” doesn’t mean “specific.” Beta 1 effects are still possible.
Most effects mediated through contraction of smooth muscle. Hypertension is a contraindication.
Phenoxybenzamine and phentolamine only used with pheochromocytoma until the tumor is removed. Prazosin more commonly used for other hypertension. Remember the first dose effect with prazosin.
What is the problem with beta blockers in bronchial asthma? (life-threatening breathing problems). So would you give a beta-1 selective drug to an asthmatic? (No; selective does not mean absolutely specific).
Abrupt withdrawal from beta blockers is dangerous due to the aquired supersensitivity to norepihephrine.
Grossly oversimplified as to regulation of muscle tone and movement, but it demonstrates the rationale for Parkinson’s therapy. Though successful, what was done to make it better? (decarboxylase inhibitors)
Inhibit the metabolism (decarboxylation) in the periphery to get more L-dopa into the brain. Further inhibit subsequent metabolism with tolcapone and selegiline.
GI and hypotesive effects dramatically reduced by combining L-dopa with carbidopa. Dyskinesias and psychiatric reactions not affected.
