Autonomic NS

the study of drugs that affect the processes controlled by the nervous system. Includes Peripheral NS drugs and Central NS drugs.

A nerve impulse is sent down the axon to the axon terminal. Drugs that affect axonal transmission are non-selective and local anesthetics are about the only ones we use. Next is synaptic transmission. Various neurotransmitters are released that carry the conduction of the impulse across the synaptic gap to the receptor on the post-synaptic neuron. Drugs can alter the neurotransmitters themselves, their release into the junction, or their removal from the junction after use. Lastly is receptor activation. NT activate receptor sites on the PS cell and spread the impluse conduction. Drugs that alter receptor activity can either block or activate these sties and can be highly specific.

• 1. NT synthesis
• 2. NT storage
• 3. NT release
• 4. Receptor binding
• 5. Termination of transmission - reuptake, enzyme degredation, diffusion

There are many different subtypes in each receptor group. For example, there are B1 and B2 receptors in the B group. Drugs can be made highly specific to only activate one type of receptor and can thus narrow down the processes that are affected by that drug.

• Sympathetic -fight or flight
• regulates CV system, body temp, blood flow during trauma or exertion, oxygenation, energy mobilization
• Parasympathetic - rest and digest
• slows HR, digestion, elimination, pupil cons, focus near vision, constrict bronchi, reduce cardiac work to conserve energy

• Both Para and sympathetic NS have preganglionic neurons that go from the spinal cord to the ganglion. Then another neuron that goes from the ganglion to the various organs. Drugs can affect these nerves at ganglionic junctions or at organ junctions.
• *The sympathetic NS also has nerves that go from the spinal cord to the adrenal medulla and stimulate the release of epinephrine in the fight or flight repsonse.

• Almost all organs are innervated by both branches of the ANS. Much like the gas and brakes of a car. At each organ there is usually one system that is in primary control. It will maintain function until a receptor tells the brain that it's too much, and the brain will stimulate the other system to back things down. Once balance is restored the brain will turn off the extra and normal control will take back over.
• * In a few cases, such as blood vessels, only one system (sympathetic) has innervation.
• * The male anatomy has innervation by both systems but the effects work together to produce erection and ejaculation.

• Ach - ALL ganglionic junctions, ALL parasympathetic effector organ sites, sympathetic sweat glands, ALL motor neurons
• NE - ALL sympathetic effector organ sites (except sweat)
• Epi - Adrenal medulla (sympathetic)

N

• Nicotinic N - Ach at Ganglionic Junctions
• Nicotinic M - ACh at Motor Neurons
• Muscarinic - ACh at Para Junctions and Sweat Glands
• a or B - NE and Epi and Symp Junctions

• alpha 1 - eye, arterioles, veins, male sex organs, prostate, bladder (constrict/contract)
• alpha 2 - presynaptic nerve terminals (inhibit transmitter release)
• beta 1 - heart (incr rate, force, conduction), kidney (renin release)
• beta 2 - arterioles, bronchi, uterus, liver, skeletal muscle (dilate/ relax; make sugar)
• dopamine - kidney (dilate vasculature)

• Nicotinic N - ALL ganglionic junctions and adrenal medulla
• Nicotinic M - ALL neuroMuscular junctions
• Muscarinic - eye contranction, heart (decr rate), lung (constrict/secretions); bladder (elimination), GI (salivation, incr secr, tone and motility, defecation), sweating, erection, VasoDilation

choline + CoA = ACh > storage vesicles > release into junction > broken down by Acetylcholinesterase (AChE); left over choline is taken back up for re-use

• Phenylalanine-Tyrosine-Dopa - storage vesicles - transformed to NE > released for use > taken back up into cells > 1. reused or 2. broken down by MOA
• *There are drugs that can alter almost every step in the synthesis, storage, release, use and reuptake of NE

same as NE, then, in adrenal medulla, and enzyme changes NE into Epi and stores for release. After working, mostly is broken down by hepatic metabolism.

rest and digest system; uses cholinergic receptors (Nn, Nm, and M) and therefore ACh; receptors in eye, heart, bladder, bowel, pupil, bronchial smooth muscle, gastric glands. Primary functions are digestion of food, energy conservation and rest

Effects - bradycardia, incr sweating/salivation/ bronchial secretions/gastric acid, bronchial constriction, incr GI tone and motility, bladder emptying, vasoDilation thus hypotension, pupil const.

• Precautions - Watch people with brady, asthma, GI/ bladder obstruction, hypotensive
• *causes unpleasant sweating, salivation, diarrhea and cramping in some people.

Effects - incr HR, decr salivation/bronchial secretions/gastric acid, bronchial dilation, decr GI motility and tone, delayed bladder emptying, pupil dilation

• Adverse - pts complain of dry mouth , photophobia and blurred vision, constipation, urinary retention, tachycardia.
• * poisoning can be treated with physostigmine (AChE inhibitor) - symptoms include dry mouth, hyperthermia, hallucinations and dreams, dry hot/skin. death can result from resp depression

• Prevent the breakdown of ACh and therby increase stores at the synaptic gap. Can be considered indirect cholinergic agonists. Neostigmine attaches to ChE but takes a long time to be broken down, thus taking up the ChE's time and letting more ACh build up in the junction. Primarily work at muscarinic receptors on organs and Nm receptors at the NMJ.
• Cause the usual cholingeric effects PLUS increase force of contraction in muscles.

cholinergic effects of these two drugs will be virtually the same. They have the same end result, incr stimulation of M receptors.

• Main clinical application is Myesthenia Gravis, also to reverse NM blockade
• Adverse effects - excessive muscarinic stimulation, NM blockade at toxic levels because it keeps muscles depolarized.
• Contraindications - GI/urinary obstruction, peptic ulcer disease, asthma, hyperthyroidism

bind to ChE and can't be broken down for so long that new ChE must be made before ACh can be degraded. Used primarily as an insecticides. Extreme caution must be taken. Causes cholinergic crisis and depolarizing NMJ blockade which can cause respiratory parylsis and death. Give Pralidoxime to reverse binding, atropine to counteract overstim with ACh, intubate with oxygen to protect airway and diazepam to supress convulsions.

Used for muscle relaxation during surgery, intubation, mechanical ventilation and ECT therapy. Make sure they are accompanied by adequate anesthesia and pain control because they don't block consciousness or perception of pain. Make sure airway and rescue meds are immediately available. Be very careful in pts with MG or hx of malignant hyperthermia. Never give with AChE inhibitors and certain abx.

Epi and NE, dopamine

• alpha 1 - eye, bladder, prostate, arterioles, veins, male sex organs (constriction/contraction)
• beta 1 - heart (incr rate, force, conduction), kidney (renin release)
• beta 2 - arterioles, lung, uterus, liver, skeletal muscle (dilation/relaxation)

• 1. direct receptor binding
• 2. promotion of NE release
• 3. inhibition of NE reuptake
• 4. inhibition of NE inactivation

• alpha 1 - vasoconstriction, mydriasis
• Central alpha 2 - reduction of symp outflow to heart and BV, relief of severe pain
• beta 1 - cardiac arrest, heart failure (+ inotropic effect), shock, AV heart block
• beta 2 - bronchodilation, delay of preterm labor

• epinephrine - a1, a2, B1, B2
• norepi - a1, a2, b1
• isoproterenol - b1, b2
• dobutamine - b1
• dopamine - a1, B1, dopamine

• ephedrine - a1, a2, B1, B2
• phenylephrine - a1
• terbutaline - b2

• Used for HTN and BPH, also pheochromocytoma and Raynaud's
• Adverse effects - orthostatic hypotension, reflex tachycardia, nasal congestion, inhibition of ejaculation

• Reduce heart rate, contractility and conduction, inhibit renin release thus tx for angina, HTN, dysrhythmias, MI, HF, hyperthyroidism, stage fright
• Adverse effects - bradycardia, reduced CO, precipitation of HF, AV heart block
• beta 2 blockade - bronchoconstriction, inhibition of glycogenolysis (careful with asthma and diabetics)

• Prazosin and Hytrin both block alpha 1's in the blood vessels and are used for HTN.
• tamulosin and afluzosin are selective for alpha1's in the prostatic capsule and bladder neck and are used only for BPH.

These drugs are used primarily for HTN, angina and tx after MI. They have a limited but tricky use in HF also. Patients with asthma, diabetes or other respiratory disease should be given B1 selective blockers to prevent bronchoconstriction and inhibition of glycogenolysis.

• Propranalol - B1 and B2, dangerous for asthma, diabetes
• Atenolol - B1 selective
• Labetalol - B1, B2 and A1, these drugs also cause vasoD which can help further with HTN.

Watch out for patients with severe allergy with certain BB because they can inhibit epinephrine. Watch for asthma and diabetics with Beta 2 blockers. If given with CCB, watch out for over suppression of cardiac due to similar actions of some.