Autonomic Nervous System: Organ Effects

• Particular organ: The following notes are about how the sympathetic and parasympathetic nervous systems affect particular organs

Eye (Pupil Size)

• Parasympathetic stimulation constricts pupils via the sphincter pupil muscle, which is a circular muscle, using M1 receptors
• Sympathetic stimulation dilates pupils via the dilator pupil muscle, which is a radial muscle, using Alpha 1 receptors

Eye (Lens Accommodation)

• Parasympathetic stimulation causes the ciliary muscle to contract, making the lens bulge for close vision
• Ciliary muscle contraction enhances the drainage of aqueous humor
• Glaucoma treatment involves contracting the ciliary muscle to drain excess aqueous humor, requiring stimulation of M1 or M3 receptors
• Sympathetic stimulation inhibits the ciliary muscle via Beta 2 receptors, allowing for far vision

Heart Muscle

• Sympathetic stimulation increases heart rate and force of contraction via Beta 1 receptors; norepinephrine at heart; adrenaline/epinephrine in circulation
• Parasympathetic stimulation decreases heart rate via M2 receptors

Arterioles

• Located between major arteries and capillary beds, arterioles regulate blood pressure and flow and typically only have sympathetic innervation
• Alpha 1 stimulation causes smooth muscle to contract, leading to vasoconstriction and increased blood pressure in systemic arteries and arterioles
• Alpha 2/Beta 2 stimulation causes smooth muscle relaxation, resulting in vasodilation
• Vasodilation in coronary arteries increases blood flow to the myocardium
• Vasodilation can also increase blood flow to skeletal muscles
• There is more alpha 1 than beta 2 stimulation, therefore stimulation increases blood pressure system-wide
• Arterioles supplying erectile tissues in the penis/clitoris are an exception and can be doubly innervated
• Parasympathetic stimulation results in erection
• Sympathetic stimulation results in ejaculation

Lungs

• Sympathetic stimulation relaxes smooth muscle around bronchi, causing bronchodilation, and stops bronchiole gland secretion via B2 receptors
• Parasympathetic stimulation constricts smooth muscle around bronchi, causing bronchoconstriction and stimulates bronchiole gland secretion via M1, M3 receptors
• Asthma medication may stimulate B2 receptors or inhibit M1, M3 receptors

Lacrimal/Nasopharyngeal Glands

• Only parasympathetic innervation occurs via M1 receptors
• Decongestants like neosynephrine (phenylephrine) and CLARITIN-D (pseudoephedrine) are potent alpha 1 receptor agonists
• They cause vasoconstriction of vessels going to glands and stops mucus secretion
• There is no sympathetic innervation; they act to inhibit blood flow

Urinary Bladder

• The urinary bladder is innervated by both sympathetic and parasympathetic nerves
• The two muscles include the detrusor muscle (bladder wall) and the sphincter muscle (at the juncture of the bladder and urethra)
• Sympathetic stimulation relaxes the DETRUSSOR muscle (beta 2) and contracts the sphincter (alpha 1), which inhibits urination/promotes continence
• Parasympathetic stimulation contracts the detrusor muscle (M3) and relaxes the sphincter muscle (M2), which promotes urination/can cause incontinence
• Duvoid is a strong muscarinic stimulator (agonist) used for trouble urinating
• This is helpful after surgical anesthetic to treat non obstructive urinary retention

Gastrointestinal Motility

• Gastrointestinal motility receptors are Beta 2 / M1, M3
• Parasympathetic stimulation enhances motility via M3 receptors
• Sympathetic stimulation inhibits motility via B2 receptors and secretions

Other Organs Innervated by ONLY Sympathetic Nerves

• Piloerector muscles
• Eccrine sweat glands

Cholinergic Drugs: Overall Considerations

• Cholinergic drugs overall stimulate more muscarinic receptors than nicotinic receptors
• More visceral effects are expected if stimulating Acetylcholine (ACH)

Cholinomimetics (Agonists): Drug Info and Clinical Use

• Not broken down as well as ACHase, increases have life of ACH
• Are drugs which mimic the actions of acetylcholine
• Clinical use is glaucoma where there is a buildup of aqueous humor
• Pilocarpine(isopto-carpine) is an M STIMULATOR (RECEPTOR AGONIST) that causes contraction of the ciliary muscle, which bulges eyeball, so it increases drainage
• Duvoid is an M STIMULATOR (agonist) used to promote urination with Non-obstructive Urinary Retention
  • After REACTION TO SURGICAL ANESTHETIC
  • Contraction of detrussor muscle relaxes sphincter muscle
• Nicotine, nicorette, nicoderm- used as a tobacco substitute
  • N STIMULATOR –USED TO QUIT SMOKING – BIPHASIC ACTION
  • AT LOW DOSES STIMULATES, but at HIGH doses INHIBITS - toxic

Receptor Antagonists

• N1 RECEPTOR ANTAGONISTS (BLOCKERS)
  • Are muscle relaxants/intubation
  • Curare (TUBADIL or DTC) – N1 BLOCKER, Succinylcholine =(ANECTINE) – ALLOWS ONE DEPOLARIZATION THEN BLOCKS N1
• N2 RECEPTORS ANTAGONISTS (BLOCKERS)
  • CLINICAL USE – HYPERTENSIVE CRISIS, Trimethaphan -used during anesthesia to produce a controlled hypotension
  • Mecamylamine – treatment for essential hypertension
• MUSCARINE RECEPTOR ANTAGONISTS (BLOCKERS)
  • Blocks post ganglionic parasympathetic sites
  • Atropine is a muscarinic blocker and causes pupils to dilate
    • It takes hours to wear off
  • Mydriacyl is used today and wears of quickly
  • Treats Bladder Instability - Incontinence – uncontrolled urination, because stimulating makes the detrussor muscle contract and the sphincter to relax, to cause more bladder stability use DETROL
  • BENTYL-Used to treat IRRITABLE BOWL SYNDROME to decrease motility GI TRACT-USED TO BLOCK M RECEPTORS -TO DECREASE MOTILITY
    • Scopolamine treats Nausea, motion sickness
    • Is also known as levo-duboisine and hyoscine
    • deadly nightshade derivative

ANTI-CHOLINESTERASES

• Counteract the effects of ACHase
• They Prolong life of ACH, same effect same as cholinomimetics
• Physostigmine treats Myasthenia gravis, this is an autoimmune disease where immune cells inappropriately target ACH receptors (N1)
• Anti-cholinesterases are used to keep ACH in neuromuscular junction longer
• Found in Insecticides/ war gases
• MALATHION; PARATHION; SARIN

Adrenergic Presynaptic Effects

• BLOCK TRANSMITTER SYNTHESIS
  • DEMSER which blocks synthesis of norepinephrine and epinephrine - By blocking the ENZYME TYROSINE HYDROXYLASE that catalyzes L-TYROSINE TO L-DOPA (so less precursor)
    • Results in a decrease in sympathetic effect, once used to treat hypertension
• FALSE TRANSMITTER, methyldopa = ALDOMET
  • Enters the catecholamine pathway instead of L-DOPA
  • Is converted by an enzyme to methyl norepinephrine, which has no effect on ALPHA 1 OR B1 receptors
  • Does bind to ALPHA 2 receptors, inhibits the release of norepinephrine and neurotransmitters which results in shutting down the sympathetic effect
  • Is anti-sympathetic and once used to treat hypertension
• BLOCK RELEASE
  • ISMELIN is used for HTN, used to decrease sympathetic activity by blocking the release of norepinephrine and epinephrine
• BLOCK TRANSPORT OF NE INTO THE STORAGE VESICLES
  • RESERPINE which inhibits the transport into vesicles, it’s results is MAOs breakdown and MAOs help decrease sympathetic activity
• False displacement
  • Amphetamines, e.g. ephedrine (DEXADRINE) that increase sympathetic activity which inhibits dopamine and increases noradrenaline and serotonin
  • Results an increases sympathetic effect to treat hypotension and narcolepsy

Adrenomimetics, Post-synaptic (Receptor) Effects

• Alpha 1 agonists: Promote sympathetic effects, used to treat Shock
• Epinephrine - Alpha 1 (& Alpha 2, & Beta 1 and Beta 2, EPIPEN
• Norepinephrine = LEVOPHED Alpha1 & Alpha 2; Beta 1 & Beta 2
• Nasal decongestants-Alpha 1 agonists- decrease blood flow to glands, ex: Phenylephrine=NEOSYNEPHRINE; pseudoephedrine
• Alpha 2 agonist – causes inhibitory effect, e.g, Clonidine (CATAPRES), used to treat hypertension

Receptor Effects (Continued), Beta Agonists

• Beta 1 agonist –Increases Cardiac output, treats Cardiac Arrest, Heart Failure, Shock
• Beta 2 agonist- asthma / delay labo
• Both beta 1 and 2: can bind either /not as specific
  • ISUPREL treats shock
• Beta 1 agonist – more selective which is DOBUTREX
• Beta 2-agonist – more selective
  • Asthma treatment: Albuterol, PRO-AIR, PROVENTIL, MAXAIR
  • Decrease uterine myometrial activity: Ritodrine

Sympathetic Antagonists; Alpha Blockers

• Treats hypertension by blocking Alpha Receptors on Arterioles and decreasing BP
• MINIPRESS which block Alpha 1
• HYTRIN blocks Alpha 1
• Treat enlarged prostates by blocking the sympathetic effects of relaxing detrusor muscle and constricting sphincter
  • FLOMAX
  • CARDURA

Post-synaptic (Receptor) effects; Beta Blockers

• Decrease heart rate and force of contraction and lower O₂ demand
• Are used to treat hypertension and angina
• B1 & B2 blocker: Propranolol (generalized beta blocker - non-specific)
  • Used for HYPERTENSION but not good for people with asthma)
  • B1 specific blockers GOOD HYPERTENSIVE DRUGS
    • TENORMIN
    • Metoprolol
• Alpha and beta combinations
  • COREG - Beta 1 and Beta 2 blocker AND alpha 1 blocker
    • Alpha 1 working at vasculature while beta is working at the heart