CHE 360 - Autonomic Nervous System

parasympathetic

rest and digest

sympathetic

fight or flight

nicotinic Ach receptor

receptors at the ganglia that bind with both nicotine and acetylcholine

muscarinic Ach receptor

receptors that bind to ACH

nicotinic and muscarinic Ach receptor

two main types of cholinergic receptors in the body that bind the neurotransmitter acetylcholine

adrenergic receptors (a1, a2, b1, b2)

mainly bind with epinephrine and norepinephrine to mediate the sympathetics fight or flight response

monomine oxidase (MOA) and catechol orthomethyl transferase (COMT)

Two enzymes that inactivate and metabolize norepinephrine (NE) in the afferent neuron

acetylcholine

the neurotransmitter at the ganglia of both the sympathetic and parasympathetic nervous systems

epinephrine

acts on all 4 types of receptors and gives a full “fight or flight” response

bethanechol (Urecholine)

stimulates contraction of the detrusor muscle of the bladder and relaxation of the bladder sphincter, promote urination bymimicking the effects of the parasympathetic nervous system to contract the bladder wall and assist in emptying, muscarinic agonist

atropine

Muscarinic antagonist, administered before an operation (pre-op) to decrease GI motility and secretions. It also increases the heart rate and may be used to treat bradycardia, particularly in emergency medicine. It is used as an antidote for poisoning by insecticides, nerve gases, and some mushroom toxins (Amanita muscaria) that act by inhibiting acetylcholinesterase

Historically, it was used by ophthalmologists to cause mydriasis (pupil enlargement), but it has been largely replaced for that purpose because of its inconveniently long half life. The plant bella donna is a natural source of atropine which was used during the Renaissance to dilate women’s eyes to increase their “sex appeal”

tropicamide (Mydriacyl)

muscarinic agonist, common replacemnt for atropine, eye drops also act as an anticholinergic but has shorter (3-4 hour) half life

ipratropium bromide (Atrovent)

anticholinergic drug administered with an inhaler for treatment of emphysema and chronic bronchitis (chronic obstructive pulmonary disease or COPD). Its onset of action occurs in about 15 minutes and lasts for 3-4 hours. It is most commonly used in combination with albuterol (a sympathetic system stimulator) as the product Combivent. It reduces symptoms, but does not slow progression of the disease.

tiotropium bromide(Spiriva)

a newer anticholinergic administered as a dry powder inhaler that has an onset of about 15 minutes but a half life of 5-6 days! Its major advantage over ipratropium bromide is its longer half life; its major disadvantage is that it is under patent and expensive.

oxybutynin (Ditropan)

is an antispasmodic used in the treatment of some types of nocturia, incontinence, and frequent urination. It is given bid or tid. It is now available as Ditropan XL taken qd, and as a biweekly patch.

epinephrine (EpiPen)

Epinephrine stimulates all the adrenergic receptors: α1, α2, β1, and β2 receptors, nonspecifically. It produces the full fight or flight response. Epinephrine is a catecholamine, so it cannot be given orally. It must be administered by nasal inhalation, IV, SQ, or topical.

pseudoephedrine (Sudafed)

affects α1, β1, and β2, Is a non-specific adrenergic agonist and non-catecholamine drug used as a nasal decongestant. Its decongestant action is a result of nasal vasoconstriction (via α1 receptors). Formerly OTC

phenylephrine (Sudafed PE)

Many cold formulas are replacing pseudoephedrine with phenylephrine, although several studies suggest that phenylephrine is no more effective than placebo.

amphetamine (Benzedrine, Adderall) and Methamphetamine

synthetic analogues of epinephrine which have structures very similar to epinephrine. They were originally marketed for nasal congestion and as appetite suppressants, but rapid development of tolerance negated usefulness. They are now common street drugs, either injected as hydrochloride salt (crystal) or smoked in free base form (“ice”). They produce a relatively long lasting high (up to 24 hours) but tolerance develops quickly and psychoses (omnipotence, paranoia) often develop.

MDMA (ecstasy)

has a structure similar to amphetamines, produces an energy rush and “self-awareness” while eliminating anxiety and inhibition. It has been popular at parties and “raves”. There is some evidence that it may change serotonin receptors permanently. Adverse effects include increased heart rate (tachycardia), and hyperthermia, which sometimes results in heat stroke and death.

methylphenidate (Ritalin, Concerta)

Used for treatment of ADHD (attention deficit hyperactivity disorder) and other hyperkinetic syndromes. The original short-acting form must be given bid or tid, which can create scheduling problems for children in schools. However, several extended release forms (Ritalin LA, Concerta) are now available. It acts to inhibit the reuptake of dopamine and norepinephrine in the brain, effectively raising the levels and effects of those natural neurotransmitters.

doxazosin (Cardura)/tamsulosin (Flomax)

both now available in generic form. These drugs cause peripheral vasodilation but their primary use is the treatment of benign prostate hypertrophy (BPH) where they relax the prostate muscles surrounding the urethra, allowing easier urine flow in males.

metoprolol, atenolol

_______is available as a generic and is given bid. It is also available in a once-a-day form, Toprol XL. _______(Tenormin) is similar and is given once a day

carvedilol

non-specific adrenergic antagonist that blocks both α1, β1 and β2 receptors. It causes both peripheral vasodilation and slowing of the heart rate, and is used as an adjunct in congestive heart failure (CHF) and to prevent atrial fibrillations after cardiac surgery. It should not be used by asthmatics or patients with respiratory difficulties because it blocks response to beta-2 agonists.

clonidine

blocks receptors in the CNS, which inhibits sympathetic nervous system activity and decreases heart rate.

Succinylcholine

still commonly used as a neuromuscular blocking agent. Its major advantages are its very fast actions and its very fast metabolism, allowing fairly fine control of its duration of action. It is given IV, although IM injection is occasionally done in emergency intubations where starting an IV has failed. Succinylcholine is short acting because it is metabolized very quickly. Blood levels go down rapidly when administration is terminated. It is normally inactivated by a plasma pseudo-cholinesterase.

Rocuronium (Rocuronium bromide, Zemuron)

is a newer drug with a short half life (a few minutes), similar to the half-life of succinylcholine. The “bromide” part of the name simply indicates the negative ion used to balance the ionic ammonium salt form of the drug. As described above, its mechanism of action is different from succinylcholine, but the net effect is similar, and it also carries serious risks, including prolonged apnea in some patients.

varenicline (Chantix)

gives effects similar to nicotine, but lesser in degree. As such it gives less positive feedback than nicotine itself and prevents nicotine from binding to the nicotinic receptors. It has been highly touted for helping smoking cessation.

betel

Betel is a non-western nicotine-like drug that consists of a piece of the betel palm seed wrapped inside a leaf of betel pepper. The betel palm seed contains several compounds with structures close to that of nicotine which probably stimulate nicotinic receptors and may be as addictive. One side effect is copious salivation and the regular spitting of dark red saliva from pigment in the betel.