Pharm: Physiology of the Peripheral Nervous System

Peripheral nervous system

somatic-voluntary

autonomic-involuntary (parasympathetic, sympathetic)

Overview of autonomic nervous system

-regulates heart

-regulates secretory glands

-regulates smooth muscle

-shared between parasympathetic and sympathetic

Parasympathetic

housekeeping (GI, bladder, eye)

Sympathetic

fight or flight (heart/lungs)

Autonomic nervous system regulation

-innervation and control

-feedback regulation

-autonomic tone

Receptors of nervous system: cholinergic

ACh

nicotinicN, nicotinicM, muscarinic

Receptors of nervous system: adrenergic

E and NE

-alpha1, alpha2, beta1, beta2

-dopamine

Beta 1 receptor dominate in

heart

Beta 2 receptor dominate in

lungs

Bethanechol

cholinergic drugs, muscarinic agonist

-use: relieves urinary retention

-side effects: hypotension, excessive salivation and gastric acid secretion, bronchoconstriction in asthmatics

-pilocarpine - glaucoma

-acetylcholine - ophthalmic surgery

Muscarinic Poisoning from

mushrooms, muscarinic agonists, cholinesterase inhibitors

Muscarinic poisoning effects

excessive sweating, tearing, and hypotension

Muscarinic antagonist

parasympathetic or muscarinic blockers

Atropine

cholinergic drug, muscarinic antagonist

-uses: preanesthetic medication, disorders of the eye, bradycardia, decrease intestinal motility, and muscarinic agonist poisoning

-side effects: dry mouth, blurred vision, elevation of eye pressure, constipation, tachycardia

Atropine drug interactions

antihistamines, antipsychotics, antidepressants (additive effects)

hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter

Cholinesterase inhibitors

-prevent degradation of ACh by acetylcholinesterase

-reversible and irreversible

Neostigmine

reversible cholinesterase inhibitors

-use: myasthenia gravis

-side effects: excessive salivation, increased GI secretion, sweating

Neostigmine mechanism

(does not cross membranes) binds to cholinesterase preventing it from catalyzing breakdown of ACh

Neostigmine drug interactions

muscarinic antagonist, neuromuscular blockers

Physostigmine

reversible cholinesterase inhibitor

-use: atropine poisoning

Neostigmine vs physostigmine which crosses membranes and which does not?

neostigmine does not cross membranes but physostigmine does

Myasthenia gravis

fluctuating muscle weakness and rapid fatigue

Myasthenia gravis symptoms

drooping eyelids, difficult swallowing, weakness of muscle, difficulty breathing

Myasthenia gravis: autoimmune antibodies against ________ receptors

nicotinicM

Myasthenia crisis

-extreme muscle weakness

-paralysis of muscles of respiration

Irreversible cholinesterase inhibitors

highly toxic - insecticides and nerve agents

Irreversible cholinesterase inhibitors only use is

glaucoma (Echothiopate)

Irreversible cholinesterase inhibitors poisoning symptoms

profuse sweating, urination, and bronchoconstriction, paralysis

Irreversible cholinesterase inhibitors poisoning treatment

ventilation, atropine, pralidozime

-specific to irreversible agents (binds to organophosphate)

Neuromuscular blocking agents blocks _____________ which results in ______________

nicotinicM which results in muscle relaxation

Ganglionic blocking agents block

nicotinicN (largely replaced)

Neuromuscular blocking agents: excitation - contraction: depolarization ___________ charge in vs depolarization pumps _____________ out

depolarization positive charge in vs depolarization pumps repolarization out

Tubocurarine

neuromuscular blocking agent - non depolarizing

-uses: muscle relaxation during surgery, mechanical ventilation, endotracheal intubation, and electroconvulsive therapy

-side effects: respiratory paralysis, hypotension

Tubocurarine drug interactions

anesthetics, antibiotics, cholinesterase inhibitors

Succinylcholine

neuromuscular blocking agents - depolarizing

-uses: endotracheal intubation, electroconvulsive therapy, endoscopy

-side effects: apnea, malignant hyperthermia, postoperative muscle pain, hyperkalemia

Succinylcholine mechanism of action

binds to nicotinicM receptors and remains bound resulting in constant depolarization

Succinylcholine drug interactions

cholinesterase inhibitors, antibodies

Uses of neuromuscular blocking agents

-muscle relaxation during surgery: requires anesthesia for unconsciousness

-mechanical ventilation: anesthetic required, stops movements that fight respirator

-electroconvulsive therapy: prevent convulsive movements

-endotracheal intubation: suppresses gag reflexes

Ganglionic blocking agents lack

lack selectivity

Trimethaphan

ganglionic blocking agents

-uses: controlled hypertension in surgery, hypertensive crisis

-side effects: antimuscarinic effects, hypotension

Trimethaphan competes with ACh for binding to _____________ receptors

nicotinicN

Can catecholamines cross BBB?

no

Catecholamines have a long or brief duration of action?

brief

Noncatecholamines have a long or brief duration of action?

long

Can noncatecholamines penetrate the BBB?

yes

Alpha1 activation uses

-vasoconstriction, homeostasis (epi)

-nasal decongestion (phenylephrine and ephedrine)

-delay of anesthetic absorption (epi)

-elevation of blood pressure

-pupil dilation

Alpha1 activation side effects

related to vasoconstriction

-hypertension, necrosis, bradycardia

Alpha2 activation uses

-peripheral: inhibits NE release, little clinical value

-CNS: reduce stimulation of adrenergic receptors; indirect antiadrenergic agents

Beta1 activation uses

-cardiac arrest

-heart failure

-shock

-AV heart block

Beta1 activation side effects

-altered heart rate or rhythm

-angina pectoris

Beta2 activation uses

-asthma (bronchodilator)

-delay of preterm labor (relaxation of uterus muscle)

Beta2 activation side effects

-hyperglycemia (breakdown of glycogen to glucose)

-tremor

Dopamine receptor activation uses

shock (dopamine)

-dilation of kidneys vasculature

Anaphylactic shock

-hypotension

-bronchoconstriction

-edema

What is used to treat anaphylactic shock?

Epi (all receptors)

Epinephrine

catecholamine

-receptors: alpha1, alpha2, beta1, beta2

-use: anaphylactic shock, delay of absorption of anesthetics, hemostasis, reduce nasal congestion, overcome AV heart block, pupil dilation, asthma

-side effects: hypertensive crisis, dysrhythmias, angina, necrosis, hyperglycemia

Epinephrine drug interactions

-MAO inhibitors (intensify)

-tricyclic antidepressants (block uptake)

-general anesthetics

-alpha and beta blocking agents

Norepinephrine

catecholamines

-receptors: alpha1, alpha2, beta1

-uses: hypotension and cardiac arrest

-side effects: same as epi minus hyperglycemia

Norepinephrine drug interactions

same as epi

-MAO inhibitors (intensify)

-tricyclic antidepressants (block uptake)

-general anesthetics

-alpha and beta blocking agents

Isoproterenol

catecholamine

-receptors: beta1, beta2

-uses: AV heart block, asthma, bronchospasm

-side effects: dysrhythmias, angina, and hyperglycemia

Isoproterenol drug interactions

same as epi

-MAO inhibitors (intensify)

-tricyclic antidepressants (block uptake)

-general anesthetics

-alpha and beta blocking agents

Dopamine

catecholamine

-receptors: dopamine, beta1, beta2

-uses: shock, heart failure, acute renal failure

-side effects: tachycardia, dysrhythmias, angina, necrosis

Dopamine drug interactions

same as epi

-MAO inhibitors (intensify)

-tricyclic antidepressants (block uptake)

-general anesthetics

-alpha and beta blocking agents

Dobutamine

catecholamine

-receptors: beta1

-uses: heart failure

-side effects: tachycardia

Dobutamine drug interactions

-MAO inhibitors

-tricyclic antidepressants

-anesthetics

Terbutaline

noncatecholamines

-receptors: beta2

-uses: asthma, delay of preterm labor

-side effects: tremor

Ephedrine

noncatecholamines

-receptors: alpha1, alpha2, beta1, beta2

-uses: nasal congestion, narcolepsy

-side effects: same as epi plus insomnia

Ephedrine is a mixed drug and has direct activation of ___________ and indirect activation by releasing ______

Ephedrine is a mixed drug and has direct activation of alpha/beta and indirect activation by releasing NE

Alpha adrenergic antagonists uses

hypertension, reversal of alpha1 agonist toxicity, benign prostatic hyperplasia, pheochromocytoma, Raynaud's disease

Alpha adrenergic antagonists side effects

orthostatic hypotension, reflex tachycardia, nasal congestion

Prazosin

alpha adrenergic antagonist

-receptors: alpha1

-uses: hypertension, BPH

-side effects: orthostatic hypotension, reflex tachycardia, nasal congestion

Phentolamine

alpha adrenergic antagonists

-receptors: alpha1, alpha2

-uses: pheochromocytoma

-side effects: orthostatic hypotension, great reflex tachycardia, nasal congestion

Beta adrenergic antagonist uses

angina pectoris, hypertension, dysrhythmias, MI, heart failure

Beta adrenergic antagonist side effects (beta1 and beta2)

beta1: bradycardia, precipitation of heart failure, AV heart block

beta2: bronchoconstriction, inhibits glycogenolysis (so don't give to ppl with asthma)

Propanolol

beta adrenergic antagonist

-receptors: beta1, beta2

-uses: hypertension, angina pectoris, MI

-side effects: bradycardia, heart failure, inhibition of glycogenolysis, bronchoconstriction, CNS effects

Propanolol contraindications

diabetics, severe allergic reaction, heart failure, asthma, depression

Propranolol drug interactions

calcium channel blockers, insulin

Metoprolol

beta adrenergic antagonist

-receptors: beta1

-uses: hypertension, patients with asthma or diabetes and angina or MI

-side effects: bradycardia, AV heart block

Metoprolol contraindications

heart failure, sinus bradycardia

Indirect acting antiadrenergic agents

-adrenergic neuron blocking agents (terminal of neurons)

-centerally acting alpha2 agonists (reduce outflow of impulses)

Reserpine

adrenergic neuron blocking agents

-uses: hypertension

-side effects: depression, bradycardia, orthostatic hypotension

Reserpine mechanism of action

suppresses NE synthesis and displaces NE from vesicles

-guanethidine: no CNS effects

Clonidine

centrally acting alpha2 agonists

-uses: hypertension and severe pain

-side effects: drowsiness, dry mouth, rebound hypertension

Clonidine mechanism of action

activates alpha2 receptors to decrease transmitter release

Methyldopa

centrally acting alpha2 agonists

-uses: hypertension

-side effects: hemolytic anemia and liver toxicity

Methyldopa mechanism of action

similar to clonidine except must be converted to methylNE

(clonidine: activates alpha2 receptors to decrease transmitter release)