Study Guide Peripheral Nervous System

1. What are the basic principles of synaptic transmission and what are basic
receptor functions?
 Axonal conduction is the process of conducting an action potential
down the axon of the neuron.
 Synaptic transmission is the process by which information is carried
across the gap between the neuron and the postsynaptic cell.
 Synaptic transmission requires (1) the release of neurotransmitter
molecules from the axon terminal and (2) binding of these molecules
to receptors on the postsynaptic cell.
 As a result of transmitter-receptor binding, a series of events are
initiated in the postsynaptic cell, leading to a change in behavior.
 Synaptic transmission consist of five basic steps: transmission release,
transmitter storage, transmitter release, binding of transmitter to its
receptors, and termination of transmitter action by dissociation of
transmitter from the receptor followed by transmitter reuptake or
degradation.
 Many drugs act differently at receptors.
 These agents can either: (1) bind to receptors and cause activation, (2)
bind to receptors and thereby block receptor activation by other
agents, or (3) bind to receptor components and thereby enhance
receptor activation by the natural transmitter at the site.
 Most neuropharmacologic agents act by altering synaptic
transmission. Synapses, unlike axons, differ from one another.
 Drugs that alter synaptic transmission can produce effects that are
much more selective than those that alter axonal conduction.
 Local anesthetics are the only drugs proved to work by altering axonal
conduction.
 Cholinergic receptors mediate responses to ACh
 Adrenergic receptors mediate responses to epinephrine
(adrenalin) and norepinephrine

2. What are the functions of muscarinic agonist (Cholinergic) drugs? What is

the prototype direct-acting muscarinic agonist? What is it used for?
 Stimulates the PSNS, binds to cholinergic receptors (agonist)
Action similar to ACh but longer acting.
 Prototype: bethanechol (urecholine)
  Major use- urinary retention; relaxes sphincter and contracts detrusor
muscle

3. What is the difference between a direct-acting muscarinic agonist and a

cholinesterase inhibitor? What is the prototype cholinesterase inhibitor and
what is it used to treat?
 Cholinesterase inhibitors prevent the breakdown of ACh by
acetylcholinesterase
 Prototype: Neostigmine; it is a reversible cholinesterase inhibitor,
prevents the breakdown of ACh
 Used in treatment of Myasthenia Gravis
 Adverse effects: excessive muscarinic stimulation (excessive
salivation, increased gastric secretions, increased tone and motility of
the GI tract, urinary urgency, bradycardia, sweating, miosis, and
spasm of accommodation), neuromuscular blockade (paralysis of
respiratory muscles can be fatal)

4. What are common adverse reactions to these drugs and what is the
antidote?
 Common adverse reactions to muscarinic agonists: decreased
intraocular pressure, miosis (constriction of pupil), sweating,
increased salivation, increased bronchial secretions, bronchial
constriction, increased GI tone, diarrhea, decreased BP, bradycardia,
contraction of bladder detrusor muscle
 Antidote is atropine- often referred to as anticholinergic. So it is the
antidote for cholinergics but frequently used prototype antimuscarinic
 Common adverse reactions to cholinesterase inhibitors: excess
cholinergic stimulation
 Antidote is respiratory support and atropine

5. How does a muscarinic antagonist (anticholinergic) work and what are the
uses? What is the prototype drug?
 Block Ach at muscarinic receptor sites; competes at muscarinic
receptor sites and blocks the action of ACh; Actions: increases heart
rate, decreases secretions, relaxes bronchi, decreases bladder tone,
decreases GI tone and motility, dilates the pupil, CNS excitation
 Uses: dry secretions postoperatively, acute cardiac emergencies-treats
bradycardia, treat ophthalmic disorders, treatment of motion sickness
 (more likely scopolamine) and diarrhea, treat bronchoconstriction,
treat cholinergic poisoning
 Prototype drug: Belladonna alkaloids aka atropine

6. What are common side effects to anticholinergic drugs?

 Dry mouth, blurred vision, photophobia, increased intraocular
pressure, urinary retention, constipation, tachycardia, anhydrosis-
decreased sweating, asthma- from drying of secretions; cant pee, can’t
see, cant spit, cant #x?it

7. What type of drug is epinephrine? What receptors does it act on? How can
it be given?
 A type of non-selective adrenergic agonists (sympathomimetics),
catecholamine; stimulates all alpha and beta receptors
 Can be applied topically, by injection, and by inhalation, NOT orally

8. What are its uses and what adverse reactions can occur?
 Uses: (alpha1) delay absorption of local anesthetics, control
superficial bleeding, reduce nasal congestion, elevate blood pressure,
(alpha2) overcome AV heart block, cardiac arrest, (beta2)
bronchodilation in patients with asthma; cardiopulmonary arrest,
ventricular fibrillation, anaphylactic shock
 Adverse effects related to stimulation of all receptors are common
 CNS and cardiac adverse effects are the most common and may be the
most serious
 Adverse effects: hypertensive crisis, arrhythmias, myocardial
ischemia, tissue necrosis following extravasation, hyperglycemia
(gluconeogenesis), drug interactions

9. What type of drug is isoproterenol? What receptors does it act on? What
are common adverse reactions?
 An adrenergic agonist; non-selective beta agonist; Non-selective
beta 1&2 stimulant
 Beta 1&2
 Uses: AV heart block, cardiac arrest, increase cardiac output during
shock, bronchospasm during anesthesia
 Adverse effects are primarily related to cardiac stimulation
10. What is clonidine? What are side effects?
 Centrally acting alpha2 agonist; selective stimulation of alpha2
receptors
 Side effects: drowsiness, rebound hypertension, xerostomia

11. What are the uses of alpha and beta blockers? What type of adverse
reactions can occur? What are the prototype drugs and what type of client
instructions are needed?
 Alpha1 blockade-used to treat: essential hypertension, benign
prostatic hyperplasia, pheochromocytoma, Raynaud’s disease,
overdose of alpha1 agonist
 Adverse effects: orthostatic hypertension, reflex tachycardia, nasal
congestion, inhibition of ejaculation, sodium retention
 Nonselective- produces alpha1 and alpha2 blockade Prototype:
Phentolamine (Regitine)
 Selective- produces alpha1 blockade Prototype: Prazosin
(Minipress)
 Tell client the first dose may cause syncope: lie down if feeling
faint, no driving for 4 hours after taking, take before bedtime
 Beta blockade-therapeutic effects: reduces heart rate, reduces force of
contraction, reduces velocity of impulse conduction; Uses: angina
pectoris, hypertension, cardiac arrhythmias, myocardial infarction,
heart failure, migraine prevention, hyperthyroidism, stage fright,
glaucoma, pheochromocytoma
 Adverse effects: bradycardia, reduced cardiac output, precipitation of
heart failure, AV heart block, bronchoconstriction, inhibition of
glycogenolysis, rebound cardiac excitation
 Nonspecific beta blocker Prototype: Propranolol (Inderal)
 Cardioselective: blocks b1 receptors Metoprolol (Lopressor)
 Tell client to discontinue slowly to prevent rebound tachycardia
leading to angina and possibly myocardial infarction

Study Guide CNS Drugs

1. What is the impact of the blood brain barrier and CNS drugs?
 The blood brain barrier impedes the entry of drugs into the brain
  Passage across the barrier is limited to lipid-soluble agents and to
drugs that are able to cross by way of specific transport systems.
 Drugs that are protein bound and drugs that are highly ionized
cannot cross.
 The barrier can be a significant obstacle to entry of therapeutic agents

2. What is the effect of tolerance?

 Tolerance is defined as a decreased response occurring in the
course of prolonged drug use

3. What is the significance of physical dependence?

 Physical dependence is defined as a state in which abrupt
discontinuation of drug use will precipitate a withdrawal
syndrome
 Once physical dependence and tolerance have taken place, continued
drug use is required for the brain to function “normally”
 If drug use is stopped, the drug-adapted brain can no longer function
properly and a withdrawal syndrome ensues
 The withdrawal reaction continues until the adaptive changes have
had time to revert, thereby restoring the CNS to its pretreatment state

4. What is Levodopa? What is its use and what are key education principles?
 A dopaminergic agent: stimulates dopamine receptors
 Used as a drug therapy for Parkinson’sPromotes dopamine
synthesis (most common use)
 Take with food to decrease nausea and vomiting, avoid high
protein meals-may decrease drug effect and cause an “off episode,”
may take weeks or months to work, monitor on/off phenomenon-
abrupt loss of effect, end of dose wearing off, inform/monitor for
cardiac problems, monitor for orthostatic hypotension, monitor for
signs of psychosis

5. What are other treatments for Parkinson’s disease and treatments – how
do they work?
 Dopamine agonists work by stimulating the dopamine receptors in the
brain. Do not need to be converted in the brain- first line treatment for
mild to moderate disease. Pramipexole (Mirapex) and othersusually
used in younger patients less likely to develop the hallucinations
postural hypotension and daytime sleepiness they cause
  MAO-B inhibitorSelegiline (Eldepryl)-third line treatment. May be
used in combination with levodopa to decrease end of dose wearing
off. Not real effective. Some question as to whether it has
neuroprotective properties so may be used early after diagnosis
 Centrally acting Anticholinergicsblock muscarinic (cholinergic)
receptors, thereby restoring the functional balance between dopamine
and ACh ; block the action of ACh Benzotropine (Cogentin) and
Trihexyphenidyl (Artane)Anticholinergics are the oldest drug
therapy for Parkinson’s. While not as effective they are better
tolerated than Levodopa. Used most often to manage tremor in young
patients

6. What are common AEDs, adverse effects, how do they work?

 Traditional: Phenytoin (Dilantin), Carbamazepine (Tegretol),
Valproic acid (Depakote) **GI effects, Phenobarbital; Newer
agents: Oxcarbazipine (Trieptal), Gabapentin (Neurontin)
 Phenytoin (Dilantin)CNS depression, nystagmus, diplopia,
sedation, cognitive impairment, ataxia, gingival hyperplasia, skin rash,
teratogenic, cardiac dysrythmias, endocrine effects
 Carbamazepine (Tegretol)CNS effects including visual disturbances
(nystagmus, blurred vision, diplopia), ataxia, vertigo, unsteadiness,
and headache. Tolerance usually develops to these side effects.
Carbamazepine-induced bone marrow suppression can cause
leukopenia, anemia, and thrombocytopenia. Rare: fatal aplastic
anemia. Teratogenic, hypo-osmolarity, and dermatologic effects.
Avoid grapefruit juice.
 Valproic acid (Depakote)minimal sedation and cognitive
impairment. GI effects are most common and can be reduced by
administering with food. Hepatotoxicity and pancreatitis are rare but
serious.
 All drugs are CNS depressants; Phenytoin-selective inhibition of
sodium channels!!!

7. What is the drug of choice for absence seizures?

 Ethosuxemide

8. What is the classification of the drugs – baclofen and dantrolene and how
do they work? What are common adverse reactions and important education
principles?
  Drug therapy for spasticity- centrally acting muscle relaxants
 Baclofen (Lioresal)acts in the spinal cord, suppresses hyperactive
reflexes, mechanism unknown, may mimic the action of GABA on
spinal neurons, decreases flexor and extensor spasms, suppresses
resistance to passive movement, no direct effect on skeletal muscle
 Dantrolene (Dantrium)suppresses the release of calcium from
the sarcoplasmic reticulum (SR) (Does not act directly on CNS!!)
 Adverse effects of Baclofen: no antidote for overdose, gradual
withdrawal over 1 to 2 weeks, CNS depressant, GI symptoms-nausea,
constipation, urinary retention
 Adverse effects of Dantrolene: weakness, drowsiness, hepatic toxicity,
diarrhea, acne-like rash
 Important Education Principles: Patients should be advised to avoid
alcohol and all other CNS depressants
 See Diazepam

9. How do local anesthetics work? When can a vasoconstrictor be used and

what is its effect? What is the difference between an amide and an ester?
 Local anesthetics block axonal conduction by blocking sodium
channels in the axonal membrane. Recall that propagation of an action
potential requires movement of sodium ions from outside the axon to
the inside. By blocking axonal sodium channels, local anesthetics
prevent sodium entry, and thereby bring conduction to a halt.
 Block pain impulse conduction along axons by blocking sodium
channels, block both sensory and motor function
 A vasoconstrictor (usually epinephrine) decreases blood flow and
thereby delays systemic absorption of the anesthetic, which
prolongs anesthesia and reduces the risk of toxicity
 A vasoconstrictor can be used as long as the local anesthetic itself
does not have vasoconstrictive properties, if increased duration is
needed. Vasoconstrictors may be contraindicated in patients with
significant cardiovascular disease or in patients taking medications
that may increase the activity of the vasoconstrictor
 Ester RCOORmetabolized in the blood by enzymes known as
esterases; more rapid onset due to being metabolized in blood;
probably more likely to cause systemic toxicity; shorter duration of
action
 Amide RCONmetabolized by enzymes in the liver; less rapid onset;
longer duration of action