Module 2: Peripheral Nervous System Drugs (Adrenergic/Cholinergic Drugs) Flashcards
Nervous System Divisions
Central Nervous System (CNS):
- Brain: receives and processes sensory information, initiates responses, stores memories, and generates thoughts and emotions
- Spinal cord: conducts signals to and from the brain, and controls reflex activities
Peripheral Nervous System (PNS):
- Sensory neurons (sensory organs to CNS)
- Motor neurons (CNS to muscles and glands); it is further divided into the (1) Somatic Nervous System (controls voluntary movements) and (2) Autonomic Nervous System (controls involuntary responses)
Autonomic Nervous System (ANS) divisions:
1. Parasympathetic Nervous System (PSNS) — “rest or digest” (cholinergic system)
- Sympathetic Nervous System (SNS) — “fight or flight” (adrenergic system)
ANS Functions
Functions of the ANS:
1. Regulation of the heart
- Regulation of the secretory glands
- Regulation of smooth muscle of the bronchi, blood vessels, urogenital tract, and GI
Mechanism of Action Potential (AP) and Neurotransmitter (NT)
Mechanism of NT release:
1. NTs are synthesized from precursor molecules
- NTs are packaged into a vesicle
- NTs are released in response to an AP
- NTs travel across the synaptic cleft, bind to receptors on the post-synaptic cell, and produce a response; at some point NTs dissociate from the receptors, terminating the action and response
- After dissociation, a NT can undergo (1) re-uptake into the pre-synaptic nerve terminal, (2) enzymatic degradation, or (3) diffuse away from the nerve terminal
PNS Anatomy
Pre-ganglionic neurons originate in the CNS, innervate at a ganglion (synapse), and release acetylcholine (ACh) at the nicotinic receptor on the post-ganglionic neuron (which leads to the end organ)
**If drugs targeted the pre-ganglionic neuron and NT, they would NOT be specific; instead, drugs target post-ganglionic neurons, NTs, and end organ receptors
**In the somatic system, there is just one neuron that originates in the CNS, and extends to the skeletal muscles where it releases ACh on nicotinic receptors in the neuromuscular junction
Parasympathetic Nervous System (PSNS)
a.k.a. Cholinergic system
Receptor = Muscarinic (M) NT = ACh
Location of M receptors (in the PSNS):
- Cardiac and smooth muscle
- Gland cells
- Nerve terminals
**Sweat glands (in the SNS) also use M receptors and ACh
Acetylcholine (ACh)
Drugs that interfere with ACh function:
1. Agonist drugs — mimic ACh by binding at M or N receptors
- Antagonist drugs — block the effect of ACh, by binding at M or N receptors
- Influence enzymatic breakdown of ACh via acetylcholinesterase (AChE)
Parasympathetic Stimulation
Effects (“rest and digest”):
1. Slowing HR
- Increased gastric secretion
- Empty bowel and bladder
- Focusing the eye for near vision
- Constricting the pupil
- Contracting bronchial smooth muscle
Parasympathetic Blockade
Causes the opposite effects of parasympathetic stimulation
Excess blockade results in:
1. “Mad as a hatter” — psychosis and seizures
- “Dry as a bone” — decreased secretions
- “DrySLUDS” — Decreased: salivation, lacrimation, urination, defecation, sweating
- “Blind as a bat” — eyes cannot accommodate (cannot see up close), pupils cannot constrict, and photophobia
- “Red as a beet” — dilation of cutaneous blood vessels
- “Hot as a hare” — skin feels warm
Sympathetic Nervous System (SNS)
a.k.a Adrenergic system
Adrenergic receptors:
1. Alpha-1: BVs, bladder, liver, pupils — NT: EPI, NE, DA, and phenylephrine
- Alpha-2: CNS — NT: EPI and NE
- Beta-1: Heart — NT: EPI, NE, DA, and dobutamine
- Beta-2: Lungs, BVs, bladder, liver, uterus — NT: EPI and albuterol
- DA: Kidneys — NT: DA
**Non-adrenergic: M: Sweat glands — NT: ACh
Norepinephrine (NE) & Epinephrine (EPI)
The “fight or flight” response is mediated by the release of NE or EPI by the adrenal medulla (there is no post-ganglionic neuron) upon ACh binding on N receptors
NE is synthesized from precursors like dopamine, and is then stored in vesicles; when an AP travels down the axon, it is released and binds to either alpha-1 or beta-2 post-synaptic receptors
After NE dissociates from the receptor, it can either (1) undergo re-uptake into the pre-ganglionic cell, or (2) bind to alpha-2 receptors on the pre-receptor neuron (acting as a shut-off valve)
Sympathetic Stimulation
Effects (“Fight or flight”):
1. Regulating CV system
- Regulating body temp.
- Increase HR and BP
- Shunt blood away from skin and viscera and into skeletal muscles
- Dilate bronchi
- Dilate pupils
- Mobilize stored energy
**Sympathetic blockade: cause opposite effects of sympathetic stimulation
Baroreceptor Reflex and Feedback Loop of the ANS
The baroreceptor reflex helps regulate BP; thus, it opposes pharmacologic interventions that alter BP (and often requires multiple drug therapies)
Baroreceptors are specific receptors located in the carotid sinus and the aortic arch in the heart that monitor changes in BP, and send information to the brain
If a drug that lowers BP is admin., the baroreceptors in the heart detect that information, and in response, the brain sends impulses along nerves to the ANS, instructing the heart and blood vessels to vasoconstrict in attempt to increase CO, and bring the BP back to previous basal range
Somatic Nervous System
Receptor = Nicotinic (N) NT = ACh
N receptors in skeletal muscle
Musculoskeletal blockade: opposite effects of somatic stimulation (skeletal muscle paralysis)
Cholinergic Drugs
Types of cholinergic drugs:
1. Muscarinic agonists
- Muscarinic antagonists (Anticholinergics)
- Cholinesterase inhibitors
- Neuromuscular blocking agents (NMBAs)
Cholinergic Drug Type #1: Muscarinic Agonists
Prototype: Bethanechol
MOA: Direct muscarinic agonist (GI tract and bladder selective)
Therapeutic use:
- Non-obstructive urinary retention (promotes urination)
- GI paralysis (promotes digestion and absorption)
AEs:
- Hypotension
- Bradycardia
- Excessive GI secretions
- Asthma exacerbation (due to bronchoconstriction)
RN implications:
- Admin. on empty stomach
- Have bedpan readily available
- Monitor I&Os and cholinergic excess
Muscarinic agonist overdose:
- S/S: Profuse salivation, lacrimation, visual disturbances, bronchospasm, diarrhea, bradycardia, hypotension
- Tx: Atropine — blocks muscarinic receptors, preventing activation
Cholinergic Drug Type #2: Muscarinic Antagonist (Anticholinergics)
Prototype: Atropine
MOA: Blocks muscarinic receptors (prevents ACh from binding)
Therapeutic uses:
- Dilate pupil for eye exam
- Treat bradycardia
- Muscarinic agonist overdose/poisoning
- Preanesthetic agent — decrease salivations and bronchial secretions
AEs:
- Dry eyes and mouth
- Blurred vision
- Photophobia
- Constipation
- Urinary retention
- Tachycardia
RN implications: Pt education on minimizing anticholinergic AEs
Anticholinergic overdose:
- S/S: PSNS blockade mnemonics
- Tx: Activated charcoal (absorbs drug in GI tract), and Physostigmine (increases amount of ACh at receptors)
- Warning: Differentiate between overdose and actual psychotic episode
**Anticholinergics are on “Beers List”
Cholinergic Drug Type #3: Cholinesterase Inhibitors
Prototype: Neostigmine
MOA: Blocks the action of AChE, increasing the amount of ACh that is available at receptor sites
Therapeutic uses:
- Myasthenia gravis
- Reversal of non-depolarizing NMBAs
AEs:
- Muscarinic effects: N/D/, increased salivation and bronchial secretions, bronchoconstriction
- Nicotinic effects: muscle cramps
DDIs:
- Anticholinergic (opposing effects)
- Competitive depolarizing NMBAs — increase the activity of NMBA
RN implications: Pt education on recognizing extreme AEs (specifically for those with Myasthenia gravis)
Cholinesterase inhibitor overdose:
- S/S: Excessive muscarinic stimulation and respiratory depression; DrySLUDS, and killer Bs (bradycardia, bronchospasm, and bronchorrhea)
- Tx: Atropine, suction (due to increased secretions), and mechanical ventilation (reverses respiratory depression, and counteracts muscle weakness or paralysis)
Myasthenia Gravis
Autoimmune disorder in which antibodies attack N receptors on the motor end plate, causing fluctuating muscle weakness and rapid fatigue
Cholinesterase inhibitor drug therapy (used for symptomatic relief) increases the amount of ACh at receptor sites, allowing for a more prolonged effect of ACh; thus, there is increased muscle strength
Cholinergic Drug Type #4: Non-depolarizing Neuromuscular Blocking Agents (NMBAs)
Prototype: Pancuronium (-ronium & -curium)
MOA: Blocks the action of ACh at neuromuscular junction (mainly on nicotinic receptors)
Therapeutic use:
- Adjunct to general anesthesia
- Mechanically ventilated pts
- Intubation
AEs:
- Respiratory arrest — must provide mechanical ventilation
- Electrolyte disturbances
DDIs:
- General anesthetics
- Some antibiotics
Med. safety concerns:
- Caution in pts with renal and hepatic dysfunction, and Myasthenia gravis
- Tx: Cholinesterase inhibitors for reversal
- Sedate prior to admin.
- High alert med.: use is restricted to ICU/OR/ED or with code team (due to risk for respiratory arrest and death)
Cholinergic Drug Type #4: Depolarizing Neuromuscular Blocking Agents (NMBAs)
Prototype: Succinylcholine
MOA: Depolarizes muscle fiber, preventing the action of ACh at neuromuscular junction (mainly on nicotinic receptors)
Therapeutic use: Muscle relaxation during endotracheal intubation (short-acting)
AEs:
- Respiratory arrest
- Hyperkalemia (due to depolarization)
- Muscle pain
- Malignant hyperthermia — Antidote: Dantrolene inhibits heat generation by reducing the metabolic activity of skeletal muscle; Tx: Discontinuation, ice packs, IV infusion
Med. safety concerns:
- Caution in pts with Myasthenia gravis
- Cholinesterase inhibitors do NOT reverse AEs — they increase the activity of succinylcholine
- High alert meds.: use restricted to ICU/OR/ED or with code team (due to risk for respiratory arrest and death)
Adrenergic Drugs
Types of adrenergic drugs:
1. Adrenergic agonists
- Adrenergic antagonists
Adrenergic Agonists
a.k.a. Sympathomimetics, catecholamines (not all)
4 receptor types: alpha-1, alpha-2, beta-1, and beta-2
Adrenergic Agonists #1: Alpha-1, Beta-1 Agonists
Prototype: NE, EPI, and DA
Therapeutic uses:
- Support cardiac function
- Vasoconstriction and/or increased force of contraction
- EPI (IM) used for anaphylaxis
- Phenylephrine (topically) used for nasal congestion
Route: Continuous IV infusion, IM (EPI), and topical (Phenylephrine)
AEs:
- Cardiac complications (i.e. dysrhythmias)
- Necrosis after extravasation
- Hyperglycemia
- Tremors
RN implications:
- Identify high risk pts (i.e. heart disease)
- Monitor IV site for extravasation (necrosis), EKG, BP
- IV admin. via continuous infusion pump in critical care setting
Med. safety concerns:
- High alert meds.
- Continuous infusions should be administered via library in smart pump
- EPI autoinjecter devices — pen design has led to incorrect use and accidental self-admin.
Adrenergic Agonist #2: Beta-2 Agonist
Prototype: Albuterol
MOA: Activation of beta-2 receptors
Therapeutic use: Bronchodilator
AEs:
- Tremors
- Tachycardia
- Palpitations
Adrenergic Agonist #3: Alpha-2 Agonist
Prototype: Clonidine
MOA: Alpha-2 agonist (central effect) — large amounts of NE or EPI bind to alpha-2 receptors on pre-synaptic neuron (acting as a shut-off valve)
Therapeutic use:
- HTN
- Narcotic withdrawal
- Pain
- ADHD
- Analgesia
AEs:
- Drowsiness & dry mouth
- Rebound HTN — when discontinued abruptly
- Orthostatic hypotension
- CNS effects
Forms: Oral, transdermal patch, epidural
RN implications:
- Abuse potential
- Beers criteria
- Patch admin. issues
Issues associated with transdermal patch admin.:
- Remove old patch
- Rotate site of application — prevents local irritation
- Partial patches — can be cut (for children or small adults)
- Anonymous patches
- Unintentional overdose from heat — increases absorption rate
- Disposal
- Adhesion failure
- Electronic ordering/eMAR issues
Adrenergic Antagonist #1: Non-selective Alpha Blocker
Prototype: Phentolamine
MOA: Blocks alpha-1 and alpha-2 receptors
Therapeutic use: Reverses local vasoconstriction effect of extravasated alpha-1 agonists (NE, EPI, and DA)
Admin.: Region should be infiltrated per institutional extravasation management guidelines
Adrenergic Antagonist #2: Selective Alpha Blocker
Prototype: Prazosin (-osin)
MOA: Blocks alpha-1 receptors
Therapeutic use:
- BPH (primary use) — relaxes smooth muscle
- HTN
AEs:
- Orthostatic hypotension
- Reflex tachycardia — if discontinued abruptly
- Nasal congestion — due to vasodilation
RN implications:
- Orthostatic hypotension
- First-dose effect — 1% lose conscious (rare) within first 30-60 min. of admin. (use small first dose)
Adrenergic Antagonist #3: Non-selective Beta Blocker
Prototype: Propranolol (-olol, -alol, -ilol)
MOA: Blocks beta-1 and beta-2 receptors
Therapeutic use:
- HTN
- Angina
- Dysrhythmias
- HF
- Migraine prophylaxis — can cross BBB and elicit CNS effects (vasodilation improves migraine symptoms)
AEs:
- Bradycardia (most common) that can lead to AV block and reflex tachycardia
- Bronchospasm — avoid in pts with asthma and COPD
- CNS effects
- Can mask hypoglycemia (especially tachycardia)
Individual variation:
- HF — improves mortality, but can also worsen heart function (use low dose)
- Asthma
DDIs: Calcium channel blockers (used to treat angina and HTN) — jointly cause bradycardia
RN implications: Warn pts of abrupt discontinuation — reflexive issues (i.e. rebound HTN, tachycardia, or worsening HF)
Med. safety concerns:
- High alert meds. (especially IV)
- Dose conversion from PO to IV (first pass effect)
- Mix ups with ER dosage forms
- Sotalol on Beers list
Adrenergic Antagonist #4: Selective Beta Blocker
Prototype: Metoprolol (-olol, -alol, -ilol)
MOA: Blocks beta-1 receptors — less likely to cause bronchospasm (high doses may become nonselective)
Therapeutic use:
- HTN
- Angina
- HF
- Dysrhythmias
- Post-MI care
AEs:
- Bradycardia which can lead to AV block and reflex tachycardia
- HF
- Can mask hypoglycemia
Individual variation:
- HF
- Asthma (high doses)
DDIs: Calcium channel blockers
RN implications: Warn pts of abrupt discontinuation
Med. safety concerns:
- High alert meds. (especially IV)
- Dose conversion from PO to IV (first pass effect)
- Mix ups with ER dosage forms
