Autonomic Pharmacology Flashcards
Describe the anatomic and functional organization of the Sympathetic division
Sympathetic: 1st neuron is SHORT, 2nd is longer
○ SHORT preganglionic fibers
○ ACH binds to nicotinic receptors & muscarinic receptors
○ LONG postganglionic fibers
○ NE binds to alpha or beta adrenergic receptors at effector organ
Describe the anatomic and functional organization of the Parasympathetic division
Parasympathetic: 1st neuron is LONGER, 2nd shorter
○ LONG preganglionic fibers ○ ACH binds to nicotinic receptors ○ SHORT postganglionic fibers ○ ACH binds to muscarinic receptors at effector organ ○ 2nd synapse is muscarinic
First synapse regardless of division (symp & parasymp) is ___________________.
Ach bind to _______________ receptors.
We block at the _______________ synapse where type of receptor varies.
- cholinergic
- nicotinic receptors
- second synapse
Adrenal Medulla:
- Innervated by ____________of the SANS.
- Stimulation causes ______________ and ____________.
- preganglionic fibers
- release of epinephrine and norepinephrine
Adrenal Medulla:
-The diffuse response of the SANS is produced because _______________ or ____________ results from systemic release of epinephrine & noreeponeprine and their effects on _____________ and ___________
- fight or flight response
- pre and post ganglionic fibers
How do drugs modify ANS activity?
1) Storage
2) Synthesis
3) Release
4) Receptor interaction
5) Dispostion (termination of neurotransmitter activity in synapse) = enzyme degradation or reuptake
Which 4 groups of drugs exert their effects on organs or tissues innovated by the ANS?
1) Parasympathetic (PANS) stimulatory
2) Parasympathetic (PANS) inhibitory (blocking)
3) Sympathetic (SANS) stimulatory
4) Sympathetic (SANS) inhibitory (blocking)
A drug that acts at the location where acetylcholine is released is termed _____________
cholinergic
A drug that acts at the location where norepinephrine is released is termed _____________
Adrenergic
A drug that acts at the location where the PANS acts has the prefix ______________
Parasympatho-
A drug that acts at the location where the SANS acts has the prefix ______________
Sympatho-
A drug that acts at the location where a division of the ANS acts & produces the SAME effect as the neurotransmitter has the suffix- ___________
-MIMETIC (AKA Agonist)
Acts the same as the neurotransmitter
A drug that acts at the location where a division of the ANS acts & blocks the action of the neurotransmitter has the suffix ______ or ______
- Lytic
- Blocker (AKA ANTAGONISTS)
Antagonists do not produce any drug effect: they ________ the receptor site (acting like a plug) to prevent the ______from producing the desired effect.
- block
- agonist
What are the STIMULATORY Parasympathetic (PANS) Drugs?
1) Cholinergics
2) Parasympathomimetics
What are the INHIBITORY Parasympathetic (PANS) Drugs?
1) Anticholinergics
2) Parasympatholytics
3) Cholinergic blockers
What are the STIMULATORY sympathetic (SANS) Drugs?
1) Adrenergics
2) Sympathomimetics
What are the INHIBITORY sympathetic (SANS) Drugs?
1) Adrenergic blockers
2) Sympathetic blockers
3) sympatholytics
What are 2 types of Cholinergic Agonists?
1) Direct acting:
- Agonists (Act at ACH receptor)
2) Indirect acting :
- Causes release of ACH (neurotransmitter)
- Cholinesterase inhibitors = cause accumulation of ACH = stimulating PANS
Describe direct acting Cholinergic Drugs
1) Act like acetylcholine (“Mimic” its effect) on receptors
2) Agonists
3) Longer duration of action
4) More selective in the effects produced
5) STIMULATE PANS
What is the receptor function ?
1) To be effective mediator, ACH must fit physically & chemically at receptor
2) there are differences among receptors that have ACH
3) Subtypes of ACH receptors are located in different synapses
What are examples of ACH receptors?
1) CNS (muscarinic & nicotinic)
2) Autonomic (muscarinic & nicotinic)
3) Neuromuscular (nicotinic)
What are other factors that account for differences in the response of the receptor to drugs at ACH-medicated junction receptors?
1) Amount of ACH release
2) Size of synaptic cleft
3) Tissue penetration of drug
What are the Pharmacologic effects of Cholinergic Drugs on the heart, eye & GI?
1) Cardiovascular:
- Bradycardia, decreased BP & CO
2) Eye:
- Produce miosis
- Decreases intraocular pressure
3) GI:
- Excites smooth muscle of gut
- Increase in activity, motility & secretion
What are the primary indication for use of direct acting cholinergic drugs?
1) Glaucoma
2) Myasthenia gravis (autoimmune disease)
3) DI disorders (INC GI motility)
4) Reverse urinary retention after surgery
What are examples of Direct Acting Cholinergic Agonists?
1) ACH (Miochol) -eye surgery
2) Bethanechol (Urecholine)- urinary retention
3) Carbachol (Miostat)-glaucoma
4) Cevimeline (Ecoxac) - Sjogren’s syndrome
5) Pilocarpine (Salagen)- glaucoma, Sjogren’s syndrome
Describe how pilocarpine (ophthalmic) works
1) Used in eye for glaucoma
2) Causes constriction allowing for drainage of fluid from eye thru canal of Schlem
3) Glacoma = increased intraocular pressure due to fluid. Can cause blinds if untreated.
4) Pilocarpine allows for DRAINAGE which DECREASES intraocular pressure
What is pilocarpine(Brand name: SALAGEN) used in dentistry for?
To stimulate SALIVARY SECRETIONS in patients w/ xerostomia
Another drug in this class of “pilocarpine” is _______________ , which is used for salivary stimulation in patients w/ Sjogren’s syndrome
-Cevimeline (Evoxac)
What are indirect-acting cholinergic drugs also known as and what do they do?
- Cholinesterase inhibitors
- They STOP the BREAKDOWN of ACH (via cholinesterase), which allows fro the concentration of acetylcholine to build up= ACH remains active
- They produce PANS stimulation
What are the primary indications for indirect-acting Cholinergic Agonists (Cholinesterase Inhibitors)
1) Myasthenia Gravis
2) Glaucoma
3) Postoperative urinary retention
4) Paralytic ileum (malfunction of nerves w/out blockage)
5) Antidotes to agents that produce non depolarizing neuromuscular blockage (poisons)
Indirect-Acting Cholinergic Drugs are divided into groups based on what?
The degree of reversibility with which they are bound to the enzyme
1) Reversible
- Also includes centrally acting drugs
2) Irreversible
How does Reversible Indirect-Acting Cholinergic Drugs affect ACH?
Increases it
Note: Causes skeletal muscle activation followed by blockage (prevent repolarization at motor end plate) = no muscle contraction
What is Reversible Indirect-Acting Cholinergic Drugs used to treat?
Myasthenia gravis & glacoma
What are examples of Reversible Indirect-Acting Cholinergic Drugs?
1) Edrophonium (Enlon)-rapidly reversible
2) Physostigmine (Reverses toxic life-threating delirium caused by overdose of anticholinergic drugs)
3) Pyridostigmine (for myasthenia gravis pretax for nerve gas exposure)
How does centrally acting Acetylcholinesterase Inhibitors affect ACH in the brain?
INCREASES it
What is Reversible CENTRALLY Acting Acetylcholinesterase Inhibitors used to treat?
1) Dementia w/ Alzheimer’s disease
2) Investigational for mild to moderate dementia w/ Parkinson’s disease
What are examples of CENTRALLY Acting Acetylcholinesterase Inhibitors?
1) donepezil (Aricept)
2) rivastigmine (Exelon) = patch
3) galantaminei (Razadyne)
What are examples of Irreversible Acetylcholinesterase Inhibitors?
1) malathion, parathion= poisons
- used as agricultural insecticides
2) Sarin, Soman, tabun= nerve gases
chemical warfare
What is the treatment of overdose of Cholinesterase Inhibitors (If poisoned w/ insecticides or organophosphates) ?
1) paralidoxime (2-PAM, Protopam)
- Regenerates the irreversibly bound ACH receptor sites that are bound by the inhibitors
2) Atropine (antimuscarinic)
- Competitively blocks muscarinic effects of excess ACH
What are the side effects of Cholingeric Drugs?
1) S= salivation
2) L= lacrimation
3) U= urinaation
4) D= defecation
What are the side effects of Direct-Acting & Indirect-Acting Cholinergic Drugs?
1) Nausea, vomiting, diarrhea (by increasing GI activity)
2) Salivation, lacrimation, sweating (inc gland secretions)
3) bradycardia
4) bronchoconstriction
5) constricted pupils (mitosis), loss of accommodation
6) paralysis at high doses (effect NMJ)
7) CNS (if drug crosses BBB) = confusion, excitation, pathy, ataxia, respiratory depression
What are Cholinergic Antagonists?
Anticholinergics= Parasympatholytics
1) Anticholinergics= Antimuscarinics
2) Neuromuscular blocking agents
3) Ganglionic blocking agents
Describe Anticholinergic Drugs (Parasymatholytics)
1) Prevent action of acetylcholine at the postganglionic PANS nerve endings
2) “blocker” drugs or antagonists
3) Block the receptor site for acetylcholine
4) Do not prevent release of ACH
5) Acetylcholine cannot act on receptors in smooth muscle, glands or the heart
6) Also called antimuscarinic drugs (block muscarinic receptors but not nicotinic receptors)
What are the Pharmacologic CNS Effects of Anticholinergic Drugs? (reduce PANS)
1) CNS = effects determined by dose (Therapeutic dose of scopolamine)
- Sedation, motion sickness
2) Atropine in high doses
- Stimulation: delirium, hallucinations, convulsions, coma
What are the Pharmacologic Exocrine glands Effects of Anticholinergic Drugs?
-What is it used for in dentistry?
1) Dries up secretions
- Reduce flow & volume
2) Respiratory, GI and GU tracts
- Treat COPD
- Antipasmodics GI/GU
- Overactive bladder
2) In dentistry used to decrease salivation and create dry field for bonded restoration and impressions (atropine)
What are the Pharmacologic Smooth muscle, (Respiratory tract) Effects of Anticholinergic Drugs?
1) Bronchodilators to facilitate breathing
- Ipratropium (Atrovent) used to decrease secretions in emphysema & asthma
What are the Pharmacologic Smooth muscle, (GI tract) Effects of Anticholinergic Drugs?
GI tract= Antispasmotics- decrease gut motility
- Adjunctive treatment for peptic ulcer disease
- Delay gastric emptying, decrease esphageal & gastic motility
- Cause constipation as side effect
What are the Pharmacologic “Eye” Effects of Anticholinergic Drugs?
1) Mydriasis (dilated pupils)
2) cycloplegia (paralysis of accommodation so that the lens is focused for distance vision and near vision is blurred)
3) Drops used for opthalmologic examination
What is the PANS activity( eyes, skin, GI, urinary, respiratory, CNS, & CVS) uses of anticholinergic drugs in medicine ?
Eyes= mydriasis (eye exams)
Skin= decrease sweating
GI= decrease salivation (dries) , decreased gut motility (antispasmodics)
Urinary tract= urine retention
Respiratory = bronchodilation, dries secretions
CNS= sedation; decreased concentration/memory; possible hallucinations, delirium and coma
CVS= large therapeutic doses = vagal blockade, resulting in tachycardia
***Used to prevent cardiac slowing during vernal anesthesia
What are the clinical uses of Anticholinergic drugs (Preoperative medications)?
1) stop salivation and bronchial muscous (normally stimulated by gen. anesthesia)
2) Block slowing of heart rate cause by gen anesthesia
What are the clinical uses of Anticholinergic drugs (GI disorders)?
1) Produce excess secretions & increased gut motility
2) Stops excess acid secretion (Peltic ulcer disease)
3) Stops diarrhea & cramping- antispasmodic for IBS
What are the clinical uses of Anticholinergic drugs (Eye examination)?
1) causes pupil dilation to allow for examination of retina
2) relaxes lens for determining prescription for eyeglasses
What are the clinical uses of Anticholinergic drugs (Parkinson’s disease & GU disorders)?
Parkinson’s disease:
Reduces tremors & muscle rigidity
GU disorders: Overactive bladder (urinary antispasmodic)
What are the clinical uses of Anticholinergic drugs (Motion sickness)?
- Scopolamine “patch” behind the ear
- CNS depressant
What are the dentistry uses for atropine and pilocarpine?
- To maintain a dry field
- atropine = anticholinergic = dries saliva
- pilocarpine= cholinergic= salivation
Which popular anticholinergic is the drug of choice for emphysema = stops bronchial secretions ?
Ipratropium (atrovent)
What is the mnemonic for atropine toxicity(overdose of an anticholinergic drug)?
○ Dry as a bone (lack of sweating)
○ Red as a beet (flushed skin)
○ Blind as a bat (blurred vision; mydriasis and cycloplegia)
○ Mad as a hatter (delirium, hallucinations)
NM blocking drugs do what?
1) block cholinergic transmission at NMJ
2) Act as Antagonists (non-depolarizing) or Agonists (depolarizing)
3) inhibit release of ACH
What are examples of NM Blocking agents?
1) Tubocurarine (Curare) Competitive-Non depolarizing
2) Succinylcholine (Depolarizing agents)
3) Botulinum toxin
Describe Tubocurarine (Curare)
Tubocurarine (Curare):
○ Competitively & reversibly inhibits nicotinic receptors at NMJ; BLOCKS action of ACH
○ Competitive blockers can be overcome by administration of cholinesterase inhibitors
○ skeletal muscle relaxant
Describe Succinylcholine
○ Constant stimulation of receptor causes sodium channel to open, producing depolarization
○ transient fasciculations of muscles → flaccid paralysis (lasts min) drug broken down by plasma cholinesterase
○ indications: endotracheal intubation, reduce intensity of muscle contractions
○ binds to nicotinic receptor (mimics ACH) → depolarization
○ gets degraded almost immediately by cholinesterase
Describe Botulinum toxin (Botox)
○ produces state of denervation
○ PREVENTS calcium- dependent release of ACH
○ Indications: muscle tics, muscle disorders, cosmetic procedures
○
What is the site of action of (Ganglionic Blocking Agents) NICOTINE and its use in medicine and dentistry?
● Inhibit nicotinic receptors so blocks neurotransmission in both PANS and SANS
● LOW doses: produces stimulation due to depolarization
● HIGH doses: produces no response at nicotinic receptors (nicotinic escape) but stimulates muscarinic receptors
● Indications: tobacco cessation, “insecticide”
What are 3 endogenous “naturally occurring” (Adrenergic drugs) catecholamines.
● Epinephrine: adrenal medulla
● Norepinephrine: terminal nerve endings
● Dopamine: brain, splanchnic, renal vasculature
Differentiate between beta 1 and beta 2 effects produced by sympathetic stimulation.
● Beta 1:
○ cardiac stimulation: increases HR and contractility
○ glycogen → glucose
● Beta 2:
○ smooth muscle relaxation
○ vasodilation of skeletal muscle vessels
○ bronchodilation
List the primary pharmacologic effects produced by ALPHA
● Alpha:
○ alpha-1 = smooth muscle contraction
○ alpha-2 = inhibition of transmitter release, smooth muscle contraction
○ Agonist:
■ Vasoconstriction of vessels → pale pallor, protection from bleeding out
■ Smooth muscle contraction
○ Antagonist (blockers):
■ BLOCK vasoconstriction in skin
■ DECREASE TPR and BP
■ REVERSE dilation of pupils
List the primary pharmacologic effects produced by BETA antagonists.
Antagonists:
■ CV: dec. HR, contractility, cardiac output, conduction velocity (Cardiac arrhythmias)
■ decreases cardiac muscle oxygen demand (angina)
■ reduces intraocular pressure (Glaucoma)
■ Hypertension (diuretics)
■ Migraine headache
■ Anxiety
■ Hyperthyroidism
■ Parkinsons disease
What do Beta receptors 1 & 2 do ?
Stimulation of beta 1:
1) Cardiac stimulation
2) Increased RATE & FORCE of contraction
3) breakdown of glycogen to INCREASE glucose
Stimulation of beta 2:
1) Smooth muscle relaxation
2) Vasodilation of vessels in skeletal muscle
3) Bronchodilation (for breathing)
What are the clinical uses of Adrenergic agonists?
Adrenergic agonists
1) Vasoconstriction
2) Decongestants
3) Tx for shock - elevate low bp
4) Tx for cardiac arrest - epi to “jump start” heart
5) Asthma and emphysema
6) CNS stimulation - Amphetamines to tx ADD/ADHD
What are the clinical uses of Alpha blockers?
Alpha blockers
1) Second line agents for the tx of hypertension
2) Tx of peripheral vascular disease (Raynaud’s Syndrome)
3) Diagnosis and treatment of pheochromocytoma
4) Tx of benign prostatic hypertrophy - Most common users of alpha blockers → old men
5) phentolamine (OraVerse)- reverses dental anesthesia
What are the clinical uses of Beta blockers?
Beta blockers (Selective: only B1 / Non-selective: B1&B2)
1) Cardiac arrhythmias - slows heart rate, decreases contractility and cardiac output
2) Angina - Decreases cardiac muscle oxygen demand
3) Hypertension
4) Hyperthyroidism - Stops tremors/heart palpitations caused by Grave’s disease or thyrotoxicosis
5) Parkinson’s disease - Stops tremors
6) Anxiety
7) Glaucoma
8) Migraine headache
Selective drug name begins with letter_______?
-What is it used for?
Examples?
- a-m
- used if patient has diabetes or respiratory issues
- atenolol
- metoprolol
Non-selective (drug name begins with letter _______?
-Examples
-n-z
○ propranolol
○ nadolol
○ timolol
What is the beta 2 agonist included in dental office emergency kits and discuss its indication for use?
● Albuterol - potent bronchodilator “rescue drug”
State the dose for epinephrine in dental anesthetics that is given to patients with heart disease.
● 0.04 mg of epinephrine (2 cartridges of epinephrine 1:1000,000)
- Note: Must limit dose when patients taking non- selective Beta blockers given epinephrine as they have a 2 to 4 fold increase in pressor response.
- Hypertension (MI /stroke)
- Reflex bradycradia
What is the effects of epinephrine on heart rate and blood pressure if given to a patient taking a selective versus a non-selective beta blocker?
● When patients taking NON-selective beta blockers are given epinephrine, they have a 2-4 fold INCREASE in pressor response to epinephrine:
○ Hypertension (INCREASED risk for MI and stroke)
○ Reflex bradycardia
What are popular Adrenergic Agonists (non-catecholamines?)
1) Albuterol (Beta 2 )
- Potent bronchodilator
- Included in all dental kits for realization of smooth muscle
2) Amphetamines for ADHD & narcolepsy
3) Clonidine
4) Dopamine for treatment of shock & INC blood flow
5) Oxymetazoline
6) Phenylephrine (Sudafed PE)
7) Phentermine = diet pills
8) Pseudophedrine (Sudafed)
9) Tetrahydrozplone (Visine eye drops)
What are the side effects for Adrenergic Agonists (non-catecholamines?)
1) Anxiety/irritability
2) Tremors
3) Cardiac arrhythmias (tachycardia)
4) Hypertension
5) Constipation
6) Urinary retention
What are the uses of Alpha Antagonists (Blockers)
Examples?
1) Second line agents for Tx for hypertension
2) Treatment of peripheral vascular disease (Raynaud’s)
3) Diagnossi & Tx of pheochromoocytoma (tumor)
4) Tx of benign prostatic hypertrophy
Examples:
-Phenotolamine (OraVerse) reverses dental anesthesia
Causes VASODILATION
Cardiac drugs:
- Prazosin (Minipress)
- Terazosin (Hytrin)
- Doxazosin (Cardura)
Which Beta Antagonist is commonly used in the US?
SELECTIVE blockers that only block B1 receptors
- Fewer side effects
- Greater action on heart & BV
- FEWER interactions w/ drugs
Most people with diabetes will be on a ______________ beta blocker ?
SELECTIVE
Most people with heart disease/respiratory will will be on _______ blocker
BETA 2 blocker in lungs blocked
What are the popular Beta Antagonist Selective & Non-selective Blockers?
Selective:
1) atenolol (Tenormin)
2) metoprolol (Lopressor, Toprol)
Non-Selective:
1) propranolol Iinderal)
2) nadolol (Cordard)
3) timolol (Timoptic) = eyedrops used for glaucoma
