Transcript WS0201_Unit_ Two

Drugs Unit 2
Introduction to the
Autonomic Nervous System
Nervous System
CNS
PNS
Autonomic
Sympathetic
Somatic
Parasympathetic
2
Ion Diffusion
 Key to neurophysiology
 Dependent upon:
 Concentration gradient
 Electrical gradient
 Modified by:
 ‘Gated ion channels’
3
Where Does Diffusion Take the Ion?
Na+
150 mM
K+
5 mM
ClHigh
Exterior
I
N
Na+
15 mM
O
U
T
K+
150 mM
ClLow
Cell
Interior
4
Major Networks of CNS
Motor Systemvoluntary musculoskeletal movement
Extra Pyramidal System (EPS) –
controls fine movements
(defective in Parkinson’s disease)
Autonomic Nervous System (ANS)controls fight/flight and rest/digest body actions
Reticular Activating Systemresponsible for maintenance of consciuosness and alertness
Limbic Systemresponsible for control of emotions/happiness etcetera
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Organization of the Nervous System:
Reticular Activating System
Key Regulatory Functions:
CV, respiratory systems
Wakefulness
Clinical Link:
Disturbances in the RAS are
linked to sleep-wake
disturbances
Radiation Fibers
Thalamus
Visual Inputs
Reticular Formation
Ascending Sensory Tracts
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Organization of the
Peripheral Nervous System
Three major divisions:
EFFERENT AFFERENT
Somatic (motor)
Autonomic
Sensory
Sympathetic
and
Parasympathetic
AFFERENT
Sensory
EFFERENT
Parasympathetic
Sympathetic
Motor
Parasympathetic
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Preganglionic Nerves
Sympathetic and Parasympathetic
preganglionic fibres release
Acetylcholine (ACh)
ACh has two types of receptors:
Muscarinic and Nicotinic
Postganglionic nerves have
Nicotinic receptors
Sympathetic
Parasympathetic
ACh
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Postganglionic Nerves
Sympathetics release Norepinephrine
Parasympathetics release ACh
Norepinephrine binds to adrenergic
Sympathetic
Parasympathetic
receptor
ACh binds to Muscarinic receptors
ACh
NE
9
Autonomic Nervous System
(ANS)
Definition
Involuntary or visceral nervous system
Function
Mostly with little conscious awareness of its activity
Regulate and integrate the body’s internal functions
Integrate parts of the CNS and PNS to react to changes
in the internal and external environment
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Bodily Functions Regulated by
the ANS
Blood pressure
Heart rate
Respiration
Body temperature
Water balance
Urinary excretion
Digestive functions
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12
Classifications of the Receptor Sites
Reacting With Sympathetic
NeurotransmittersNorepinephrine and Epinephrine
α alpha-receptors
alpha1- (Peripheral vasculature)
alpha2- (Brain vasculature)
β beta-receptors
beta1- (Heart)
beta2- (Lungs)
13
14
What do these receptors do?
Alpha 1
Vasoconstriction, ↑ BP, ↑ tonus of sphincter muscles
Alpha 2
Inhibit norepinephrine, insulin release
Beta 1
Tachycardia, ↑ lipolysis, ↑ myocardial contractility
Beta 2
Vasodilation, bronchodilation, insulin release
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Location and Function of
Alpha1 Receptors
Blood vessels
Cause vasoconstriction and increase peripheral
resistance, raising blood pressure
Iris
Cause pupil dilation
Urinary bladder
Cause the increased closure of the internal sphincter
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Location and Function of
Alpha2 Receptors
Nerve membranes
Act as modulators of norepinephrine release
Beta cells in the pancreas
Help to moderate the insulin release stimulated by
sympathetic nervous system activation
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Location and Function of
Beta1 Receptors
Cardiac tissue
Can stimulate increased myocardial activity and
increased heart rate
Responsible for increased lipolysis or breakdown of
fat for energy in peripheral tissues
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Location and Function of
Beta2 Receptors
Smooth muscle in blood vessels
Stimulation leads to vasodilation
Bronchi
Stimulation leads to bronchodilation
Periphery
Increased muscle and liver breakdown of glycogen and
increased release of glucagon
Uterine muscle
Results in relaxed uterine smooth muscle
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Sympathetic NS Drugs
Predictable response based on knowledge of affects of
adrenergic receptor stimulation
Each receptor may be:
Stimulated (sympathomimetic)
Inhibited (sympatholytic) (‘blocker’)
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Alpha1 Agonists
Profound vasoconstriction
Increases afterload & blood pressure when given
systemically
Decreases drug absorption & bleeding when given
topically
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Alpha- and Beta-Adrenergic
Agonists and Their Indications
Dobutamine (Dobutrex): Congestive heart failure
Dopamine (Intropin): Shock
Ephedrine (Pretz-D): Seasonal rhinitis;
hypotensive episodes
Epinephrine (Adrenalin, Sus-Phrine):
Shock; prolongs effects of regional anesthetic
Norepinephrine (Levophed): Shock; cardiac arrest
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Alpha-Specific Adrenergic
Agonists (Alpha-Agonists)
Definition
Drugs that bind primarily to alpha-receptors
rather than to beta-receptors
Drugs in this class
Phenylephrine (Neo-Synephrine, Allerest, AK-Dilate, and others)
Midodrine (ProAmantine)
Clonidine (Catapres)
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Beta1 Agonists
Increases heart rate, contractility,
and conductivity
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Beta-Specific Adrenergic Agonists
and Their Indications
Isoproterenol (Isuprel)
Treatment of shock, cardiac standstill, and heart block in
transplanted hearts; prevention of bronchospasm during
anesthesia; inhaled to treat bronchospasm
Ritodrine (Yutopar)
Management of preterm labor (uterine beta receptors – relaxes
pregnant uterus on stimulation)
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Adrenergic Blocking Agents
Adrenergic Blocking Agents
Definition
Called sympatholytic drugs because they lyse, or
block, the effects of the SNS
Therapeutic and adverse effects
Related to their ability to react with specific
adrenergic receptor sites without activating them
Action
Prevent norepinephrine from activating the receptor
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Alpha- and Beta Blocking Agents
and Their Indications
Carvedilol (Coreg): Hypertension,
congestive heart failure (adult)
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Selective Alpha1- Blocking Agents*
Doxazosin (Cardura): Used to treat hypertension;
also effective in the treatment of benign prostatic
hypertrophy
Prazosin (Minipress): Used to treat hypertension,
alone or in combination with other drugs
Terazosin (Hytrin): Used to treat hypertension as
well as BPH
Tamsulosin (Flomax) and alfuzosin (Uroxatral):
Used only in the treatment of BPH
*Inhibits peripheral vasoconstriction
*Used for hypertension
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Indications for Beta- Blocking
Agents
Treating cardiovascular problems
Hypertension
Angina
Migraine headaches
Preventing reinfarction after MI
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Focus on the Beta-Blocker Prototype:
Propranolol (Inderal)
Indications: Treatment of hypertension, angina
pectoris, supraventricular tachycardia, tremor;
prevention of reinfarction after MI; prophylaxis of
migraine headache; management of situational anxiety
NON SELECTIVE- Blocks both
Beta 1 and Beta 2 receptors
And Timolol
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Adverse Effects of BetaBlocking Agents
GI upset
CNS changes
Respiratory problems
CV effects
Loss of libido
Impotence
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Selective (blocks ONLY)
Beta1- Blocking Agents
Advantage
Do not usually block beta2-receptor sites,
including the sympathetic bronchodilation
Preferred for patients who smoke or have
asthma, obstructive pulmonary disease, or
seasonal or allergic rhinitis
Uses
Hypertension, angina, some cardiac arrhythmias
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Selective Beta1- Blocking Agents
and Their Indications
Acebutolol (Sectral): Hypertension and premature
ventricular contractions
Atenolol (Tenormin): MI, chronic angina, and
hypertension
Metoprolol (Lopressor):MI, chronic angina, and
hypertension
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Word of the Day:
SYMPATHOMIMETIC (Agonist)
Adrenergic drug which acts directly on adrenergic
receptor, activating or stimulating it
SYMPATHOLYTIC (Antagonist)
Anti-Adrenergic drug which acts directly on
adrenergic receptor, blocking it
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Cholinergic Neurons
(Parasympathetic-Acetylcholine)
Na+
Choline
Acetylation
Ca++
Acetylcholinesterase

Receptor
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Cholinergic Receptors
Muscarinic receptors come in 5 subtypes
M1, M2, M3, M4, M5
Found in different locations
Research is on-going to identify specific agonists
and antagonists
Nicotinic receptors come in 2 subtypesNn – neurosynaptic receptor (autonomic)
Nm – muscular motor endplates (voluntary)
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Drugs 2
Cholinergic Agents
Cholinergic Agonists
Acetylcholine
Bethanechol
Carbachol
Pilocarpine
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General Effects of Cholinergic
Agonists
Decrease heart rate and cardiac output
Decrease blood pressure
Increases GI motility and secretion
Pupillary constriction
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Cholinergic Agonists
Cholinergic agents
cause SLUDGE!
HINT!
These effects are
predictable by knowing
PNS physiology (slide 22)
Salivation
Lacrimation
Urination
Defecation
Gastric motility
Emesis
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Results of Parasympathetic
Nervous System Stimulation
Increased motility and secretions in the GI tract- diarrhea / belly
cramps
Decreased heart rate and contractility- bradycardia
Constriction of the bronchi, with increased secretion- wheezing
Relaxation of the GI and urinary bladder sphincters- urination
(P is for Peeing)
Pupillary constriction – (MIOSIS- useful in glaucoma therapy)
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Cholinergic Neurons
Na+
Choline
Acetylation
Ca++

Acetylcholinesterase
Receptor
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Types of Cholinergic
Agonists
Direct-acting cholinergic
•Indirect acting cholinergic
agonists
Occupy receptor sites for
ACh on the membranes of
the effector cells of the
postganglionic cholinergic
nerves
Cause increased
stimulation of the cholinergic
receptor
agonists
React with the enzyme
acetylcholinesterase and
prevent it from breaking down
the ACh that was released from
the nerve
Causes increased stimulation
of the ACh receptor sites
44
Examples of Direct-Acting Cholinergic
Agonists and Their Indications
Bethanechol (Duvoid, Urecholine)
Treat urinary retention; neurogenic bladder atony
Diagnose and treat reflux esophagitis
Carbachol (Miostat); pilocarpine (Pilocar)
Induce miosis or pupil constriction
Relieve intraocular pressure of glaucoma
Perform certain surgical procedures
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Indirect-Acting Cholinergic
Agonists (Useful in Myasthenia Gravis)
Do not react directly with ACh receptor sites
React chemically with acetylcholinesterase in the synaptic
cleft to prevent it from breaking down Ach
ACh released from the presynaptic nerve accumulates,
stimulating the ACh receptors
Bind reversibly to acetylcholinesterase, so effects will pass
with time
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Myasthenia Gravis
Definition
Chronic muscular disease caused by a defect in
neuromuscular transmission
Autoimmune disease; patients make antibodies to ACh
receptors, causing gradual destruction of them
Symptoms
Progressive weakness and lack of muscle control with
periodic acute episodes
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Acetylcholinesterase Inhibitors
‘Indirect’ Used to Treat Myasthenia
Gravis
Neostigmine (Prostigmine): Has a strong influence at the
neuromuscular junction
Pyridostigmine (Regonol, Mestinon): Has a longer duration of
action than neostigmine
Ambenonium (Mytelase): Available only in oral form; cannot be
used if patient is unable to swallow tablets
Edrophonium (Tensilon, Enlon): Diagnostic agent for
myasthenia gravis
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Alzheimer’s Disease
A progressive disorder involving neural
degeneration in the cortex
Leads to a marked loss of memory and of the
ability to carry on activities of daily living
Cause of the disease is not yet known
There is a progressive loss of ACh-producing
neurons and their target neurons
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Drugs Used to Treat
Alzheimer’s Disease
Tacrine (Cognex)
First drug to treat Alzheimer’s dementia
Galantamine (Reminyl)
Used to stop progression of Alzheimer’s dementia
Rivastigmine (Exelon)
Available in solution for swallowing ease
Donepezil (Aricept)
Has once-a-day dosing
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Adverse Effects of
Acetylcholinesterase Inhibitors
ENHANCE parasympathetic effec6ts:
Bradycardia
Hypotension
Increased GI secretions and activity
Increased bladder tone
Relaxation of GI and genitourinary sphincters
Bronchoconstriction
Pupil constriction
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Cholinergic Drugs
Bethanechol (Duvoid,
Neostigmine
Urecholine)
Treat urinary retention; neurogenic
influence at the neuromuscular
junction
(Prostigmine): Has a strong
bladder atony
Diagnose and treat reflux
esophagitis
Pyridostigmine (Regonol,
Carbachol (Miostat);
Ambenonium (Mytelase):
pilocarpine (Pilocar)
Induce miosis or pupil constriction
Relieve intraocular pressure of
Mestinon): Has a longer
duration of action than
neostigmine
Available only in oral form; cannot
be used if patient is unable to
swallow tablets
Edrophonium (Tensilon,
glaucoma
Enlon): Diagnostic agent for
Perform certain surgical procedures myasthenia gravis
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Drugs 2
Anticholinergic Agents
Anticholinergic Drugs
Action
Used to block the effects of acetylcholine
Lyse, or block effects of the PNS; also called
parasympatholytic agents
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Anticholinergic Drugs
Decrease GI activity and secretions (treat ulcers)
Decrease parasympathetic activities to allow the
increase in sympathetic activity
55
Anticholinergics/
Parasympatholytics
Derived from the plant Belladonna
Block only the muscarinic effectors in the PNS and
cholinergic receptors in the SNS (sweat glands)
Act by competing with acetylcholine for the muscarinic
acetylcholine receptor sites
Do not block the nicotinic receptors
Have little or no effect at the neuromuscular junction
56
Types of Anticholinergic Agents
and Their Indications
Atropine
Blocks parasympathetic effects in many situations
Dicyclomine (Antispas, Dibent, and others)
Relaxes GI tract; treats hyperactive or irritable bowel
Glycopyrrolate (Robinul)
Adjunct in the treatment of ulcers
Propantheline (Pro-Banthine)
Adjunct in the treatment of ulcers
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Actions of Atropine
Depresses salivation and bronchial secretions
Dilates the bronchi
Inhibits vagal responses in the heart
Relaxes the GI and genitourinary tracts
Inhibits GI secretions
Causes mydriasis (Dilated pupils)
Causes cycloplegia (Blurring)
58
Adverse Effects of Atropine
Hot
Hotas
asHell
Hell
Blurred vision
Blind
Mydriasis (Dilated pupils)
Blindas
asaaBat
Bat
Cycloplegia
Dry
Dryas
asaaBone
Bone
Photophobia
Red
Redas
asaaBeet
Beet
Palpitations, bradycardia
Mad
as
aaHatter
Mad
as
Hatter
Dry mouth, altered taste perception
Urinary hesitancy and retention
Decreased sweating; predisposition to heat prostration
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Warning Signs That Patients Should
Report to the Health Care Team
Eye pain
Skin rash
Fever
Rapid heartbeat
Chest pain
Difficulty breathing
Agitation or mood changes
Impotence
60
Effects of Blocking the
Parasympathetic System
Increase in heart rate
Decrease in GI activity
Decrease in urinary bladder tone and function
Pupil dilation
Cycloplegia (unable to focus)
61
Types of Anticholinergic Agents and
Their Indications
Atropine
Blocks parasympathetic effects in
Depresses salivation and
many situations
bronchial secretions
Dicyclomine (Antispas, Dibent,
and others)
Dilates the bronchi
Relaxes GI tract; treats hyperactive Inhibits vagal responses in
or irritable bowel
the heart
Propantheline (Pro-Banthine)
Relaxes the GI and
Adjunct in the treatment of ulcers
Hot
Hotas
asHell
Hell
Blind
Blindas
asaaBat
Bat
Dry
Dryas
asaaBone
Bone
Red
Redas
asaaBeet
Beet
Mad
Madas
asaaHatter
Hatter
genitourinary tracts
Inhibits GI secretions
Causes mydriasis (Dilated
pupils)
Causes cycloplegia (Blurring)
62
FACTS TO REMEMBER!
ANS is an efferent system
Has 2 major divisions:
Sympathetic and Parasympathetic
There are differences between the two divisions
in terms of anatomy/ physiology/ neurotransmitters
ANS is involuntary and is responsible
for maintaining
Internal environment
Sympathetic: Alpha 1 and 2/ Beta 1 and 2 receptors/
Norepinephrine (NE) is the neurotransmitter at target sites
Parasympathetic: Nicotinic and Muscarinic receptors/
Acetylcholine neurotransmitter
63
Drugs 2
Drugs Acting on the Upper Respiratory
Tract
Drugs That Affect the
Respiratory System
Antitussives
Block the cough reflex
Decongestants
Decrease the blood flow to the upper respiratory
tract and decrease the overproduction of secretions
Antihistamines
Block the release or action of histamine that
increases secretions and narrows airways
65
Drugs That Affect the
Respiratory System
Expectorants
Increase productive cough to clear airways
Mucolytics
Increase or liquefy respiratory secretions to aid
clearing of airways
66
Antitussives
Definition
Drugs that suppress the cough reflex by acting directly on
the medullary cough center of the brain
Traditional antitussives
Codeine (generic only) (Robatussin)
Hydrocodone (Hycodan)
Dextromethorphan (Benylin and many others)
67
Decongestants
Definition
Cause local vasoconstriction
Decrease the blood flow to the irritated and dilated
capillaries of the mucous membranes lining the nasal
passages and sinus cavities
Types
Usually adrenergics or sympathomimetics
68
Types of Topical Nasal
Decongestants
Ephedrine (Kondon’s Nasal)
Oxymetazoline (Afrin, Allerest, and others)
Phenylephrine (Coricidin and many others)
Tetrahydrozoline (Tyzine)
Xylometazoline (Otrivin)
phenylephrine (Neo-Synephrine®)
pseudoephedrine (Sudafed®, Actifed®)
69
Types of Topical Nasal Steroid
Decongestants
Beclomethasone (Beclovent and others)
Budesonide (Rhinocort)
Dexamethasone (Decaderm and others)
Flunisolide (AeroBid and others)
Fluticasone (Flovent)
Triamcinolone (Kenacort)
70
Antihistamines
Found in multiple OTC preparations
Designed to relieve respiratory symptoms and to treat
allergies
Act by blocking the effects of histamine
Bring relief to patients suffering from itchy eyes,
swelling, congestion, and drippy nose
71
Antihistamines:
Histamine receptors
H1 receptors (Skin, Resp.
tract)
Vasodilation
Increased capillary
permeability
Bronchoconstriction
Other histamine receptors
(Brain)
Sedation
H2 receptors (Gastric)
Increase gastric acid
secretion (Zantac®), etc)
72
Antihistamine Agents
First generation
Sedation
chlorpheniramine
(Chlor-Trimeton®)
diphenhydramine
(Benadryl®)
clemastine (Tavist®)
promethazine (Phergan®)
Second generation
No sedation
fexofenadine (Allegra®)
cetirizine (Zyrtec®)
loratadine (Claritin®)
73
Mucolytics
Action
Break down mucus in order to aid the high-risk
respiratory patient
Administration
Nebulization or direct instillation into the trachea
Types
Acetylcysteine (Mucomyst and others)
Dornase alfa (Pulmozyme)
74
Indications for Mucolytics
Patients who have difficulty coughing up
secretions
Patients who develop atelectasis
Patients undergoing diagnostic bronchoscopy
Postoperative patients
Patients with tracheostomies
75
Cough medications -Recap
Antitussives
Decrease cough reflex
Opioids
codeine & hydrocodone
Non-opioids
dextromethorphan
benzonatate (Tessalon®)
Expectorants
guaifenesin may work
others are doubtful
Mucolytics
Decreases viscocity
acetlycysteine (Mucomyst®)
hypertonic saline
76
Drugs 2
Drugs Used to Treat Obstructive
Pulmonary Disorders
Changes
in the
Airway
With
COPD
78
Antiasthma Drugs
The problem:
Narrowing of the respiratory
passages
Normal
The causes:
Bronchiole
smooth muscle constriction
mucous production
Narrowed
Bronchiole
79
Asthma Drugs
The Solutions:
Bronchodilators
Adrenergic agonists (β2)
Terbutaline, salmeterol, albuterol
Cholinergic Antagonists
Ipratropium
Theophylline
Why has this been replaced with other drugs?
80
Asthma Drugs
(continued)
Anti inflammatories
Cromolyn – mast cell stabilizer
Corticosteroids
Inhaled: beclamethasone
Systemic: prednisone
Side effects?
81
Drugs to Treat COPD
The Problem:
Chronic, irreversible airflow obstruction
Variety of causes
The Solutions:
β2 agonists- Terbutaline, salmeterol, albuterol
Theophylline
glucocorticoids
82
Xanthines (Theophylline)
Come from a variety of sources
Include caffeine and theophylline
Once the main choice for treatment of asthma and
bronchospasm
Relatively narrow margin of safety; interact with many
other drugs
No longer considered the first-choice bronchodilators
83
Asthma therapy
Bronchodilators
(Sympathomimetics)
Anticholinergics
Anti-inflammatory Agents
Leukotriene Antagonists
Mast cell stabilizers
84
Bronchodilators
ß2 agonists
albuterol (Proventil®),
metaproterenol (Alupent®)
terbutaline (Breathair®)
Nonselective
epinephrine (Adrenalin®)
Methylxanthines theophylline (TheoDur®)
aminophyllin, (Aminophylline®)
Anticholinergics ipratropium bromide (Atrovent®)
85
Anti-inflammatory Agents
Glucocorticoids
inhaled
oral
injected
beclomethasone (Beclovent®)
flucticasone (Flovent®)
prednisolone (Deltasone®)
Mast cell Stabilizer
methylprednisolone
(Solu-Medrol®)
dexamethasone(Decadron®)
cromolyn (Nasalcrom®, Intal®)
Leukotriene
Antagonists
zafirlukast (Accolate®)
zileuton (Zyflo®)
86
Leukotriene Receptor
Antagonists
Action
Developed to act more specifically at the site of the problem
associated with asthma
Drugs in this class
Zafirlukast (Accolate) (first one developed)
Montelukast (Singulair)
Zileuton (Zyflo)
87
“long-acting beta 2-adrenergic
agonists” (LABA)
Advair (combination of salmeterol and fluticasone)
“may increase the chance of severe asthma episodes,
and death when those episodes occur.”FDA warning
88