Download Drugs Unit 2 - Cat`s TCM Notes

Drugs Unit 2
Introduction to the
Autonomic Nervous System
Nervous System
Ion Diffusion
 Key to neurophysiology
 Dependent upon:
 Concentration gradient
 Electrical gradient
 Modified by:
 ‘Gated ion channels’
Where Does Diffusion Take the Ion?
Major Networks of CNS
Motor System- voluntary 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 System- responsible for maintenance of consciuosness and alertness
Limbic System-responsible for control of emotions/happiness etcetera
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
Organization of the
Peripheral Nervous System
Three major divisions:
EFFERENT
Somatic (motor)
Autonomic
Sympathetic
and
Parasympathetic
AFFERENT
Sensory
Preganglionic Nerves
Sympathetic and Parasympathetic
preganglionic fibres release Acetylcholine (ACh)
ACh has two types of receptors:
Muscarinic and Nicotinic
Postganglionic nerves have Nicotinic receptors
Postganglionic Nerves
Sympathetics release Norepinephrine
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Parasympathetics release ACh
Norepinephrine binds to adrenergic receptor
ACh binds to Muscarinic receptors
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
Bodily Functions Regulated by the ANS
Blood pressure
Heart rate
Respiration
Body temperature
Water balance
Urinary excretion
Digestive functions
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)
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
Location and Function of
Alpha1 Receptors
Blood vessels
Cause vasoconstriction and increase peripheral resistance, raising blood pressure
Iris Cause pupil dilation
Urinary bladderCause 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
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
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
Sympathetic NS Drugs
Predictable response based on knowledge of affects of adrenergic receptor stimulation
Each receptor may be:
Stimulated (sympathomimetic)
Inhibited (sympatholytic) (‘blocker’)
Alpha1 Agonists
Profound vasoconstriction
Increases afterload & blood pressure when given systemically
Decreases drug absorption & bleeding when given topically
Alpha- and Beta-Adrenergic Agonists and Their Indications
Dobutamine (Dobutrex): Congestive heart failure
Dopamine (Intropin): Shock
Ephedrine (Pretz-D): Seasonal rhinitis;
Epinephrine (Adrenalin, Sus-Phrine):
Shock; prolongs effects of regional anesthetic
Norepinephrine (Levophed): Shock; cardiac arrest
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
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)
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
Alpha- and Beta Blocking Agents and Their Indications
Carvedilol (Coreg): Hypertension, congestive heart failure (adult)
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
Indications for Beta- Blocking Agents
Treating cardiovascular problems
Hypertension
Angina
Migraine headaches
Preventing reinfarction after MI
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
Adverse Effects of Beta- Blocking Agents
GI upset
CNS changes
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Respiratory problems
CV effects
Loss of libido
Impotence
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
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
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
Cholinergic Neurons (Parasympathetic-Acetylcholine)
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 subtypes-
Nn – neurosynaptic receptor (autonomic)
Nm – muscular motor endplates (voluntary)
Drugs 2
Cholinergic Agents
Cholinergic Agonists
Acetylcholine
Bethanechol
Carbachol
Pilocarpine
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
Salivation
Lacrimation
Urination
Defecation
Gastric motility
Emesis
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)
Cholinergic Neurons
Types of Cholinergic Agonists
Direct-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
•Indirect acting cholinergic 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
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
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
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
‘IIndirect’ 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
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
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
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
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
Anticholinergic Drugs
Decrease GI activity and secretions (treat ulcers)
Decrease parasympathetic activities to allow the increase in sympathetic activity
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
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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
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)
Adverse Effects of Atropine
Blurred vision
Mydriasis (Dilated pupils)
Cycloplegia
Photophobia
Palpitations, bradycardia
Dry mouth, altered taste perception
Urinary hesitancy and retention
Decreased sweating; predisposition to heat prostration
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
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)
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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
Cholinergic Drugs
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
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
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
Propantheline (Pro-Banthine)
Adjunct in the treatment of ulcers
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)
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
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Drugs That Affect the Respiratory System
Expectorants
Increase productive cough to clear airways
Mucolytics
Increase or liquefy respiratory secretions to aid clearing of airways
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)
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
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®)
Types of Topical Nasal Steroid Decongestants
Beclomethasone (Beclovent and others)
Budesonide (Rhinocort)
Dexamethasone (Decaderm and others)
Flunisolide (AeroBid and others)
Fluticasone (Flovent)
Triamcinolone (Kenacort)
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
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Antihistamines:
Histamine receptors
H1 receptors (Skin, Resp. tract)
Vasodilation
Increased capillary permeability
Bronchoconstriction
H2 receptors (Gastric)
Increase gastric acid secretion (Zantac®), etc)
Other histamine receptors (Brain)
Sedation
Antihistamine Agents
First generation
Sedation
chlorpheniramine (Chlor-Trimeton®)
diphenhydramine (Benadryl®)
clemastine (Tavist®)
promethazine (Phergan®)
Second generation
No sedation
fexofenadine (Allegra®)
cetirizine (Zyrtec®)
loratadine (Claritin®)
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)
Indications for Mucolytics
Patients who have difficulty coughing up secretions
Patients who develop atelectasis
Patients undergoing diagnostic bronchoscopy
Postoperative patients
Patients with tracheostomies
Cough medications -Recap
Antitussives
Decrease cough reflex
Opioids
codeine & hydrocodone
Non-opioids
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dextromethorphan
benzonatate (Tessalon®)
Expectorants
guaifenesin may work
others are doubtful
Mucolytics
Decreases viscocity
acetlycysteine (Mucomyst®)
hypertonic saline
Drugs 2
Drugs Used to Treat Obstructive Pulmonary Disorders
Changes in the Airway With COPD
Antiasthma Drugs
The problem:
Narrowing of the respiratory passages
The causes:
smooth muscle constriction
mucous production
Asthma Drugs
The Solutions:
Bronchodilators
Adrenergic agonists (β2)
Terbutaline, salmeterol, albuterol
Cholinergic Antagonists
Ipratropium
Theophylline
Why has this been replaced with other drugs?
Asthma Drugs
Anti inflammatories
Cromolyn – mast cell stabilizer
Corticosteroids
Inhaled: beclamethasone
Systemic: prednisone
Side effects?
Drugs to Treat COPD
The Problem:
Chronic, irreversible airflow obstruction
Variety of causes
The Solutions:
β2 agonists- Terbutaline, salmeterol, albuterol
Theophylline
glucocorticoids
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
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No longer considered the first-choice bronchodilators
Asthma therapy
Bronchodilators (Sympathomimetics)
Anticholinergics
Anti-inflammatory Agents
Leukotriene Antagonists
Mast cell stabilizers
Bronchodilators
Anti-inflammatory Agents
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)
“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
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