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TRANSCRIPT
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PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM
YORAM ORON, PhD
PROFESSOR OF PHARMACOLOGY
SACKLER FACULTY OF MEDICINE
TEL AVIV UNIVERSITY
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ANATOMY OF ANS - I
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ANATOMY OF ANS
• ANS IS DEFINED BY TWO GROUPS OF PERIFERAL NERVES, WHICH ORIGINATE IN GANGLIA OR THE CRANIUM (CRANIAL NERVES)
• GANGLIA ARE RELAY PLEXI THAT TRANSMIT CNS INFORMATION VIA PRE-GANGLIONIC TO POST GANGLIONIC FIBERS
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OUTLINE OF THE ANS
S P
CERV
THOR
LUMB
SACRAL
VAGUS
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ANATOMY OF ANS - II
TARGET TISSUES
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Responses to ANS Stimuli
Effector OrganSympathetic Response
Parasympathetic Response
HeartSA node
RateContractilityConduction Velo.
RateContractilityConduction Velo.
AV node Conduction Velo. Conduction Velo.
HeartVentricles
ContractilityConduction Velo. -----
Lungs Relaxation of bronchial muscle
Contraction of bronchial muscle
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Responses to ANS Stimuli
Effector OrganSympathetic Response
Parasympathetic Response
-
ArteriolesSkin
Constriction -----
Mucosa Constriction -----
Abdominal viscera Constriction -----
Skeletal muscle Dilation -----
Coronary Dilation Dilation
Glands Constriction Dilation
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Responses to ANS Stimuli
Effector OrganSympathetic Response
Parasympathetic Response
-
Veins (systemic) Constriction -----
Gastrointestinal tract
Motility and toneContraction of sphincters
Motility and tone Relaxation of sphincters
Skin Pilomotor muscles
Piloerection-----
Sweat glands Secretion -----Spleen capsule Contraction
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Responses to ANS Stimuli
Effector OrganSympathetic Response
Parasympathetic Response
-
EyeRadial muscle of iris
Contraction -> mydriasis
-----
Sphincter muscle of iris
----- Contraction -> miosis
Ciliary muscle Relaxation for far vision
Contraction for near vision
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Effector OrganSympathetic Response
Parasympathetic Response
-
GlandsGastrointestinal Inhibition of
secretionSecretion
Lacrimal ----- Secretion
Nasopharyngeal ----- Secretion
Respiratory Inhibition of secretion
Secretion
Salivary Thick secretion Thin secretion
Responses to ANS Stimuli
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ANATOMY OF ANS - III
PRE- AND POST-GANGLIONIC FIBERS
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SCHEMATICS OF ANS GANGLIA
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ANATOMY OF ANS SYMPATHETIC NERVOUS SYSTEM
• POST-GANGLIONIC FIBERS EXHIBIT VARICOSITIES THAT SERVE AS PRE-SYNAPTIC ELEMENTS IN MANY LOCATIONS ALONG THE FIBRE (SYNAPSES EN PASSENT), IN ADDITION TO THE TERMINAL SYNAPSE
• THE ADRENAL MEDULLA SERVES AS A POST-GANGLIONIC ELEMENT, RELEASING EPINEPHRINE (EPI) AS A HORMONE INTO THE CIRCULATION
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ANATOMY OF ANS SYMPATHETIC NERVOUS SYSTEM
• GANGLIA ARE LOCATED CLOSE TO THE SPINAL COLUMN (SHORT PRE- AND LONG POST-GANGLIONIC FIBERS)
• GANGLIA ARE OFTEN INTERCONNECTED
• LARGE RATIO OF POST- TO PRE-GANGLIONIC FIBER NUMBER
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ANATOMY OF ANS SYMPATHETIC NERVOUS SYSTEM
• THE ANATOMY OF SYMPATHETIC ANS IS STRUCTURALLY DESIGNED TO PRODUCE DIFFUSE SYSTEMIC RESPONSES BY SIMULTANEOUS TARGETTING OF MULTIPLE TISSUES
• IN ADDITION TO THE ROUTINE HOMEOSTATIC MAINTENANCE OF VITAL FUNCTIONS, THE SYMPATHETIC NERVOUS SYTEM IS DESIGNED TO RESPOND TO PHYSIOLOGICAL STRESS
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ANATOMY OF ANS PARASYMPATHETIC NERVOUS SYSTEM
• NO VARICOSITIES ON POST-GANGLIONIC FIBERS, NO SYNAPSES EN PASSENT
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ANATOMY OF ANS PARASYMPATHETIC NERVOUS
SYSTEM
• GANGLIA ARE LOCATED CLOSE TO OR WITHIN THE TARGET TISSUE (LONG PRE- AND SHORT POST-GANGLIONIC FIBERS)
• GANGLIA ARE NOT INTERCONNECTED
• RATIO OF POST- TO PRE-GANGLIONIC FIBER NUMBER = 1
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ANATOMY OF ANS PARASYMPATHETIC NERVOUS SYSTEM
• THE ANATOMY OF ANS IS STRUCTURALLY DESIGNED TO PRODUCE PRECISE PIN-POINT RESPONSES BY TARGETTING OF SPECIFIC TISSUES
• IN ADDITION TO THE ROUTINE HOMEOSTATIC MAINTENANCE OF VITAL FUNCTIONS, THE PARASYMPATHETIC NERVOUS SYTEM IS DESIGNED TO LIMIT RESPONSES TO PHYSIOLOGICAL STRESS
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SIGNAL TRANSMISSION IN THE ANS - I
PRINCIPLES
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SIGNAL TRANSMISSION IN ANS
• ALONG THE PRE- AND POST GANGLIONIC FIBERS, ELECTRICAL PROPAGATION OF ACTION POTENTIAL BY FAST Na CHANNELS
• INHIBITION BY LOCAL AND GENERAL ANESTHETICS OR TTX
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SIGNAL TRANSMISSION IN ANS
• BETWEEN PRE-GANGLIONIC NERVE ENDING AND POST-GANGLIONIC CELL BODY, CHEMICAL NEUROTRANSMISSION
• GANGLIONIC TRANSMITTER - ACETYLCHOLINE (ACh) / NICOTINIC CHOLINERGIC RECEPTORS
• POST-GANGLIONIC TRANSMITTERS: PARASYMPATHETIC - Ach / MUSCARINIC CHOLINERGIC RECEPTORS SYMPATHETIC - NOREPINEPHRINE (NE) / ADRENERGIC RECEPTORS
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ACETYLCHOLINE
NOREPINEPHRINE
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SIGNAL TRANSMISSION IN THE ANS - II
TRANSMITTER SYNTHESIS
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SIGNAL TRANSMISSION IN ANSTRANSMITTER SYNTHESIS
• ACh SYNTHESIZED IN CHOLINERGIC NERVE ENDINGS FROM AcCoA AND CHOLINE BY CHOLINE-ACETYL TRANSFERASE
• CHOLINE ENTERS NERVE ENDINGS VIA A SPECIAL TRANSPORT SYSTEM
• INHIBITION BY HEMICHOLINIUM. HOWEVER, THERE IS NO THERAPEUTIC USE IN GENERALIZED INHIBITION OF Ach SYNTHESIS
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SIGNAL TRANSMISSION IN ANSTRANSMITTER SYNTHESIS
• NE SYNTHESIZED IN ADRENERGIC NERVE ENDINGS BY A SERIES OF REACTIONS:
• 1. TYROSINE->DOPA / TYROSINE HYDROXYLASE (TH)
• A PATHWAY BRANCHING POINT (AMINO ACIDS TO NEUROTRANSMITTERS), ALLOSTERICALLY AND TRANSCRIPTIONALLY REGULATED ENZYME, SENSITIVE TO CATECHOLAMINES CONCENTRATION
• INHIBITION BY ALPHA-METHYL TYROSINE - TRANSIENT AND WITH SERIOUS SIDE EFFECTS
• USED RARELY (E.G. PHEOCHROMOCYTOMA)
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SIGNAL TRANSMISSION IN ANSTRANSMITTER SYNTHESIS
• 2. DOPA -> DOPAMINE / DOPA DECARBOXYLASE
• 3. DOPAMINE ENTERS SECRETORY VESICLES BY VESICULAR TRANSPORT (H+ ANTIPORTER)
• IN DOPAMINERGIC NERVES THIS IS THE TERMINAL STEP IN SYNTHESIS
• VESICULAR TRANSPORT INHIBITABLE BY RESERPIN (ANTI-HYPERTENSIVE DRUG, NO LONGER IN USE, SIDE EFFECT - DEPRESSION) OR GUANETHIDINE (CURRENTLY SELDOM USED)
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SIGNAL TRANSMISSION IN ANSTRANSMITTER SYNTHESIS
• 4. DOPAMINE -> NOREPINEPHRINE (NE)/ BETA HYDROXYLASE
• ALPHA-METHYLDOPA IS HANDLED BY ALL THE CATECHOLAMINES SYNTHETIC ENZYMES TO PRODUCE ALPHA-METHYL NE, A HIGHLY POTENT ALPHA-2-ADRENERGIC AGONIST, STORED AS NE
• ALPHA-METHYLDOPA (OR CLONIDINE) ACTS PRE-SYNAPTICALLY TO INHIBIT NE RELEASE AND CENTRALLY TO INHIBIT SYMPATHETIC OUTFLOW
• ANTI-HYPERTENSIVE
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SIGNAL TRANSMISSION IN THE ANS - III
TRANSMITTER REMOVAL
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SIGNAL TRANSMISSION IN ANSTRANSMITTER REMOVAL-ACh
• ACh IS REMOVED BY NEURONAL (TRUE) ACETYLCHOLINE ESTERASE(AChE)
• NEURONAL AChE IS LOCATED IN CHOLINERGIC SYNAPSES
• IT IS A SERINE HYDROLASE AND ONE OF FASTEST ENZYMES KNOWN
• IT HYDROLYZES ACh TO CHOLINE AND ACETATE BY FORMING AN EXTREMELY UNSTABLE ACETATE ESTER WITH A SERINE AT THE ACTIVE SITE
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SIGNAL TRANSMISSION IN ANSTRANSMITTER REMOVAL-ACh
• AChE CAN BE INHIBITED BY: COMPETITIVE INHIBITORS (EDROPHONIUM, t1/2~2 MIN; AMBENONIUM, t1/2~3 HRS) REVERSIBLE COVALENT INHIBITORS (PHYSOSTYGMIN, NEOSTYGMINE, PYRIDOSTYGMINE THAT FORM RELATIVELY STABLE CARBAMOYL ESTER WITH THE ACTIVE SERINE)
• VIRTUALLY IRREVERSIBLE INHIBITORS, USUALLY ORGANOPHOSPHORUS COMPOUNDS (PARATHION, NERVE GASES, ECOTHIOPHATE)
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SIGNAL TRANSMISSION IN ANSTRANSMITTER REMOVAL-ACh
• EDROPHONIUM IS USED FOR DIAGNOSIS AND TITRATION OF ACh INHIBITORS DOSAGE IN MYASTHENIA GRAVIS
• AMBENONIUM, NEOSTYGMINE, PYRIDOSTYGMINE ARE USED IN MYASTHENIA GRAVIS
• PHYSOSTYGMIN AND ECOTHIOPHATE ARE USED IN POAG
• ORGANOPHOSPHORUS POISONING IS TREATED SYMPTOMATICALLY BY ATROPINE TO PREVENT MUSCARINIC OVERSTIMULATION AND BY PRALIDOXIME ((TO RELEASE PHOSPHORUS ESTER TO RELEASE PHOSPHORUS ESTER FROM AChE AND PREVENT FROM AChE AND PREVENT ”AGING”)
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SIGNAL TRANSMISSION IN ANSTRANSMITTER REMOVAL-NE
• NE IS REMOVED BY NEURONAL UPTAKE 1 AND BY TISSUE UPTAKE 2 (NOT ONLY INTO THE POST-SYNAPTIC CELL!)
• UPTAKE 1 AND 2 ARE ACTIVE, Na+ GRADIENT POWERED TRANSPORTERS
• UPTAKE 1 - HIGH-AFFINITY / LOW CAPACITY UPTAKE 2 - LOW AFFINITY / HIGH CAPACITY
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SIGNAL TRANSMISSION IN ANSTRANSMITTER REMOVAL-NE
• NE UPTAKE IS INHIBITED BY MANY DRUGS, THE MOST IMPORTANT ARE COCAIN (ACUTE) AND TRI-CYCLIC ANTIDEPRESSANTS (CHRONIC)
• ACUTE INHIBITION POTENTIATES THE ACTION OF ENDOGENOUSLY-RELEASED NE
• PERIFERALLY, ACUTE INHIBITION RESULTS IN INCREASED HEART RATE AND BLOOD PRESSURE (VASOCONSTRICTION) AND CENTRALLY BY A FEELING OF “HIGH” AND “RUSH”
• CHRONIC COCAIN USERS SUFFER FROM NASAL SEPTUM NECROSIS, DUE TO CELL DEATH FROM REPEATED ISCHEMIA
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SIGNAL TRANSMISSION IN ANSTRANSMITTER REMOVAL-NE
• NE IS METABOLIZED IN MANY TISSUES BY TWO ENZYMES: MONOAMINE OXIDASE (MAO) AND CATECHOL-O-METHYL TRANSFERASE (COMT)
• THE FINAL PRODUCTS RECOVERED IN URINE ARE VMA FROM PERIFERAL METABOLISM AND DOPEG FROM CENTRAL METABOLISM
• INHIBITION OF NE METABOLISM PREVENTS NE BREAKDOWN IN NON-SYNAPTIC SITES, HENCE NO ACUTE EFFECT
• INHIBITION OF MAO HAD BEEN USED TO TREAT HYPERTENSION (SEE BELOW) AND TO-DAY, TO TREAT PARKINSON
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SIGNAL TRANSMISSION IN THE ANS - IV
TRANSMITTER RELEASE
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SIGNAL TRANSMISSION IN ANSTRANSMITTER RELEASE
• ACh IS ACUTELY AND MASSIVELY RELASED BY A BLACK WIDOW SPIDER VENOM COMPONENT (ALPHA-LATROTOXIN) AND THE RELEASE IS BLOCKED BY CLOSTRIDIUM BOTULINUM TOXIN
• CLOSTRIDIUM BOTULINUM TOXIN (BOTOX) IS USED IN NYSTAGMUS AND WRINKLE REMOVAL
• NE IS RELEASED BY INDIRECT SYMPATHOMIMETICS (AMPHETAMINE, EPHEDRINE, GUANETHIDINE, TYRAMINE...)
• THESE DRUGS ENTER THE NEURON VIA UPTAKE 1 AND THE GRANULE BY VESICULAR UPTAKE AND DISPLACE VESICULAR NE
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SIGNAL TRANSMISSION IN ANSTRANSMITTER RELEASE
• ACUTELY REPLACED VESICULAR NE IS PARTLY METABOLIZED AND PARTLY RELEASED INTO THE SYNAPSE, PROBABLY VIA REVERSAL OF UPTAKE 1
• INHIBITION OF MAO POTENTIATES THE EFFECT OF INDIRECT SYMPATHOMIMETICS
• THE POOL OF NE AVAILABLE FOR RELEASE IS ONLY 10-20% OF TOTAL NEURONAL NE
• THIS LIMIT EXPLAINS THE PHENOMENON OF TACHYPHYLAXIS, I.E. DECREASING RESPONSES TO REPEATED EXPOSURES TO INDIRECT SYMPATHOMIMETICS
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ADRENERGIC SYNAPSE
Beta1-receptor
+
M2-receptor
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SIGNAL TRANSMISSION IN ANSMAO AND “CHEEESE EFFECT”
• PERIPHERAL INHIBITION OF MAO PREVENTS INTESTINAL DEGRADATION OF TYRAMINE (FROM INTESTINAL FLORA, FOOD), WHICH SLOWLY REPLACES NE WITH FALSE TRANSMITTER OCTOPAMINE
• DECREASED RELEASE OF NE LEADS TO DECREASED BP, MOOD ELEVATION, BUT ALSO INCREASED DENSITY OF ALPHA-1 RECEPTORS (HYPERSENSITIVITY)
• LARGE AMOUNTS OF TYRAMINE (CHEESE, WINE, FISH...), WITH INHIBITED MAO, ACUTELY RELEASE SUFFICIENT NE TO PRODUCE HYPERTENSIVE CRISIS IN HYPERSENSITIVE VASCULAR MUSCLE
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SIGNAL TRANSMISSION IN THE ANS - V
TARGET TISSUE RECEPTORS
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RECEPTORS IN ANSCHOLINERGIC
• NICOTINIC - SYMPATHETIC AND PARASYMPATHETIC GANGLIA, ADRENAL MEDULLA, STRIATED MUSCLE
• HETEROPENTAMER RECEPTOR-CHANNEL, Na+ CONDUCTANCE, EXTREMELY RAPID ACTIVATION/INACTIVATION
• PROLONGED ACTIVATION->DESENSITIZATION (E.G. FLACCID PARALYSIS)
• NATURAL AGONIST - ACh
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RECEPTORS IN ANSCHOLINERGIC
• MUSCARINIC - SMOOTH AND CARDIAC MUSCLE, EXOCRINE GLANDS
• GPCRs - TWO FAMILIES• M1 (CORTICAL); M3 (GLANDULAR); M5 (CNS)• SIGNAL TRANSDUCTION VIA PI-PLC-Ca
PATHWAY• M2 (CARDIAC); M4 (CNS) • SIGNAL TRANSDUCTION VIA INHIBITION OF
ADENYLYL CYCLASE OR DIRECT ACTIVATION OF CHANNELS (E.G. CARDIACK+ CHANNEL)
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RECEPTORS IN ANSADRENERGIC
• ENDOGENOUS STIMULATION BY NE AND EPI• BETA - SMOOTH AND CARDIAC MUSCLE, LIVER,
FAT CELLS, ALMOST EVERY CELL (INCLUDING ERYTHROCYTES)
• GPCRs - THREE FAMILIES• BETA-1 (CARDIAC, KIDNEY, FAT); BETA-2
(SMOOTH MUSCLE); BETA-3 (FAT)• SIGNAL TRANSDUCTION VIA STIMULATION OF
ADENYLYL CYCLASE
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RECEPTORS IN ANSADRENERGIC
• ALPHA - SMOOTH MUSCLE, LIVER, FAT CELLS, EXOCRINE GLANDS, PRESYNAPTIC ADRENERGIC ELEMENTS
• GPCRs - TWO FAMILIES• ALPHA-1 (SMOOTH MUSCLE, LIVER, FAT,
GLANDS)• SIGNAL TRANSDUCTION VIA STIMULATION OF PI-
PLC-Ca PATHWAY• ALPHA-2 (CNS, PRESYNAPTIC)• SIGNAL TRANSDUCTION VIA INHIBITION OF
ADENYLYL CYCLASE AND DIRECT ACTIVATION OF ION CHANNELS
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AUTONOMIC DRUGS
CHOLINERGIC
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AUTONOMIC DRUGSCHOLINERGIC-MUSCARINIC AGONISTS
• URECHOLINE: ACh ANALOG, AChE-RESISTANT, SELECTIVITY FOR INTESTINAL AND URINARY TRACT THAN FOR CARDIAC RECEPTORS
USE: ATONIC (POSTOPERATIVE) ILEUS, BLADDER• PILOCARPINE: ALKALOID, PARTIAL AGONIST
USE: POAG (TOPICAL)
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AUTONOMIC DRUGSCHOLINERGIC-MUSCARINIC ANTAGONISTS
• ATROPINE: BELLADONNA ALKALOID, NON-SPECIFIC, HIGH AFFINITY, CNS STIMULANT
USE: MAINLY TREATMENT OF AChE-I POISONING, SINUS BRADYCARDIA, PRE-OPERATIVE, GI HYPERMOTILITY
• SCOPOLAMINE: BELLADONNA ALKALOID, CNS DEPRESSANT
USE: MOTION SICKNESS, NAUSEA• IPRATROPIUM:USE: ASTHMA, BRONCHOSPASM INHALATIONS• PIRENZEPINE: SYNTHETIC, M1-SELECTIVEUSE: PEPTIC ULCER
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AUTONOMIC DRUGSCHOLINERGIC DRUGS-SIDE EFFECTS
• AGONISTS: BRADYCARDIA, INCREASED SECRETIONS (BRONCHIAL, SALIVARY, URINARY, GI, SWEAT), INCREASED GI MOTILITY, BRONCHOSPASM, MICTURITION, MIOSIS
• ANTAGONISTS: DECREASED SECRETIONS BRONCHIAL, SALIVARY, URINARY, GI, SWEAT- E.G. XEROSTOMIA, DRY SKIN), TACHYCARDIA,, ELEVATED TEMPERATURE SET-POINT, CNS STIMULATION >DEPRESSION, MYDRIASIS, CYCLOPLEGIA, URINARY RETENTION, BRONCHODILATION
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AUTONOMIC DRUGS
ADRENERGIC
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AUTONOMIC DRUGSADRENERGIC-BETA AGONISTS
• ISOPROTERENOL: SYNTHETIC NE ANALOG, BETA 1,2,3
USE: ASTHMA, OBSOLETE• DOBUTAMINE: SYNTHETIC NE ANALOG,
BETA 1USE: CARDIOGENIC SHOCK• SALBUTAMOL, SALMETEROL,
TERBUTALINE: SYNTHETIC, BETA 2-SELECTIVE
USE: ASTHMA, BRONCHOSPASM
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AUTONOMIC DRUGSBETA-ADRENERGIC ANTAGONISTS
• PROPRANOLOL: SYNTHETIC, BETA 1,2 SPECIFIC
USE: ANGINA, HYPERTENSION, ARRHYTHMIAS, ANXIETY TREMOR, HYPERTHYROIDISM
• ALPRENOLOL: AS PROPRANOLOL, BUT PARTIAL AGONIST
USE: AS PROPRANOLOL • PRACTOLOL, METOPROLOL:BETA-1
SPECIFICUSE: AS PROPRANOLOL
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AUTONOMIC DRUGSBETA DRUGS-SIDE EFFECTS
AGONISTS: TACHYCARDIA, TACHYARRHYTHMIAS, NERVOUSNESS, ANXIETY, LIMB TREMOR, INCREASED BMR
ANTAGONISTS: BRONCHOSPASM, BRADYCARDIA, AV BLOCK, HEART FAILURE, COLD EXTREMITIES, FATIGUE, DEPRESSION, HYPOGLYCEMIA, DEPRESSION OF SIGNS OF HYPOGLYCEMIA (DIABETES!)
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AUTONOMIC DRUGSALPHA-ADRENERGIC AGONISTS
• METARAMINOL: ALPHA 1 SELECTIVE
USE: MAINLY TO RAISE AND MAINTAIN BLOOD PRESSURE IN SHOCK
• PHENYLEPHRINE: ALPHA 1-SELECTIVE
USE: DECONGESTANT• CLONIDINE: ALPHA-2 PARTIAL AGONIST
USE: HYPERTENSION, MIGRAINE
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AUTONOMIC DRUGSALPHA-ADRENERGIC ANTAGONISTS
• PHENOXYBENZAMINE: ALPHA 1,2, IRREVERSIBLE, UPTAKE-1 INHIBITOR
USE: PHEOCHROMOCYTOMA• PRAZOSIN: ALPHA 1-SELECTIVE
USE: HYPERTENSION• YOHIMBINE: ALPHA-2 SELECTIVE
USE: NOT USED, BUT APHRODYSIAC?
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AUTONOMIC DRUGSALPHA DRUGS-SIDE EFFECTS
AGONISTS: HYPERTENSION, REFLEX BRADYCARDIA
ANTAGONISTS: HYPOTENSION, TACHYCARDIA, NASAL CONGESTION, IMPOTENCE
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AUTONOMIC DRUGSMIXED ADRENERGIC AGONISTS
• NE: ALPHA 1,2- BETA 1 SELECTIVE USE: NOT USED• EPINEPHRINE: ALPHA/BETA NON-
SPECIFIC USE: ANAPHYLACTIC SHOCK, ASTHMA,
CARDIAC ARREST, VASOCONSTRICTOR IN LOCAL ANESTHETICS AND SUPERFICIAL BLEEDING
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AUTONOMIC DRUGSMIXED ADRENERGIC ANTAGONISTS
• LABETALOL: ALPHA-BETA
USE: HYPERTENSION, ESPECIALLY IN PREGNANCY
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AUTONOMIC DRUGS
ORGAN CONTROL - CVS
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AUTONOMIC CONTROL OF CVS
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AUTONOMIC CONTROL OF CVS
ISO – VASODILATION, INCREASED HR, DECREASED MEAN BP, SYMPATHETIC REFLEX
NE – VASOCONSTRICTION, INCREASED MEAN BP, VAGAL REFLEX, DECREASED HR
EPI – VASODILATION & VASOCONSTRICTION, NO CHANGE IN MEAN BP, NO REFLEX, INCREASED HR
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AUTONOMIC CONTROL OF CVS
DOPAMINE – (LOW - DARs) VASODILATION OF SPLANCHNIC BED, DECREASED PERIFERAL RESISTANCE, INCREASED URINE OUTPUT
DOPAMINE – (MEDIUM -betaRs) VASODILATION OF SEVERAL BEDS, DECREASED PERIFERAL RESISTANCE, INCREASED URINE OUTPUT & CO
DOPAMINE – (HIGH - alphaRs) VASODILATION & VASOCONSTRICTION, DECREASED PERIFERAL RESISTANCE, INCREASED URINE OUTPUT, INCREASED CO, INCREASED BP
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GLAUCOMA THERAPY
Primary Open-Angle Glaucoma (POAG)
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GLAUCOMA
CILLIARY BODY
LENS
IRIS
CORNEA
SCLERA
PUPIL
TRABECULAR MESH
AQUEOUS OUTFLOW
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GLAUCOMA THERAPYPrimary Open-Angle Glaucoma (POAG)
ETHIOLOGY?
INCREASED IOP (BUT ALSO NORMOTENSIVE GLAUCOMA)(BUT ALSO INCREASED IOP W/O GLAUCOMA – OCULAR HYPERTENSION)
PROGRESSIVE DEATH OF GANGLION CELLS
PROGRESSIVE DAMAGE TO OPTIC NERVE HEAD
PROGRESSIVE LOSS OF VISION
NEURODEGENERATIVE SYNDROME?
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PROGRESSIVE LOSS OF VISION
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POAG THERAPY
DRUGSAQUEOUS PRODUCTION
AQUEOUS OUTFLOW
TIMOLOL
BETAXOLOL
SIDE EFFECTSHEART FAILURE
BRONCHOSPASM
DRUG CLASS – BETA BLOCKERS
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POAG THERAPY
DRUGSAQUEOUS PRODUCTION
AQUEOUS OUTFLOW
PHYSOSTYGMINE
PILOCARPINE (PA)
CARBACHOL
SIDE EFFECTSBROW ACHEMIOSIS
IMPAIRED VISION
DRUG CLASS – MUSCARINIC STIMULATION
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POAG THERAPY
DRUGSAQUEOUS PRODUCTION
AQUEOUS OUTFLOW
EPINEPHRINE
DIPIVEFRINE (PRO)
APRACLONIDINE
BROMONIDINE
SIDE EFFECTSPUPIL DILATIONMACULAR EDEMA
TACHYCARDIAHYPOTENSION (CHILDREN)
CONTACT ALLERGY
DRUG CLASS – ALPHA AGONISTS
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POAG THERAPY
DRUGSAQUEOUS PRODUCTION
AQUEOUS OUTFLOW
ACETAZOLAMIDE
DORZOLAMIDE (TOPICAL)
SIDE EFFECTSGIMALAISE
APLASTIC ANEMIARENAL STONES
CONFUSION
DRUG CLASS – CARBONIC ANHYDRASE INHIBITORS
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POAG THERAPY
DRUGSAQUEOUS PRODUCTION
AQUEOUS OUTFLOW
LATANOPROST
SIDE EFFECTSLASH GROWTH
IRIS COLOR CHANGE
DRUG CLASS – PROSTAGLANDINS
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ESSENTIAL HYPERTENSION THERAPY
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ESSENTIAL HYPERTENSION