PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM

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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
VAGUS
THOR
LUMB
SACRAL
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ANATOMY OF ANS - II
TARGET TISSUES
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Responses to ANS Stimuli
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Responses to ANS Stimuli
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Responses to ANS Stimuli
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Responses to ANS Stimuli
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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-gtDOPA / 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 -gt 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 -gt 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, t1/22 MIN
  AMBENONIUM, t1/23 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 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-gtDESENSITIZATION (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-SELECTIVE
• USE 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 gtDEPRESSION,
  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 1
• USE 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, METOPROLOLBETA-1 SPECIFIC
• USE 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
CORNEA
TRABECULAR MESH
AQUEOUS OUTFLOW
PUPIL
IRIS
LENS
CILLIARY BODY
SCLERA
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GLAUCOMA THERAPY
Primary 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
DRUG CLASS BETA BLOCKERS
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POAG THERAPY
DRUG CLASS MUSCARINIC STIMULATION
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POAG THERAPY
DRUG CLASS ALPHA AGONISTS
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POAG THERAPY
DRUG CLASS CARBONIC ANHYDRASE INHIBITORS
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POAG THERAPY
DRUG CLASS PROSTAGLANDINS
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ESSENTIAL HYPERTENSION THERAPY
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ESSENTIAL HYPERTENSION