Topic 10-2 Drugs of the Nervous System-Adrenergic · 2009. 4. 24. · specific β adrenergic...
Transcript of Topic 10-2 Drugs of the Nervous System-Adrenergic · 2009. 4. 24. · specific β adrenergic...
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Topic 10-2 Drugs of theNervous System-Adrenergic
Ch 19,20 PatrickPart VI- Nervous system -Corey
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1. Nerve Transmission1. Nerve Transmission
Peripheral nervous systemPeripheral nervous system
Peripheral nerves
Muscle
Gastro-intestinal tract (GIT)
Brain
Spinal cord
CNS
Heart
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1. Nerve Transmission1. Nerve Transmission
Peripheral nervous systemPeripheral nervous system
CNS(Somatic)
CNS(Autonomic)
Sympathetic
Parasympathetic
NA
Ach(N)
Synapse
Ach (N)
Ach(N)
Ach(N)
Ach(M)
Adrenalmedulla
Adrenaline
Skeletalmuscle
Synapse
AUTONOMIC
Smooth muscleCardiac muscle
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NerveNerve
1. Nerve Transmission1. Nerve Transmission
SynapsesSynapses100-500A
ReceptorsReceptors
Release ofneurotransmitters
Receptor binding and new signal
Nerve impulseNerve impulse New signalNew signal
Vesicles containingneurotransmitters
Adrenergic endogenous agonists: catechols
In adrenal medulla
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1. Nerve Transmission1. Nerve Transmissionαα and and ββ adrenergic G-protein receptors-adrenergic G-protein receptors-
many overlapping functionsmany overlapping functionsIn General:
•β adrenergic receptors•Relax smooth muscle (except heart muscle)•β1 blockers slow heart muscle contraction,lowers BP
•α adrenergic receptors•Contract smooth muscle(except gut)•α1 agonists -used for vasoconstriction in localanesthesia, α2 for glaucoma•α1 antagonists relax smooth muscle forhypertension and angina
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1. Nerve Transmission1. Nerve Transmissionαα and and ββ adrenergic G-protein receptors-adrenergic G-protein receptors-
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1. Nerve Transmission1. Nerve TransmissionNoradrenalin (norepinephrine) system drug targets
Negative feedback system
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Adrenergic Binding SiteAdrenergic Binding Site
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Adrenergic Binding Site: Adrenergic Binding Site: α α vsvs. . ββ
Stimulates β, not α due to bulky groups
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Adrenergic Binding Site: spec. Adrenergic Binding Site: spec. β2 β2 agonists and asthmaagonists and asthma
selective selective β2 β2 agonists, adrenalin is less specificagonists, adrenalin is less specific
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αα Adrenergic antagonists: Adrenergic antagonists:
general general α/βα/β for for antihypertensionantihypertension α1 α1 for urinary tract relaxation prostatefor urinary tract relaxation prostateenlargement treatmentenlargement treatment
Mirtazepine Mirtazepine ((RemeronRemeron) ) α2α2 blocker for depression-increases serotonin and NA blocker for depression-increases serotonin and NA
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ββ adrenergic blockers:cardiovascular drugs for BP adrenergic blockers:cardiovascular drugs for BP
partialpartial β β agonistsagonists
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specific specific ββ adrenergic blockers:cardiovascular drugs for BP adrenergic blockers:cardiovascular drugs for BP
Extra ring converts agonist to antagonistExtra ring converts agonist to antagonist
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specific specific ββ adrenergic blockers:cardiovascular drugs for BP adrenergic blockers:cardiovascular drugs for BP
β−blockers effects
• Reduce cardiac output• Reduce renin release from kidneys (which
produces Angiotensin I and II)• Reduces general activity of CNS
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specific specific ββ adrenergic blockers:cardiovascular drugs for BP adrenergic blockers:cardiovascular drugs for BP
β−blockers side effects
• Bronchoconstriction due to β2 blocking• lethargy• Dizziness, dreams from bbb passage of
hydrophobic propanolol• Potential heart failure
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More selective β1−blockers-Next generation
β1 receptor
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More selective β1−blockers-3rd generation !
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Other Adrenergic drugs
• Biosynthesis “dummies” down regulateadrenergic system
α−methyl tyrosine: a fake amino acid
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Other Adrenergic drugs• The tricyclic antidepressants• NA reuptake inhibitors-desensitize a2
receptors leading to more serotonin and NAreleased to get effect.
Similar 3D structure to NA
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Other Adrenergic drugs• Newer antidepressants• Bupropion (Welbutrin) and others inhibit reuptake of
both NA and dopamine in CNS.• Reuptake inhibitors also used for ADHD (ritalin,
Strattera)
Ritalin
WelbutrinEdronax
Strattera
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Other Adrenergic drugs• Cocaine-inhibits NA uptake in peripheral
nervous system and dopamine in CNS
cocaine
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Other Adrenergic drugs• Amphetamine-inhibits NA carrier uptake in CNS
• Monoamine oxidase inhibitors-increase[catecholamine] by stopping breakdown
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