Topic 10-2 Drugs of the Nervous System-Adrenergic
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Topic 10-2 Drugs of the Nervous System-Adrenergic Ch 19,20 Patrick Part VI- Nervous system -Corey
Transcript of Topic 10-2 Drugs of the Nervous System-Adrenergic
Topic 10-2 Drugs of theNervous System-Adrenergic
Ch 19,20 PatrickPart VI- Nervous system -Corey
1. Nerve Transmission1. Nerve Transmission
Peripheral nervous systemPeripheral nervous system
Peripheral nerves
Muscle
Gastro-intestinal tract (GIT)
Brain
Spinal cord
CNS
Heart
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
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
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
1. Nerve Transmission1. Nerve Transmissionαα and and ββ adrenergic G-protein receptors-adrenergic G-protein receptors-
1. Nerve Transmission1. Nerve TransmissionNoradrenalin (norepinephrine) system drug targets
Negative feedback system
Adrenergic Binding SiteAdrenergic Binding Site
Adrenergic Binding Site: Adrenergic Binding Site: α α vsvs. . ββ
Stimulates β, not α due to bulky groups
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
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
ββ adrenergic blockers:cardiovascular drugs for BP adrenergic blockers:cardiovascular drugs for BP
partialpartial β β agonistsagonists
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
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
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
More selective β1−blockers-Next generation
β1 receptor
More selective β1−blockers-3rd generation !
Other Adrenergic drugs
• Biosynthesis “dummies” down regulateadrenergic system
α−methyl tyrosine: a fake amino acid
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
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
Other Adrenergic drugs• Cocaine-inhibits NA uptake in peripheral
nervous system and dopamine in CNS
cocaine
Other Adrenergic drugs• Amphetamine-inhibits NA carrier uptake in CNS
• Monoamine oxidase inhibitors-increase[catecholamine] by stopping breakdown
