Sympathetic Nervous System Flashcards

Flashcards for the sympathetic nervous system, neurotransmitters, physiological effects, and adrenergic receptors.

Sympathetic Nervous System

Prepares the body for "fight or flight" situations.

Acetylcholine (ACh)

Released by pre-ganglionic neurons at the synapse with post-ganglionic neurons in autonomic ganglia.

Noradrenaline (NA)

Released by most post-ganglionic sympathetic neurons in target organs.

Adrenaline (A)

Secreted by the adrenal medulla directly into the bloodstream.

Physiological effects of sympathetic stimulation

Increases heart rate and contraction strength; causes peripheral vasoconstriction and bronchodilation; inhibits gastrointestinal motility and secretions; increases hepatic gluconeogenesis and glycogenolysis.

Action Potential

Rapid, transient change in membrane potential when a neuron is stimulated.

Role of Calcium (Ca²⁺)

Triggers the fusion of synaptic vesicles releasing neurotransmitters into the synaptic cleft

Synthesis of Noradrenaline and Adrenaline

Tyrosine converted to DOPA via tyrosine hydroxylase, then to Dopamine via DOPA decarboxylase, then to Norepinephrine via dopamine Beta-hydroxylase, then to Epinephrine via PNMT (only in the adrenal medulla).

Degradation of Noradrenaline and Adrenaline

By the action of enzymes that inactivate NA and A into inactive metabolites, excreted in the urine. MAO & COMT.

MAO (monoamine oxidase)

mitochondrial - interior of cells > axon terminals - NOR - production of acid diidroximandélico (DHMA).

COMT (catecol-O-methyltransferase)

cytoplasmic and extracellular - Widely distributed in neuronal and non-neuronal tissues. - The main metabolite of NOR is acid 3-metoxi-4- hidroximandélico (VMA).

Adrenergic Neuroeffector Junction

Region where the post-ganglionic sympathetic neuron contacts the target organ, releasing noradrenaline.

Adrenergic nerve terminal

Contains vesicles with noradrenaline.

Relative Potency of Adrenaline, Noradrenaline, and Isoproterenol on Adrenergic Receptors

A1 - NA > A >> ISO; A2 - A > NA >> ISO; B1 - ISO > NA > A; B2 - ISO > A > NA

Effect of Noradrenaline on Blood Pressure

Noradrenaline strongly activates A1 receptors causing intense vasoconstriction and a large increase in blood pressure.

Adrenaline's role in anaphylactic shock treatment

Adrenaline is effective because it activates B2 receptors promoting bronchodilation, A1 receptors promoting vasoconstriction, and inhibits histamine release.

Noradrenaline's role in cardiogenic shock treatment

Noradrenaline is indicated because it increases blood pressure and peripheral vasoconstriction via α1

Regulation of Noradrenaline in the synaptic cleft

Uptake 1 (NET), diffusion, uptake 2, MAO, COMT.

Neuronal reuptake (uptake 1):

Transportador NET retira a NA da fenda para o terminal pré-sináptico.

MAO (monoamine oxidase):

mitochondria pré-sinápticas, Degrada NA recaptada, dentro do neurônio.

COMT (catecol-O-metiltransferase):

degrada NA na fenda sináptica e nas células alvo, circulação.

Sympathomimetic Drugs

Act directly on receptors; increase NA release or inhibit reuptake/degradation; combine both mechanisms.

Direct-acting sympathomimetic drugs

Drugs such as phenylephrine (A1), and adrenaline (A and B).

Indirect-acting sympathomimetic drugs

Drugs such as amphetamine and tyramine.

Mixed-acting sympathomimetic drugs

Drugs such as ephedrine and dopamine.

Phenylephrine:

Agonist A1 → vasoconstriction → nasal decongestant.

Midodrina:

pró-fármaco ativado a agonista A1 → trata hipotensão ortostática.

Oximetazolina:

agonista A1 e A2 local → vasoconstrição nasal (uso tópico).

Clonidina:

agonista A2 central → ↓ descarga simpática → trata hipertensão.

Dobutamina:

agonista B1 → ↑ contratilidade cardíaca (choque, ICC).

Salbutamol:

agonista B2 de ação curta → broncodilatador (crise asmática).

Salmeterol/Formoterol:

agonistas B2 de longa duração → prevenção da asma/COPD.

Indirect-Acting Adrenergic Agonists

Increase NA in the synaptic cleft. Stimulate release (e.g., amphetamine); inhibit reuptake (e.g., cocaine); inhibit degradation (e.g., selegiline – MAO inhibitor)

Alpha-Adrenergic Antagonists

Block A1 (vasodilation) and A2 (↑ noradrenaline release).

Beta-Adrenergic Antagonists

Block B1 (↓FC, contractility) and B2 (bronchoconstriction).

Phentolamine and Phenoxybenzamine

Used to treat pheochromocytoma and hypertensive crises; non-selective alpha-adrenergic antagonists.

Prazosin, Doxazosin, and Tamsulosin

Used to treat hypertension and benign prostatic hyperplasia; selective alpha-1 adrenergic antagonists.

Ioimbina

Used to treat erectile dysfunction; selective alpha-2 adrenergic antagonist.

Propranolol, Nadolol, and Timolol

Used to treat hypertension, arrhythmias, migraine, and tremors; non-selective beta-adrenergic antagonists.

Atenolol, Metoprolol, and Bisoprolol

Used to treat hypertension and angina; selective beta-1 adrenergic antagonists.

Carvedilol and Labetalol

Used to treat heart failure and hypertension; non-selective beta-adrenergic antagonists with additional vasodilatory effects.

Nebivolol

Used to treat hypertension and heart failure; selective beta-1 adrenergic antagonist with vasodilatory effects due to NO release.

Prazosin:

Block A1 → vasodilatation → ↓ PA → Trata HPB (Benign Prostatic Hyperplasia) E HIPERTENSÃO

Ioimbina:

Block A2 → ↑ NA release → USADO EM DISFUNÇÃO ERÉTIL

Propranolol

Block B1/B2 → ↓ FC, ↓ PA → TRATA HIPERTENSÃO

Metoprolol:

Selective B1 → seguro para asmáticos/IC → CARDIOSELETIVO, MENOS EFEITOS PULMONARES

Parasympathetic Nervous System (SN Parasympathetic)

Is part of the autonomic nervous system and regulates involuntary functions, typically associated with resting and digesting.

Pre-Ganglionic Synapse

The preganglionic neuron originates in the central nervous system and projects to a ganglion near the target organ. It releases acetylcholine (ACh) at the synapse with the postganglionic neuron, which acts on nicotinic receptors.

Post-Ganglionic Synapse

The postganglionic neuron projects to the target organ. It also releases acetylcholine, but it acts on muscarinic receptors located on the cells of the effector organ.

Muscarinic Receptors

M1, M3, and M5 are coupled to G proteins that stimulate phospholipase C. M2 and M4 are coupled to G proteins that inhibit adenylyl cyclase and activate K+ channels.

M1

Gânglios autônomos e neurônios corticais > glândulas exócrinas, Potencial pós-sináptico excitatório (PPSE) tardio, Complexas: pelo menos despertar, atenção, analgesia

M3

músculo liso, tecido glandular, vasos sanguíneos, pulmão, bexiga, TGI e pupila, Contração

M2:

diminuição da frequência cardíaca (bradicardia) e da contratilidade cardíaca (efeito cronotrópico e inotrópico negativos) > NO SA > NO AV > átrio > ventrículo

M4:

Inibição da liberação de neurotransmissores (como dopamina em certas vias do SNC) e modulação da atividade neuronal.

Nicotinic Receptors

ACh is released from the nerve terminal and binds to the nicotinic receptor, which is a pentameric ion channel. Binding causes a conformational change that opens the channel, allowing Na+ (and Ca²⁺) to enter and K⁺ to exit, leading to rapid depolarization

Receptor N Muscular

Located at the neuromuscular junction of skeletal muscles. Activation leads to muscle contraction and is inhibited by curare.

Receptor N Neuronal

Located in autonomic ganglia, adrenal medulla, and CNS. Participates in synaptic transmission between pre- and post-ganglionic neurons.

Neuromuscular Junction

Action potential at the motor neuron opens Ca²⁺ channels, causing ACh release into the synaptic cleft. ACh binds to Nm receptors on the muscle fiber, leading to depolarization and muscle contraction.

AGONISTAS DOS RECEPTORES MUSCARÍNICOS

mimic the action of acetylcholine (ACh) by directly binding to and activating muscarinic receptors

M1

SNC, células gástricas, Estimula secreção e excitação neuronal

M2

Coração, Diminui frequência cardíaca (bradicardia)

M3

Músculo liso, glândulas, olho, Contração do m. liso, secreção, miose

M4/M5

SNC, Modulação da transmissão sináptica

Muscarina

Alta afinidade pelos receptores muscarínicos, sem ação nos nicotínicos. - Altamente tóxica: ingestão acidental causa síndrome colinérgica grave (salivação, diarreia, broncoconstrição, bradicardia, miose). Antídoto: atropina (antagonista muscarínico).

Pilocarpina

Agonista muscarínico potente, especialmente em receptores M3 (glândulas exócrinas e músculo ciliar). - Atravessa a BHE → pode causar efeitos no SNC. Usado in Glaucoma, Xerostomia.

Bexiga e Barriga (ativa M3: trato urinário e gastrointestinal)

Betaecol

Mucosa respiratória (diagnóstico de asma)

Metacolina

Colírio para Claucoma

Carbacol

Ação curta e ampla (sem uso sistêmico)

Acetilcolina

Nicotina

Pequenas doses: alerta, taquicardia, aumento da PA. Altas doses: bloqueio dos gânglios (efeito paradoxal).

Succinilcolina

Agonista Nm de ação prolongada → causa bloqueio despolarizante. Primeiro estimula contração muscular → depois impede novo estímulo → paralisia flácida. - Uso clínico: Intubação rápida, anestesia geral.

Vareniclina

Agonista parcial dos receptores Nn no SNC. Ativa suavemente os receptores nicotínicos cerebrais → reduz desejo e sintomas de abstinência. Uso clínico: Cessação do tabagismo

Antagonistas dos Receptores Muscarínicos

Competem with ACh for muscarinic receptor binding and block the parasympathetic response.

Atropina

Bloqueia M1–M5 (não seletiva), Bradicardia, intoxicação por organofosforados, midríase

Escopolamina

Mais efeito no SNC, Cinetose (enjoo de movimento)

Antagonistas Ganglionares (bloqueiam Nn)

Inibem a transmissão nos gânglios simpáticos e parassimpáticos, afetando todo o SNA