Sympathomimetics in Autonomic Nervous System

Credit Hours

• Tanta Medical Program
• Credit hours for the program

Sympathomimetics

• Topic: Sympathomimetics
• Presenter: Dr. Ola Mousa Salem
• Interactive session

Objectives

• Recognize catecholamine synthesis, storage, and release.
• Identify different types of adrenergic receptors and their function.
• Recognize sympathomimetics (action, uses, side effects, and contraindications).

Autonomic Nervous System

• Component of the nervous system
• Consists of:
  • Nervous system
  • Central
  • Sensory
  • Preph.
  • Somatic
  • Motor
  • ANS
• Has branches:
  • Sympathetic
  • Parasympathetic

Adrenergic Neuronal Transmission

• Diagram illustrating the process of adrenergic neuronal transmission
• Shows different steps in the process:
  • Tyrosine
  • Dopa
  • Dopamine
  • Norepinephrine
  • MAO-A
  • Exocytosis
  • Reuptake
  • COMT
  • Receptors (alpha and beta)
  • Effector cells

Fate of Catecholamines

• Neuronal uptake (major part).
• Granular uptake (vesicular uptake).
• Metabolism by specific enzymes (MAO-COMT).
• Stimulation of presynaptic alpha adrenoreceptors

Alpha & Beta Adrenoreceptors

• Diagram showing different types of Alpha and Beta receptors
• Detailing their signaling pathways.
• Showing if they are Gq or Gs coupled

Alpha1 Adrenoreceptors (Postsynaptic)

• Location: Postsynaptic
• Effects:
  • Contraction of erector pilae muscle
  • Mydriasis
  • Vasoconstriction in skin
  • Salivation
  • GIT and UB sphincter spasm
  • Uterine contraction in pregnancy
  • Nm transmission facilitation
  • Ejaculation
• Agonist: phenylephrine
• Antagonist: prazosin

Alpha2 Adrenoreceptors

• Location: Pre/Postsynaptic
• Effects:
  • Sympathetic outflow from CNS reduction
  • Noradrenaline release regulation
  • Renin release reduction
  • Insulin release reduction
  • Lipolysis reduction
  • Platelet aggregation increase
• Agonist: clonidine
• Antagonist: yohimbine

Beta1 Adrenoreceptors

• Location: various
• Effects:
  • CNS stimulation
  • Cardiac stimulation
  • Renin release increase
  • Lipolysis (fatty acid)
• Agonist: dobutamine
• Antagonist: atenolol

Beta2 Adrenoreceptors

• Location: various
• Effects:
  • Vasodilation (general)
  • Bronchodilation
  • Insulin release stimulation
  • Glycogenolysis in liver and skeletal muscle
  • GIT and bladder relaxation
  • Uterine relaxation
  • Skeletal muscle tremors
• Agonist: Salbutamol
• Antagonist: butoxamine
• Beta 3 (fat cells lipolysis)

Sympathomimetics

• Drugs mimicking sympathetic nerve stimulation.

Adrenaline (Epinephrine)

• Sympathomimetic catecholamine
• Present in adrenal medulla and CNS
• Prepared in dark brown ampoules due to instability in alkaline medium
• Absorption: Not absorbed orally, taken by IV, IM, sc, inhalation etc
• Distribution: Not passed BBB
• Fate: nerve and tissue reuptake, metabolism by MAO and COMT, found in urine (2%)
• Mechanism of action: Stimulates all adrenergic receptors (α1, α2, β1, β2, β3)
• Pharmacological effects: Local and Systemic effects
• Uses: Local (glaucoma, haemostasis), Systemic (shock, asthma)
• Adverse effects: CNS (anxiety, headache), α effects (gangrene, hypertension, cerebral hemorrhage), β effects (tachycardia, palpitation, arrhythmia, skeletal muscle tremors)
• Contraindications: Around finger and toes (gangrene), Hypertension, Hemorrhagic shock.

Noradrenaline (Norepinephrine)

• Natural sympathomimetic catecholamine
• Not absorbed orally, not pass BBB
• Used by IV infusion.
• Mechanism of action: Very effective α-adrenergic receptor agonist, limited β2-adrenergic receptor activity
• Pharmacological effects: Generalized vasoconstriction (except coronary), increase in blood pressure (COPX↑PR), bradycardia, ↑ stroke volume (β1), ↑ excitability and automaticity (β1 leading to arrhythmia)
• Uses: Acute hypotension during spinal anesthesia, post-operative shock, added to local anesthetics.
• Adverse effects: Necrosis and gangrene (extravasation), hypertension → cerebral hemorrhage, reflex bradycardia, headache, anxiety.

Isoprenaline (Isoproterenol)

• Synthetic direct-acting sympathomimetic catecholamine
• Non-selective β agonist
• Used in acute heart block and acute bronchial asthma
• Adverse effects: Tachycardia, angina, arrhythmia.

Dopamine

• Natural sympathomimetic catecholamine
• Mechanisms of action: Stimulates dopamine, α and β receptors
• Dopaminergic receptor
• D1: stimulation leads to peripheral effects
• D2: stimulation leads to central effects
• D3: presynaptic autoreceptor stimulation leads to decrease dopamine release
• Peripheral effects (Small dose:D1:VD->RBF, Moderate Dose: D1+B1 >ve inotropic, large Dose: a1: VC->PR)
• Central effects (Limbic system: euphoria and psychosis, Basal Ganglia: anti parkinsonism, Hypothalamus: Pyrexia & ↓ appetite & ↓ prolactin, CTZ, Nausea&vomiting).
• Uses in shock (positive inotropic, improve microcirculation and increase renal blood flow), resistant heart failure
• Side effects: Tachycardia and arrhythmia, Nausea and vomiting

1- Vasopressors(Alpha-stimulants)

• Stimulation of α1 receptors
• Vasoconstriction > Increase TPR > Increase BP. Used to treat hypotension (noradrenaline, ephedrine, phenylephrine, midodrine)

2- Nasal Decongestants

• α1 agonists
• Topical application
• Local vasoconstriction of nasal mucosa
• Longer duration than ephedrine
• Uses: Allergic rhinitis, common cold
• Side effects: Orally → hypertension (caution in hypertensives and MAO inhibitors patients), chronic use → atrophic rhinitis (persistent vasoconstriction), repeated local administration → rebound congestion.
• Preparations: Oral (Pseudoephedrine, phenylephrine), Topical (Xylometazoline, Naphazoline, Tetrahydrozoline, Oxymetazoline).

Ephedrine

• Mechanism of action: Indirect and direct α,β receptor action
• Effects similar to adrenaline but weaker, slower, longer duration, and tachyphylaxis
• Pharmacological effects: Similar to adrenaline, but weaker and longer.

Additional Information

• The following are different drugs and their functions

  • Prazosin
  • Dobutamine
  • Fenoldopam

• The following are uses and issues for various conditions

  • Anaphylactic shock
  • Acute hypotension.
  • Spinal anesthesia
  • Cardiac arrest.
  • Open angle glaucoma
  • Epistaxis
  • Nasal decongestion.

Adverse effects for Epinephrine

• Anxiety
• Headache
• Gangrene (if injected around finger or toe)
• Hypertension
• Cerebral hemorrhage

Contraindications and Drug Interactions for adrenaline

• Around finger and toes → Gangrene
• Hypertension
• Hemorrhagic shock (Hemorrhage → hypovolemia → hypotension → reflex V.C. → renal V.C → renal failure→death)

Other information from the presentation

• Non-selective beta blocker treatment of hypertension & hyperkalemia
• Ganglion blockers, adrenergic neuron blockers, and MAO inhibitors cause supersensitivity
• Various additional uses for adrenaline

This quiz covers the essential aspects of sympathomimetics including their action, uses, side effects, and contraindications. It provides an overview of catecholamine synthesis, adrenergic receptors, and neuronal transmission processes. Join Dr. Ola Mousa Salem for an interactive learning experience.