Autonomic Pharmacology Flashcards
SNS
Sympathetic Thoracolumbar Ganglia in perivertebral chain Short pre-ganglion Long post-ganglion ACh Nicotinic receptor Target tissue Adrenergic receptor
PSNS
Parasympathetic Cranial nerves III, VII, IX, X Cervical & sacral S2-4 Ganglia in end organ tissue Long pre-ganglion Short post-ganglion ACh Nicotinic receptor Target tissue Muscarinic receptor
Adrenal Medulla
Hormone release 80% Epi 20% NE
Only one neuron
Pre-ganglion to adrenal medulla
Chromaffin cell
Neurotransmission Steps
Synthesis Storage Release Action at receptor Termination - reuptake, enzyme degradation, diffusion
Nicotinic Cholinergic Receptor
Ligand-gated Na+/K+ depolarizing channel
Subtypes: Nn & Nm
Nn located in all ANS ganglia, adrenal medulla, CNS (nerve)
Nm located at skeletal NMJ (muscle)
Muscarinic Cholinergic Receptor
GPCR
Subtypes: M1, M2, M3, M4, M5
Stimulatory = M1, M3 (smooth muscle, glands, endothelium, eye), M5 ↑ Ca2+ release Inhibitory = M2 (heart) & M4 ↓cAMP
Alpha Adrenergic Receptors
α
GPCR
Epi, NE, dopamine
α1
Excitatory
↑ Ca2+ ↑ calmodulin activation ↑ actin-myosin interaction ↑ smooth muscle contraction
Vasoconstriction
Smooth muscle, GU sphincters, skin, GI
α2
Inihibitory
↓cAMP ↓NE release
Pre-synaptic nerve terminal
Ex: Precedex or Clonidine
Beta Adrenergic Receptors
β
GPCR
Adenyl cyclase activation ↑ cAMP ↑ kinase activation & phosphorylation
β1
ONE heart
Heart chronotropy (SA node) & inotropy (cardiomyocytes)
Renal JG cells → renin release RAAS activation
β2
TWO lungs Vasodilation Bronchial & uterine smooth muscle Liver glycogenolysis & gluconeogenesis Skeletal muscle
β3
Adipose fat cells
Phosphodiesterase 5
PDE5
Enzyme that breaks down cGMP 2nd messenger
Inhibitor drugs - Sildenafil, Viagra, Cialis
Adrenergic
Neurons or receptors that use NE
Drugs that mimic sympathetic nerve stimulation
Catecholamine
Molecule that contains catechol & amine group
Epi, NE, dopamine
Cholinergic
Neurons or receptors that use ACh
Drugs that mimic parasympathetic nerve stimulation
Epinephrine
Epi or adrenalin
Produced in the adrenal medulla
Neurotransmitter in CNS
Norepinephrine
NE or noradrenalin
Produced in the adrenal medulla
Neurotransmitter at sympathetic effector tissues in periphery & in CNS
Muscarinic Agonists
Direct acting cholinergic
Acetylcholine
↑ACh
- Salivation
- Lacrimation
- Urination
- Diarrhea
- GI upset
- Emesis
Nicotinic Agonists
Direct acting cholinergic
Acetylcholine
Succinylcholine
Acetylcholinesterase Inhibitors (Reversible)
Indirect acting cholinergic
Edrophonium (short-acting)
Neostigmine (intermediate)
Donepezil (Alzheimer’s)
AChEi (Irreversible)
Indirect acting cholinergic
Organophosphates
Insecticides
Succinylcholine
Cholinergic nicotinic agonist
Depolarizing skeletal muscle paralysis
Contraindications:
- GI/GU obstruction
- CV disease
- Respiratory disorder (asthma or COPD)
Edrophonium
Short-acting polar alcohol
Onset 30-60sec
Duration 10min
Admin w/ Atropine
Neostigmine
Intermediate-acting moderately polar carbamate
Onset 10-30min
Duration 2-4hr
Admin w/ Glycopyrrolate
Physostigmine
Parasympathomimetic Intermediate-acting Non-polar Crosses blood-brain barrier Onset 3-8min Duration 1hr
Anticholinergics
Muscarinic & nicotinic antagonists
↓ACh
- ↓secretions
- Urinary retention
- Hyperthermia
- ↑HR
- Flushed skin
- Mydriasis (dilation)
- Confusion/delirium
- Tremors
- Absent bowel sounds
Muscarinic Antagonists
Non-selective muscarinic antagonist - Atropine - Glycopyrrolate - Scopolamine Selective M3 antagonist
Nicotine Antagonists
NicotinicN (neuron)
NicotinicM
Non-depolarizing neuromuscular blocking drugs
Atracurium, Cisatracurium, Vecuronium, Rocuronium, Pancuronium
Atropine
Non-selective muscarinic antagonist Lipophilic tertiary amine Crosses blood-brain barrier Half-life 4hr (prolonged in elderly) ↑HR ↑demand → cardiovascular concerns
Contraindications:
- Glaucoma d/t ↑IOP
- Prostate hypertrophy
- GU obstruction
Glycopyrrolate
Non-selective muscarinic antagonist
Quaternary amine
Less CNS effects (unable to cross blood-brain barrier)
Onset 1min
Duration 7hr
Half-life 1hr
Contraindications:
- Glaucoma d/t ↑IOP
- Prostate hypertrophy
- GU obstruction
Scopolamine
Non-selective muscarinic antagonist More lipophilic than Atropine Tertiary amine Crosses blood-brain barrier CNS effects (amnesia) \+++ sedation
Onset 10min
Duration 2hr
Half-life 2hr
Contraindications:
- Glaucoma d/t ↑IOP
- Prostate hypertrophy
- GU obstruction
Direct Acting Adrenergic Agonists
α agonist Norepinephrine α1,2 Phenylephrine α1 Clonidine α2 Dexmedetomidine α2
β
Isoproterenol β1,2
Dobutamine β1
Albuterol β2
α/β
Epinephrine α1 β1,2
NE α1 β1
Indirect Acting Adrenergic Agonists
NT releaser
- Amphetamine
- Ephedrine
NE reuptake inhibitor
- Cocaine
- SNRI
MAO inhibitor
- Tranylcypromine (non-selective)
- Selegiline (selective MAO-B)
α1
Vasoconstriction
Smooth muscle contraction
GI/GU sphincters contract
Mydriasis
α2
↓NE release (pre-synaptic)
CNS inhibition
Platelet aggregation
↓insulin secretion
β1
↑HR/contractility
↑renin release
β2
Bronchodilation Vasodilation (skeletal muscle) Smooth muscle relaxation - Uterine - GI/GU Glycogenolysis ↑glucose
α Adrenergic Blockers
α receptor blockers Non-selective (phen...amine) - Phenoxybenzamine α1 > α2 - Phentolamine α1 = α2 α1 Prazosin α2 Yohimbine
Used to treat HTN (later agent), BPH, & pheochromocytoma (non-selective)
Cause smooth muscle relaxation, ↓SVR, ↓BP
β Adrenergic Blockers
Non-selective Propranolol
β1
- Metoprolol
- Esmolol
↓MVO2
Epinephrine
α1,2 β1,2 agonist ↑β receptor affinity 1-20mcg/min Hepatic CYP450 metabolism w/ renal excretion Elimination 1/2 life <5min
Norepinephrine
α1 β1 (minimal effect on β2) 1-20mcg/min Hepatic, renal, & plasma metabolism via CYP450 Renal excretion Elimination 1/2 life 1min
Isoproterenol
Non-selective β1,2
2-20mcg/min
Hepatic CYP450 metabolism w/ renal excretion
Dopamine
Low dose D1 (renal) vasodilation 1-4mcg/kg/min
Moderate dose β1 inotrope 5-10mcg/kg/min
High dose α1 vasoconstriction 11-20mcg/kg/min
Hepatic, renal, & plasma metabolism via CYP450
25% metabolized to NE
Renal excretion
Elimination 1/2 life 2min
Dobutamine
β1 1-20mcg/kg/min Hepatic metabolism via CYP450 Renal excretion Elimination 1/2 life 2min
