Vasoactive Drugs

Question 1

The Autonomic NS

Answer 1

Responsible for the involuntary control of autonomic body functions

Question 2

Divisions of the Autonomic Nervous System (Sympathetic)

“FIGHT or FLIGHT”

Answer 2

Thoracolumbar outflow
Postganglionic neurotransmitter is Noradrenaline bind Αlpha and Beta receptors
Temperature, glucose, vascular responsiveness, ventilation, cardiac output and GIT
Stress response

Question 3

Divisions of the Autonomic Nervous System (ParaSympathetic)

“HOMEOSTATIC”

Answer 3

Craniosacral outflow (cranial nerves (3,7,9,10) and sacral (2-3)
Postganglionic neurotransmitter is Acetylcholine
bind to (cholinergic) Nicotinic and muscarinic receptors

Question 4

The Stress Response

Answer 4

Series of Neurohumoral responses to optimise the bodily defence mechanisms for short-term survival ….. “fight or flight”

Question 5

The Stress Response (Neural: HAEMODYNAMIC)

Answer 5

Increased sympathetic outflow
Blood flow
Increased: heart, lungs, brain and muscle (β)
Decreased: GIT, kidney, liver (splanchnic circulation) and skin (α)

Question 6

The Stress Response (Humoral: HORMONAL)

Answer 6

Defence of blood volume
Increased: aldosterone and ADH - salt and water retention
Mobilisation of glucose stores to supply vital organs with energy
Insulin inhibited

Question 7

The Adrenal Medulla

Answer 7

Specialised sympathetic ganglion with no postganglionic fibres
Postganglionic fibres are secretory cells
The medulla secretes hormones when stimulated (Noradrenaline (NA) – 70%; Adrenaline (Adr);
Dopamine (DA) – small amount)

Question 8

Cholinergic Receptors

distribution

Answer 8

All autonomic ganglia (including the adrenal medulla)
All parasympathetic postganglionic nerve terminals
Sympathetic postganglionic nerve terminals in sweat glands (exception!)

Question 9

Cholinergic Receptors
(subtypes)

Answer 9

Nicotinic= At skeletal NMJ and ALL autonomic ganglia (incl adrenal medulla)
Stimulated by nicotine and Ach
Inhibited by Neuromuscular blocking agents
Muscarinic= At parasympathetic postganglionic fibres
Stimulated by muscarine and Ach
Inhibited by atropine, glycopyrrolate

Question 10

Adrenergic receptors: distribution

Answer 10

Only found at the sympathetic postganglionic nerve terminals

Question 11

Adrenergic receptors: subtypes

Answer 11

Alphaα1: post-synaptic – smooth muscle vasoconstriction (e.g. blood vessels)
Increases the BP ± reflex bradycardia
α2: pre-synaptic – inhibits further NA release (central)  sedation, analgesia, hypotension
Beta:β1: increased contractility, HR, AV node conduction, refractory period, renin secretion and lipolysis
β2: increased skeletal muscle vessel dilatation, bronchial relaxation, uterine relaxation, bladder relaxation, glycogenolysis

Question 12

Neostigmine: stimulation of PNS

Answer 12

Blocks acetylcholinesterase, therefore natural concentration of Ach increases
This will displace neuromuscular blocking agents (NMBs) and facilitates reversal of these drugs
BUT… this also results in parasympathetic stimulation of muscarinic receptors (which are not blocked by NMBs)
This causes side-effects!

Question 13

Anticholinergic drugs: muscarinic blockade of the PNS

Answer 13

Blockade inhibits muscarinic effects (e.g. atropine and glycopyrrolate)
Unmasks background effects of sympathetic nervous system
Prevents Side-Effect
Glycopyrroloate: does not cross the blood brain barrier

Question 14

Sympathomimetics

stimulants

Answer 14

Have β1 effects are termed inotropes as they increase the force of contraction.
Have α1 effects are termed vasopressors as they contract vessels and raise blood pressure
Direct acting: Adrenaline (all alpha and beta) and NA (alpha 1&2 and beta1)are both inotropes and vasopressors
Phenylephrine (only alpha1) is a vasopressor but not an inotrope
Dobutamine is an inotrope
Indirect acting:
Ephedrine
releases NA from sympathetic terminals, as well as direct (α1 β1) effects

α2= Clonidine
Dexmedetomidine
Sedative, analgesic

(Isoprenaline
β1 and 2 effects)

β2= Salbutamol
Bronchodilatation
Uterine relaxation

Question 15

SNS Blockers

Answer 15

α receptor antagonists (blockers):
Occasionally used as antihypertensives but are agents of choice in phaeocromocytoma
Phentolamine – α1 and 2
Phenoxybenzamine - α1 (noncompetitive)
Prazosin and Doxazosin - α1 

β blockers:
All competitive with varying β1 or β2 effects
Bradycardia, antiarrythmics, sedative, lower BP
Decrease cardiac mortality
Bronchospasm in asthmatics
Inhibit gluconeogenesis in liver and lipolysis

Combined α and β antagonists: Labetalol b>a

Question 16

Vasopressors: EPHEDRINE

Answer 16

Drug of choice for management of hypotension in most cases – given as 5-10 mg boluses IV
Raises blood pressure but tends to cause tachycardia (Beta effects predominate)

Question 17

Vasopressor: PHENYLEPHRINE

Answer 17

Preferred vasopressor in obstetric spinal anaesthesia
Extremely potent a1 agonist  reflex bradycardia
MUST BE DILUTED (comes in 10mg ampoules  dose is only50-100 µg!!
10 mg is diluted into 200 mL N saline to give 50 µg / mL
UNDILUTED PHENYLEPHRINE IS FATAL

Question 18

magnesium

Answer 18

used to rapidly decrease bp in pre-eclamptic patients