Pharmacodynamics 2 - Mechanisms of Drug Action - ANS as a model Flashcards
What is the ANS
Autonomic Nervous System
- INVOLUNTARY
What is the main function of the ANS?
- maintaining homeostatic function
- regulates internal environment
e. g. heart, gut, lungs etc.
Outline the x2 branches of the ANS
- states key roles (individual & combined)
x2 branches with different function & structure:
- Sympathetic (fight/flight/fright)
> prepares body for action
> speeds up HR - Parasympathetic (rest/digest)
> slows HR
the influence of these systems produces the homeostatic balance
Basic ANATOMY of the ANS
- sympathetic & parasympathetic branches arise from the Spinal cord
- both have ganglia
> break in the nerve coming out of the spinal cord
> synaptic gap
> post-ganglionic nerves that go to various parts of the body - neuroeffector junction
What part of the spinal cord does the sympathetic system arise from?
Describe the response
- from the thoracic & lumbar sections (middle) of the spinal cord
- paravertebral sympathetic chain
- activation is an all or nothing response
What part of the spinal cord does the parasympathetic system arise from?
- from the medullary & sacral regions of the spinal cord
- goes to discrete organs, single nerve tracts to…
e. g. eye, lacrimal & salivary glands
State the main x2 SYMPATHETIC NEUROTRANSMITTERS
NORADRENALINE (norepinephrine)
ADRENALINE (epinephrine)
State the main x2 SYMPATHETIC RECEPTORS on SMOOTH MUSCLE
ADRENERGIC RECEPTORS (ADRENOCEPTORS) > divided in alpha- & beta-receptors with subtypes
Identify the key PARASYMPATHETIC NEUROTRANSMITTER
ACETYLCHOLINE
Identify the key PARASYMPATHETIC RECEPTORS on smooth muscle
CHOLINOCEPTORS
> muscarinic receptors on smooth muscle
Upon activation of the sympathetic nervous system:
- what neurotransmitters are released & from where?
1) noradrenaline released at the sympathetic nerve endings onto the smooth muscle (neuroeffector junctions)
> e.g. myocardium, bronchi
It’s effects are SUPPLEMENTED by the action of ADRENALINE (which enhances the ‘all or nothing’ response
2) noradrenaline + adrenaline released into the bloodstream from the ADRENAL MEDULLA
- acts on smooth muscle via a variety of ADRENOCEPTORS
Outline the FOUR MAJOR SUB-TYPES of ADRENOCEPTORS
- α1 and α2
- β1 and β2
Specify the distribution of adrenoceptor sub-type:
α1 in various tissues & organs (2)
> effect of stimulation
- SMALL SURFACE blood vessel in the surface of skin & gut are predominantly α1
> vasoconstriction - LIVER
> glycogenolysis
(process by which glycogen, the primary carbohydrate stored in the liver and muscle cells, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting)
Specify the distribution of adrenoceptor sub-type:
α2 in various tissues & organs (1)
> effect of stimulation
SYMPATHETIC NERVE ENDINGS
> inhibition of noradrenaline release
Specify the distribution of adrenoceptor sub-type:
β2 in various tissues & organs (6)
> effect of stimulation
- specify receptor target & action
- LARGE DEEP blood vessels (muscles)
> vasodilation - BRONCHIAL TREE
> bronchodilation
* β2 agonists - UTERUS
> relaxation
* β2 agonist can be used to delay premature labour - SKELETAL MUSCLE
> muscle tremor
* high doses of β2 agonist can cause this (e.g. salbutamol) - CILIARY MUSCLE (EYE)
> relaxation
* β2 blockers used to treat glaucoma by increasing aqueous humor - LIVER
> glycogenolysis
(process by which glycogen, the primary carbohydrate stored in the liver and muscle cells, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting)
Explain the physiological benefits of stimulating adrenoceptor subtypes in the blood vessels by the sympathetic nervous system?
In situations where one needs to be ‘primed for action’ this causes:
- stimulation of α1 adrenoceptors in the small surface blood vessels in the surface of the skin & intestine causing VASOCONSTRICTION
- stimulation of β2 adrenoceptors in the large deep vessels of the muscles causing VASODILATION
This diverts (causes a big shift in) blood to where it is needed in the muscles, away from the skin & intestine
Distribution in various tissues & organs of adrenoceptor sub-type: β1
> effect of stimulation
- specify receptor target & action
1. HEART > increased HR > Increased contractility > decreased arrhythmia threshold * β1 antagonist (blocker) will reduce the above
- JUXTAGLOMERULAR CELLS
> increased renin release causing higher levels of angiotensin II –> vasoconstrictor
* β blockers (β1 antagonist) used in treatment of hypertension, antagonise the release of renin
State the 3 main physiological changes that occur upon sympathetic system activation & why…
- specify the receptors & neurotransmitters involved
Due to the COMBINED actions of NORADRENALINE & ADRENALINE at α- and β-adrenoceptors the following effects occur:
- increased heart rate
- shift of blood to larger blood vessels
- bronchodilation
Outline the amount of activity at receptors by noradrenaline & adrenaline.
NORADRENALINE has greater activity at α-adrenoceptors then at β-adrenoceptors.
ADRENALINE has equal activity at α- and β-adrenoceptors.
SYMPATHOMIMETICS
Drugs that
- act as AGONISTS at adrenoceptors
- MIMIC STIMULATION of the SNS
SYMPATHOLYTICS
Drugs that
- acts as ANTAGONISTS at adrenoceptors
- MIMIC ‘DAMPENING’ of the SNS, may be thought of as allowing the parasympathetic NS to dominate
Outline the effects of NORADRENALINE AS DRUGS
> main effects & therefore e.g. of uses
NORADRENALINE (mainly α-stimulation)
> vasoconstriction (α1-) - used to raise BP (after shock) or to reduce local blood flow (in surgery)
Outline the effects of ADRENALINE AS DRUGS
> main effects & therefore e.g. of uses
ADRENALINE (both α- and β-stimulation) > vasoconstriction (α1-), uses as for noradrenaline, also to increase duration of local anaesthetics by constricting surface blood vessels e.g. lignocaine with adrenaline > increased heart rate (β1-) > bronchodilation (β2-)
What is an important consideration related to usage of Noradrenaline & Adrenaline as drugs
VERY SHORT PLASMA HALF-LIFE
- have to be administered parenterally which limits versatility as drugs
Four main groups of drugs affecting the SNS
- Alpha-agonists
- Beta-agonists
- Alpha-antagonists (alpha-blockers)
- Beta-antagonists (beta blockers)
CARDIOPROTECTION
Reducing sympathetic NS effects
- Stopping the action of noradrenaline & adrenaline
Neuroeffector junction
- state the neurotransmitters involved
- adrenaline & noradrenaline is released from here to have action on the muscle
- innervates the smooth muscle of the body & certain glands (sweat, adrenal)
What is the MAIN therapeutic effect of:
Alpha-agonists
VASOCONSTRICTION
What is the MAIN therapeutic effect of:
Beta-agonists
BRONCHODILATION
What is the MAIN therapeutic effect of:
Alpha-antagonists
VASODILATION
alpha-blockers
What is the MAIN therapeutic effect of:
Beta-antagonists
CARDIOPROTECTION
(beta blockers)
