Pharmacology Pha3011

Front 1

How is noradrenaline synthesised?

Back 1

Synthesised from tyrosine precursor, converted to DOPA in cell by tyrosine hydroxylase → converted to dopamine by DOPA decarboxylse → (enters storage vesicle) → dopamine converted to noradrenaline by dopamine β carboxylase

Front 2

What is the rate limiting step of noradrenaline synthesis?

Back 2

Tyrosine hydroxylase converts tyrosine to DOPA
This enzyme is found only in noradrenergic neurones
This is inhibited by α-methyl-tyrosine

Front 3

What is the function of Vesicle Monoamine Transport (VMAT)?

Back 3

Storage vesicles that take up dopamine and noradrenaline by active transport (in exchange for H+ ions)
Inhibited by reserpine

Front 4

What are the two types of NA storage vesicles?

Back 4

Large dense core vesicles (LDCVs) take up noradrenaline and can convert dopamine to noradrenaline
Small synaptic vesicles can only take up released NA

Front 5

How is acetylcholine synthesised?

Back 5

Choline is taken up by HACU (high affinity choline transporter) → choline and acetyl CoA are converted to acetylcholine by choline acetyl transferase (ChAT) → taken into vesicle by VAT (vesticular ach transporter)

Front 6

Where does acetylcholine act as a neurotransmitter?

Back 6

Neurotransmitter for somatic (voluntary) and parasympathetic systems (post-ganglionic)
Preganglionic neurotransmitter for sympathetic and parasympathetic systems

Front 7

What is the neurotransmitter at all pre-ganglionic nerve fibres?

Back 7

Acetylcholine (acting on nicotinic receptors that are different to those in skeletal muscle)

Front 8

What neurotransmitters are released by post-ganglionic nerve fibres?

Back 8

Sympathetic post-ganglionic nerve fibres release NA
Parasympathetic nerve fibres release ACh

Front 9

What is the organisation of neurons in the sympathetic NS?

Back 9

Nerves arise from thoraco (T) and lumbar (L) parts of the spinal cord
Ganglia are organised as a chain beside the spinal cord
Postganglionic fibres are long

Front 10

What is the organisation of neurons in the parasympathetic NS?

Back 10

Nervs arise from cranio (C) and sacral (S) parts of the spinal cord
Ganglia are often within innervated organ
Pre-ganglionic fibres are long, post ganglionic fibres are short

Front 11

Compare and contrast the actions of the sympathetic and parasympathetic nervous systems at the heart.

Back 11

Sympathetic nerves activate β1 receptors via noradrenaline to increase the rate, force and automaticity of heart contractions.
Parasympathetic nerves activate M2 receptors via ACh to reduce the rate, force and conduction velocity of the heart.

Front 12

Compare and contrast the actions of the sympathetic and parasympathetic nervous systems on blood vessels.

Back 12

Sympathetic nerves activate α receptors (via noradrenaline) on arterioles in coronary, internal organs, skin, brain, erectile tissue and salivary glands to cause constriction of blood vessels, but also cause dilation in muscle blood vessels via β2 receptors. Sympathetic neurons can also cause constriction (αR) and dilation (β2 R) in veins.
Parasympathetic nerves act on M3 receptors to dilate blood vessels (arterioles) in erectile tissue and salivary glands.

Front 13

How are the actions of noradrenaline terminated?

Back 13

Re-uptake via active transport into noradrenergic nerves and extraneuronal cells.
{Following re-uptake can also be metabolised by MAO (at nerve terminal) and COMT (in smooth muscle cytoplasm)}

Front 14

How are the actions of Acetylcholine terminated?

Back 14

Degradation by actetyl-cholinesterase (AChE) enzymes at the synaptic cleft, or pseudo ChE in blood or other tissues

Front 15

Edrophonium

Back 15

inhibits AChE

Front 16

How do the different adrenergic neurotransmitters act at each of the adrenoreceptors?

Back 16

Noradrenaline acts most potently at α adreno-receptors, followed by adrenaline and isoprenaline.
Isoprenaline acts most potently at β adrenoreceptors, followed by adrenaline and noradrenaline.

Front 17

What is the result of sympathetic action on blood vessels

Back 17

Activation of α-receptors constricting arterioles increases blood pressure.
Activation of β2-receptors dilating arterioles increases blood supply to working muscles. (EG phenylephrine)
Antagonists inhibit vasoconstriction and lower blood pressure (eg prazosin)

Front 18

What are the actions of β1 receptor sympathetic antagonists (eg propraolol and metropolol) on the heart?

Back 18

Decreases cardiac excitability, reduces exercise tolerance, reduce blood pressure in hypertensive individuals (side effects include fatigue, cold extremities, nightmares?)

Front 19

What would a β2-adrenoreceptor blocker do in the lung?

Back 19

Β2 adrenoreceptors are responsible for relaxation in the lung. Therefore β2 receptor blocker would cause bronchial spasm.?

Front 20

What are β2 agonists commonly used to treat?

Back 20

Asthma – they relax (dilate) bronchial SM (asthma constricts it)
Salbutamol is a common example

Front 21

How do can adrenoreceptors be indirectly activated?

Back 21

Sympathomimetics (eg tyramine) can enter nerve terminal via uptake 1 and displace noradrenaline into nerve terminal cytoplasm

Front 22

What is the effect of M3 muscarinic receptor stimulation on the ocular system?

Back 22

M3 agonists (such as pilocarpine) cause pupillary constriction (miosis) by contracting circular muscle and decreasing intraocular pressure

Front 23

What will the effect of M3 receptor antagonists be on the pupil?

Back 23

M3 antagonists such as atropine dilate the pupil

Front 24

What is the effect of M3 receptor agonist on bronchial smooth muscle?

Back 24

Contraction and secretions of the bronchial SM

Front 25

What is the effect of M3 receptor agonists and antagonists on secretions?

Back 25

Agonists increase salivary and sweat secretions; antagonists (eg atropine) stop secretions (dry mouth, no sweating so increased body temp)

Front 26

What are the effects of M3 receptor agonism/antagonism on GIT and urinary tract?

Back 26

Parasympathetic M3 stimulation increases gastrointestinal and urinary tract activity.
Antagonists such as darifenacin inhibit GIT and bladder contractility

Front 27

What are some effects of excessive cholinergic stimulation?

Back 27

Excessive secretions, bronchospasm, bradycardia (slow heart rate), diarrhoea, miosis (pupillary constriction)

Front 28

What are some side effects of muscarinic antagonism?

Back 28

Dry mouth, decreased sweat, tachycardia (fast heart rate), urinary retention, mydiasis (pupillary dilation)

Front 29

What is the function of presynaptic α2 receptors?

Back 29

NA released from adrenergic neurones activates presynaptic α2 receptors which in turn inhibit exocytotic release of NA.

Front 30

What effect does clonedine (α2 receptor agonist) have on NA release?

Back 30

By stimulating α2 receptors, clonedine inhibits/ diminishes the release of NA

Front 31

What effect does yohimbine (α2 receptor antagonist) have on NA release?

Back 31

Yhimbine blocks the action of the α2 receptor, thereby preventing negative feedback of NA release, and increasing the amount of NA released into the synapse