Pharmacology of the Autonomic Nervous System I - Adrenergic Drugs Flashcards
How are the autonomic NS and somatic NS different in terms of connectivity to CNS?
Autonomic NS: Between CNS and organ there is one preganglionic neuron and one postganglionic neuron.
Somatic NS is a single motor neuron.
What is the primary role of the autonomic NS?
Maintains homeostasis through:
CO
Digestion
Blood flow
What is the primary role of the somatic NS?
Voluntary control
What type of receptors does acetylcholine bind to?
Nicotinic cholinocepter (within the ganglia)
Muscarinic cholinocepter (within the target tissue)
What neurotransmitter do sympathetic preganglionic nerves produce in paravertebral ganglia?
Acetylcholine
What is the name of the postganglionic nerve of the sympathetic NS?
Adrenergic nerve
Do all sympathetic nerves go to paravertebral ganglia?
No some go to the adrenal medulla and release acetylcholine which results in the adrenal medulla releasing adrenaline and noradrenaline.
What type of drugs are targeted by ANS drugs?
Muscarinic cholinoceptors or adrenoceptors on effector cells.
What occurs if neurotransmission is blocked at the ganglia?
Acting or blocking neurotransmission at ganglia produce complex and widespread changes that can be dangerous.
How is the autonomic NS organised so that it can produce desired effect when required?
It contains a chain of varicosities (swellings) with neurotransmitters inside them and they are released as the AP passes them in the neuron.
What do sympathetic postganglionic nerves release at the target tissue?
Most release NorAdrenaline (they are known as adrenergic nerves)
Several release Acetylcholine (several sympathetic postganglionic nerves are cholinergic)
What do parasympathetic postganglionic neurons release at target tissue?
Acetylcholine only (they are known as cholinergic nerves)
Example of cholinergic sympathetic nerves:
Sweat gland innervating nerves
What are the 2 major families of cholinoceptors and where are they found?
Nicotinic receptors (these are found in ganglia and are what triggers action potential in post ganglionic nerves)
Muscarinic (found on target tissues and are of 3 classes)
What are the classes of muscarinic receptors?
M1 (nerve cell body)
M2 (heart to decrease heart rate)
M3 (smooth muscle and glands)
There are 5 of these but the important ones to know are M2 and M3.
What are the major families of adrenoceptors?
Alpha (alpha1 and alpha2)
Beta (beta1 and beta2)
Where are the alpha receptors located and what do they do?
Alpha 1 receptors on vascular smooth muscle which cause them to contract in peripheral tissue.
Alpha 2 receptors are located on nerve varicosities.
Where are the beta receptors located and what do they do?
Beta1 receptors are located on the heart and increase its contractility and rate.
Beta2 receptors stimulate smooth muscle to dilate (relax) in the ariways.
Beta3 receptors act on fat
Which ANS receptors are drugs commonly made for?
Alpha1
Beta1
Beta2
M2
M3
What do drugs do to inhibit or stimulate activity of ANS?
They can increase or decrease levels of NT
They can activate NT receptors
They can inhibit NT receptors.
What are the most important adrenoceptor agonists?
Adrenaline
Phenylephrine
Salbutamol
What is another name for adrenoceptor agonists?
Sympathomimetics
Adrenomimetics
What is the action of adrenaline?
It stimulates all adrenoceptor subtypes.
Local injection causes vasoconstriction and IV injection increases mean arterial blood pressure.
Can adrenaline be administered orally?
No it gets inactivated because it gets metabolised in the GIT and the liver.
What are the clinical uses of adrenaline?
Added to local anaesthetic solutions in dentistry to prolong action and delay systemic absorption of local anaesthetics due to constriction of blood vessels.
Cardiac rhythm can be restored in patients with cardiac arrest. (beta1 ARs)
Increase TPR during resuscitation (alpha1-ARs) (+CPR/defibrillation)
Acute anaphylactic reactions (beta2 ARs)
How does adrenaline assist in anaphylactic reactions?
It binds to beta2 receptors which dilate airways and inhibit mast cells
Which receptor is phenylephrine selective for?
alpha1
Which receptor is salbutamol selective for?
beta2
How is salbutamol structure different to adrenaline?
It lacks a hydroxyl group at the 4’ position.
What is phenylephrine used for?
To decongest nasal passages.
It is given orally or topically (as a spray)
How is salbutamol different to adrenaline?
It has 3 methyl groups attached to amide group
Where are beta2 receptors located?
Smooth muscle of airways, uterus, and blood vessels
What is salbutamol used clinically for?
It is given topically to relieve bronchoconstriction in asthma
Why is salbutamol administered as an aerosol rather than orally?
Lower dose needed
Fewer side effects
More rapid bronchodilator response
Which sympathetic adrenoceptors are targetted for antagonistic drugs?
Alpha1 (for hypertension)
Beta1 (CV diseases)
alpha and beta2 are associated with adverse side-effects
What antihypertensive drug is a selective alpha1 blocker?
Prazosin (Not first line treatment of hypertension and is always used in conjunction with other antihypertensive agent)
What is the overall effect of prazosin?
reverses alpha1 vasodilation and lowers Blood pressure
What common side effect is seen with use of prazosin?
Dizziness on standing especially with initial use
What other alpha1 adrenoceptor antagonist is commonly used?
It can reverse alpha1 contraction of prostatic smooth muscle (tamsulosin used for this purpose)
What class of drugs are propranolol and metoprolol?
Beta adrenoceptor antagonists (propranolol is non selective and binds to both beta1 and beta2)
What does propranolol do?
It reduces heart rate and contractility thus reducing cardiac output and blood pressure.
What are the possible side effects of propranolol?
May exacerbate bronchoconstriction in asthma
May impair circulation in peripheral arterial disease.
May worsen glycaemic control in diabetic patients
Adverse side-effects in patients with co-morbidities
What are the possible side effects of propranolol?
May exacerbate bronchoconstriction in asthma
May impair circulation in peripheral arterial disease.
May worsen glycaemic control in diabetic patients
Adverse side-effects in patients with co-morbidities
What does metoprolol do?
Reduces heart rate and contractility without the effects on beta2 such as bronchoconstriction (this is the case at lower doses)
What other desirable actions in addition to blocking beta1 receptors can beta blockers have?
Vasodilation
Antioxidant activity
Partial agonist activity
Membrane stabilizing activity
K+ channel blockade
