Autonomic Pharmacology Flashcards
What are the principle NTs in the ANS?
Acetylcholine
Noradrenaline
How is the CNS connected to sweat glands?
CNS -> ACh (nic) -> ACh (mus) -> sweat glands (sympathetic system)
How is the CNS connected to blood vessels?
CNS -> ACh (nic) -> NA -> blood vessels (sympathetic)
How is the CNS connected to the adrenal medulla?
CNS -> ACh (nic) -> adrenal medulla (sympathetic)
How is the CNS connected to salivary glands?
CNS -> ACh (nic) -> ACh (mus) -> salivary glands (parasympathetic)
Which receptors do ACh and NA act on?
nAChRs, mAChRs, alpha and beta adrenoreceptors
What is cAMP?
Second messenger
Moves freely in cytoplasm
What are kinases?
Add phosphates to molecules/proteins
What do G-Alpha-S proteins do?
Stimulatory G protein that changes cAMP and protein kinase A levels
- Increases adenylyl cyclase activity
- Increases [cAMP]
- Activates protein kinase A (PKA)
Mediated by alpha G protein subunits
What do G-Alpha-i proteins do?
Inhibitory G protein that changes cAMP and protein kinase A levels
- Decreases adenylyl cyclase activity
- Decreases [cAMP]
- Decreases PKA
- Increased K+ channel opening
What do G-Alpha-q proteins do?
Increases intracellular Ca2+ levels through Phospholipase C enzyme
- Increases PLC
- Increases IP3 + DAG
- Increases [Ca2+] + Protein kinase C (PKC)
Mediated by alpha G protein subunits
Which G protein subunits mediate Gi action?
Alpha - Inhibits adenylyl cyclase
Beta-Gamma - Activates K+ channels
What type are muscarinic receptors?
Cholinergic
Where are muscarinic receptors located structurally?
Postsynaptic to parasympathetic ganglion neurones and sweat glands
Which mAChR subtypes couple to Gq proteins?
M1, M3, M5
Which mAChR subtypes couple to Gi proteins?
M2, M4
Where are M2 receptors found?
Heart - Nodal tissue and Atria
Widely distributed in CNS
Where are M3 receptors found?
Exocrine glands - e.g. salivary
Smooth muscle - GI tract, eye, airways, bladder
Blood vessels - endothelium
What response do M2 receptors cause?
Cardiac inhibition
- Decreased heart rate
- Slowing of AV conduction
- Decreased force of contraction (atria only)
What response do M3 receptors cause?
Gastric, salivary secretion
GI smooth muscle contraction
What is the mechanism for decreasing heart rate?
- M2 receptor activation via ACh
- Gai protein activation
- By subunits open K+ channels
- Increased K+ moving out of nodal cell
- More negative membrane potential (hyperpolarisation)
What does M1 and M3 AChR activation cause?
Stimulates contraction of smooth muscle
- Bronchoconstriction
- GI motility
- Bladder voiding - urination
Stimulates secretion from exocrine glands?
- Mucus in lungs
- Lacrimal glands - tears
- Salivary glands
- Sweat glands
What are the effects of muscarine?
- Decrease blood pressure
- Increase saliva
- Increase tearflow
- Increase sweating
- Abdominal pain
- Nausea
Overdose = death from cardiac + respiratory failure
What is atropine?
Non-selective mAChR antagonist
- Blocks all muscarinic receptors
What effects does atropine have?
- Inhibition of secretion from glands
- Smooth muscle relaxant
- Pupillary dilation
- Modest increase in HR
- Decrease GI motility and acid secretion
What are cholinomimetic drugs?
Drugs acting indirectly to enhance cholinergic transmission
What are the properties of Anticholinesterase drugs?
- Prevents ACh breakdownby AChE
- Long acting (irreversible)
- Affects all cholinergic transmission including CNS
e.g. nerve gas (sarin), pesticides - Muscarinic agonists can be used to reverse poisoning by anticholinesterases
Whare are the receptors for NA?
GPCRs
- Found on tissues responding to postganglionic sympathetic neurones
Where do all B adrenergic receptors couple to?
G-alpha-s
- Thus increase cAMP levels
How is heart rate increased?
1) NA released from sympathetic neurones
2) B1 adrenergic receptor activation via NA
3) G-alpha-s protein activation
4) Increases adenylyl cyclase
5) Increase cAMP
6) Increase PKA
7) Increase phosphorylation of calcium channels - increases time open for
8) Increase Ca2+ into myocytes
9) Increased contraction
Where are B1 adrenergic receptors located?
Nodal tissue and ventricular myocytes (cardiac muscle cells)
What is the mechanism for bronchiole smooth muscle contraction?
1) Adrenaline released from chromaffin cells
2) Activates B2 adrenergic receptors n bronchial smooth muscle cells
3) G-alpha-s protein activation
4) Increases adenylyl cyclase
5) Increases cAMP
6) Increases PKA
7) Phosphorylation of smooth muscle cell machinery
8) Bronchodilation
What are the clinical uses of adrenoceptor agonists?
Adrenaline (non-selective)
CV system:
- Cardiac arrest
- Anaphylaxis
B2 selective
Respiratory system:
- Bronchodilator to treat asthma:
- Salbutamol
What are the clinical uses of adrenoceptor antagonists?
Treat:
- Hypertension
- Heart failure
- Somatic anxiety symptoms
Unwanted effects:
- Bronchoconstriction - beta blockers avoided in asthma patients
- Cardiac depression
