From Physiological Systems To Molecular Drug Targets I Flashcards
Name the 4 major sites of action of drugs
- Enzymes
- Transporters
- Ion channels
- Receptors
What does PNS stand for?
Peripheral Nervous System
What is the role of the PNS?
To regulate the body’s internal environment
What does the PNS represent?
The output of the CNS
What 2 systems does the PNS consist of?
- ANS = autonomic nervous system
- SNS = somatic (motor) nervous system
How is the ANS controlled?
The ANS is usually outside of voluntary control
How is the SNS controlled?
The SNS is under concious control
Name the 2 nerves that make up the SNS
Efferent and Afferent
What is the role of the efferent nerves?
Control movement by innervating skeletal muscle
What is the role of afferent nerves?
Respond to external stimuli e.g. pain-sensing (nociceptive) fibres
What is the CNS made up of?
The brain and the spinal cord
List 5 processes that the ANS regulates
- Heart beat
- Smooth muscle contraction and relaxation
- All exocrine function
- Some endocrine function
- Some steps in intermediate metabolism
Name the 3 major systems/divisions of the ANS
- PNS = Parasympathetic Nervous System
- SNS = Sympathetic Nervous System
- ENS = Enteric Nervous System
What effect does blocking the noradrenaline receptors have?
Activates the sympathetic system
What effect does blocking the muscarinic ACh receptors have?
Blocks the parasympathetic system
What effect does activating the muscarinic ACh receptors have?
Activates the parasympathetic system
Describe the SNS
The SNS evokes a ‘fight or flight’ response
Describe the PNS
The PNS mediates a ‘rest and digest’ state
Define: Endocrine gland
A gland which secretes hormones directly into the bloodstream
Define: Exocrine gland
A gland which secretes hormones via ducts onto an epithelium rather than directly to the blood
List 3 actions of the SNS
- Pupil dilation (wide)
- Blood flow directed to the skeletal muscle
- Bronchodilation (more O2)
List 3 actions of the PNS
- Pupil constriction
- Blood flow directed to the viscera (organs)
- Bronchoconstriction
What is the role of ACh-esterase?
Convert ACh —> acetate + choline
What are ACh-esterase inhibitors also known as?
Anti-cholinesterases
What does blocking ACh-esterase do?
Increase the amount of ACh in the synaptic cleft
Where is ACh broken down by ACh-esterase?
The synaptic cleft
Which receptor does atropine block?
Muscarinic ACh receptor (mAChR)
Antagonist
Which receptor does succinylcholine block?
Nicotinic ACh receptor (nAChR)
Name the substance that blocks the muscarinic ACh receptor
Atropine
Name the substances that block the nicotinic ACh receptor
Succinylcholine and Tubocurarine
Which receptor does tubocurarine block?
Nicotinic ACh receptor
What effect does tubocurarine have on the body?
Paralyses muscles
By blocking the nicotinic ACh receptor
Name a condition that anticholinesterases are used to treat
Alzheimer’s Disease
What effect does ACh have on the blood pressure?
ACh decreases the blood pressure
More ACh = greater decrease in BP
What substance does atropine block the effects of?
ACh
What substance blocks the effects of ACh?
Atropine
How does atropine block the effects of ACh?
By blocking (antagonist) the muscarinic ACh receptor
Name the receptor that causes an increase in BP when bound to ACh (as atropine has blocked the muscarinic receptor)
Nicotinic receptor
How many subtypes of muscarinic receptor exist?
5: M1, M2, M3, M4, M5
What type of receptor do muscarinic receptors exist as?
G protein-coupled receptors
What response do M1, M3 and M5 (odd numbers) cause?
They cause an increase in IP3
What type of G protein are M1, M3 and M5?
Gαq
What type of G protein are M2 and M4?
Gαi/o
What response do M2 and M4 (even numbers) cause?
Decrease in cAMP
Why is it not recommended to target agonist drugs at the mAChR subtypes?
The agonists are non-selective - could target any/all of the subtype receptors = unpredictable effects
Why is it preferable to target mAChR subtype receptors with antagonist drugs
Drugs that are antagonists are more selective so they have a more predictable effect, only targeted at 1 receptor
What are the benefits of having a more selective drug?
- More likely to be safe
- More likely to be potent/efficacious
What is the role of Gαq? (M1/M3/M5)
Activates phospholipase C (which converts PIP2 into IP3 + DAG)
What is the role of phospholipase C?
It converts PIP2 into IP3 + DAG
What effect does IP3 + DAG have on the cell?
Increases intracellular calcium:
- Secretion
- Contraction
- Vasodilation
List 3 effects of an increase in intracellular calcium
- Secretion
- Contraction
- Vasodilation
Name the enzyme that is inhibited by Gαi/o (M2/M4)
Adenylate cyclase (so ATP can’t be converted to cAMP)
What enzyme do M2/M4 inhibit?
Adenylate cyclase (so ATP can’t be converted to cAMP)
What is the role of adenylate cyclase?
Convert ATP to cAMP
Name a physiological effect of a reduction in cAMP
Bradycardia = reduced heart rate
Define: Cholinergic
Relating to nerve cells in which ACh acts as a neurotransmitter
The actions of mAChRs mimic which nervous system?
Parasympathetic nervous system
List 4 parasympathetic effects caused by the actions of mAChRs
- Bradycardia
- Vasoconstriction
- Increased secretion
- Increased gut motility
List 4 physiological effects of the actions of atropine (blocking mAChRs)
- Tachycardia (increased heart rate)
- Pupillary dilation
- Block secretion
- Inhibits gut motility
Name 3 indications of atropine
- Smooth muscle relaxants (e.g. IBS)
- Cardiovascular (e.g. to treat bradycardia after heart attack)
- Anaesthesia (to prevent vagal inhibition of the heart)
What is the mechanism of action of atropine?
- Antagonist
- Blocks at muscarinic ACh receptors
- Non-selective
- Doesn’t block nicotinic receptors
