Cholinergic Drugs Flashcards
What are the steps in how Ach is used as a signal between cells? (11)
(1) Choline is taken up by the cell
(2) Acetyl-CoA is a product of cell metabolism
(3) Choline-acetyl transferase synthesizes ACh
(4) ACh is pumped into vesicles and stored
(5) Nerve impulses reach the terminal
(6) Calcium enters the cell
(7) Relsease of ACh into the synapse
(8) ACh binds to receptors on the post-synaptic cell
(9) ACh may also bind to pre-synaptic receptors
(10) ACh is broken down by esterases
(11) Membrane is recycled
What are 3 types of drug moderators?
(1) Agonists
(2) Antagonists
(3) Modulators (Choline esterace inhibitors)
What are the main 2 types of ACh receptors?
(1) Nicotinic- affinity for nicotine
(2) Muscarinic - affinity for muscarine
What do nicotinic receptors do?
- Mediate fast activity because they directly convert a chemical signal into an electrical event
- Activation of these receptors causes opening of channels which are permeable to sodium and potassium
- Receptor embedded in membrane
What nicotinic receptors have different specificity and selectivity for agonists and antagonists?
Autonomic ganglia and neuromuscular junction
T/F The muscle-type receptor is only weakly activated by nicotine.
TRUE
What do muscarinic receptors do?
- G-protein coupled receptors
- ACh binds to this receptor that reacts to make 2nd messenger mediated signals inside cell
- Slower, non ion channel
Activation of muscarinic receptors in the target tissues can lead to various cellular responses including: (3)
(1) Activation of phospholipase C
(2) Opening or closing of ion channels
(3) The regulation of adenyl cyclase
What are some examples of 2nd messenger mediated responses? (4)
(1) IP3, Ca2+, cAMP, cGMP
- ion channels, kinases, phosphates, proteases, gene regulation-
What will happen with drugs that target nicotinic ganglionic receptors?
They will affect the entire autonomic system
What is the agonist in nicotinic ganglionic receptors?
Nicotine (lipid soluble tobacco alkaloid)
- Works for a brief period of time and then desensitizes after
- Stimulates ganglionic nicotinic receptor
- Also a CNS stimulant
What is the clinical usage of Agonist nicotinic ganglionic recepors?
- Cigarette smoking withdrawal; transdermal or oral
- Varenicline (Chantix); partial agonist for high affinity nAChR
Therapeutic Indications for Neuronal Nicotinic AChR? (7)
(1) Addiction- depression
(2) Tourette’s syndrome- cancer
(3) Parkinson’s disease- AIDS
(4) Schizophrenia
(5) Analgesia
(6) Alzheimer’s disease
(7) Inflammation
What are Antagonists of nicotinic ganglionic receptors? What was it once used for?
Ganglionic blockers; once used for antihypertensives but too many side effects
What are the side effects of antagonist ganglionic blockers?
Since ganglionic blockers interrupt transmission through both sympathetic and parasympathetic ganglia, they will have BROAD spectrum of effects, generally manifested as an antagonism of the dominant tone in any given organ.
