Cholinergic Drugs

Question 1

What are the steps in how Ach is used as a signal between cells? (11)

Answer 1

(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

Question 2

What are 3 types of drug moderators?

Answer 2

(1) Agonists
(2) Antagonists
(3) Modulators (Choline esterace inhibitors)

Question 3

What are the main 2 types of ACh receptors?

Answer 3

(1) Nicotinic- affinity for nicotine

(2) Muscarinic - affinity for muscarine

Question 4

What do nicotinic receptors do?

Answer 4

• 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

Question 5

What nicotinic receptors have different specificity and selectivity for agonists and antagonists?

Answer 5

Autonomic ganglia and neuromuscular junction

Question 6

T/F The muscle-type receptor is only weakly activated by nicotine.

Answer 6

TRUE

Question 7

What do muscarinic receptors do?

Answer 7

• G-protein coupled receptors
• ACh binds to this receptor that reacts to make 2nd messenger mediated signals inside cell
• Slower, non ion channel

Question 8

Activation of muscarinic receptors in the target tissues can lead to various cellular responses including: (3)

Answer 8

(1) Activation of phospholipase C
(2) Opening or closing of ion channels
(3) The regulation of adenyl cyclase

Question 9

What are some examples of 2nd messenger mediated responses? (4)

Answer 9

(1) IP3, Ca2+, cAMP, cGMP

- ion channels, kinases, phosphates, proteases, gene regulation-

Question 10

What will happen with drugs that target nicotinic ganglionic receptors?

Answer 10

They will affect the entire autonomic system

Question 11

What is the agonist in nicotinic ganglionic receptors?

Answer 11

Nicotine (lipid soluble tobacco alkaloid)

• Works for a brief period of time and then desensitizes after
• Stimulates ganglionic nicotinic receptor
• Also a CNS stimulant

Question 12

What is the clinical usage of Agonist nicotinic ganglionic recepors?

Answer 12

• Cigarette smoking withdrawal; transdermal or oral

- Varenicline (Chantix); partial agonist for high affinity nAChR

Question 13

Therapeutic Indications for Neuronal Nicotinic AChR? (7)

Answer 13

(1) Addiction- depression
(2) Tourette’s syndrome- cancer
(3) Parkinson’s disease- AIDS
(4) Schizophrenia
(5) Analgesia
(6) Alzheimer’s disease
(7) Inflammation

Question 14

What are Antagonists of nicotinic ganglionic receptors? What was it once used for?

Answer 14

Ganglionic blockers; once used for antihypertensives but too many side effects

Question 15

What are the side effects of antagonist ganglionic blockers?

Answer 15

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.

Question 16

What are 3 Antagonist nicotinic ganglionic blockers?

Answer 16

(1) Hexamethonium- no CNS penetration
(2) Mecamylamine- will block CNS effects of nicotine
(3) Trimethapham- short acting can acutely lower BP

Question 17

What are the muscarinic cholinergic actions? (9)

Answer 17

(1) Salivation
(2) Lacrimation
(3) Urination
(4) Defecation
(5) Decreased heart rate (decreased AV production)
(6) Miosis (constricted pupils)
(7) Vasodilation
(8) Bronchoconstriction
(9) Increased GI motility and secretions

Question 18

What are 3 Choline esters that are muscarinic agonists? Which ones are used?

Answer 18

(1) Acetylcholine
(2) Methacholine
(3) Bethanechol
- NOT Acetylcholine-

Question 19

What are 2 Alkaloids that are muscarinic agonists? What do they have specificity for?

Answer 19

(1) Muscarine
(2) Pilocarpine
- agonists with specificity for parasympathetic target organs-

Question 20

What is Pilocarpine used for?

Answer 20

• Used to stimulate salivation

- Used to treat glaucoma (in combo with anticholinesterase)

Question 21

What are 2 muscarinic antagonists? Where do they come from?

Answer 21

Atropine and Scopolamine; from Belladonna (longer-lasting)

Question 22

What are antimuscarinic signs? (7)

Answer 22

(1) Inhibition of sweating
(2) Vasodilation (a CNS effect)
(3) Xerostomia, dry eyes
(4) CNS effects, hallucination in high dose
(5) Mydriasis
(6) Blurred vision due to cyclopegia
(7) urinary retention

Question 23

Clinical use of antimuscarinics (5)

Answer 23

(1) Eye examinations: induce mydriasis
(2) Asthma: blocks cholinergic component of bronchoconstriction
(3) MI: blocks vagal response to pain permits increased heart rate
(4) Insecticide poisoning: antidote for anticholinesterases
(5) Oral surgery: to inhibit salivation

Question 24

What is Ipratropium?

Answer 24

Antimuscarinic; bronchodilator (given as inhaled aerosol, charged molecule stays in lung, limiting systemic effects)

Question 25

What do cholinesterase inhibitors do?

Answer 25

Prolong the presence of acetylcholine in the synapse

Question 26

What are the 3 cholinesterace inhibitors?

Answer 26

(1) Physostigmine (uncharged, enters CNS)
(2) Neostigmine (charged, does NOT enter CNS)
(3) Donepezil

Question 27

What are cholinesterace inhibitors used for?

Answer 27

(1) Myastenia gravis
(2) Glaucome
(3) Reversal of neuromuscular blockade after surgery
(4) Alzheimer’s disease: DONEPEZIL