Pharm Flashcards
3 toxins that are known to block the function of Acetylcholine
1) Black Widow Spider venom - Acts as a generalized lipase and destroys the Ach Nerve terminal membrane
2) Botulinum toxin (botox) - Prevents Ach exocytosis by blocking Ca2+ entry. Botox paralyzes the NMJ of facial muscles.
3) Snake Venom & Frog Toxin
Muscarinic receptors
Describe the structure & location
Structure - Metabotropic; Single macromolecule spans the membrane 7 times and forms a channel for Ach to fit into.
Location - Cardiovascular systems (including blood vessels), smooth muscles and glands (including the SNS sweat glands)
Nicotinic receptors
Describe the structure & location
Structure - Ionotropic; Composed of 2 alpha, 1 beta, 1 gamma and 1 delta subunit. Both alpha subunits must bind Ach for activation.
Location - ANS ganglia ( Both SNS & PSNS), Neuromuscular junction, Adrenal Medulla
Why does acetylcholine bind to both muscarinic and nicotinic receptors?
Because Ach can flip between low energy and high energy state.
At low energy confirmation, Ach binds Muscarinic receptor ( distance b/w N and C centers is 4.4 angstrom)
At high energy confirmation, Ach binds Nicotinic receptor ( distance b/w N and C centers is 5.9 angstrom)
M1, M2 and M3 receptors
List the location of these receptors
M1 - neuronal ganglia (modulatory in nature)
M2 - heart and CV tissue
M3- glands and smooth muscle ( GI track, bladder, etc)
Location of subneuronal nicotinic receptor and Submuscular nicotinic receptor …
Subneuronal receptors - located in ganglia, brain and adrenal medulla; they have 6 carbons b/w the 2 quarternary N binding sites.
Submuscular receptors - located in NMJ; they have 10 carbons b/w the 2 N binding sites.
Methacholine
List some properties
- It is a muscarinic agonist.
- Same confirmation as Ach but with an extra methyl group –> makes it less susceptible to attack by acetylcholinesterase.
- It stimulates M2 receptor, acting on CV tissue –> produces immediate decrease in heart rate.
- Used in diagnostic precedures for asthma - Methacholine challenge. ( Not used as an official drug b/c causes bronchoconstriction)
Carbachol
List some properties
- It is a muscarinic agonist.
- Same confirmation as methacholine but with a NH2 in place of methyl –> makes it less susceptible to attack by acetylcholinesterase.
- Dosage is important : low dose affects muscarinic sites and high dose affects nicitonic sites.
- Used for the treatment of glaucoma –> causes smooth muscle constriction of the ciliary muscle, opening up Canal of Schlemm, thereby providing more drainage for the eye and decreasing ocular pressure.
Bethanechol
List some properties
- It is a muscarinic agonist.
- Combination of methacholine & carbachol (Has both methyl group & NH2 group) –> allows the drug to act purely on muscarinic receptor for a long period of time.
- It can be given orally or injected.
- Often used post GI surgery, when gastric motility is required to jump- start the GI system.
Atropine
List some properties
- It is a muscarinic antagonist (competitive inhibitor).
- Atropine has a tertiary Nitrogen ( no + charge) –> can be absorbed orally and can cross the BBB.
- It is a weak base. It has pKa (or pKb) and take charge or lose its charge depending on pH of the surrounding.
What are some of the effects of giving Atropin to a patient?
Blocks PSNS effects and allows SNS effects to predominate:
- Pupils dilate ( mydriasis), Loss of accommodation, Photopbobia
- Blocking of lacrimal glands resulting in inability to cry
- Blocking of salivary glands causing dry mouth.
- Bronchial dilation and decreased bronchial secretion.
- Decreased GI motility and decreased GI secretion
- Urinary retention
- Increased Heart Rate
- Increased body temperature due to absence of sweating
- Failure of penile erection.
- Blood Pressure stays the same!
Name 2 commonly used drugs that exhibit anti-muscarinic effects.
1) Detrol LA ( tolterodine) - Used to treat overactive bladder disorder.
2) Benadryl - Antihistamine
Side effects of these drugs include constipation, dry mouth, difficulty urinating etc due to anti-muscarinic effects.
Curare (Tubocurarine).
List some properties
1) It is a cholinergic antagonist at the NMJ, which leads to muscle paralysis.
2) It is a competitive antagonist for Nm receptor (found at NMJ)
2) Curare is used by surgeons for anesthesia.
Hexomethonium
List some properties
- It is a competitive antagonist for Nn receptor ( found at the autonomic ganglia and adrenal medulla).
- Used to treat patients with HTN in 1950s - Problem : It blocks ganglia and so it affects both SNS and PSNS outflow.
Trimethaphan
List some properties
- It is a competitive antagonist for Nn receptor ( found at the autonomic ganglia and adrenal medulla).
Name 3 classes of drugs that block the effects of acetylcholinesterase.
Group 1 : Esters of Carbonic acid ( Ex: Physostigmine, Neostigmine, Pyridostigmine, doneprezil, rivastigmine)
Group 2: Edrophonium
Group 3 : Organophosphates
Physostigmine Neostigmine Pyridostigmine, Doneprizil (aricept) Rivastigmine
( Describe the functions of these drugs)
They are all Carbonic ester drugs, that block the effects of acetylcholinesterase.
Physostigmine - Absorbed orally; gets into the brain and causes massive increase of Ach leading to death.
Neostigmine - Used to reverse curare blockade. Does not easily cross the BBB b/c of its charge quaternary N.
Pyridostigmine - Used in treatment of myasthenia. Can be taken orally but absorption is erratic.
Doneprizil & Rivastigmine - Used in the treatment of Alzheimer’s. Doneprizil is taken orally while Rivastigmine can be used in a patch.
