If one of your patients has decreased secretion of ACh at the neuromuscular junction, which receptors will be stimulated first?
Muscarinic receptors. Nicotinic receptors do no have as high of an affinity for ACh as muscarinic receptors do.
What type of ACh receptors are at the effector organ? The post ganglionic neuron?
Muscarinic at the effector organ and nicotinic at the post ganglionic neuron.
Where in the body might you find muscarinic receptors that don't act the way you'd expect them to if you administered ACh?
Sympathetic neurons to sweat glands release ACh and cause sweating. Muscarinic receptors are also on peripheral blood vessels that result in relaxation and vasodilation when stimulated.
Which muscarinic receptor type is found in sympathetic postganglionic neurons? Myocardium and smooth muscle? Exocrine glands and blood vessels?
M1= sympathetic ganglia. M2= myocardium and smooth muscle. M3= Blood vessels and exocrine glands.
Where do most cholinergic drugs such as atropine act?
All muscarinic receptors, they are normally not selective.
Why do M1,3,5 muscarinic receptors typically result in excitation?
G-coupled signal transduction activates phospholipase C -> PIP2 -> IP3 and DAG -> PKC and increase in Ca2+ -> excitation
How does an M2, M4 muscarinic agonist slow heart rate?
Activation of these channels release G protein subunits -> disable adenylyl cyclase -> blocks pacemaker channels (Ca). It also opens K+ channels to hyper polarize the cell.
What are the direct acting cholinergic receptor agonists?
ACh is not typically used clinically because acetylcholinesterase uses it up rapidly.
A patient comes out of the operating room and experiences severe constipation and urinary retention. What is a good drug to prescribe to this patient?
Bethanechol. It is a specific muscarinic receptor agonist and will activate the parasympathetic nervous system.
If you injected muscarine at the post ganglionic neuron would you see an effect?
No, muscarinic receptors only exist at the effector organs.
What drug would you give to someone who ingested a poisonous mushroom?
Atropine. It is an anti-muscarinic drug and will decrease parasympathetic activation caused by the muscarine in the mushroom.
What are the alkaloid cholinergics?
Muscarine, pilocarpine and nicotine (active at nicotinic receptors)
What drug could you prescribe to a patient with glaucoma?
Piolocarpine. It stimulates parasympathetic activation of the eye and constricts the pupils, decreasing intraocular pressure.
What side effects do you need to consider when giving a muscarinic agonist?
How does atherosclerosis result in an increase in blood pressure that is related to muscarinic receptors?
Stimulation of M3 receptors on vascular endothelial cells is diminished in atherosclerosis and you lose that aspect of NO production by endothelial cells to vasodilate smooth muscle.
What cholinergic drugs are contraindicated in patients with glaucoma?
Anti-muscarinic drugs, these will increase intraocular pressure.
Why do patients on antimuscarinics often complain of fevers?
Inhibition of muscarinic receptors makes it so patients can't sweat and they gain internal heat.
Why would you prefer to prescribe someone a quaternary amine over a tertiary amine anticholinergic?
Quaternary amines cannot enter the CNS and you can eliminate CNS side effects if you don't want them.
You are preparing a patient for colorectal surgery and want to limit GI activity. What drug could you prescribe that would not have any CNS activity?
Propantheline. It is an antimuscarinic that inhibits GI motility and secretions. It is a quaternary amine that cannot enter the CNS because of its positive charge.
What drug is preferential in opthalmology eye exams over atropine or scopolamine?
Homatropine. Atropine and scopolamine can block muscarinic receptors in the eye for days, homatropine is fast acting and sometimes the patient can actually drive home.
An elderly patient comes to see you complaining of urinary incontinence. What antimuscarinic drugs could you prescribe to help her out?
Oxybutynin and tolterodine.
What are some of the atropine toxicities?
HOT as a hare, DRY as a bone, RED as beet, BLIND as a bat MAD as a hatter.
How do you treat atropine toxicity?
Atropine is a COMPETITIVE antagonist, so you can give anticholinesterases that will increase ACh levels which can outcompete atropine at muscarinic receptors.
You are riding in the car, reading, and begin to feel sick. What anticholinergic is often taken for motion sickness?
Why does someone with high levels of injected nicotine have a different response to a smoker?
When there is too much nicotine circulating, sodium channels remain in their inactivated recovery state. This results in smooth muscle relaxation and nerve depolarization. This is contrary to smoking which supplies low levels of nicotine that are excitatory on most receptors.
What receptors cause postganglionic hyperpolarization and IPSP after nicotinic receptor stimulation of an action potential?
M2 muscarinic receptors.
What part of the autonomic nervous system is affected by nicotine?
All parts. It stimulates sympathetic and parasympathetic pathways because it acts at all postganglionic neurons.
Why did Pinocchio get sick when he smoked the cigar?
Nicotine acts on other receptors outside of the autonomic nervous system. In his case Pinocchio activated the emetic trigger zone that causes nausea and vomiting.
Why do smokers tend to activate hormones that increase their blood pressure?
Nicotine acts on the hypothalamus and induces secretion of vasopressin (ADH) which goes on to raise blood pressure
Why are you able to focus better after a smoke or a dip? Why are these habits addicting?
Nicotine stimulates the CNS and it also induces dopamine secretion that causes pleasure centers to activate.
What clinical patients could possibly see physiological benefits from smoking?
Alzheimer's = CNS stimulation. Ulcerative colitis = increased GI secretions
You are doing a rotation in the rural areas of NC. A patient comes to see you complaining of rapid onset of nausea, salivation, vomiting, blurry vision and metal confusion. History reveals that this man works in the tobacco industry. What is your diagnosis and how do you treat this patient?
This patient has green tobacco sickness, a result of nicotine poisoning. You would give this patient atropine to block further parasympathetic stimulation and induce vomiting to get rid of nicotine.
A 22 year old male comes to see you concerned that he cannot stop smoking. He says he's tried everything from gum to patches. What drug can you prescribe to help him quit?
Varenicline (Chantix). It is a patrial nicotinic receptor agonist (partially activates the receptor and blocks the binding of nicotine when taken in)
What are the competitive nicotinic antagonists that are ganglionic blocking agents?