Autonomic Drugs - Cholinergics (Krasowski) Flashcards
direct transmission from the central nervous system, as well as post-ganglionic parasympathetic neurons, use what neurotransmitter?
acetylcholine
post-gangionic sympathetic neurons use this neurotransmitter, with what exception?
norepinephrine (except for certain sweat glands, which use acetylcholine)
neurotransmitter that acts at receptors in the renal vasculature, influencing blood flow
dopamine
neurotransmitter that is produced in the adrenal medulla, transported in the blood, and can activate most adrenergic receptors.
norepinephrine
what enzyme is found in the adrenal medulla that is required for the conversion of norepinephrine to epinephrine?
phenethanolamine N-methyltransferase
what is the rate limiting step in the catecholamine synthesis pathway?
conversion of L-tyrosine to L-dopa by tyrosine hydroxylase
Which of the following is an INCORRECT statement regarding muscarininc acetylcholine receptors?
A. The prototype agonist muscarine comes from mushrooms
B. The endogenous agonist is acteylcholine
C. They are found on targets of sympathetic innervation
D. Their release of acetylcholine is impaired by the toxin botulinum
E. When activated they tend to increase secretions and intestinal activity
C.
They are found on targets of parasympathetic innervation.
Which of these muscarinic receptor subtypes is INCORRECTLY matched with its site of action?
A. M1 - GI tract B. M2 - cardiac C. M3 - glandular/smooth muscle D. M4 - central nervous system E. M5 - unclear function
A.
M1 receptors are found on postganglionic neurons (ie, the ‘neural’ receptor subtype)
Which of the muscarinic receptors act via the inositol triphosphate (IP3) pathway involved in smooth muscle contraction?
odd-numbered (M1, M3, M5)
Which of the muscarinic receptors act by inhibiting adenyly cyclase? What is the effect of this?
even-numbered (M2, M4); this reduces cAMP in the cell, creating an inhibitory effect
class of receptors present at neuromuscular junctions, autonomic pre-ganglionic terminals, and the brain
nicotinic acetylcholine receptors
this receptor agonist is involved in complex pathways affecting cognitive function and reward
nicotine
partial agonist of α4β2 neuronal nicotinic receptors that helps treat nicotine dependence
varenicline
what is the therapeutic use for the nicotinic receptor antagonists mivacurium, pancuronium, and vecuronium?
used as neuromuscular blockers, primarily in surgeries to prevent smooth muscle contraction
inhibitors that affect both muscarinic and nictonic receptors and include neuromuscular reversal agents and myasthenia gravis drugs
acetylcholinesterase inhibitors
pesticides, insecticides and nerve gas are examples of _____ AChE inhibitors
organophosphate
AChE inhibitor that is used to reverse neuromuscular blockers (e.g., vecuronium, pancuronium)
neostigmine
AChE inhibitor that is used most often in the treatment of myasthenia gravis
pyridostigmine
this conidition is the antibody-mediated destruction of muscle nicotinic acetylcholine receptors leading to skeletal muscle fatigue
myasthenia gravis
donepezil, galantamine, and rivastigmine are examples of this class of drug, used in the palliative treatment of Alzheimer’s disease
AChE inhibitors
what does the term ‘aging’ mean, as applied to a unique property of organophosphate AChE inhibitors like insecticides and nerve gas?
aging means that after a few hours of exposure, the binding of these toxins to AChE is irreverisble
what drug can be used to prevent irreversible binding of AChE inhibitors if given soon enough (within 1-2 hours)?
pralidoxime (2-PAM)
what is usually the cause of death for people who die of AChE inhibitor poisoning? how is poisoning treated?
respiratory paralysis; poisoning treated by atropine to antagonize the muscarinic (parasympathetic) effects and pralidoxime if it is soon enough, to prevent irreverisble binding of AChE
Which of the following is NOT an effect of activation of the muscarinic receptor?
A. contraction of the sphincter of the eye (miosis) B. contraction of detrussor muscle C. bronchoconstriction D. decreased secretion of glands E. accommodation for near vision
D. You would see an increased secretion of glands. All of these are parasympathetic responses
what clinically important muscarinic agonist is used in the treatment of urinary retention?
bethanechol
for overactive bladder or urinary incontinence, antagonists such as tolterodine, oxybutynin, and solifenacin are used
what drugs are used in the treatment of a glaucoma attack, that work by constricting the pupil and allowing for aqueous fluid to drain from the eye?
bethanechol, carbachol, pilocarpine
in addition to having anithistamine properties, this drug is also used for its antimuscarinic properties
diphenhydramine (tricyclic antidepressants, especially amitriptyline, also have antimuscarinic properties)
muscarinic receptor antagonists like atropine (belladonna) differ mainly in their pharmacokinetic properties; importantly, whether or not they have the ability do do what?
cross the blood-brain barrier
All of these except which are anti-muscarinic effects?
A. Dry mouth
B. Mydriasis (dilated pupils)
C. Hypothermia
D. Tachycardia
E. Sedation (if drug crosses the blood-brain barrier)
F. Urinary retention and constipation
G. Hallucinations (if drug crosses the blood-brain barrier)
C. Remember that anti-muscarinic effects are anti-parasympathetic effects (ie, they will look like sympathetic effects). Hyperthermia, not hypothermia, would be one of these effects.
what are the two primary clinical uses of atropine?
treatment of severe bradycardia;
treatment of AChE inhibitor poisoning
in addition to atropine, name 3 other clinically important muscarinic antagonists
scopolamine - treats motion sickness, sedative
glycopyrrolate - dry up secretions during surgery (no CNS penetration)
benzatropine - treats parkinsonism
muscarinic antagonist used to dilate your pupils during an eye exam
tropicamide
anti muscarinic indicated in the treatment of asthma and COPD, marketed as an inhaler together with albuterol
ipratropium
anti muscarinic indicated in the treatment of COPD, whose capsules are pierced and placed into a special inhalation device
tiotropium
class of drugs that is useful in treating antimuscarinic overdose
AChE inhibitors
______ is a nonselective agonist of all adrenergic receptors, including the major subtypes α1, α2, β1, β2, and β3. i
epinephrine
_____ is a nonselective agonist that mediates its effects on α1, α2, and β1 receptors, stimulating increased heart rate, contractility, and vasoconstriction.
norepinephrine
