Cholinergic Antagonists Flashcards
What is the prototypical muscarinic antagonist? What are these drugs used to treat?
atropine
-GI disorders, COPD, and Ophthalmic issues
What is the mechanism of action of atropine? What other drugs are similar but at other receptors?
- surmountable antagonist (can be revered by increasing Ach, usually with an AchEI) at all 5 M receptors. Atropine traps the Ach M receptor in the inactive state blocking binding and signal transduction at the site.
- scopolamine, ipratropium
What is oxybutynin and tolterodine?
-M3 preferred antagonists that are used in the management of hyperactive bladder
T/F Ipratropium crosses the BBB
False
What are the side effects of atropine? Pneumonic?
- increased body temp (due to decreased sweating)
- rapid pulse
- dry mouth
- dry, flushed skin
- cyclopledgia (blocking of M3)
- constipation
- disorientation
- Hot as a hare, dry as a bone (no bowels sounds, no spit, no tear, no sweat), red as a beet, blind as a bat (no accomodation), mad as a hatter (CNS toxidrome leading to delusions, hallucinations, confusion)
What receptors induce relaxation of ciliary body? Contraction? Effects on vision and lens, fibers, etc?
- beta 2: induces relaxation, ciliar muscles relaxes, fibers taut, lens at minimum strength for distant vision
- M3 induces contraction: ciliary muscles contracted, fibers slack, lens rounds to greater strength for close vision
What is scopolamine solubility? What is it used to treat?
- lipid soluble (absorbed across the skin)
- used to treat motion sickness as the vestibular system uses a number of cholinergic fibers in its projects
Why aren’t atropine and scopolamine drops used for eye exams? What is used instead?
- they have very long acting symptoms (increased pupil dilation and lack of accomdation)
- tropicamide
What muscarinic antagonist is used for the treatment of asthma and COPD? What receptor does it block and what effects does that have? What is unique about its structure? Pneumonic?
- ipratropium, tiotropium
- blocks M3 in the bronchial tree and redces mucous production and increase airway caliber
- quaternary coup that can’t cross membranes so it stays in lungs
- “I pray I can breathe soon”
What are the urinary disorder medications that are muscarinic antagonists? What are its effects?
- oxybutynin, darifenacin, and solifenacin, tolerodine (Detrol)
- reduce urgency in mild cystitis and reduce bladder spasms.
What is glycopyrrolate? How is it given and how does this influence effect?
- muscarinic antagonist
- Paraenteral: preop use to reduce airway secretion
- oral: drooling peptic ulcer
What are some other random uses of muscarinic antagonists?
- mushroom poisoning treatment: muscarin is derived from mushrooms so toxicity is reversed by anticholinergics
- insecticide exposure: can produce cholinomimetic effects that can be reversed by muscarinic antagonists
Describe the process at which a muscle fiber fires at the neuromuscular junction?
- Ach is released and action potential generated and propagates along the sarcolemma and down the t tubules
- action potential triggers Ca release from terminal cisternae of Sr
- Calcium ions bind to troponin; troponin changes shape, removing the blocking action of tropomyosin, actin active sites exposed
- contraction; myosin cross bridges alternately attach to actin and detach, pulling the actin filaments toward the center of the sarcomere; release of energy by ATP hydrolysis powers the cycling process
- removal of Ca by active transport in the SR after the action potential ends
- tropomyosin blockage restored blocking actin active site; contraction ends and muscle fibers relaxes
What are the two types of neuromuscular junction blockers?
- nicotinic antagonists which blocks the action of Ach
2. depolarization blockers which hyper stimulate the NMJ producing depolarization blockage
What are the major Nm direct acting antagonists? MOA? Effects? Clinical? Toxicity? Pharmacokinetic considerations?
- atracurium, pancuronium (long acting) , rocuronium, D-tubocurarine
- MOA: competitive antagonists at the NMJ with “surmoutable affinity” for the Nm receptor.
- Effects: dose dependent NMJ blockade leading to weakness and eventually flaccid paralysis
- Clinical: surgery, intubations
- Toxicity: respiratory compromise
- D-tubocurarine stimulates release of histamines (h1 receptor which increases vascular perm) and leads to hypotension
- Pharmacokinetic considerations: poorly lipid soluble and have peripheral effects
