cholinergic agonists and antagonists Flashcards
sympathetic postganglionic neurons act on what type of receptors
adrenergic receptors
in cholinergic transmission, Ach can stimulate what two types of receptors
- muscarinic
- nicotinic
hemicholinium has what effect on cholinergic transmission
inhibits transporter that would take up choline into nerve terminal
botulinum toxin has what effect on cholinergic transmission
inhibits the release of ACh
List the Direct-Acting Cholinergic Agonists
- acetylcholine
- methacholine
- carbachol
- bethanechol
- pilocarpine, Cevimeline
- nicotine
define direct acting drugs
Drugs that bind to and activate the receptor are direct-acting, and most will discriminate between muscarinic and nicotinic receptors
define indirect acting drugs
Cholinesterase inhibitors are considered “indirect-acting”; they amplify the effects of ACh, and increase its effectiveness at both nicotinic and muscarinic receptors.
- what cholinergic agonist
- will act at both muscarinic and nicotinic receptors
- is rapidly hydrolyzed by AChE
acetylcholine
which cholinergic agonist is
- resistant to AChE
- selective for muscarinic receptors
- does not enter brain
Bethanechol
which cholinergic agonist/muscarinic agonist is
- an alkaloid
- selective for muscarinic receptors
- easily absorbed orally
Pilocarpine
sweat and salivary glands are very sensitive to what cholinergic agonist
pilocarpine
which muscarinic agonist is selective for M3 receptors
Cevimeline
define muscarinic receptor agonist
is an agent that activates the activity of the muscarinicacetylcholine receptor.
MOA of muscarinic receptor agonists
Muscarinic agonists interact with specific G-proteins to increase DAG and IP3 vua Gq/11, M1 and M3 receptors), or inhibit adenylate cyclase and open K+ channels (Gi, M2 receptors)
Effects of Muscarinic Agonists in the Eye
- constrict pupil
- facilitate accomodation for near vision
- decrease intraocular pressure
what class of drugs are used to treat glaucoma
Muscarinic Agonists
- pilocarpine : decrease intraocular pressure
- use for reversal of narrow-angle glaucoma attack
- will cause blurred vision so drug of last choice
side effects of using Muscarinic Agonists like Pilocarpine in the eye
blurred vision
effects of muscarinic agonists on cardiovascular function
muscarinic agonists used clinically have very few cardiovascular effects: HOWEVER, vagal stimulation can have profound effects on the heart, so injecting acetylcholine can have effects on CV function
Muscarinic receptors are located on smooth muscle, and the effect of stimulation of muscarinic receptors resembles that of ?
parasympathetic activation
Vagal inputs releasing acetylcholine (cholinergic agonist) has what effects on cardiovascular system
- bradycardia
- The effect of cholinergic stimulation in the heart is primarily on the atrium
- slows conduction through AV node
- vasodilation
- stimulation of cholinergic receptors on endothelial cells releases nitric oxide
Effects of Muscarinic Agonists on respiratory function
Bronchoconstriction can be quite striking in asthmatics exposed to cholinergic agonists.
which muscarinic receptor agonist is used to diagnose asthma
Methacholine
muscarinic receptor agonist effect on GI tract
- motility and peristalsis is increased in the GI tract
- sphincters are relaxed
- salivary and gastric secretions increase
which muscarinic receptor agonist has the most GI effect
Bethanechol
which muscarinic receptor agonist has the most bladder effect
Bethanechol
muscarinic receptor agonist effect on urinary bladder
- tone and peristalsis increase
- void pressure increases
- bladder capacity decreases
- detrusor contracts
- tirgone and sphincter relax
muscarinic receptor agonist effect on glands
- increased secretion
- sweat
- lacrimal
- nasopharyngeal
- tracheobronchial
which muscarinic receptor agonist has the most effect on sweat glands
pilocarpine
effect of muscarinic receptor agonist on brain activity
- improvement of memory
- alertness and arousal
- used for treatment of alzheimer’s disease
which muscarinic receptor agonist is used to increase GI motility
- Bethanechol (urecholine)
- treats postoperative abdominal distension
- treats gastric atony
which muscarinic receptor agonist is used to treat urinary retention and inadequate emptying
Bethanechol (Urecholine)
which muscarinic receptor agonist is used to treat Xerostomia: dry mouth due to Sjogren’s syndrome or head and neck radiation
- pilocarpine
- sweating will be common side effect
- Cevimeline (Evoxac): selective M3 agonist
- long lasting action and fewer side effects
Side Effects of Muscarinic Agonists
- Nausea, vomiting, diarrhea
- Abdominal cramps, belching
- Salivation and sweating
- Cutaneous vasodilation
- Bronchoconstriction
- Bladder tightness
- Blurred vision
contraindications of muscarininc receptor agonists
- peptic ulcer
- increases GI acid production
- Asthma/COPD
- bowel obstruction
- increases peristalsis
mushrooms contain muscarine thus a person can get muscarine toxicity. What is the treatment for this patient
- treat with atropine (antagonist)
- albuterol (to reverse bronchoconstriction)
Nicotinic receptors are located where?
- the autonomic ganglia (NN)
- the brain (NM)
- skeletal muscle (NM)
what type of receptors are nicotinic receptors
ligand-gated ion channels
- Nicotinic agonists cause an immediate activation, followed by a rapid desensitization if the receptors continue to be stimulated
effects of nicotinic stimulation on the brain
- Low doses of nicotine: increase alertness and attention
- Higher doses: tremor, vomiting and increased respiration.
- toxic doses: convulsions
peripheral effects of nicotinic stimulation are similar to which autonomic pathway
Effects of nicotine may be similar to discharge of both parasympathetic and sympathetic neurons, due to stimulation of autonomic ganglia.
nicotinic effects on CV and GU function
-
Cardiac effects are mostly sympathetic
- hypertension and increased heart rate, which may alternate with vagal bradycardia
-
Gastrointestinal and urinary effects are parasympathetic
- vomiting, diarrhea and urination.
Nicotinic agonists effects on neuromuscular junction
- initially cause stimulation of the muscle depending on the size of the stimulus, which may range from twitches to a strong contraction
- Long-lasting stimulation which is not rapidly hydrolyzed, will then desensitize the NMJ
- resulting in loss of strength and flaccid paralysis.
Nicotine toxicity
- vomiting
- CNS stimulation
- convulsions, coma, respiratory arrest
- skeletal muscle depolarization
- NMJ block and paralysis
- CV
- HTN, cardiac arrhythmia
treatment of nicotine toxicity
- with atropine to block muscarinic receptors
- with anticonvulsants to decrease seizures
- with mechanical respiration
what is Varenicline (Chantix)
- partial agonist on nicotinic receptor subtype in brain
- prevents craving from nicotine withdrawal but also blocks effect of nicotine if smoke cigarettes
Varenicline (Chantix) side effects
- nausea, vomiting
- constipation, flatulence
- sleep, psychiatric disturbance
MOA of Cholinesterase Inhibitors
- increase duration of time that ACh is available to activate receptors in the synaptic cleft
Name the Cholinesterase Inhibitors
- Neostigmine
- Physostigmine
- Edrophonium
- Organophosphates
