ANS 1 (Parasympathetic) Cholinergic Agonists Flashcards
Parasympathetic state/ acetylcholine effect and the muscarinic receptor (involved) of heart
Bradycardia; M2 receptor
Parasympathetic state/ acetylcholine effect and the muscarinic receptor (involved) of lungs
Bronchoconstriction; M2 receptor
Parasympathetic state/ acetylcholine effect and the muscarinic receptor (involved) of gastric acid secretiond
increased gastric secretion; M1 receptor
Influx of what ions causes the vesicles to fused with the plasma membrane and releases ACh
Ca
enzyme that breaks down ACh
Acetylcholinesterase (AChE) or cholinestrase
Cholinergic Agonist or Cholinergic Antagonist: Pilocarpine
Cholinergic Agonist
Cholinergic Agonist or Cholinergic Antagonist: Scopolamine
Cholinergic Antagonist
Cholinergic Agonist or Cholinergic Antagonist: Atropine
Cholinergic antagonist
Cholinergic Agonist or Cholinergic Antagonist: Succinylcholine
Cholinergic antagonist
Two general groups of cholinergic agonists based on MOA
Direct and indirect Acting
Brains, spinal cord
Central Nervous system
nerves outside the brain and spinal cord
Peripheral Nervous System
Composed of sensory neurons
Conducts signals from receptors to CNS
Sensory or Afferent Division
Composed of motor neurons
Conducts signals from CNS to effectors
Motor or Efferent Division
conducts voluntary movement with stimulatory effect only 1 neuron Neurotransmitter: ACh/nicotinic targets skeletal muscles
Somatic NS
conducts involuntary or automatic movements
with ganglion (postsynaptic or presynaptic)- 2 neurons
with stimulatory or inhibitory effect (sympathetic or parasymathetic)
Neurotransmitter: ACh/muscarinic or NE/ Alpha or beta
targets smooth muscles glands, adipose tissues
Autonomic NS
mobilises body systems
“flight or fight” responses
“catabolic” process
Ganglia: near SPINAL CORD ( short Preganglionic & long Postganglionic fibers)
NT:(pre) ACh, (post) NE, E, dopamine
receptors: (ganglia) nicotinic, (target organ) alpha, beta, dopamine
Sympathetic Division/ Adrenergic
conserves energy
“rest and digest” responses
anaboic process
Ganglia: near TARGET ORGAN ( long preganglionic & short postganglionic fibers)
NT: (pre &post) ACh
Receptor: (ganglia) nicotinic, (target organ) muscarinic, nicotinic
Parasympathetic Division / Cholinergic
NT:
- transmits all parasympathetic signals to end organs by binding to M (muscarinic) receptors
- transmits both sympathetic and parasympathetic impulses fr preganglionic neurons to N (nicotinic) recpetors of postganglionic neurons
Acetylcholine (ACh)
Manifestations of Rest and Digest / Parasympathetic
DUMBBELSS Diarrhea Urination Mydriasis Bradycardia Bronchoconstriction Emesis Lacrimation Salivation Sweating
Erection
Enzyme needed for synthesis of ACh
choline acetyltransferase (acetyl coa + choline forms ACh)
transporter needed for choline to enter presynaptic cell needed in synthesis of ACh
Na-dependent choline transporter
Drug which inhibits ACh to be stored in vesicles
Vesamicol
ion needed for the release (exocytosis) of ACh to synapse
Calcium
acetylcholine receptor in postsynaptic cell
Cholinoceptor
enzyme that degrades ACh to acetate and choline thru hydrolysis
Acetylcholinesterase or Cholinesterase
Drug that inhibits transport of choline or synthesis of ACh
Hemicholinium
Drug that blocks the release of ACh to synapse Wrinkle treatment (botox)
Botulinum toxin (Clostridium botulinum)
Location of M1
exocrine glands (secretion) autonomic ganglia (inc seizure activity) CNS ( inc cognitive and function )
Location of M2
Heart (cardiac inhibition)
CNS (neural inhibition, inc tremors, hypothermia, analgesia)
smooth muscle (inc contraction)
Peripheral nerves ( neural inh, dec ganglionic transmission)
Location of M3
exocrine glands ( inc secretion) smooth muscles ( inc contraction) eye ( miosis, ocular accommodation) blood vessels: endothelium ( vasodilation) CNS
location of M4
CNS (enhanced locomotion)
Location of M5
CNS
Salivary glands
Iris/ciliary muscle
Location of Nn or Ng (nicotinic ganglionic receptor)
Ganglion ( stimulation)
CNS ( neurotransmission)
Location of Nm (Nicotinic neuromuscular junction)
skeletal muscle (contraction)
2 divisions of Cholinergic agonists
Direct Acting and Indirect acting
2 divisions of direct acting cholinergic agonists
Choline esters and Alkaloids
Drugs under choline esters (choline bound to an acetyl derivative by an ester bond and ester bond is hydrolyzed by cholinesterase or AChE)
"Mag- CAB" Methacoline Carbachol ACh Bethanecol
Drugs under alkaloids
"NAP Muna" Nicotine Arecoline Pilocarpine Muscarine
MOA of direct acting cholinergic agonists
drugs directly binds to receptors
most potent cholinergic agonist
prototype
employed to cause miosis during cataract surgery
can produce brief 10 min miosis
ester of acetic acid and choline, a quaternary amino alcohol
Muscarinic receptors (M1, M2, M3, M4, m5) and Nicotinic
Acetylcholine
T/F: Acetylcholine is selective agonist for different types of cholinoreceptors and has no limited therapeutic use.
FALSE: ACh has both Muscarinic (1-5) and Nicotininc activity therefore, it has LIMITED therapeutic use due to lack of selectivity as an agonist for different types of cholinoreceptors.
T/F: Acetylcholine is rapidly hydrolyzed by cholinesterases.
True
Strong muscarinic (1-3) activity (only) specific for GIT and bladder inc intestinal motility after surgery more resistant to hydrolysis acute non-obstructive urinary retention duration: 1hr
Bethanechol
ester of carbamic acid
has both muscarinic (1-5) and nicotinic activity
tx of pilocarpine-resistant open-glaucoma
more resistant to AChE/hydrolysis
duration: 1hr
Carbachol
has muscarinic (1-3) and weak nicotinic activity
Methacoline challenge: diagnosis of asthma
reserves for px with Normal Lung Function tests but has Positive asthma symptoms
measures hyperresponsiveness / hypersensitivity of the lungs
Result: admin of initial, secondary and the highest dose
In its highest dose:
no asthma if FEV= 20% or higher
asthma/hypersensitive lungs if FEV> 20%
Methacholine (Provocholine)
“provoc” Provoking bronchial asthma
T/F: Alkaloids are not metabolized by AChE.
TRUE
DOC for glaucoma
exhibits muscarinic (1-3) activity
can cross blood-brain barrier
Pilocarpine (alkaloid fr Pilocarpus sp.)
muscarinic (1-3) ; no therapeutic use
Muscarine
muscarinic (1-3) and nicotinic activity
Potential for Alzheimer’s
Arecoline
aqueous humor production exceeds outflow, resulting in increased intraocular pressure
most common type of glaucoma
Open-angle Glaucoma
(glaucoma-related) ______ causes constriction of the sphicter muscle which surrounds the iris. The iris is drawn away from the Schlemm canal, enhancing outflow of aqueous humor.
Acetylcholine
M(1-5) and nicotinc receptors
ACh,
Carbachol
M(1-3) and nicotinic receptors
Methacoline,
Arecoline
M (1-3) receptors
Bethanechol,
Pilocarpine,
Muscarine
Divisions under Indirect acting
Organophosphates
Carbamates
Quaternary Amine (Edrophonium)
highly lipid-soluble liquids
have very high affinity for the active site of AChe forming phosphorylated enzyme
inactivates enzyme (AChE) thru phosphorylation
Organophosphates
MOA of indirect acting cholinergic agonists
cholinesterase inhibitors
Drugs under Organophosphates
Isofluorophate
Echothiophate
Malathion, Parathion
Tabun, Sarin, Soman
Chronic tx of open-angle glaucoma
duration: 1 week
route: eye drops
Isofluorophate (DFP: di-isoflurophate)
tx of open-angle glaucoma
duration: 3-7 d
Route: eye drops
Echothiophate
insecticide/pesticides
No clinical use
Active metabolites: Malaoxon, Paraoxon
Malathion, Parathion
Used in 1945 as delousing powder and used with soldiers to combat the spread of life thratening diseases like typhus and malaria
DDT (Dichlorodiphenyltrichloroethane)
nerve gases used in chemical warfare
poisons of war
penetrates skin, eyes, lungs
loss of consciousness, seizures , apnea, and death
Tabun(GA), Sarin(GB), Soman (GD)
antidote for organophosphate toxicity or “cholinergic crisrs”
2-PAM (Pralidoxime chloride) ,
Atropine
antidote for organophosphate toxicity that inactivates AChE thru dephosphorylation; does not cross the blood brain barrier
2-PAM (Pralidoxime chloride)
antidote for organophosphate toxicity that is a prototype anticholinergic agent and a muscarinic blocker
Atropine
Carbamyl ester inhibitors
MOA: carbamyl group prevents ACh from binding to the active site of AChE for a period of min to hours and forms CARBAMYLATED enzyme (can be decarbamlated)
Carbamates
Drugs under carbamates
Physostigmine
Neostigmine
Pyridostigmine
Carbamate Insecticides (CAP)
for intestinal and bladder atony (no muscle tone)
mitotic agent for open- angle glaucoma
tx of overdoses of anticholinergic drugs ( atropine, TCA, Phenothiazine)
duration: 6-12 h
Physostigmine (Eserine)
Physosstigma venenosum
can enter and stimulate the CNS
inhibit AChE in th eCNS
stimulates muscarinic, nicotinic sites of ANS + nicotinic of NMJ
Physostigmine (Eserine)
tx of Myasthenia Gravis (attacking self tissues) , paralytic ileus, or atony of the urinary bladder
antidote for Tubocurarine poisoning and other neuromuscular blocking agents
direct agonist at NM
more polar and does not enter CNS
duraion: 3-6h
Neostigmine (Prostigmin)
Symptoms of Myasthenia gravis
drooping eyelid difficulty in swallowing slurred speech weak muscles weak breathing muscles
MOA of Neostigmin tx for MG:
AChE inh prevent ACh degradation: which increases the probability that remaining receptors will bind ACh
direct agonist activit at NM
tx of MG (other than Neostigmine)
duration: 4h
Pyridostigmine (Mestinon)
Enumerate: Carbamate insecticides
CAP Carbaryl Aldicarb Propoxur increases ACh
competitive AChE, which contains QUATERNARY ammonium
reversible binding to AChE
used for Myasthenia grvis diagnosis (Tensilon test)
short duration: 1-2h
Edrophonium (Tensilon)
Effect of Cholinergic antagonist
dec ACh
3 Divisions of Cholinergic Antagonists
Muscarinic Blockers
Ganglion BLockers
Neuromuscular Blockers
MOA of Muscarinic BLockers
blocks the binding of ACh to muscarinic receptors
