Term
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Definition
| inhibits ACh transport system on the vesicles, thus leading to a decreased amount of ACh in vesicles, thus decreasing available ACh for transmission |
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Term
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Definition
| Botulinium Toxin (BoTox), a toxin produced by Clostridium sp., binds to sites on the nerve terminal and causes irreversible inhibition of the release of ACh from the nerve terminal. This occurs by blocking the ability of ACh vesicles to fuse with the internal nerve terminal cell wall and exocytosis. This substance is used clinically to decrease fine wrinkles on the face by relaxing the muscles around the wrinkle. Small amounts of BoTox is injected around the wrinkle, which leaves the muscles unable to contract. |
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Term
| black widown spider venon |
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Definition
| Black Widow Spider Venom binds to sites on the nerve terminal in a manner similar to BoTox, but instead of blocking release, this substance triggers the exocytosis of ACh-containing vesicles. This leads to an initial overstimulation via cholinergic transmission, followed by blockade as the nerve terminals are depleted of their neurotransmitter. Symptoms of poisoning include early severe stomach cramping, and potential fatality due to respiratory paralysis. |
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Term
| two types of nicotinic receptors are |
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Definition
| ganglionic, neuromuscular |
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Term
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Definition
| autonomic ganglia and CNS/ late epsp in ganglia-- blocked by atropine, pirenzepine is a fairly selective antagonist |
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Term
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Definition
| supraventricular regions of the heart/ decreases AV node conduction and SA automaticity thus slowing the heart-- blocked by atropine |
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Term
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Definition
smooth muscles and glands and vascular endothelial cells/mainly at neuroeffector junctions (glands, smooth muscles) (ex-salivation, urination, defecation, pupillary constriction, bronchoconstriction)
blocked by Atropine (like M1)
Hexahydrosilafenidol is a selective antagonist |
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Term
| m1 and m3 are couples to phospholipase C via |
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Definition
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Term
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Definition
| water soluble and in cytoplasm acts on IP3 receptors in the sarcoplasmic reticulum, increasing CA release which can then act on the cell |
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Term
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Definition
| lipid soluble, stays in cell membrane and along with increased CA activated protein kinase C which can then control many other enzymes |
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Term
| ACH on blood vessels causes what |
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Definition
| vasodilation-- via m3 receptor |
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Term
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Definition
| mainly in CNS/ antagonized by Himbacine |
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Term
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Definition
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Term
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Definition
found at autonomic ganglia and neurons.
Blocked by hexamethonium (non-depolarizing)
N1 comprised of a wide variety of different subunit combinations, some all one type, others are mixtures |
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Term
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Definition
found at neuromuscular junction.
Blocked by d-tubocurarine (non-depolarizing)
N2 made up of 2 α1, 1 β1, 1 δ and 1 ε subunits (embryonic form has 1 γ instead).
N2 ACh binding site located at subunit interfaces of αε and αδ subunits. |
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Term
| if spincter muscle contracts what happens |
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Definition
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Term
| if circular muscle contracts what happens |
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Definition
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Term
| ciliary muscle is controlled by |
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Definition
| parasympathetic- causes lense to thicken (near vision) |
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Term
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Definition
Muscarinic agonists
Choline esters
Acetylcholine (Miochol)
short t½ (secs in blood).
used as ophthalmic for glaucoma or surgery i.e., cataracts, or for eye exam – causes miosis.
acts by contraction of sphincter muscles of iris and also contraction of ciliary muscle leading to accomodation (for near vision).
stimulate ciliary muscles, opening traebeclear network and increasing aqueous humor outflow. |
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Term
| if someone has glaucome you dont what to use |
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Definition
|
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Term
| methacholine(provocholine) |
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Definition
Muscarinic agonists
Choline esters
Methacholine (Provocholine)
β-methyl group gives more muscarinic activity
longer duration than ACh (less well hydrolyzed by AChE)
main use is in vivo diagnosis of airway hyperreactivity in asthmatics who do not show symptoms (asthmatics much more sensitive than healthy population)
adverse reactions – headache, dizziness, pruritus
given by inhalational route
NOTE: - keep emergency meds and equipment ready due to asthmatic type reaction |
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Term
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Definition
Muscarinic agonists
Choline esters
Carbachol (Miostat)
resistant to AChE hydrolysis due to carbamyl group
nicotinic and muscarinic effects
use – antiglaucomic, miosis induction for surgery/exam
much longer duration than ACh (6 – 8 hours in eye)
adverse reactions
stinging/burning of eye, corneal clouding
may cause systemic effects (salivation, GI cramps, nausea and vomiting in sensitive persons) |
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Term
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Definition
muscarinic agonists
Choline esters
Bethanechol (Urecholine)
β-methyl group + carbamyl group
So, muscarinic mainly, slow hydrolysis
older agent used for treating urinary retention and to stimulate GI motility (only urinary retention now)
occasionally used to counteract anticholinergic effects of tricyclic antidepressants.
Minimal CV effects
In bladder, stimulates detrusor muscle, which decreases bladder capacity and triggers urination
Also relaxes urinary sphincters
Good in paraplegics since it is direct acting and CNS pathway not needed
In GI tract, stimulates peristalsis, increases motility
Triggers defecation by increased peristalsis and decreased sphincter tone
Not destroyed by AChE (at least very slowly)
Drug of choice for post partum and post op urinary retention
Not well absorbed via oral dosing
Onset 30-90 min, duration is one hour orally, two hours subQ |
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Term
| Pilocarpine (isopto Carpine) (salagen tabs) |
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Definition
Muscarinic agonist
Alkaloids and synthetic analogs
Pilocarpine (Isopto Carpine) (Salagen tabs)
alkaloid from Pilocarpus microphyllus
especially active on sweat glands and eyes – used to treat glaucoma
also used as miotic for exam/surgery
Occusert® is an ocular slow release system for glaucoma
Salagen Tabs used for treatment of symptoms of Sjogren’s syndrome (a chronic auto-immune disorder affecting the exocrine glands, resulting in dry eyes, dry mouth, dry skin, fatigue, and aching joints).
MOA : directly stimulates muscarinic receptors
in open angle glaucoma, contracts ciliary muscle, increasing outflow of aqueous humor
in closed angle glaucoma, miosis opens angle of anterior chamber – allowing aqueous humor to exit
given orally, stimulates glandular secretions, including salivary flow
Duration : – ophthalmic : 4 – 14 hours for solution, 18 – 24 hours for gel, orally : 3 – 5 hours |
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Term
| true acetylcholinesterase is found |
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Definition
| RBC and pre/post synaptic membrane |
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Term
| pseudocholinesterase is found |
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Definition
|
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Term
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Definition
|
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Term
| acetylcholinesterase inhibitors act as what |
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Definition
| parasympathomimetics in the autonomic system and neuromuscular stimulants in he somatic system |
|
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Term
| irreversible acetylcholinesterase inhibtors belong to a class of compounds known as |
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Definition
| organophosphates- form long term bonds at the serine esteratic site |
|
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Term
| acetylcholineterase inhibitors that are reversible are treated by |
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Definition
| pralodoxime (2-pam)- only works if OP has not been aged/ treatment also needs atropine |
|
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Term
| symptomology of ACHE-I toxicity |
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Definition
| salvation, lacrimation, urinatiion, defecation as well as sweating and miosis |
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Term
| Echothiophate (phospholine) |
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Definition
acetylcholinesterase inhibitors
Irreversible Agents
Echothiophate (Phospholine)
Ophthalmic miotic agent used for glaucoma and diagnosis.
Member of the organophosphate class of compounds.
Great care must be used in asthmatic and cardiac patients.
Ophthalmic application causes initial stinging/burning in most patients.
Long-term use may lead to cataract formation. |
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Term
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Definition
acetylcholinesterase inhibitor
Irreversible Agents
Malathion (Ovide)
Used as topical agent (lotion, shampoo) for the treatment of external parasites, including head lice.
While a member of the potentially dangerous OP class, malathion is one of the least human toxic of that group. However, it is a very potent insecticide. Must be converted to malaoxon, the active form, via metabolism to be effective. This occurs faster in insects than humans, who eliminate much of the parent compound before it can be converted. Very little of a dose is absorbed topically, and poisoning concerns are only realized on ingestion or pulmonary aspiration.
Advantage over pyrethroid type lice agents is its ability to kill the eggs (nits).
Potential poisoning is treated with atropine and pralidoxime. |
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Term
| Physostigmine (eserine) (antilirium) |
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Definition
ACH-I Reversible Agents
Physostigmine (Eserine) (Antilirium)
Isolated from the Calabar bean, it was used as an ordeal poison by West African natives in witchcraft trials.
Currently available in ophthalmic and parenteral preparations.
Main use is in treating open-angle glaucoma, but has been used to treat Alzheimer’s disease with limited success.
This is a tertiary compound and crosses the BBB better than Neostigmine (a quat).
Is occasionally used to treat the toxic anticholinergic effects of some drugs (such as the tricyclic antidepressants), especially in overdose cases. But this use is not recommended due to the seizure potential of this drug.
Potentiates the effects of ACh at peripheral nicotinic and muscarinic sites, and in the CNS mainly at muscarinic sites.
Normal responses to parenteral administration of this drug include increased skeletal muscle tone, increased GI tone and motility, bradycardia, sweat and salivary gland stimulation, bronchoconstriction, miosis, and decreased intraocular pressure mainly by widening the trabecular network, which allows increased outflow of aqueous humor.
At high doses, physostigmine acts directly at neuromuscular and ganglionic nicotinic receptors as a depolarizing blocker.
Rapidly hydrolyzed by cholinesterase in the body, yielding a short (1 – 2 hours) duration by I.V. Duration as an ophthalmic is 12 – 36 hours |
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Term
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Definition
ACHe-I Reversible Agents
Neostigmine (Prostigmin)
Available in both oral and parenteral forms. Like pyridostigmine, it is a quaternary agent with similar actions, but it has a shorter t½.
Used I.V. to treat acute episodes of Myasthenia Gravis and also is used occasionally for diagnosis of this disorder (but edrophonium is preferred for diagnosis due to its extremely short half-life.
Other uses include antagonizing the effects of non-depolarizing neuromuscular blockers (such as tubocurarine), and to treat post-op urinary retention and abdominal distention (but bethanechol is better).
The mechanism of action is the same as seen with physostigmine, but because this agent is a quat., it shows no CNS effects.
Action at different muscle groups depends on the sensitivity of the muscle group to the agent and how well the agent distributes to that site. Neostigmine also shows some direct neuromuscular nicotinic stimulating action.
When given orally, only a small percentage (1% – 2%) is absorbed, with onset of effects within 2 – 4 hours. Onset from parenteral administration is 10 – 30 minutes.
Elimination is primarily through metabolism by liver microsomal enzymes, with some excreted unchanged in the urine. |
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Term
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Definition
ACHE-I
Reversible Agents
Pyridostigmine (Mestinon)
Available in regular and sustained release oral tablets.
Like neostigmine, this agent is a quat., but with a little longer duration and slower onset. It also differs from neostigmine in that it shows fewer muscarinic effects, being better directed to the neuromuscular junction.
Most common use is in the treatment of Myasthenia Gravis.
Oral absorption is poor, and a wide range of population variability of absorption is seen.
Excretion is mainly in unchanged form via the kidneys, but some is metabolized through the liver microsomal enzyme system and cholinesterases. |
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Term
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Definition
ACHE-I Reversible Agents
Edrophonium (Tensilon)
Available in parenteral form only since it has a very short duration in the body. Onset of effect is also thus very rapid.
Structurally different, it is not a carbamate. Binds to the anionic site by ionic forces (it is a quat), and by hydrogen bonding over the rest of the molecule. Hence this compound’s bond is easily broken and helps explain its short duration (it is also rapidly eliminated via renal mechanisms unchanged).
Mainly used as the drug of choice for diagnosis of Myasthenia Gravis (but not for treatment due to short half-life), and for accessing potential benefits/risks of AChE-I therapy. Occasionally used post-op to reverse effects of non-depolarizing neuromuscular blockers, but short duration of effect makes this use risky. When combined with atropine, this agent has also been used to treat the respiratory depression seen following curare poisoning.
Few muscarinic effects are seen in challenge dosing with this drug due to the short duration of action.
Onset of effects following I.V. administration is 30 – 60 seconds, with a duration of 5 – 10 minutes. If given I.M., onset is 2 – 10 minutes, with a duration of 5 – 30 minutes. |
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Term
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Definition
ACHE-I
Reversible Agents
Tacrine (Cognex)
First drug approved to treat Alzheimer’s disease to improve cognitive function. However, there is no proof that use will slow the progression of the disease. It only improves functioning as long as cholinergic neurons in the forebrain related to memory are still in sufficient number. Once the number of these neurons falls below a certain point, there is not enough ACh released for even this drug to be able to help, and the patient’s cognitive functions suddenly decrease markedly (rather than seen without therapy, where a more progressive decline is seen).
Actions are similar to donepezil, but there are more peripheral effects seen. Tacrine also demonstrates a potential for hepatotoxicity (40% of patients), which is not seen with donepezil.
Inhibits both true AChE and pseudo ChE almost equally.
High first pass metabolism seen orally (up to 95%), and food can decrease absorption 30%. So give on an empty stomach.
Half life is 1 – 4 hours P.O. |
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Term
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Definition
ACHE-I
Reversible Agents
Donepezil (Aricept)
A piperidine type reversible ChE-I.
Used for mild to moderate Alzheimer’s disease. It also will not prolong the course of the disease, only make the earlier stages better for the patient and family.
Does not possess the hepatotoxicity risk seen with Tacrine, and it has fewer peripheral effects, due to its greater affinity for CNS cholinesterase.
Also binds by hydrogen bonding, thus is easily reversed. Half-life is longer than Tacrine mainly due to higher affinity for CNS cholinesterase, and slower elimination.
More selective for true AChE than Tacrine. This is unlike most of the AChE-I’s which show little selectivity between true AChE and pseudo ChE.
Well absorbed orally (~100%).
Metabolism is via the P450 system, which converts donepezil into two active and two inactive metabolites. Because of this, the half-life of effect of the parent compound and active metabolites combined is approximately 70 hours. |
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Term
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Definition
ACHE-I
Reversible Agents
Rivastigmine (Exelon)
used to treat Alzheimer's disease.
improve thinking and memory in patients with Alzheimer's disease. |
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Term
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Definition
ACHE-I Reversible Agents
Galantamine (Razadyne)
Also used to treat cognitive loss due to Alzheimer’s disease.
acts as a reversible, competitive antagonist of AChE |
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Term
| anticholinergic toxicity symptoms |
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Definition
Anticholinergic toxicity symptoms: hot as a hare (hyperthermia - secondary to decreased sweating), blind as a bat (mydriasis and cycloplegia), mad as a hatter (CNS stimulation), and dry as a bone (xerostomia).
Other side effects include: tachycardia, constipation, mental confusion, and urinary retention. |
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Term
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Definition
cholinergic antagonists Tertiary Agents
Atropine (USP)
From belladonna plant - (l-hyoscyamine is active, d form is not)
Prototype of its class
Wide variety of uses, but most commonly used to treat bradycardia and as a pre-op agent to decrease secretions
Also used as a mydriatic for ophthalmic exam
No longer used for Parkinson's disease (better agents with fewer side effects available)
Important in AChE-I toxicity to counteract excessive ACh (ex. Reversal of neuromuscular blockade)
MOA - competitive inhibitor at autonomic postganglionic cholinergic receptors (muscarinic) even in sympathetic systems at sweat glands.
Does not block at neuromuscular junction at therapeutic doses
Effect at specific sites are dose dependent. Salivary, bronchiole, and sweat glands are most receptive, followed by eye and heart, then the GI tract
At low doses, a paradoxical decrease in heart rate is seen
At higher doses, the effects seen include restlessness, hallucinations (abuse potential), disorientation.
Doesn't cause much CNS depression (drowsiness, euphoria, etc) like scopolamine does.
Potent bronchodialator (good for asthmatics), also decreases bronchial secretions, but it's side effects limit this use.
half - life is approximately 12 hours |
|
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Term
| scopolamine (transderm scop) (i-hyoscine) |
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Definition
anticholinergic
Naturally occurring alkaloid from belladonna plant
More potent than atropine on iris, ciliary body, secretions, but less potent at heart, bronchial and GI smooth muscles
High incidence of CNS depression at therapeutic doses
Very effective in preventing motion sickness (most common use) by blocking output from vestibular nuclei in inner ear going to brain's vomiting center
Also used occasionally to treat Parkinsonism
Truth drug in WWII - produces twilight sleep and lowers inhibitions
Tert amine - crosses into CNS well
Also used to decrease bronchial secretions prior to surgery
Half - life approximately eight hours |
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Term
| Benztropine mesylate (cogentin) |
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Definition
anticholinergic
Tertiary Agents
Benztropine mesylate (Cogentin)
Oral and parenteral forms available
Synthetic muscarinic antagonists (structure similar to atropine)
Used to treat Parkinsonian syndromes, including antipsychotic induced extrapyramidal symptoms
Tert - crosses BBB, but minimal CNS stimulation
Therapeutic effects may take 2 - 3 days to observe
Also has antihistaminic and local anesthetic effects
Blocks CNS muscarinic receptors (M1) thus decreasing excessive cholinergic activity seen in Parkinsonism. Also blocks dopamine reuptake, prolonging dopamine activity |
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Term
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Definition
anticholinergic
Tertiary Agents
Trihexyphenidyl (Artane)
Synthetic antimuscarinic
Used to treat Parkinsonism - also blocks dopamine reuptake prolonging action
Also has a direct antispasmodic action on smooth muscles
In small doses, has minor CNS depressant effects, but in longer doses can cause atropine-like CNS stimulation
Tolerance has been seen to its effects with prolonged use (especially in Parkinson's disease) |
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Term
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Definition
anticholinergic
Tertiary Agents
Dicyclomine (Bentyl)
Used as an antispasmodic in treatment of irritable bowel syndrome
Tert amine, but little CNS activity
Limited effects on salivary glands, sweat glands, or cardiovascular system
Fairly widely used
Effects on GI tract due to antimuscarinic effects and direct action on smooth muscles in GI tract |
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Term
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Definition
anticholinergic
Tertiary Agents
Darifenicin (Enablex)
Used to treat overactive bladder and urgency
Competitive agent
More potent at M3 receptors
98% plasma protein bound (mostly to alpha-1-acid-glycoprotein)
P-450 metabolism (CYP2D6 and CYP3A4) is major elimination route (97%)
Caution in hepatic insufficiency or with P-450 inhibitors such as clarithromycin
Major SE’s: dry mouth, dry eyes, constipation, UTI’s |
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Term
| homatropine (isopto homatropine) |
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Definition
anticholinergic
Tertiary Agents
Homatropine (Isopto Homatropine)
Structurally similar to atropine
Used as an ophthalmic to produce mydriasis and cycloplegia for diagnosis
Contraindicated in patients with glaucoma or a sensitivity to anticholinergics
May cause temporary stinging/burning on application, and increase intraocular pressure |
|
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Term
| cyclopentolate (cyclogyl) |
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Definition
anticholinergic
Tertiary Agents
Cyclopentolate (Cyclogyl)
Used as an ophthalmic to produce mydriasis and cycloplegia for diagnosis
Contraindicated in patients with glaucoma or a sensitivity to anticholinergics
May cause temporary stinging/burning on application, and increase intraocular pressure |
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Term
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Definition
anticholinergic
Tertiary Agents
Tropicamide (Mydriacyl)
Used as an ophthalmic to produce mydriasis and cycloplegia for diagnosis
Contraindicated in patients with glaucoma or a sensitivity to anticholinergics
May cause temporary stinging/burning on application, and increase intraocular pressure |
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Term
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Definition
anticholinergic
Quaternary Agents
Glycopyrrolate (Robinul)
Main use as GI antispasmotic or to treat bronchospasms
No CNS effects - should not be used to treat OP toxicity
Used as a pre-op med to decrease salivary, GI and pulmonary secretions and decrease risk of acid aspiration during surgery
Also used to block the effects of vagal stimulation during surgery, and to block the muscarinic stimulation seen when anticholinesterases are used as reversal agents (Ex. – after or with Neostigmine) |
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Term
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Definition
anticholinergic
Quaternary Agents
Ipratropium (Atrovent)
Structurally similar to atropine, but is a quat
Given by oral inhalation or nasal spray
Main use is as a bronchodialator for chronic obstructive pulmonary disease (superior to albuterol in COPD, but not as good as some other β2 adrenergic agonists)
Also useful to treat acute asthma attacks
Nasal spray approved to treat rhinorrhea in colds and allergies |
|
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Term
| propantheline (pro-banthine) |
|
Definition
anticholinergic
Quaternary Agents
Propantheline (Pro-Banthine)
an older drug, used infrequently now
Use mainly in cases of duodenal ulcers and irritable bowel syndrome
Absorption incomplete (10 – 25%) and variable. Food further decreases absorption. |
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