test 2 Flashcards
Where do direct acting agonist bind?
Directly to cholinergic receptors
What affects do direct acting agonists have on the heart?
Decrease conduction
Brady cardia
What affects do direct acting agonists have on visceral smooth muscle?
Increase motility in the Gi
Increase detrusor muscle tone
Decrease sphincter tone
What affect do direct acting agonist have on the eyes?
Contracts the sphincter of the iris, contraction of the ciliary muscle, decrease ocular pressure (allows for accomodation)
What affects do direct acting agonists have on exocrine glands?
Increase in SLUDD
Sweat
Lacrimation
Urination
Digestion
Diarrhea
What is acetylcholine used for?
It is a direct acting agonist used for ophthalmology
What is methacholine used for?
Test bronchial hyper reactivity (Bronchiolar constriction of direct acting agonist)
Has muscarinic selectivity
What is carbachol used for?
Direct acting agonist used for opthalmology
Has increased stability
What is bethanechol (urecholine) used for?
Bladder and GI Hypotonia
Direct acting agonist that is more stable and has muscarinic selectivity
What is pilocarpine used for?
Glaucoma and xerostomia it is a muscarinic selective direct acting agonist
What is cevimeline used for?
Xerostomia
Sojourn’s Syndrome
Selective on the M3 receptor direct acting agonist
What is the treatment for toxicity of cholinomimetic compounds?
Atropine (or other muscarinic receptor antagonist)
How do indirecting acting Cholinomimetics work?
They are cholinesterase inhibitors (increase amounts of ACH in the synaptic terminal)
What is the main difference in responses between direct acting and indirect acting cholinomimetics?
Indirect acting has the addition of nicotinic responses (muscle and CNS)
What are the main therapeutic targets of AChE inhibitors?
Skeletal muscle
Central nervous system for Alzheimers
Decrease intraocular pressure of the eye
SLUDD
What is the role of edrophonium?
To diagnose myasthenia gravis but it is a simple alcohol so too short acting so we do not use anymore
What are carbamate esters also called?
Medium acting anticholinesterases
Sometimes called suicide inhibitors (parent compounds are cleaved by enzyme)
What kind of AChEI is neostigmine?
Reversible medium acting anticholinesterase (carbamate ester)
What does neostigmine do?
Prostigmin or neostigmine is used to reverse competitive neuromuscular block that happens during myasthenia gravis
What is pyridostigmine used for?
Mestinon
Used for myasthenia gravis (better absorption and duration of action than neostigmine)
What is physostigmine used for?
Used in eye drops for treatment of glaucoma
What is the most common type of irreversible dementia?
Alzheimer’s disease
What is the most common type of reversible dementia?
Delirium
What is the most common drug associated with delirium that has anticholinergic activity?
Diphenhydramine
What enzyme is lost in alzhiemers disease?
Choline Acetyltransferase (makes ach)
What are the two forms of acetylcholinesterases?
AChE (CNS) and BuChE (plasma)
What kind of drug is Donepezil (Aricept)
Reversible and noncompetitive inhibitor of AChE
(less adverse effects due to high selectivity)
Alzheimers
How is Aricept metabolized?
Liver and kidney
What kind of drug is Rivastigmine (Exelon)
Carbamate Acetylcholinesterase Inhibitor
Active at both AChE and BuChE
Alzheimers
What kind of drug is galantamine (razadyne)
Competitive and reversible AChE inhibitor
Allosterically modulates nAChR
Alzheimers long term
What is the main problem with taking Alzheimers drugs long term?
May exacerbate behavioral problems with long term use
What is the mechanism for organophosphate inhibition of AChE
Form a covalent bond between the phosphate and hydroxyl group of the active site serine
What is isoflurophate?
DFP
Dyflos
Long acting anticholinesterase (organophosphate)
Sarin
What is echothiophate?
Phospholine
Used as eye drops for glaucoma
Organophosphate has a quat amine
What are the signs and symptoms of organophosphate exposure/ due to the muscarinic receptors?
Vomiting
Bronchospasm
Hypotension
Bradycardia
SLUD
Overstimulation of the muscarinic acetylcholine receptors in the parasympathetic system
What are the signs and symptoms of organophosphate exposure due to overstimulation of muscle nicotinic receptors at the NMJ?
Muscle weakness
Fasciculations
Paralysis
What are the signs and symptoms of organophosphate exposure due to overstimulation of nicotinic and muscarinic receptors in the CNS?
Confusion
Agitation
respiratory failure
Coma
What kind of drugs can reverse overstimulation of the Parasympathetic system?
Oximes
2Pam
Obidoxime
HI6
What is the primary cause of death with AChEIs?
Failure of the muscles of respiration
Why is the treatment of organophosphates long term?
They are lipophilic in nature
What is glaucoma associated with?
Ocular hypertension
What can untreated glaucoma lead to?
permanent damage of the optic nerve and resultant visual field loss and blindness
What is the primary strategy in glaucoma?
To reduce the production of aqueous humor and then to increase the outflow of aqueous humor
Opens the trabecular meshwork
What antimuscarinic drugs are selective for muscarinic receptors over nicotinic receptors?
Tertiary amines and alkaloids
What kind of drug is atropine?
Anticholinergic
Dilates the pupils
What saying can be used to recognize the antimuscarinic overdose?
Dry as a bone
Blind as a bat
Red as a beet
Hot as a hare
Mad as a hatter
Why do antimuscarinics cause dryness?
Blocks sweating and salivation
What do antimuscarinics cause blindness?
Dilates pupils and causes blurred vision
Blocks ciliary muscle contraction and loss of accommodation
Why do antimuscarinics cause redness?
Causes flushing of the skin and an atropine rash
Why do antimuscarinics cause hotness?
Marked rise in body temperature due to decreased sweating
What do antimuscarinics cause anger?
Delirium and toxic psychosis
How is scopolamine unlike atropine if they are both antimuscarinics?
It crosses the bbb more readily so it can be used for motion sickness and can cause CNS effects at lower doses
What is dicyclomine (bentyl) used for?
IBS
What is tropicamide used for?
Mydriatic agent
What is cyclopentolate used for?
mydriatic agent
What does flavoxate HCl do?
Urispas
Oral urinary antispasmodic
Relaxes spasms and increases the capacity of the bladder
What does oxybutinin HCl do?
Ditropan
Decreases hyperreflexively of bladder and urge to void
Can be sold OTC
What does tolterodine do?
Detrol
Used for urinary incontinence, frequency and urgency/bed wetting
Causes detrusor muscle relaxation
What does darifenacin do?
Enablex
Has M3 selectivity (antispasmodic)
What does solifenacin do?
Vesicare
M3 selectivity for antispasmodic urinary incontinence
What is significant about trospium?
Sanctura
Only quaternary amine for urinary incontinence
What is fesoterodine?
Toviaz
Newest oral antispasmodic for over active bladder
Non selective muscarinic receptor antagonist
What kind of antispasmodics have fewer side effects?
Extended release forms
What is myrbetriq?
Mirabegron
Beta 3 adrenergic receptor agonist
Treats over active bladder
Relaxes detrusor muscle
What are the uses of Quaternary amines?
GI hypermotility
Peptic ulcers
Presurgical adjuncts
COPD
What kind of antimuscarinic drugs have higher affinity for nicotinic receptors?
Quaternary amines
What is methscopolamine Br (Pamine) used for?
Reducing stomach acid secretion through M1 receptors (peptic ulcers)
Quaternary amines
What is Tussigon used for?
Homatropine methylbromide
Used with hydrocodone as an antitussive to discourage abuse
What is glycopyrrolate used for?
Robinul
Peptic ulcer disease or before surgery
Quaternary amine
Long acting one is used for COPD
How do anticholinergics help COPD?
Block parasympathetic cholinergic induced bronchoconstriction and mucus hypersecretion
What is ipratropium used for?
Atrovent
Used for bronchospasms/ limits secretions
Muscarinic antagonist
Quaternary amine - short acting but cheaper
What is tiotropium used for?
Spiriva
Longer duration than ipotropium
Has selectivity for M1 and M3 receptors
Decrease secretions and bronchospasms
What is Aclidinium Br used for?
Tudorza Pressair
Long acting quat amine muscarinic antagonist use for COPD
Hydrolyzed in the plasma
What is Umeclidinium used for?
Incruse Elipta
COPD
Quat amine antimuscarinic that blocks ACh in the M3 receptors which causes relaxation of smooth muscle
Extended duration of action
What is glycopyrronium Br used for?
Seebri
COPD
Highly selective for M3 over M2 so more focused on secretions and brochodilations
What is beztropine used for?
Cogentin
Parkinsons disease used for the tremors (tertiary)
What is trihexyphenidyl (artane) used for?
Parkinsons disease
What are the side effects of anticholinergics?
Anti Slud
What is the antidote for anticholinesterase poisoning?
Atropine
What are the treatments for antimuscarine toxicity?
Physostigmine IV (to overcome muscarine block)
Diazepam IV for cns effect
What diagnoses should you not use antimuscarinics for?
BPH
Glaucoma
Tachycardia
MI
CHF
GI or Gu obstructions
What OTC medication should be avoided when taking antimuscarinics?
Antihistamines
What kind of channels are nicotinic receptors?
Ligand gated inotropic channels that mediate fast ach neurotransmission
What are the two families of nicotinic receptors?
Neuronal nicotinic (CNS and ganglia)
Muscle nicotinic (neuromuscular junction)
When does nicotine act as a ganglionic blocker?
Following chronic exposure
Sustained depolarization of postganglionic membranes inducing a depolarization block
Why is nicotine addictive?
It stimulates nicotinic receptors on dopaminergic neurons which causes a dopamine reward pathway
What are the first line therapies for smoking cessation?
Nicotine replacement therapies
Psychotropics (buproprion)
Partial nicotinic receptor agonist (varenicline)
How does varenicline chantix work?
It is a partial agonist that binds selectively with high affinity to the alpha 4 beta 2 neuronal nicotinic ach receptors in the cns
(competitively inhibits binding of nicotine so the reward does not occur)
Why is the chantix dose gradually increased over time?
Minimize treatment related nausea and insomnia
Why have ganglionic blocking agents been largely abandoned?
They lack selectivity so they block all autonomic responses (cause tachycardia)
What are the side effects of neuromuscular junction blockers?
Histamine release (bronchial secretions, hypotension, bronchospasm)
What are the indications for NMJ blockers?
Partial or full muscle paralysis
What is d-Tubocurarine?
It is a nondepolarizing (competitive inhibitor) of the Neuromuscular junction
What kind of NMJ blocker is vecuronium?
Ammonio steroids
(act as a spacer for quaternary centers)
Little to no effect on blood pressure and fewer side effects
What type of drugs are rocuronium, vecuronium and pancuronium?
Ammonio steroids
Nondepolarizing competitive inhibitors
What is significant about atracurium and cisatracurium?
They are nondepolarizing agents that are not cleared renally (cleared through hoffman elimination) so they can be give to those with impaired renal function
What is the antidote for rocuronium and vecuronium?
Sugammadex (bridion)
What is succinylcholine?
Non competitive / depolarizing inhibitor of the NMJ
What is phase 1 block?
has to do with succinylcholine
Depolarizes the end plate and induces neuromuscular blockade (muscle relaxation after faciculations)
How is succinylcholine a noncompetitive inhibitor?
It is not antagonized by achei
What is phase 2 block?
With continued presence of succinylcholine, desensitizes nicotinic receptors
What are the side effects of succinylcholine?
Hyperthermia
Metabolic acidosis
Tachycardia
What is the treatment for succinylcholine?
Admin of dantrolene IV
Blocks the release of Calcium from SR at the ryanodine receptor
What is tizanidine?
Zanaflex
Centrally acting alpha 2 agonist
Increases presynaptic inhibition of motor neurons and nociceptive transmission in the dorsal horn (relieve spasms )
Fewer side effects than clonidine
What is baclofen?
Lioresal
GABA b receptor agonist
Gi-coupled metabotropic gaba receptor linked to channels
Hyperpolarization of muscles (reduce Ca influx)
What is dantrolene?
Dantrium
Works directly on the skeletal muscle
Blocks release of Ca from SR by binding to the ryanodine receptor
