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57 Cards in this Set
- Front
- Back
Hemicholinium
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-Blocks the action of the Na+ dependent membrane carrier that transports choline
-there is a decrease in ACh synthesis and ultimately decreased ACh release |
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Vesamicol
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inhibits ACh antiporter resulting in a decrease in ACh
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Botulinum toxin (BOTOX)
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-blocks the action of vesicular associated membrane proteins and synaptosome associated proteins (SNAPs)
-This prevents vesicle fusion and inhibits ACh release |
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Metyrosine
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-inhibits tyrosine hydoxylase blocking catecholamine synthesis and adrenergic neurotransmission
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Reserpine
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-inhibits a catecholamine carrier that transports dopamine (DA) and norepinephrine (NE)
-causes DA and NE to accumulate and then degredation by MAO. -decreases chatecholamine and synaptic transmission |
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bretylium
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-increases NE release
-blocks fusion of vesicles which result in exoctosis of NE |
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guanethidine
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-increases NE release
-blocks fusion of vesicles which result in exoctosis of NE |
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How are the actions of ACh terminated?
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by acteylocholinesterase (AChE)
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list 4 AChE inhibititors?
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Malathion, Edophonium, Pesticides and chemical warfare
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M1
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-located in nerves and glands
-stimulatory, IP3/DAG -Increases gland secretion |
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M2
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-located in heart, nerve terminals smooth muscle
-inhibitory, decreases AC -Slows heart rate/force of contraction (atria SA node). Decrease in contractile force of ventricle |
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Mechanism of M1?
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-increases Ca+2 intracell
-activate PKC |
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Mechanisms of M2
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-decreases cAMP
-decreases Ca+2 intracell -increases K+ channels |
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M3
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-located in the glands, smooth muscle and endothelium
-stimulatory, IP3/DAG -secretion and contraction of smooth muscle; Relax sphincters in GI/bladder, release of NO from vascular endothelium |
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mechanisms of M3
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-increases Ca+2 activate PKC
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How do muscarinic agonist effect the eye?
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they decrease intraocular pressure
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What are the some of the effects of muscarinic agonists on the cardiovascular system? How is this altered?
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-Vasodilation, decreased heart rate and reduced atrial contractility
-reflex arcs will cause tachycardia |
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what is the NET effect of muscarinic agonism on heart rate dependent on?
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-on the local agonist concentration in the heart and vasculature and the amount of reflex activity
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Innervation of blood vessels
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-NO parasymp.
-circulating muscarinic agonists cause vasodilation when acting on M3 receptors in endothelial cells -NO is produced and causes relaxation |
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What do muscarinic agonists cause in vessels without endothelium?
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-constriction through direct activation of muscarinic receptors present on the smooth muscle
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Effect of muscarinic agonism (M3) on the tracheobronchial mucosa?
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-bronchoconstriction and increased secretion from mucosa
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What type of drug is contraindicated in asthma pts?
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-cholinergic agonists
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muscarinic agonists effect on the GI tract?
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-increase secretory and motor activity
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muscarinic agonists effect on the genitourinary tract?
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-increased voiding
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Muscarinic over activation?
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Diarrhea
Uriniation Miosis Bradycardia, Brochoconstriction Emesis Lacrimation Salvation, Sweating |
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Nicotinic over activation?
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Muscle weakness or fasciculations
Adrenal Medulla (increased activation) Tachycardia Camping of skeletal muscle Hypertension |
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Contraindications of Esters of choline
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Hyperthyoidisms, asthma, coronary artery disease, acid-peptic disorders, obstructive urinary retention
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Actylocholine (Miochol)
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-High IV doses only
-ocular surgery -sweat spot test for autonomic neuropathy in diebetic pt |
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Methacholine (Provacholine)
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-longer lasting ACh more resistant to cholinesterase
-used to provoke bronchoconstriction in the diagnosis of bronchial airway hypersensitivity |
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list the esters of choline?
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-ACh (michol)
-Methacholine -Bethanecol -Carbachol |
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Describe the properties of the esters of choline?
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-they all contain permanently charged ammonium groups (do not cross the blood brain barrier)
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system adverse effects of the choline esters?
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-nausea, vomiting, abdominal pain, flushing, sweating, salivation, lacrimation, rhinorrhea,eructation, diarrhea, urinary frequency, headache, difficulty in visual accomodation, bradycardia, peripheral vasodilation leadingto hypotension and bronchoconstriction
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Desribe the cholinesterase sensitivity of the choline esters?
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ACh = highly sensitive
Methachoine = slightly sensitive Bethanecol and Carbachol are resistant |
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List the alkaloids?
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-Muscarine
-Pilocarpine (Salagen or Pilocar) -Nicotine -Varenchline (Chantix) |
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Muscarine
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-isolated from the mushroom Amanita muscaria. Original agent used in development
-no clinical uses |
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Main uses of pilocarpine?
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-topical; eye = miosis and accommodation
-treats open angle glaucoma, reduces intra-occular pressure -reverses sympathomimetic mydriatics -reverse mydratic actions of atrophine and break adhesions between iris and lens -used to treat xerostomia |
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Contrainications for pilocarpine?
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-do not use for glaucoma is IOP is higher than 45 mmHg
-at this pressure a mitotic can reduce the angle further and worsen the attack |
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Side effects of pilocarpine?
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-eye: myopia, blurred vision, ciliary body spasm.
-systemically: sweating, excess salivation etc., cardiovascular effects include sinus tachycardia and hypertension. Overdose can produce bradycardia, AV block |
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properties of pilocarpine
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-tertiary amine (not charged) crosses the BBB
-longer acting than choline esters but not as potent -parasympathomimetic with primarily muscarinic effects of Ach -particularily active on the eye and sweat glands |
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Where is nicotine specific to?
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-nicotinic receptors located at all all autonomic ganglia (including adrenal medulla), skeletal muscle and CNS
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How does nicotine effect the receptors?
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-activates and inhibits acetylcholine receptors
-First they activate receptors then they become desensitized which causes a ganglionic blockade and flaccid paralysis of muscle |
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effects of nicotine?
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-increase heart rate and BP (symp stimulation)
-simulates secretion of E at the adrenal medulla -increase GI tone and motility (para) |
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side effects of nicotine?
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-cholinergic nausea, vomiting, dizziness, diarrhea, weakness and rapid heartbeat
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Varenecline (Chantix)
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-Partial agonist at neuronal nicotinic receptors
-stimulates receptors in brain and can block the actions of nicotine at the same time. |
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side effects of Varenecline (Chantix)?
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-changes in behavior, hostility, agitation, depressed mood, suicidal thought ans attempted suicide
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how do in-direct acting chilinergic agonists work?
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inhibit acetylocholinesterase (anti-cholinesterases) and thus increasing the duration of action of ACh
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3 groups of in-direct acting cholinergic agents
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1. simple alcohols
2. Carbamic acid esters 3. organic derivatives of phosphoric acid |
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properties of the 3 chemical groups of in-direct acting cholinergic agents?
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1. simple alcohols
-reversible -acts for short periods 5-15 min 2. Carbamic acid esters -reversible not lipophilic -acts for longer periods 30min-6hrs 3. organic derivatives of phosphoric acid -irreversible lipophilic -hundreds of hrs |
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Endophonium (Tensilon)
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-Diagnosis of Myasthenia and evaluating efficacy of myasthenia therapies
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List the Reversible anticholinesterases
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-Edrophonium
-Physostigmine salicylate (antilirium) -Neostigmine -Donepezil -Tacrine -Galantamine -Pyridostigmine -Ambenonium -Demecarium -Carbaryl (D3 CAT PEGN) |
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Descibe the diagnosis test with endophonium?
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Positive (increase in m. strength) = pt has myasthenia Gravis
Negative (decrease in m. strength) = pt has cholinergic crisis (overacting of all cholinergic systems) Use atropine to teat. |
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Physostigime
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-30min to 6hrs
-opthalmic solution causes miosis, accomodation and a decrease in intra-ocular pressure |
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Neostogmine
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-.5-2hrs
-myasthenia gravis (alleviates postperopterative urinary retention and paralytic ileus) -anethesia (reverse the neuromuscular blockade) -lower IOP to manage glaucoma |
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structure/function of muscarinic antagonists?
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tertiary amines (atropine etc)
-well absorbed in gut, conjunctival membrane, systemic distribution including CNS quaternary amines (ipratropium) -not readily absorbed |
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Mechanisms of antimuscarinic agents?
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-competitive antagonist at muscarinic receptors
-block actions of parasympathetic system |
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These agents are useful in treating parkinson's disease because they decrease cholinergic activity in the basal ganglia and striatum
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-Antimuscarinic agents
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Adverse effects of antimuscarinic agents in the eye?
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-can precipitate acute glaucoma in a pt with a narrow anterior chamber angle
-Cycloplegia -dry eye |