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121 Cards in this Set
- Front
- Back
What type of autonomic receptors are on the cardiac and smooth muscle, gland cells, and nerve terminals coming out of the medulla?
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Ach and M
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What type of autonomic receptors are on the sympathetic sweat glands?
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Ach and M
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What type of autonomic receptors on the cardiac and smooth muscle, gland cells, and nerve terminals coming out of the spinal cord?
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NE, alpha, beta
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What type of autonomic recepttors on the renal vascular smooth muscle?
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D, D1
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What are the local mediator chemical signals?
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Histamine + prostaglandins
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What are the neurotransmistters?
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1. NE, 2. Ach, 3. dopamin, 4. serotonin, 5. histamine, 6. Gamma-aminobutyric acid (GABA)
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What drug interferes w/the CHT(choline transporter) transporter?
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Hemicholinums - no choline is getting into nerve terminal to make Ach
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What drug interferes w/the VAT(vesicular) transporter?
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Vesamicol - inhibit vesical transporter -> Ach is formed but cannot be put into vesicle.
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What drug interferes w/SNAPs transporters in a cholinergic axon?
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Botulinum toxin - prevents receptors to bind w/pre-synapse membrane(Thus no Ach Release)
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What drug interferes w/NET
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Cocaine, tricyclic anti-depressants
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What drug interferes w/VMAT?
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Reserpine
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What drug interferes w/SNAPS in an adrenergic axon?
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Bretylium, guanethidine
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What drug interferes w/tyrosine hydroxylase
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Methyrosine
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Receptors coupled to ion channels
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NT binds to ion channel -> allows influx of ions to induce change in membrane potential
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Receptors coupled to adenylcyclase
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Hormone/NT -> Gs/Gi -> adenylcyclase (on or off)
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Receptors coupled to diacylglycerol and inositol triphosphate
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Hormone/NT -> Gq -> phospholipase C -> DAG/IP3 -> ↑ [Ca2+]
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What are the ways of post-synaptic regulation
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1. Normal transmission, 2. up-regulation(aka sensitization), 3. down-regulation (desensitization)
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How does up-regulation of post-synaptic receptors work?
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Normal amount of NT is release but there is an Antagonist that blocks a lot of receptors thus you lose signal. The body upregulates more receptors to bring back normal amount of response to NT. Thus now w/o antagonist there is much more response to a normal [NT]
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How does down-regulation of post-synaptic receptors work?
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Normal amount of NT is released but there is an agonist that binds to the receptors. The body down regulates the receptors because it want to keep the signal transmission the same as it was. Thus now w/o the agonist there is a decreased response to a normal [NT]
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What is the sympathetic NT on the effector organs?
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Norepinephrine
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What is the parasympathetic NT on the effector organs?
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acetylcholine
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What is the function of sympathetic nervous system?
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1. ↑ heart rate, 2. ↑ blood pressure, 3. mobilize energy stores, 4. ↑ blood flow to skeletal muscles and heart, 5. dilates pupils/bronchioles
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What is the function of sympathetic NS?
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Fight or flight
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Function of parasympathetic nervous system
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Maintains essential bodily functions - digestive processes, elimination of waste, rest and digest
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What is the function of vagal parasympathetic innv
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Slows HR
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What is the function of sympathetic innv
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Increases HR
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What are the only organs that have sympathetic innv
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1. Adrenal medulla, 2. kidney, 3. pilomotor muscles, 4. sweat glands, 5. control of BP
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Which direction is feedback control?
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Afferent impulses (towards)
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What is the function of muscarinic receptors?
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Its effects are the same as the parasympathetic NS.
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Which direction is reflex arcs?
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Efferent impulses (away)
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What is the MOA of the body when it detects a decrease in BP?
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Afferent signal (senses ↓ BP) -> efferent response (↑ CO) -> ↑ BP
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What type of receptor is used in muscarinic-cholinergic receptors?
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7-transmembrane domains coupled to G-protein coupled receptors
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Location of M4 and M5
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CNS
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What is M1-M3?
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Functionally characterized
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What is the function of nicotinic-cholinergic receptors?
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Ligand-gated ion channel- binds 2 Ach molecules -> allows Na+ entry -> depolarization of cell; NOTE: Ach stimulates receptor -> then blocks
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M1 receptor - location, features, mechanism
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Location = nerves, Featuers = 7Transmembrane + Gq, Mechanism = IP3 + DAG
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M2 receptor - location, features, mechanism
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Location = heart, nerves, Smooth muscle, features = 7Transmembrane receptor + Gi/o, Mechanism = inhibition of cAMP production, activation of K+ channels
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M3 receptor - location, features, mechanism
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Location = glands, smooth muscle, endothelium, features = 7 transmembrane receptors + Gq, mechanism = IP3 + DAG
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What are the 2 ways for cholinergic activation?
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1. Direct acting (alkaloids or choline esters), 2. indirect acting (reversible or irreversible)
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What are the choline esters we need to know?
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1. Acetylcholine, 2. methacholine, 3. carbachol, 4. bethanechol
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What are the characteristics of direct-acting cholinergics?
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1. Insoluble in lipids, 2. hydrolyzed in GI tranct, 3. IV bolus has brief effect, 4. Intramuscular and subcutaneous injections produce local effects
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What are the alkaloid drugs we need to know
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Pilocarpine, nicotine, muscarine
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How are alkaloids taken?
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Liquid nicotine -> absorbed transdermally, muscarine is incompletely absorbed from gut -> but can be toxic when ingested
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What type of pH urine ↑ clearance of pilocarpine and nicotine?
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Acidification of urine accelerates clearance of pilocarbine and nicotine
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How does Ach work in the parasympathetic system?
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Ach -> activates muscarinic receptors on effector cells -> inhibits the release of their neurotransmitters (acts indirectly)
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What is the MOA of direct acting nicotinic receptor?
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Channel opens Na+ and K+ ions to diffuse -> cellular depolarization -> causes skeletal muscle depolarization -> thus contraction of muscle
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What is the MOA of depolarizing blockade of nicotinic receptor?
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Long term agonist occupies the receptor -> postganglionic neuron stops firing -> skeletal musclerelaxes even though the membrane potential is back to normal
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What are the different types of organophosphates?
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1.echothiophate, 2. soman
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What are the different thiophosphates?
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1. Parathione, 2. malathion
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Why are acting cholinomimetics dangerous?
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Lipid soluble ->
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What are some unique characterisitcs of edrophonium and neostigmine?
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Poor absorbtion of conjunctiva, skin, and lungs -> thus hard to get toxic effects
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What are some unique characteritiscs of physostigmine
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Well absorbed on all sites + used on the eye
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What is the MOA of organophosphate?
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Cholinesterase inhibitors are well absorbed skin, lung, gut, and conjuctiva -> dangerous to humans and highly effective as insecticides
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What is the MOA of thiophosphate insecticides
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Malathion are lipid soluble and rapidly absorbed -> must be activated in the body to the oxygen analogs (kills insects fast)
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What is the MOA of indircet-acting cholinomimetics
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1. Inhibis acetylcholinesterase -> ↑ [Ach], 2. butyrylcholinesterase inhibited
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What is the duration of quaternary alcohols
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Edrophonieum - 2-10 mins
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What is the duration of carbamate esters
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Phisostigmine - 30 mins -> 6 hrs
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What is the duration of organoshosphates
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irreversible
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What is the process of "aging"
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The longer the duration of action the harder it is to release an ethyl group
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What reactivates the inhibited acetylcholinesterase?
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Pralidoxime - displaces phosphate group and regenerates the enzyme
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What are the systemic effects of activation of muscarinic receptors - eye? Secretory? Gastrointestinal? Genitourinary? Respiratory? Cardiovascular?
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Activation of parasympathetics = eye = miosis, secretory = sweat, lacrimal, and nasopharyngeal glands, GI = ↑ motor activity,
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What is unique about bethanechol
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Structurally related to Ach and Not hydrolyzed by acetylcholinesterase -> thus activates the receptor for 1hr -> stimulates an atonic bladder -> neurotonic atony + megacolon is cured
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What drug mimics Ach in the eye?
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carbachol
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What is the drug pilocarpine used for?
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Produces rapid miosis and contraction of ciliary muscle
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What drug is used to treat sjogren syndrome?
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Oral Pilocarpine - dry mouth, lack of tears
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What is the cure to overdose of anti-cholinergic drugs (atropine, phenothiazines, tricyclic anti-depressants)
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physostigmine
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What is the treatment of open angle glaucoma?
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echothiophate
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What drug is used to diagnose myasthenia gravis? Treatment?
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Edrophonium = diganose, treatment = pyridostigmine
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What are they Achase inhibitors used in alzheimers disease?
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Tacrine, donepezil, rivastigmine, galantamine
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What is the cure to chronic nicotine toxicity(smoking)
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Veranicline - partial nicotinic receptor agonist and antagonist
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Where are the major sources of Achase inihibitor toxicity?
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Pesticides in agriculture + the home (RAID)
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What are the treatments of Achase inhibitor toxicity?
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Atropine + pralidoxime
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What are the symptoms seen with parasympathetic NS activation?
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DUMB-BELSS = Diarrhea, urination, miosis, bronchoconstriction, bradycardia, excitation (CNS), lacrimatino, salivation, sweating
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What are the antimuscarinic drugs?
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Atropine
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What are the antinicotinic drugs
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Ganglionic blockers and Neuromuscular junction blockers
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What is unique about antimuscarinic MOA?
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Its an inverse agonist -> receptor w/constituative activity that is switched off w/the agonist
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What are the systemic effects of antimuscarinic agents(atropine) - CNS, EYE, Cardiovascular, Respiratory
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CNS = sedative, Eye = Mydriasis, cardiovascular = SA + AV node is blocked + blocked vasodilation, Respiratory = bronchodilation and reduced secretion
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What is a side effect of antimuscarinic drugs in the skin
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Sweat lands - suppresed thermoregulatory sweating - "atropine fever" = contrainidcated in infants + children
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What is the function of pilocarpine on the eye? Atropine on the eye?
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Pilocarpine = miosis, atropine = mydriasis
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What is the MOA of atropine(antimuscarinic dugs)?
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Binds competitively to receptor -> preventing Ach binding; duration =4 hrs
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What is the antidose for cholinergic agonists - OD on choliensterase inhibitor insecticides, mushroom poisoning, blocks effects of excess Ach from acetylcholinesterase inhibitors?
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atropine
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What drug do u use to treat motion sickness?
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Scopolamine patch
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What are the action of scopolamine
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Therepeutic lvl = sedation, high doses = excitation, anti-motion sickness, blocks short-term memory
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What drug is a synthetic analog to atropine?
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Ipratropium
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What are you treating when using ipratropium?
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Treating asthma + COPD (inpatients who are unable to take beta-2 receptor agonists)
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Where in the body does scopolamine work?
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CNS - treats motion sicknes
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Where in the body does ipratropium work?
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Respiratory -treats COPD
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Where in the body does atropine work?
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Cardiovascular - treats vasodilation
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What drugs are used to treat an over active bladder
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Solifenacin
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What drugs are used to treat adults w/urinary incontinence
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tolterodine
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Which G-protein coupled receptor is stimulatory?
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Gs
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Which G-protien coupled receptor is inhibitory
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Gi
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Which G-protien is coupled w/adrenorecepotr to phospholipase C
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Gq/11
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Which receptor is present on the post synaptic membrane and is coupled w/Gq -> phosphoplipase C?
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Alpha-1 arenorecepotor
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Which receptor is present on pre-synaptic nerve endings, beta-cell of pancrease, on vascular smooth muscle -> coupled w/Gi -> inhibits adenylate cyclase
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Alpha -2 adrenoreceptor
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What are the drugs that bind to alpha-adrenoreceptors
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Epinephrine, norepinephrine, isoproterenol
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What happens when u activate the alpha-2-adrenoreceptor?
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NE binds -> activates alpha-2-receptor -> turns off adenylyl cyclase -> ↓ [cAMP] -> ↓ NE release
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If pt w/vasodilation, bronchodilation, and relaxed smooth muscle
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Exposed to beta-2 agonist
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What is the location of alpha-1-receptors?
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Vascular beds -> dleads to areril and venoconstriction
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What is the location of alpha-2-receptors
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Vasculature -> leads to vasoconstriction
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What is the location ob beta-1 recepotrs
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Heart and vasculature -> ↑ cardiac output (due to ↑ contractility and stimulation of the SA node -> thus ↑ HR)
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What si the location of the beta-2-receptors
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Vascular beds -> ↓ peripheral resistance -> vasodilation
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What effect does activation of beta-2-receptors in the respiratory system do?
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Smooth muscle bonchodilation
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What drug favors alpha-1 over alpha-2 receptor?
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Phenylephrine -> causes mydirasis + nasal decongestant
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What are the direct acting adrenergic agonists that are alpha-1-receptor selective?
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1. Phenylephrine, 2. methoxamine, 3. midodrine
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What drug causes mild stimulation of CNS -> improves athletic performance
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ephedrine
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What is the MOA of amphetamine
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CNS = stimulant, periphery = blocks reuptake of NE + releases of stored catecholamines
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MOA of cocaine
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Blocks the norepinephrine transporter - > NE accumulates in the symaptic cleft
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What is the side effect of MAOI in the presence of cheese metabolites
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↑ blood pressure
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What is the treatment for anaphylaxis
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Epinephrine injection (IM)
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What is the cytochrome system that metabolizes metoprolol
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CYP2D6 - poor metabolizers = higher plasma concentration
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What drugs do u use to treat pheochromocytoma?
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Phenoxybenzamine (Alpha-receptor antagonist )- b/c in pheochromocytoma the tumor produces too much EPI/NE
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What are the beta-receptor antagonist drugs we need to know?
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Propranolol, nadolol, metorpolol
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Which beta-blocker is a partial beta-agonist and is useful in hypertension, angina
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Pindolol + acebutolol
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Which beta-blocker is a reversible antagonist (also has alpha-1-receptor antagonist properties)
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Labetalol
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Which beta-block is a non-selective beta-receptor antagonist + has some capacity to block-alpha-receptors and has antioxidant properties
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Carvedilol
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What drug is an ultra-short acting - beta-1 antagonist?
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esmolol
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What drug is used to treat stage fright?
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propranolol
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What is the drug used to treat thyroid storm?
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Propranolol -> treats hyperthyroidism ("thyroid storm")
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What should never be done w/beta-antagonists?
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Should never be abruptly stopped -> to avoid acute tachycardia, hypertension, and/or ischemia
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What are the sympathetic symptoms?
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Hot, blind, dry, red, mad, bloated
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