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113 Cards in this Set
- Front
- Back
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Muscarinic M1 Receptor
Location? Responses? Mechanism? Prototype Agonist? Prototype Antagonist? |
Location: Autonomic Ganglia, CNS (complex: at least arousal, attention, analgesia)
Response: Late excitatory postsynaptic potential (EPSP) Mechanism: Gq -> PLC -> Increase IP3 and DAG -> Increase in Calcium and PKC Agonist: Oxotremorine, McNA343 Antagonist: Atrophine, Pirenzepine, dicyclomine |
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Muscarinic M2 Receptor
Locations? Responses? Mechanism? Prototype Antagonist? |
Mechanism: Beta-gamma of G-protein -> inhibit AC and increase K+ channel opening
Location: Heart -- SA node Response: Slowed spontaneous depolarization; hyperpolarization Location: Heart -- AV node Response: Decreased conduction velocity Location: Heart -- atrium Response: Decreased refractory period; decreased contractile force Location: Heart -- ventricle Response: Slight decrease in contractility Agonist: Carbamycholine Antagonist: Atrophine, gallamine, AF-DX 117 |
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Muscarinic M3 Receptor
Locations? Responses? Mechanism? Prototype Antagonist? |
Location: Smooth muscle
Response: Contraction Mechanism: Gq -> PLC -> Increase IP3 and DAG -> Increase in Calcium and PKC Agonist: Carbamycholine Antagonist: Atrophine, Hexahydrosiladifenidol |
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Muscarinic M4 Receptor
Locations? Mechanism? Prototype Antagonist? |
Location: CNS
Mechanism: Beta-gamma of G-protein -> inhibit AC and increase K+ channel opening Agonist: Methacholine Antagonist: Himbacine, MT-3 toxin, tropicamide |
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Muscarinic M5 Receptor
Locations? Mechanism? |
Location: CNS
Mechanism: Gq -> PLC -> Increase IP3 and DAG -> Increase in Calcium and PKC Agonist: Methacholine |
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Nicotinic Nn Receptor
Location? Responses? Mechanism? Prototype Agonist? Prototype Antagonist? |
Location: Autonomic Ganglia, Adrenal medulla, CNS (complex: at least arousal, attention, analgesia)
Response: Depolarization and firing of postganglionic neuron (Autonomic Ganglia), Secretion of catecholamines (Adrenal Medulla) Mechanism: Opening of Na+/K+ channels Agonist: Dimethylphenyl-piperazinium Antagonist: Trimethaphan |
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Contraindications of Cholinomimetics?
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Asthma - bronchial secretions
Hyperthyroidism - danger of arrythmias Ulcers - excess acid production |
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Physostigmine
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Reversible
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Neostigmine
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Reversible
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Ambenonium
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Reversible
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Pyridostigmine
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Reversible
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Edrophonium
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Reversible
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Demacarium
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Reversible
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1-naphthyl N-methycarbamate
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Reversible
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Echothiophate
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Irreversible
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Isofluorophate, diisopropyl fluorphosphate
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Irreversible
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Parathion
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Irreversible
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Malathion
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Irreversible
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tetraethylpyrophosphate (TEPP)
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Irreversible
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Octamethylpyrophosphate (OMPA)
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Irreversible
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Sarin
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Irreversible
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Soman
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Irreversible
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Tabun
Reversible or Irreversible (Organophosphate Compound) AChE Inhibitor? |
Irreversible
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Edrophonium
Short, Intermediate, or Long Acting AchE Inhibitor? |
Short Acting
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Neostigmine
Short, Intermediate, or Long Acting AchE Inhibitor? |
Intermediate Acting
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Physostigmine
Short, Intermediate, or Long Acting AchE Inhibitor? |
Intermediate Acting
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Carbaryl
Short, Intermediate, or Long Acting AchE Inhibitor? |
Intermediate Acting
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Isoflurophate
Short, Intermediate, or Long Acting AchE Inhibitor? |
Long Acting/Irreversible
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Soman
Short, Intermediate, or Long Acting AchE Inhibitor? |
Long Acting/Irreversible
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Echothiophate
Short, Intermediate, or Long Acting AchE Inhibitor? |
Long Acting/Irreversible
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Parathion -> Paraoxon
Short, Intermediate, or Long Acting AchE Inhibitor? |
Long Acting/Irreversible
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Malathion -> Malaoxon
Short, Intermediate, or Long Acting AchE Inhibitor? |
Long Acting/Irreversible
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Only Cholinesterase Reactivator available in the US and what is it used for?
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Pralidoxime- 2-PAM is used for Cholinergic Crisis by reactivating AChE is organophosphate poisoning has occurred
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Inhibitors of Acetylcholine synthesis, storage, and release?
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Hemicholinium-3, Vesamicol, Botulinum toxin
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Side Effects of Botulinum toxin?
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Cardiac arrhythmia, syncope, hepatotoxicity, anaphylaxis, dyspepsia, dysphagia, muscle weakness, neck pain, eyelid ptosis, fever
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Clinical applications of Edrophonium, Neostigmine, and Physostigmine?
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- Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, and disorders resulting in muscle weakness (edrophonium).
- Urinary or gastrointestinal motility agent, glaucoma, neuromuscular junction diseases such as myasthenia gravis (neostigmine). - Reversal of anticholinergic toxicity or induced paralysis in surgery (physostigmine) |
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Serious Side Effects of Edrophonium, Neostigmine, and Physostigmine?
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Seizure, Bronchospasm, cardiac arrhythmia, bradycardia, cardiac arrest, hypotension or hypertension, salivation, lacrimation, diaphoresis, vomiting, diarrhea, miosis
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Contraindications of Edrophonium, Neostigmine, and Physostigmine?
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- Mechanical intestinal or urinary obstruction.
- Concomitant choline ester or depolarizing neuromuscular blocker use - Cardiovascular disease |
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Clinical applications of Tacrine and Rivastigmine?
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Mild to moderate Alzheimer's disease and dementia
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Serious Side Effects of Tacrine and Rivastigmine?
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Diarrhea, nausea, vomiting, cramps, anorexia, vivid dreams
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Contraindication of Tacrine and Rivastigmine?
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Treatment-associated liver function test abnormalities
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Serious Side Effects of Diisopropyl fluorophosphate?
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Respiratory paralysis, bradycardia, bronchospasm, fasciculations, muscle cramps, weakness, CNS depression, agitation, confusion, delirium, coma, bronchorrhea, salivation, lacrimation, diaphoresis, vomiting, diarrhea, miosis
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Clinical applications of Methacholine?
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Diagnosis of Asthma
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Serious and Common Adverse Effects of Methacholine?
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Dyspnea, lightheadedness, headache, pruritis, throat irritation
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Why choose methacholine over ACh?
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It is highly resistant to AChE and selective for cardiovascular muscarinic cholinergic receptors
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Contraindications of Methacholine?
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- Recent heart attack or stroke
- Aortic Aneurysm - Uncontrolled hypertension |
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Clinical applications of Bethanechol and Carbachol?
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- Glaucoma (carbachol)
- Urinary tract motility agent (bethanechol) |
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Serious and Common Adverse Effects of Bethanechol and Carbachol?
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- Sweating, shivering, nausea, dizziness, increased frequency of urination, rhinitis
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Contraindications of Bethanechol and Carbachol?
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Acute iritis or glaucoma after cataract extraction, narrow-angle glaucoma
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Which receptors do bethanechol and carbachol work at?
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Carbachol -- Nicotinic
Bethanechol -- Muscarinic |
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Clinical applications of Atropine?
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- Anticholinesterase overdose
- Acute, symptomatic bradycardia - Premedication for anesthetic procedure |
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Serious and common adverse effects of Atropine?
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- Cardiac Arrhythmia
- Coma - Respiratory depression - Raised intraocular pressure - Tachycardia, constipation, xerostomia, blurred vision. |
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Contraindication of Atropine?
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Narrow-angle Glaucoma
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Clinical applications of Pirenzepine?
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- Peptic ulcer disease
- Surgically-induced or vagally-induced bradycardia |
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Clinical applications of Oxybutynin and Darifenacin?
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- Hyperreflexic and overactive bladder
- Urge incontinence |
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Clinical applications of Succinylcholine?
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- Induction of neuromuscular blockade in surgery
- Intubation |
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What is the mechanism of Nicotinic Receptor Agonists?
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Stimulate opening of nicotinic ACh receptor channel and produce depolarization of the cell membrane. When this happens continuously the voltage-gated sodium channels become inactivated and cannot open to support further action potentials (called "depolarizing blockade")
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Clinical applications of Pancuronium, Tubocurarine, Vecuronium?
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- Induction of neuromuscular blockade in surgery
- Intubation |
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Serious and Common Side Effects of Pancuronium, Tubocurarine, Vecuronium?
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Hypertension, tachyarrhythmia, apnea, bronchospasm, respiratory failure, salivation, flushing
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Clinical applications of Trimethaphan?
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Hypertension in patients with acute aortic dissection
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Blocking Agents
What is the class, properties (Depolarizing/Competitive), time of onset, duration, and removal of Succinylcholine? |
Dicholine ester, depolarizing, Fast onset (1-1.5), Short duration (5-8), removed by ChE hydrolysis
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Blocking Agents
What is the class, properties (Depolarizing/Competitive), time of onset, duration, and removal of Tubocaurarine? |
Alkaloid, Competitive, Longer onset (4-6), Long Duration (80-120), removed by Kidney/Liver
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Blocking Agents
What is the class, properties (Depolarizing/Competitive), time of onset, duration, and removal of Atracurium? |
Benzylisoquinoline, Competitive, Medium Onset (2-4), Intermediate duration (30-60), Removed by Hoffmann degeneration, hydrolysis by ChE, Kidney
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Blocking Agents
What is the class, properties (Depolarizing/Competitive), time of onset, duration, and removal of Doxacurium? |
Benzylisoquinoline, Competitive, Longer Onset (4-6), Long duration (90-120), Removed by Kidney
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Blocking Agents
What is the class, properties (Depolarizing/Competitive), time of onset, duration, and removal of Mivacurium? |
Benzylisoquinoline, Competitive, Medium Onset (2-4), Short duration (12-18), Removed by hydrolysis by ChE
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Blocking Agents
What is the class, properties (Depolarizing/Competitive), time of onset, duration, and removal of Pancuronium? |
Ammonio Steroid, Competitive, Longer Onset (4-6), Very Long duration (120-180), Removed by Kidney
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Blocking Agents
What is the class, properties (Depolarizing/Competitive), time of onset, duration, and removal of Rocuronium? |
Ammonio Steroid, Competitive, Medium Onset (2-4), Long duration (80-100), Removed by Kidney/Liver.
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Tetrodotoxin, batrachotoxin, local anesthetics
At which site do these drugs cause a Neuromuscular blockade? |
Blocks Nerve Action Potential (AP)
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Hemicholium, botulinus toxin, procaine
At which site do these drugs cause a Neuromuscular blockade? |
Blocks Vesicular ACh release
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Curare Alkaloids, snake alpha-toxins
At which site do these drugs cause a Neuromuscular blockade? |
Blocks depolarization (EPP) and blocks permeability of Na+ and K+
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Cholineesterase inhibitors
At which site do these drugs cause a Neuromuscular blockade? |
Blocks hydrolysis of ACh by CHe
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Quinine, letrodotoxin
At which site do these drugs cause a Neuromuscular blockade? |
Blocks muscle action potential
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Metabolic poisons, lack of Ca2+, procaine, dantrofene
At which site do these drugs cause a Neuromuscular blockade? |
Blocks muscle contraction
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alpha-1
Ga12 pathway? |
Ras-GAP-1 -> Ras -> c-Raf -> MEK -> ERK
and RhoGEF -> Rho -> JNK |
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alpha-1
Ga13 pathway? |
RhoGEF -> Rho -> JNK
and PYK2 -> PI3K -> AKT/PKB -> P38 (PYK2 can also go -> Rho -> JNK) |
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alpha-1
Gaq pathway? |
PLC -> PKC ->c-Raf ->MEK ->ERK
-> PI3K -> AKT/PKB -> p38 and PYK2 -> PI3K -> AKT/PKB -> P38 |
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What blocks the B1 and B2 receptor action between the receptor and the heterotrimeric target?
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GRK
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Adrenergic Agonist: Direct-Acting, Mixed-Acting, Indirect-Acting? Response to reserpine?
Phenylephrine, Clonidine, Dobutamine Terbutaline |
Direct-Acting (Selective)
Responses are not reduced by prior treatment with reserpine |
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Adrenergic Agonist: Direct-Acting, Mixed-Acting, Indirect-Acting? Response to reserpine?
Epinephrine, Norepinephrine |
Direct-Acting (Non-selective)
Responses are not reduced by prior treatment with reserpine |
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Adrenergic Agonist: Direct-Acting, Mixed-Acting, Indirect-Acting? Response to reserpine?
Ephedrine |
Mixed-Acting
Responses are reduced by prior treatment with reserpine |
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Adrenergic Agonist: Direct-Acting, Mixed-Acting, Indirect-Acting? Response to reserpine?
Amphetamine, Tyramine |
Indirect-Acting (Releasing Agents)
Responses are abolished by prior treatment with reserpine |
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Adrenergic Agonist: Direct-Acting, Mixed-Acting, Indirect-Acting? Response to reserpine?
Cocaine |
Indirect-Acting (Uptake Inhibitor)
Responses are abolished by prior treatment with reserpine |
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Adrenergic Agonist: Direct-Acting, Mixed-Acting, Indirect-Acting? Response to reserpine?
Pargyline, entacapone |
Indirect-Acting (MAO/COMT Inhibitor)
Responses are abolished by prior treatment with reserpine |
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Isoproternol
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- Non-selective (bronchodilation)
- Lowers PVR and diastolic pressure (B2 effect) - Maintains or raises systolic pressure (B1 effect) - Increases CO |
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Dobutamine
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- Selective B1 agonist
- Used for Heart Failure - Racemic mixture -> (-) isomer a1 and weak b1 - (+) isomer a1 antagonist and potent B1 agonis |
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Metaproterenol
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- Selective B2 agonist
- Treatment of asthma - Inhaled delivery |
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Phenylephrine and tetrahydrazoline are used for?
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Topical a1-selective agonists used for local vasocontraction (eye/nose)h
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Propranolol, Nadolol, Timolol
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Non-selective B-Adrenergic Antagonists
Propanolol (Short half-life) Nadolol (Long half-life) Timolol (Lipophilic, high CNS penetration) |
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Labetalol, Carvedilol
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Non-selective B and a1 Antagonists
Labetalol (Also partial agonist at B2-receptors) Carvedilol (Intermediate half-life) |
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Pindolol, Acebutolol
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B-Adrenergic Partial Agonists
Pindolol (B-nonselective) Acebutolol (B1-selective) |
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Esmolol, Metoprolol, Atenolol, Celiprolol
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B1-Selective Adrenergic Antagonists
Esmolol (Short half-life) Metoprolol (Intermediate half-life) Atenolol (Intermediate half-life) Celiprolol (Also agonist at B2-receptors) |
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a-Methyltyrosine
Clinical application? Serious and common Adverse Effects? |
Inhibitor of catecholamine synthesis
Used for pheochromocytoma-associated hypertension. - Side effects: Orthostatic hypotension and sedation |
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Reserpine
Clinical application? Serious and common Adverse Effects? Contraindications? |
Inhibitor of catecholamine storage
- Used for hypertension. - Side Effects: Cardiac arrhythmia, GI hemorrage, thrombocytopenia, psychotic depressions - Contraindicated in active GI disease, depression, renal failure, electroshock therapy |
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Amphetamine, Methylphenidate
Clinical application? Serious and common Adverse Effects? Contraindications? |
Inhibitor of catecholamine storage
- Used for ADHD, Narcolepsy (Amphetamine only) - Side Effects: Hypertension, tachyarrhythmia, Gilles de la Tourette's syndrome, seizure, psychotic disorder Contraindicated with MAOI |
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Pseudoephedrine
Clinical application? Serious and common Adverse Effects? Contraindications? |
Inhibitor of catecholamine storage
- Used for allergic rhinitis and nasal congestion - Side Effects:Atrial fibrillation, myocardial ischemia, hypertension, tachyarrhythmia - Contraindicated with MAOI |
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Cocaine, Methoxamine, Phenylephrine, Oxymetazoline, tetrahydrazoline are inhibitors of what?
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Inhibitors of Catecholamine Reuptake
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Clonidine, Guanabenz, guanfacine, methyldopa
Clinical application? Serious and common Adverse Effects? Contraindications? |
a2-adrenergic agonists
- Used for hypertension, opioid withdrawal + cancer pain (clonidine only) - Side effects: Bradycardia, heart failure, hepatotoxicity, hypotension, constipation - Contraindicated - MAOI therapy |
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Prazosin, Terazosin, Doxazosin, Tamsulosin
Clinical application? Serious and common Adverse Effects? Contraindications? |
a-Adrenergic antagonists
Use: Benign prostatic hyperplasia, hypertension Side Effects: Pancreatitis, hepatotoxicity, systemic lupus erythematosus, hypotension. |
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B-adrenergic antagonists
Clinical application? Serious and common Adverse Effects? Contraindications? |
- Used for hypertension, angina, heart failure, glaucoma
- Side Effects: bronchospasm, atrioventricular block, bradyarrhythmia - Contraindicated: Bronchial Asthma or COPD |
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Poiseuille's Law
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- Flow is directly proportional to the change in pressure.
- Flow is proportional to the radius^4 - Flow is inversely proportional to viscosity and length Resistance = change in P / Q (Flow) R=8nl/pi * r^4 |
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What does hematocrit doas vessel size decreases?
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Hematocrit falls
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Qr (capillary blood flow)
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is determined by the ratio of Pa and R.
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Smooth Muscle Response pathway for contraction?
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Ca2+ -> Ca2+-CaM -> activates MLCK -> phosphorylates Myosin-LC to Myosin-LCP -> Actin-myosin crossbridges -> contraction
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Smooth Muscle Response pathway for relaxation?
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NO -> activates Guanylyl cyclase -> Activates GTP to cGMP -> activates Myosin-LC phosphotase -> dephosphorylates Myosin-LCP to Myosin-LC -> Relaxation
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What are substrates in the NO synthesis Reaction?
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Arginine NADPH, O2
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What turns on NOS?
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Neurohumoral (ACh, histamine, bradykinin, serotonin), Physical (Shear stress), Metabolic (ATP)
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What receptors does Endothelin work through?
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ETa and ETb -- G-protein coupled
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What control predominates in vital organs?
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Local
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Where do nitrates work?
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- Increase Myocardial O2 supply by dilating large epicardial arteries
- Decrease Afterload and myocardial O2 demand - Highly decreased preload |
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PDE5 Inhibitors
Examples? What is use? |
Sildenafil, Varenafil, Tadalafil
For ED, Pulmonary Hypertension at high dose, prolonging the effects of NO |
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Dihydropyridines, benzothiazepines, phenylkylamine
What are they used for? |
Calcium Channel Blockers
Used for hypertension and Reynaud's phenomenon - Negative chronotropic effect on HR - Don't get venodilation or reduce preload |
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Potassium Channel Openers
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Minoxidil
- Used in severe or refractory hypertension (Alopecia) - Arteriolar dilation >> venous dilationwhich leads to reflex tachycardia and fluid retention. |
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Bosentan
What is it? |
Endothelin Receptor Antagonist
- Blocks both ETa and ETb - Used for Severe Pulmonary Hypertension |
