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192 Cards in this Set
- Front
- Back
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Pharmacology
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Study of substances that interact with living systems through chemical processes
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Medical pharmacology
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study of substances used to prevent, diagnose, treat disease
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Toxicology
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branch of pharmacology which deals with undesirable effects of chemicals on living systems
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Pharmacogenomics
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relation of individual's genetic make-up to his/her response to specific drugs
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Drug
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substance that brings about a change in biological function through its chemical actions on a receptor
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hormone
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drug synthesized in the body
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poison
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drug that has almost exclusively harmful effect
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xenobiotic
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drug not synthesized in the body
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toxin
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poison of biological origin
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Optimal drug size
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0.1 - 1 kDa
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Atropine
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Anti-cholinergic
Classical parasympathetic-effector junction antagonist |
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Curare
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NMJ antagonist
Non-depolarizing muscle relaxer at nicotinic muscle Ach receptor |
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Hexamethonium
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Ach ganglion blocker
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Mecamylamine
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Ganglionic blocker
Anti-hypertensive, block sympathetic drive to blood vessels Orally given |
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trimethophan
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Ganglionic blocker
Anti-hypertensive, block sympathetic drive to blood vessels IV |
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Ganglionic blocker side effects
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Sympathetic block: orthostatic hypertension, dry skin, exercise intolerance
Parasympathetic block: heart palpitations, blurred vision, photophobia, constipation, urinary retension, dry mouth |
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Diphenhydramine
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Anti-cholinergic
Anti-nausea due to vestibular function Sedation Antihistamine |
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Scopolamine
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Anti-cholinergic
Anti-nausea due to vestibular function Sedation |
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Imipramine
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Anti-cholinergic + Adrenergic
Muscarinic antagonist and Norepinephrine/serotonin/dopamine reuptake inhibitor Anti-depressant |
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Olanzapine
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Anti-cholinergic
Atypical anti-psychotic |
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Phenthiazines
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Anti-cholinergic
Tranquilizer |
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Physostigmine
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AchE inhibitor
Will cross into brain (tertiary amine) Used for atropine poisoning |
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Atropine poisoning
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• Expected peripheral signs, tachycardia, urinary retention, constipation, blurred vision, dry mouth, blocked sweating
Glaucoma • Central and peripheral component, hyperthermia (especially in children) • CNS effects, ataxia, hallucinations, circulatory collapse, death • Antidote is cholinesterase inhibitor, raise Ach levels; want one that will get into brain, use physostigmine; first do supportive therapy, cooling down, etc., then use antidote if necessary |
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Ipratropium
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Anti-cholinergic
Inhalational, used for bronchiodilation, decreased secretion Quantenary amine |
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Tolteridine
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Anti-cholinergic
Treatment of incontinence, urinary emergency |
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Insecticides and war gases are often...
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AchE inhibitors
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Neostigmine
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AchE Inhibitor
Quantenary amine, won't cross blood-brain barrier Used as a co-treatment for myasthenia gravis (treatment with AchE inhibitor causes systemic effect, treat with anti-muscarinic to limit side effects in non-NMJ synapses) |
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Bethanecol
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Muscarinic agonist
Used to treat dry mouth, Sjogren's, open angle glaucoma (opens canal)used post surgically to stimulate GI tract and bladder |
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Adrenergic alpha response
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Vasoconstriction in skin, mucous membranes, renal
Contraction of radial muscle of eye (pupil dilation) Piloerction Gut relaxation |
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Adrenergic beta-1 response
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Cardiac stimulation, renin release
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Adrenergic beta-2 response
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Vasodilation (skeletal muscle, heart), bronchiodilaton, uterine relaxation, gut relaxation
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Phentolamine
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Adrenergic a antagonist
Used as antihypertensive historically, less vasoconstriction, but barorecptor kicks in and because of a2 antagonism further NE release at heart is not stopped, get big increase in HR |
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Isoproterenol
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Adrenergic b agonist
Non-selective Historically given in cardiac insufficiency, also causes blood vessel dilation; bronchioconstriction, but also causes heart effects |
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Propranolol
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Adrenergic b antagonist
Non-selective Treat arrhythmias, but causes bronchiocontstriction |
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Dobutamine
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Adrenergic b1 AND a agonist
Treat cardiac insufficiency (heart rate + vasoconstriction) |
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Terbutaline
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Adrenergic b2 agonist
Used for bronchodilation |
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Metoprolol
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Adrenergic b1 antagonist
Treat arrhythmias |
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Atenol
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Adrenergic b1 antagonist
Treat arrhythmias |
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Epinephrine
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Adrenergic on alpha and beta receptors
Used to treat anaphylaxis |
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Norepinephrine
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Adrenergic on a1, a2 and b1 receptors
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Phenylephrine
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Adrenergic a1 agonist
Used as decongestant AKA neosynephrine |
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Methoxamine
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Adrenergic a1 agonist
Used to treat tachyarrhythmias; constrict blood vessels, raise BP, activate baroreceptor reflex |
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Clonidine
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Adrenergic a2 agonist
Anti-hypertensive, acts in CNS |
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Prazocin
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Adrenergic a1 antagonist
Antihypertensive, get baroreceptor reflex and subsequent inhibition by a2 receptors at heart |
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Alphamethyl-NE
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Adrenergic a2 agonist
Anti-hypertensive, acts in CNS |
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Yohimbine
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Adrenergic a2 antagonist
No clinical utility |
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Tamsulosin
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Adrenergic a1 antagonist
Inhibits bladder neck muscle tone, ease urine outflow (Flowmax) |
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Ritodrin
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Adrenergic B2 agonist
Delay parturition |
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Uses of B antagonists
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Cardiac arrhythmias
Cardiac protection after MI Hypertension Angina pectoris Migrane Panic attack/stage fright/tremors Glaucoma Congestive heart failure |
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Timolol
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Adrenergic B antagonist (non-selective)
Treat glaucoma |
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B blocker side effects
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1. Precipitate CHF
2. Bronchospasm 3. Bradyarrythmia 4. Aggravation of peripheral vascular disease 5. Withdrawal/hypersympathetic syndrome due to increased B receptors on cell surfaces, more common in drugs with short half-life |
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Adrenergic biosynthesis inhibitors
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1. Tyr-hyrdoxylase inhibitors(not used clinically)
2. Dopa decarboxylase inhibitors (co-adminstered with L-dopa in Parkinson's to control peripheral side effects) |
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Tyramine/phenethylamine
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Displaces NE and dopamine from vesicles, indirect sympathomimetic
Certain foods are high tyramine (pickled fish, beer, wine, cheese) |
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Ephedrine
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Mixed acting sympathomimetic
Decongestant by displacement of NE at blood vessels, also direct B2 stimulation of bronchodilation |
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Reserpine
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Irreversibly inhibits NE vesicular transporter, results in degradation of NE and reduction of NE signalling
First major tranquilizer Also acts at dompanine, serotonin terminals, causes depression |
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Biogenic amine uptake inhibitors
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Selective serotonin reuptake inhibtors, tricyclic antidepressants more selective for NE and serotonin, cocaine more selective for dopamine
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a-CH3-dopa
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Converted to a-CH3-NE, a selective a2 agoinst with activity similar to clonodine
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COMT inhibitors
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Block biogenic amine metabolism, increase
L-dopa half-life in Parkinson's treatment |
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MOA inhibitors
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MAO-A primarily affects NE, 5-HT, and to a lesser extent dopamine; complication of hypertensive crises if on tyramine rich diet; used for depression
MAO-B more selective for dopamine in brain, used for Parkinson's |
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Cell wall synthesis inhibitors
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Usually cidal since cell wall constantly remodeled
Examples: cycloserine, bacitracin, vancomycin, B-lactams, cephalosporin Clavulanic acid mimics B-lactam, used to inhibit B-lactamases |
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Antibiotics targeting 70S ribosome
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Mostly static
30S small subunit: Aminogylcides, tetracyclines, spectinomycin 50S large subunit: Chloramphenicol, macrolides, clindomycin/lincosamide, spectrogramins 70S ribosome: linezolid/oxalazidonones |
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Aminoglycosides
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Inhibits 30S ribosomal subunit
Bacteriocidal Broad spectrum, especially gram - aerobic Stall ribosome, misreading of RNA, lower fidelity Oto- and nephrotoxic Not orally bioavailable Resistance through drug modification Examples: streptomycin, gentamycin; used in TB |
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Tetracyclines
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Broad spectrum, orally active
Bacteriostatic Targets small ribosomal subunit Block entry of tRNA Deposit in bone, can chelate Ca Photosensitivity |
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Spectinomycin
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Targets small ribosomal subunit
Narrow spectrum, gram - Mechanism unclear Similar to aminoglycosides but does not cause misreading |
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Chloramphenicol
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Targets large ribosomal subunit
Blocks transpeptidase Bacteriostatic Orally active, broad spectrum Causes bone marrow suppression, second line drug Resistance through drug modification, decreased uptake, ribosomal protection |
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Macrolides
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Target large ribosomal subunit
Intereferes with translocations Broad spectrum, especially gram + Typically bacteriostatic Resistance in form of efflux pump ribosomal modification, drug modification Oral and IV Example: erythromycin |
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Lincosamides
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Inhibits large ribosomal subunit, similar to macrolides, but not substrate for efflux pump
Oral and IV Example: clindomycin |
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Oxalazidonones
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Targets 70S ribosome
Inhibits translocation of fMet Used in vancomycin resistant cases Oral or IV Example: linezolid |
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Type II toposiomerase inhibitors
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Targert topo IV and DNA gyrase
Antibacterials Quinolone: blocks ATPase Ciprolfloxin: wide spectrum, UTIs, lot of resistance in Gram +, Staph |
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Type I topoisomerase inhibitors
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Target topo I
Cancer therapy Campothecin: creates irreversible topo-DNA complex |
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Anti-metabolite drugs
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Bacteria require folate for 1-carbon transfers; drugs are competitive inhibitors (mimic PABA) or activated by enzyme
In chemotherapy, used to starve cells of nucleotides Exambles: PABA mimics, sulfonamides, methotrexate, trimethoprim, pyrimethamine; 6-thiopurines, 5-FU, Ara-C, 2-deoxycoformycin |
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Drug resistance mechanisms
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· Chemical inactivation of drug (B-lactamases, acetyltransferases)
· Failure to activate drug · Alteration of drug targets (tetracyclines, fluoroquinolones, penicillin [PBPs]) · Slower uptake/faster efflux, aminoglycosides taken up by active transport; decreased respiration and ATP decrease uptake · Antibiotic resistance occurs due to fast growth rate, selective pressure in hosptials · Vertical or horizontal; can pass multiple resistances at once through cassette; conjugation, transduction, transformation |
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Plasma membrane targeters
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Amphotericin, azoles in fungi
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Microtubule poisons
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Vinca alkaloids (vinblastine, vincristine) in cancer prevent spindle polymerization
Taxanes (paclitaxel, taxol) inhibit spindle depolymerization/remodeling in cancer Benzimidazoles in helminths |
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Muscle fiber targeters
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Avermectins and pyrantel in helminths
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HIV inhibitors
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Fusion/Uncoating: enturivite
RT: nucleoside analogs, closer they match nucleotides, more toxic; target any enzyme using nucleotides Protease: peptide-like bonds at active site |
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Flu virus inhibitors
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M2 proton pump inhibtors: prevent uncoating, amantadine, ramantadine
Release inhibitors: zanamavir, oseltavir sialic acid mimics |
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Cancer drug characteristics
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Target rapidly growing cells
Low therapeutic index Resistance common Combine therapies to reduce dose of any given drug and associated toxicities |
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DNA alkylating agents
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Interfere with replication and transcription, induce breaks and cross-linking
Used in cancer therapy, anti-inflammatory |
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Monoclonal Ab in cancer therapy
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Cetumaxib (EGFR)
Bevacuzimab (VEGF) Gemtuzamab (CD33 conjugated to antibiotic inducing DNA fragmentation) |
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Glucocorticoids usage
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Suppress lymphocyte proliferation
Block COX2 production Inhibit arachadonic acid metabolism Sequester lymphocytes in lymph nodes and prevent neutrophils from leaving blood |
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GnRH agonists
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Used in cancer therapy for androgen suppression
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Anti-estrogen drugs
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Used in ER-responsive cancers
Selective ER Modulators: tamoxifen, competitive antagonist Selective ER Downregulators: fulvestrant prevents dimerization Aromatase inhibitors: Type I steroidal, irreversible; Type II reversible, binds to heme group |
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Components of anesthesia
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• Immobility in response to noxious stimuli
• Analgesia • Amnesia • Sedation • Attenuation of autonomic reflexes |
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Volatile inhalational anesthetics working at GABA channels
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Halogenated anesthetics (eg isoflurane, enflurane, halothane)
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Volatile inhalational anesthetics working at NMDA channels
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N2O, Xe
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MAC (minimum alveolar concentration)
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Concentration of anesthetic at 1 atm that produces immobilization in response to a noxious stimulation in 50% of subjects
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Volatile anesthetic pharmacokinetics
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Distributes into compartments so that partial pressures (not concentrations) are equal; concentration depends on tissue solubility
Alveolar partial pressure influenced by ventilation, inspired drug [], FRC Uptake by blood depends on cardiac output, blood:gas solubility coefficient, and alveolar:blood gradient Induction influenced by ventilation, cardiac output[drug] |
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Side effects of halogenated volatile anesthetics
Cardiovascular |
Blood pressure depression
Negative inotropy Vasodilation Brady or tachycardia (halothane) Lower baroreceptor reflex Cerebral vasodilation Increased pCO2 Depressed renal and hepatic blood flow Ventricular arrhythmia |
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Non-cardiac side effects of halogenated volatile anesthetics
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Uterine relaxation
Bronchodilation Hepatitis (immune reaction) Renal failure (due to Fl-) |
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N2O Side effects
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Bone marrow depression
Some cerebral vasodilation |
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GABAergic parenteral anesthetics
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Barbiturates
Etomidate Propofol Benzodiazapene |
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NMDA-blocking parenteral anesthetics
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Ketamine
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Ketamine
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NMDA-blocking parenteral anesthetic
• Acts at PCP site • Causes catatonia (but responsive), amnesia, good analgesic • Short acting • Used in shock patients and children undergoing painful procedures • No muscle relaxation, minimal respiratory effects • Increases heart rate, blood pressure through CNS sympathetic action • Increases cerebral blood flow • Can cause hallucinations |
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Barbiturates
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GABAergic parenteral anesthetics
• Cardiac, CNS, and respiratory depressants • Decrease cerebral blood flow and metabolism, can shrink brain • Thiopental, thioamylal • IV induction agent • Rapid distribution to fat and muscle terminates CNS action, slow metabolism in liver • Can induce porphoric crises in susceptible patients |
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Etomidate
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GABAergic parenteral anesthetic
• Minimal cardiovascular, respiratory effects • Decreases cerebral blood flow • Short acting, rapid recovery, terminated by redistribution • IV induction agent • Poor analgesic, mostly sedative • Causes adrenalcortical suppression, mimics adrenocorticoids • Use limited by pain on injection and involuntary muscle movements |
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Propofol
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GABAergic parenteral anesthetic
• Euphoria upon awakening • Antiemetic • Cardiovascular and respiratory depression • Highly lipophilic, very potent • IV induction and maintenance drug • CNS actions terminated by rapid distribution, rapid metabolism, short acting • Pain on injection |
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Benzodiazapene tranquilizers
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• Diazapam and lorazepam are pre-operative sedatives and anixolytics
• Midazolam is water soluble, used as short acting IV anesthetic • Good for antegrade amnesia • Partial agonist of GABA-R |
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Stages of anesthesia
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I. Amnesia and analgesia, beginning of anesthesia to loss of consciousness
II. Delirium, loss of consciousness to regular pattern of breathing, loss of lid reflex; agitation, often see this when they wake up III. Surgical anesthesia, regular pattern of breathing to loss of respiration IV. Overdose, cessation of respiration to failure of circulation |
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Anesthetics used for someone in shock
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Want to maintain perfusion
Use: Ketamine, narcotics, etomidate, muscle relaxants Avoid: Halogenated anesthetics, barbiturates, N2O |
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Anesthetics used in neurosurgery
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Want to avoid intracranial pressure increase
Use: Barbiturates, N2O, narcotics, muscle relaxants Avoid: Halogenated anesthetics, ketamine |
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Narcotic anesthetic properties
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• Pre and intraoperative analgesics
• At high doses, can be used as complete anesthetics • Can have intraoperative awareness and chest wall rigidity • Used with short acting barbituates and N2O for balanced anesthesia • Lowers requirements for volatile anesthetics • Minimal effects on blood pressure • Morphine causes histamine release • Respiratory depression • Does not block autonomic reflexes |
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Anesthetics used for thoracic surgery
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Want to maintain oxygenation
Use: Halogenated anesthetics with 100% O2 Avoid: N2O |
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Anesthetics used for someone with liver disease
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Want to avoid drugs with extensive liver metabolism (ketamine, narcotics, barbiturates)
Use drugs excreted by lungs, eg halogenated volatile anesthetics |
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Succinylcholine
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Depolarizing muscle relaxant
Degraded by plasma butylcholinesterase, responsible for prolongation of neuromuscular junction desensitization |
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Uses of succinylcholine
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Endotracheal intubation, short surgeries
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Side effects of succinylcholine
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Muscle pain
Bradycardia Masseter muscle spasm Malignant hyperthermia Pediatric cardiac arrest Hyperkalemia (especially in recent denervation injuries) Increased intracranial, intraocular, gastric pressure |
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3 types of non-depolarizing muscle relaxants
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Curare-like alkaloids
Benzylisoquinoliniums Ammonio-steroids |
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Properties of non-depolarizing muscle relaxers
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Competitively inhibit Ach
Most elimination is not renal or hepatic (some exceptions) Most do not have CNS effects (some exceptions) Some can act as antagonists or partial agonists at other Ach receptors Used in endotracheal intubations, muscle relaxation in surgery, to lower O2 demands, and in electroconvulsive therapy Given IV Choice of drug largely depends on pharmacokinetics |
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Types of AchE inhibitors
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Carbamyl drugs
Organophosphate |
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Carbamyl drugs
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AchE inhibitors
Bind to active site, have slow hydrolysis/off rates Examples: Neostigmine, physostigmine |
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Side effects of AchE inhibitors
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Increased parasympathetic activity
In a system under high sympathetic tone, potentially tachycardia Can cause seizures if cross blood-brain barrier Can ultimately result in depolarizing block |
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Organophosphate characteristics
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AchE inhibitors
Bind to active side with neglible hydrolysis Most absorbed through all routes, used as insecticides and war gases Pralixidome can catalyse reverse reaction, harder for "aged" complex |
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Uses of AchE inhibitors
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Reverse non-depolarizing muscle relaxants; atropine given simultaneously to prevent bradycardia
Urinary atonia, paralytic ileus Reduce intraocular pressure Accomodative amblyopia Physostigmine for mite, louse infection of lashes Diagnostic and therapeutic for myasthenia gravis Alzheimer's (physostigmine) Insecticides, nerve gas |
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Factors affecting local anesthetic effect on a nerve
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Small more sensitive than large
Rapid firing more sensitive than low frequency Ad and C (pain, temperature) fiber most sensitive, then B (sympathetic preganglionic), then Aa, b, g (motor, pressure) Fibers on outside more than fibers on the inside All else equal, myelinated more sensitive than non |
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Mechanism of local anesthetic action
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Block generation and propagation of action potential, decrease rate and rise of action potential by inhibiting voltage-gated Na channels
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Two classes of local anesthetics
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Aminoamindes
Aminoesters |
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Aminoesters
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Local anesthetics
Metabolized by plasma cholinesterase Benzocaine, Procaine, Cocaine, Chloroprocaine, Tetracaine Benzocaine and procaine produce PABA, competitively compete with sulfonamide antibiotics Nearly all true allergies are to PABA |
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Aminoamides
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Metabolized by liver
Lidocaine, prilocaine, bupivacaine, mepivacaine, etidocaine Rare allergies to PABA-like preservative Prilocaine can oxidize hemoglobin to methemoglobin, get hypoxia Bupivacaine and etidocaine more cardiotoxic |
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Local anesthetic side effects
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CNS: low dose, circumoral numbness, tinnitus, light headache, twtiches, drowsiness; high does, loss of consciousness, seizures, respiratory depression
Cardiac: prolonged PR, long QRS, decreased automaticity and contractility producing bradycardia and hypotension; eventually get V-tach, V-fib, asystole |
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Intralipid
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Lipid emulsion used to treat severe local anesthetic side effects
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EMLA
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Eutetic Mixture of Local Anesthetics
Local topical anesthetic cream containing lidocaine and prilocaine |
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Uses of local anesthetics
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Topical
Subcutaneously IV Regional/Bier block (exsanguinate limb, cuff, IV anesthetic) Nerve block Neuraxial block General anesthesia Arrhythmia |
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Adjuvants for local anesthetics
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Epinehprhine: Vasoconstrict to reduce washout of anesthetic, identify inadvertent arterial penetration (indicated by tachycardia)
Sodium bicarbonate: aid in rapid diffusion of drugs, reduce injection pain |
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Factors affecting local anesthetic potency, onset, and duration of action
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Potency: drug lipophilicity
Onset: lipophilicity and pKa (low pKa better) Duration: lipophilicity, protein binding, washout |
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Methotrexate
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Inhibits dihydrofolate reductase, purine starvation
Used as antibacterial, anticancer, anti-inflammatory drug Relatively non-specific Increased risk of infection |
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Azothioprine
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Inhibits purine biosynthesis
Used to treat inflammation, cancer Relatively non-specific Increased risk of infection |
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Cyclophosphamide
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Bifunctional alkylator, induces DNA breaks
Used to treat inflammation, cancer Relatively non-specific Increased risk of infection |
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Mycophenylate
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Inhibits GMP production, which is required for production of inducible NO synthase
Used to treat inflammation Relatively non-specific Increased risk of infection |
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Leflunoamide
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Inhibits pyrimidine synthesis
Used to treat inflammation; relatively specific for T and B cells Toxicity primarily diarrhea |
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Cyclosporine
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Anti-inflammatory
Binds to calciphillin, blocks phosphotase activity of calcineurin, preventing nuclear translocation/promotes nuclear export of NFAT Relatively lymphocyte specific |
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FK506
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Anti-inflammatory
Binds to FK506 binding protein, blocks calcineurin's phosphotase activity, inhibiting nuclear translocation of NFAT Relatively lymphocyte specific |
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Rapamycin
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Anti-inflammatory drug, relatively specific for lymphocytes
Binds to FK506 binding protein, blocks proliferative signals from IL-2 receptor through binding/inhibition of mTOR, some G1-S selectivity |
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Infliximab, adalamab
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Ant-inflammatory drugs
TNF antibodies Used to treat rheumatoid arthritis, Crohn's disease Resistance due to host antibody production; given with methotrexate to suppress host immune system Can exacerbate multiple sclerosis |
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Entanercept
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Anti-inflammatory drug
TNF receptor fused with IgG Used to treat rheumatoid arthritis, Crohn's disease Resistance due to host antibody production; given with methotrexate to suppress host immune system Can exacerbate multiple sclerosis |
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Natalizumab
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Anti-inflammatory drug
Anti-VLA-4 antibody (integrin important for neutrophil extravasation) Used in MS and Crohn's disease |
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Glucocorticoid toxicities
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Mineralocorticoid mimickry (secretion of K, absorption of Na, can lead to hypokalemic acidosis)
Increased bone reabsorption and pediatric runting Cushing's-like syndrome with rounded face and muscle catabolism Increased peptic ulcers General sense of well-being, can mask problems Long treatment, get ATCH suppression and adrenalcortical atrophy Withdrawl must be slow,get adrenal cortical insufficiency, inability to maintain blood Na and glucose levels |
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Dexamethosome
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Longest lasting and most potent glucocorticoid with the fewest mineralcorticoid effects
Expensive Patients must be slowly weaned off |
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Characteristics of salicylates/aspirin
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Irreversibly inhibit COX through acetylation
Inhibits prostaglandin synthesis Anti-pyretic (prostaglandin synthesis and IL-1 inhibition) Analgesic Acetylation can produce a hapten for immune reaction Anti-thrombotic Erosion of gastric mucosa, GFR affected, clotting time increased, reversible tinnitus, vertigo, hyperpnea, respiratory alkalosis Can exacerbate asthma by pushing arachadonic acid metabolism down leukotriene pathway |
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Ibuprofen and naproxen characteristics
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Propionic acid derivatives
Similar analgesic, anti-inflammatory actions as aspirin Less GI irritation, less effect on clotting time than aspirin Naproxen long-lasting |
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Acetaminophen
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Weak effect on COX, not anti-inflammatory
Powerful analgesic and antipyretic Unlike aspirin, not involved in Reye's syndrome (encephalopathy, liver toxicity) Reduced prostaglandin production in brain; hyrdrolyzed to p-aminophenol and acetate, p-aminophenol conjugated to fatty acids, high in areas of the brain involved in analgesia and temperature regulation through endocannabinoids and TRPV1 |
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SHORTE: treatment of patient with unknown poisoning
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• S, substrate response, give biological substrates required for life (DONT)
• H, history, admits and medications • O, observations at scene • R, rule out non-toxic cause, use imaging • T, toxidrome, signs/symptoms indicative of a particular type of poisoning • E, ECG |
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DONT: treatment of patient with unknown poisoning and altered mental status
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Dextrose, O2, Naloxone, Thiamine (treat insulin overdose, CO2/hypoxia, opioid overdose, Werneke/Korsakoff)
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ECG abnormalities seen in toxicity
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Bradycardia: B-blockers, Ca channel blockers, digoxin
Tachycardia: TCAs, sympathomimetics, cocaine, theophylline, anticholinergics Wide QRS: TCAs, propafenone, flecainide, encainide, quinidine, procainamide, disopyrimide (Na channel blockers) A-V block (long P-Q): Digoxin, B-blockers, Ca channel blockers R' in aVR: TCAs |
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4 As in toxicology
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Tests to get when patient present with undefined poisoning
Acetaminophen Arterial blood gas (if abnormal respiration) Alcohol Anion gap 5th A: Aspirin |
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Antidote for acetominophen overdose
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N-acetylcysteine (glutathione substitute)
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Anion gap formula
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[Na] - ([Cl] + [HCO3])
Normal 8-12, high suggests metabolic acidosis, alcohol poisoning |
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Toxicology treatment options
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Activated charcoal within 1 hour (can be more for selected drugs with extensive enterohepatic recirculation)
Antidote Induce diarrhea to flush out bezoar (whole bowel irrigation, cathartic) Forced diuresis Alkaline diruesis for ion trapping Hemodialysis Gastric lavage rare, no better than charcoal |
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Magnificent 7 effects of tricyclic antidepressants
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Anticholinergic
Serotonin and norepinephrine reuptake inhibitors Alpha antagonists Qunidine-like sodium channel blockade (wide PRS, prologned QT causes increased amplitude on ECG) Inward K rectifier blockade GABA-A antagonist Histamine blockade |
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Fomepizole
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Alcohol dehydrogenase inhibitor
Used to treat methanol and ethylene glycol poisoning above 20 mg/dL Used with dialysis if above 50 mg/dl |
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Opiate antidote
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Naloxone
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Anticholinergic drugs antidote
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Physostigmine
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Organophosphate antidote
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Atropine, pralidoxime
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Methanol, ethylene glycol antidote
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Ethanol, fomepizole for both
MeOH: folic or folinic acid Ethylene glycol: Thiamine + Mg; pyridoxine |
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Nitrate/nitrite antidote
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Methylene blue
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Cyanide antidote
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Nitrates + sodium thiosulfate or hydroxycobalamin
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Digoxin antidote
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Digibind antibody
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B-blocker antidote
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Glucagon
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Ca channel blocker antidote
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Calcium, glucagon; in severe cases, insulin
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Iron antidote
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Deferoxamine
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Heavy metal antidote
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Chelator (EDTA, DMSA, BAL, d-penicillamine)
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Heparin antidote
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Protamine
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Coumadin, brodifacoum antidote
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Vitamin K1 (phytonadione)
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Isoniazid antidote
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Vitamine B1 (pyridoxine)
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Toxidrome:
Slow, shallow respiration Track marks Pinpoint (miotic) pupils |
Opioid
Use of ice packs also common Naloxone competitive inhibitor antidote, high doses may be required for propoyphene |
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Toxidrome:
Tachycardia Dilated pupils (mydriasis) Diarrhea Abdominal cramps Piloerection Yawning Itching |
Opioid withdrawl
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Toxidrome:
Vomiting Diarrhea Urinary incontinence Bronchorrhea/rhonci/bronchospasm Drooling |
Cholinergic toxidrome
Symptoms include SLUDGE, DUMBELS pneumonics Treat with atropine, pralidoxime, diazepan |
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Toxidrome
Fever Tachycardia Warm, dry, flushed skin Dry mouth Decreased visual acuity Agitated delerium |
Anticholinergic toxidrome
Treat with physostigmine |
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Toxidrome:
Hypertension Tachycardia Agitated delerium Hyperthermia Dilated pupils |
Sympathomimetic toxidrome:
Treat with benzadiazopines, avoid B blockers, if give them give with mixed a and B blocker to avoid unopposed alpha activity which would make hypertension worse |
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Toxidrome:
Lethargy or coma Respiratory depression Hypotension Bullae Pupillary variation Decreased temperature |
Sedative/hypnotic syndrome
Seen with barbiturates, phenobarbital |
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Toxidrome:
Weight loss drugs use Altered mental status Tachycardia Hyperthemia High respiratory rate Tinnitus Metabolic acidosis Low CSF glucose |
Salicylate toxidrome
Weight loss drugs contain aspirin to poison mitochondria Metabolic acidosis secondary to respiratory alkylosis |
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Toxidrome:
History of psychiatric illness Hypotension Tachycardia Altered mental status Wide QRS, prolonged QT Positive R' in aVR Seizure |
Tricyclic antidepressant poisoning
R' in aVR because get bigger right conduction delay than left Treatment: alkaline pH to increase protein binding, hypertonic Na to overcome Na blockade; Terminate seizure with benzodiazapene, propofol, or barbiturate |
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Toxidrome:
Recent history of depression, OTC cough medicine Anxiety/mild agitation Fever/tachycardia Tremor, hyperreflexia, motor restlessness, hypertonicity |
Serotonin syndrome
CAN: cognition, autonomic, neuromuscular, at least 1 finding in each category, along with exposure to 5-HT drug, can be used to diagnose Common agents include MAOIs, SSRIs, Serotonin/norepinephrine reuptake inhibitors, sympathomimetics, others (St. John's wort, Li, cough suppressant) |
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Toxidrome:
Positive PPD Seizures with poor response to diazepam |
Isoniazad
Treat with Vitamine B6 (pyridoxine) |
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Major reasons drugs fail in clinical trials
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Commercial reasons
Efficacy Toxicity Pharmacokinetics no longer major reason for failure |
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Dose-limited toxicity
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Toxicity considered unacceptable due to severity or duration
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Maximum tolerated dose
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US: 1 level below dose-limited toxicity
Europe, Japan: Dose at which 33% of patients experience DLT |
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Phase where most drugs fail
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Phase II
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Major cause of failure for Phase III trials
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Underpowered studies (false negative, type II error, B error)
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Spectrogramin
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Antibacterial targeting 50S ribosomal subunit
Dalfopristin + quinupristin Synergistic combination Resistance due to ribosomal methylation |
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Drugs where multi-dose activated charcoal is indicated
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Theophylline
Carbamazepine Phenobarbitol Quinine Dapsone Salicylate (for bezoar formation) |
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Carbidopa
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Dopa-decarboxylase inhibitor
Increases half-life of L-dopa |
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Butoxamine
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Adrenergic B2-selective antagonist
No clinical use |
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Important P450 Inducers
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Phenobarbitol
Rifampin Anti-epileptic drugs St. John's Wort |
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Mitodrine
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Adrenergic a1 agonist
Used to treat orthostatic hypotension |
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Oxymetazoline
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Adrenergic a1 agonist
Used to constrict eye vessels to decrease redness (Visine) |
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Phenelzine
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MAO-A inhibitor
Used to treat depression |
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Pilocarpine
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Muscarinic agonist
Used to treat glaucoma |
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Tolcapone
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COMT inhibitor
Used in Parkinson's along with L-dopa/carbidopa |
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Tranylcypromine
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MAO inhibitor
Used to treat depression |
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Anion Gap Formula
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Na - (Cl + HCO3)
Normal 8-12 |
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Osmol Gap
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Calculate Osmol: 2Na + BUN/2.8 + Gluc/18 + EtOH/4.6
Measured Osmolality - Calculated Osmolarity Normal 5-10 |
