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173 Cards in this Set
- Front
- Back
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Botulinium toxin
-MOA? -Uses (6) -Complications (3) |
MOA
-Binds vesicles so they cannot bind and therefore Ach cannot be released -Irreversible inhibition of Ach release Uses -Dystonias -Spasticity following MS, SC injury -Chronic anal fissure -Severe wrinkles -Spasmodic Dysphonia -Severe sweating Complications -Overdose (unlikely but very deadly) -Bad aim (inject wrong site --> prolonged muscle weakness) -Antibody development |
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Physostigmine
-MOA? -Uses (1) |
MOA
-Inhibits AchE Use -Alzheimer's Disease |
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Atropine
-MOA? -Effects? (6) -Efficacy? -SEs? (5) |
MOA
-Blocks ALL muscarinic receptors Effects -Increase HR -Decrease secretions -Relax bronchi -Decrease bladder tone -Decrease GI motility -Dilate pupil -High potency -Crosses BBB poorly SEs (CNS effects at high dose) -Hallucinations -Confusion -Restlessness -Irritability -Psychosis-like symptoms |
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Pirenzepine
-MOA? -Uses (1) |
MOA
-Block M1 receptors -Blocks gastric acid secretions thru blockade of ganglionic neuron Use -Helpful in conjunction with other medications for ulcers |
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Acetylcholine
-MOA? -Effects? (4) -Does not affect? (1) -Clinical use? |
MOA
-Muscarinic receptor agonist Effects -Stimulate GI smooth muscle -Stimulate exocrine gland secretion -Bronchoconstriction (stimulate bronchial smooth muscle) -Pupil constriction -Does NOT affect nicotinic receptors -Not a clinically useful drug due to rapid metabolism |
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Carbachol
-MOA? -Effects? (4) -Compared to Bethanechol -Uses (2) -SEs? (5) |
MOA
-Muscarinic receptor agonist Effects -Stimulate GI smooth muscle -Stimulate exocrine gland secretion -Bronchoconstriction (stimulate bronchial smooth muscle) -Pupil constriction -More general activity on muscarinic receptors compared to Bethanechol -Also more active nicotinic receptors which produces more cholinergic SEs -More cardiovascular effects -GI stimulation (post-op) -GI side effects = nausea, cramps, diarrhea -Impaired night vision (pupillary constriction) -Spasms of accommodation for distant vision Uses -Post-op GI stimulation -Topical application for open angle glaucoma |
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Pilocarpine
-MOA? -Effects? -Uses (1) |
MOA
-Muscarinic receptor agonist -No receptor selectivity Effects -Pupil constriction Uses -Treat increased ocular pressure in the eye -First choice of cholinomimetics for open angle glaucoma -Enhance aqueous humor outflow thru ciliary contraction which opens space of trabecular network to enhance outflow thru canal of schlemm |
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Bethanechol
-MOA? -Specific for? -Uses (2) -Contraindication? -SEs (3)-Do |
MOA
-M3 agonist -Specific for GI and bladder (minimal effects on M2 and heart) -Choline ester (not degraded by cholinesterases) Uses -Produce intestinal stimulation (post-op) -Promote urination (urinary retention) SEs -GI side effects = nausea, cramps, diarrhea Contraindications -Do NOT use in cases of intestinal obstruction |
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Cardio side effects of muscarinic agonists (3)
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-Bradycardia
-AV block -Can also produce a transient decrease in diastolic BP which leads to a reflex tachycardia |
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Main effects of muscarinic agonists of all systems
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-Increased intestinal motility
-Increase GI secretions -Promote micturition -Pupillary constriction -Contract ciliary muscle (decrease intraocular pressure) -Stimulate secretions -Contracts bronchial smooth muscle -Stimulates glandular secretions -Stimuate intestine and bladder -Open angle glaucoma |
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Contraindications for muscarinic agonists
(3) |
-Asthmatic patients
-Cononary insufficiency -Peptic Ulcer |
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Scopolamine
-MOA? -SEs (4) -Uses (2) |
MOA
-Potent muscarinic antagonist -High CNS activity Uses -Used as anesthetic adjunct --Produces drowsiness, fatigue, amnesia, euphoria Side effects -Delirium, intense reaction Other Use Prophylactically in motion sickness (patch administration) -Side effects = Sedation and dry mouth |
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General Muscarinic Antagonist Activity (6)
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-Increase HR
-Impaired accommodation (cytoplegia) -Blocks circular and ciliary muscles in the eye -Decrease tone in GI tract and bladder (constipation and urinary retention) -Decreased GI secretions -Decrease glandular secretions |
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General Muscarinic Antagonist Side effects (2)
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-CNS signs (treated with physostigmine)
-Photosensitivity |
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Clinical Uses of Muscarinic Antagonists (8)
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-Ulcer
-Eye exams -Cholinesterase Poisoning -Adjunct in anethesia -Anti-Parkinson Treatments -Motion sickness -Overactive Bladder and incontinence -Bronchodilation/Asthma patients |
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Ipratropium
-MOA? -Effects (1 main) -Adminstration? -Uses (1) -Advantage to atropine? |
MOA
-Blocks M3 receptors (muscarinic antagonist) Effects -Reduces bronchospasm -Used for bronchodilation Uses -Asthma dilation -Oral administration -Does NOT effect mucociliary clearance like atropine |
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Tiotropium
-MOA? -Uses (2) -Adminstration (1) |
MOA
-Muscarinic antagonist -Similar bronchodilation effects as ipratropium Uses -Used for asthma patients -Administered as inhalant with long duration of action (24 hours) -Also useful in COPD -Problem with administration 4times/day |
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Alpha-1 Receptor Activation
-Work thru which system? -4 general effects |
-Contraction of smooth muscle (genitourinary, intestinal and vasculature)
-Contraction of prostate muscle -Ejaculation -Eye mydriasis (pupillary dilation) -Activate IP3 and DAG system -G(q) |
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Alpha-2 Receptor Activation
-Works thru which system? -2 general effects |
-Presynaptic = negative feedback (inhibits NT release)
-Postsynaptic = inhibit insulin release from beta cells (islets) -Postsynaptic = platelet aggregation -G(i) -Blocks adenylyl cyclase --> decrease cAMP |
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Beta-1 Receptor Activation
-Works thru which system? -3 effects |
-Cardiac specific
-Positive chronotropic, inotropic and dromotopic effects -G(s) -Stimulate adenylyl cyclase --> increase cAMP |
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Beta-2 Receptor Activation
-Works thru which system? -Effects (4) |
-Mostly for respiratory system
-Also dilates/relaxes liver, vasculature and skeletal muscle -Presynaptic for positive feedback -G(s) -Stimulate adenylyl cyclase --> increase cAMP |
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Beta-3 Receptor Activation
-Works thru which system? -Effects (2) |
-Stimulates lipolysis
-Stimulates thermogenesis -G(s) -Stimulate andenylyl cyclase --> increase cAMP |
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Epinephrine Hydrochloride General Info
-Stimulates which receptors at low/high dose? -Uses? (5) -Administration? -SEs (2) --> OD? |
Dose Difference and MOA
-Stimulates alpha-1, 2 and beta-1, 2 receptors -Low conc = beta-1 and beta-2 -High conc = alpha effects Uses -Used in emergencies -Anaphylaxis (subQ followed by IV) -Acute asthma/bronchospasm (nebulized) -Glaucoma -Very small doses with local anesthetics can prolong infiltration nerve block (tooth extractions) Administration -Never administered orally -Normal route is IM or SC SEs -Strong cardiac effects (inotrophy and chronotropy) -Overdose can cause an MI -Does NOT cross BBB -Short duration of action |
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Epinephrine Hydrochloride
Vascular Actions -Low/high dose effects? -OD effects? |
-All doses decreases blood flow to skin, mucosa and kidney
-Low dose: flow to skeletal muscle increases and diastolic BP may fall (beta-2) -High dose: Flow to skeletal muscle decreased (alpha-1)--increase peripheral resistance -Overdose = pulmonary edema |
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Epinephrine Hydrochloride
Cardiac Effects (5) SEs (1)? |
-Increased cardiac output
-But cardiac efficiency is DECREASED** -Cardiac O2 consumption is increased -Increases systolic but not diastolic BP -Low dose: BP may even fall (beta-2) -Side effect = arrythmias |
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Epinephrine Hydrochloride
Other system effects -Intestinal smooth muscle -Uterus -Bronchi -Glucose/FA |
-Relaxes intestinal smooth muscle (beta-2)
-Uterine muscle contraction EXCEPT during last month of pregnancy when there is relaxation (beta-2) -Potent bronchodilator and inhibition of histamine release (beta-2) -Increase glycogenolysis and lipolysis -> increases glucose and FA in blood (beta-2) |
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Phenylephrine Hydrochloride
-MOA? -Effects (3) -Uses (3) -SE (1) |
MOA
-Alpha 1 mediated Effects -Vasoconstriction and increased peripheral resistance -Diastolic pressure increased -Cardiac effect = reflex bradycardia Uses -Relieves nasal congestion (nose drops) by constricting vasculature and secretions decrease -Also used when BP needs to be increased -Can also constrict vascular smooth muscle in the eye (opthalmic hyperemia) SE -Increased risk of hemorrhagic stroke in women* |
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Norepinephrine
-MOA? -No effect on? (1) -Effects (2) -Uses (1) |
MOA
-Alpha 1 and beta 1 -NO beta-2 effects Effects -Increase systolic AND diastolic BP -Initial increase in HR followed by reflex bradycardia (results in small change in BP) Uses -Used as adjunct to dopamine to raise BP in shock |
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Direct sympathomimetics
-3 examples -Defn |
-Epi
-NE -Isoproterenol -Direct = stimulate receptors -(indirect = increase NT release) |
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Dopamine
-MOA? -Low/high dose effects? (1) -Uses (2) -Alternative? -Used when? (1) -SEs (1) |
MOA
-Low dose = activates D1 receptors in renal and splanchnic vascular beds (vasodilator) -Higher doses = activates beta-1 in heart Uses -Raises BP and used in ER for hypotension due to shock -Danger of tachycardia -Useful in treating severe congestive heart failure if patient has low vascular resistance -Not a daily treatment -Alternative = phenylephrine (powerful pressor agent) |
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Amphetamine
-MOA? -Effect (1) |
MOA
-Indirect sympathomimetic (increase NT release) -Powerful stimulant -Displaces NE from vesicles and inhibits MAO activity Effect -Increase BP thru increased NE release |
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Tyramine
-MOA? -Found? (2) -Effects (2) -Contraindication? (1) |
MOA
-Indirect adrenergic agonists -Competes at NET (specific for NET versus DAT) -Found in foods (fermented cheese, red wine) Effects -Increases NE in cleft by blocking reuptake -Raise BP and HR Contraindicated -Pts on MAO inhibitors (can produce hypertensive state) |
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Guanethidine
-MOA? -Uses (2) |
MOA
-False NT -Indirect -Actively transported by NET -Depletes supply of NT -Sympatholytic drug (blocks catecholamine production or depletes the vesicles) Use -Severe hypertension -Pheochromocytoma -Not used often |
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Alpha-methyl-DOPA
-MOA? (2) -Uses (1) -Useful in which pts? (2) |
MOA
-Competitive inhibitor of DOPA -Sympatholytic drug -Blocks dopamine (and norepi) synthesis by blocking DOPA decarboxylase --> reduced dopaminergic and adrenergic neurotransmission in the peripheral nervous system (lower BP) -Centrally acting alpha-2 agonist --> decrease central adrenergic outflow (lower BP) Use -Used for hypertensive pts Positive SE -Renal blood flow and function is maintained --> valuable in managing hypertensive patients with renal insufficiency -Can be used during pregnacy |
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Ephedrine effects
-MOA? -Compared to epi? -Effects? (4) -Uses (3) |
MOA
-Alpha and beta receptor stimulant Effects -Causes release of stored catecholamines -Bronchial relaxation (beta-2) -Mydriasis (alpha-1) -Promotes vasospasm (can cause hypertensive episode or even MI)** -Slower and less potent than epi -Can have Tolerance |
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Ephendrine Uses
(4) |
-Asthma (bronchodilator)
-Eye exams (mydriasis) -Nasal decongestant (nasal sprays, OTC) -Urinary incontinence |
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Reserpine
-MOA? -Uses (2) -Rate of action? -SEs (3) |
MOA
-Blocks Mg2+/ATP-dependent transport of biogenic amines into vesicles (VMAT2) -First massive efflux of NT -Depletes vesicles of their content -Slow acting and long term -Decrease dopamine and NE released SEs -Parkinsonian symptoms, -Depression -Hypotension Uses -Hypertensive crisis in ER -Adrenal tumors |
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Clonidine
-MOA? -Uses (1) |
MOA
-Sympatholytic -Selective for alpha-2A at low doses Uses -Hypertension -Acts centrally |
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Isoproterenol
-MOA? -Effects (2) -SEs (4) -Contraindications? |
MOA
-PURE beta agonist (beta-1 and 2) Effects -Powerful bronchodilator -Used in ER to stimulate the heart (beta-1) SEs -Not drug of choice due to cardiac effects --AV block --Tachycardia, palpitations -Headache -Flushing -Ischemia in pts w/ coronary artery disease Contraindications -Pts w/ coronary artery disease |
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Dobutamine
-MOA? -Effects (2) -Uses (3) -SEs (2) |
MOA
-Beta-1 agonist AND alpha-1 agonist Effects -Increases cardiac output -Does NOT reduce efficiency Uses -Congestive heart failure pts. -Used more in ER situation and not a long term treatment -Used in stress testing SE -Arrhythmia -Tachycardia |
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Metaproterenol
-MOA? -Uses (2) |
MOA
-Beta-2 agonist Uses -Prototype for asthma patients (acute) -Obstructive airway disease -Acute bronchospasm |
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Salmeterol
-MOA? -Uses (1) -Combine with? -Administration? |
MOA
-Beta-2 agonist Use -Asthma patients -Combine with corticosteroid -Nebulizer -Long term therapy (12 hours) -Many times pt has another nebulizer for acute symptoms that's short acting |
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Albuterol
-MOA? -SEs with increase used? (3) -Uses? (1) |
MOA
-Beta-2 agonist Use -Asthma patients -Short acting (shortest) -If used more than 2 times per week pt may experience tachycardia -Nebulizer Other SEs -Nausea -Vomiting |
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Formoterol
-MOA? -Uses (1) |
MOA
-Beta-2 agonist Use -Long term therapy for asthma -Highly lipophilic -After inhalation effects last 4-6 hours |
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Terbutaline
-MOA? -Uses (1) |
MOA
-Beta-2 agonist Use -Treats obstructive pulmonary disease -Not really for asthma pts |
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Beta-2 Side Effects (bronchodilators)
(5) |
-Muscle tremor (rare)
-Bronchospasm -Cardiac stimulation -Nausea and tachycardia if short acting agonists are inhaled more than twice a week (sign that it is being used too often) |
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Neostigmine
-MOA? -Effects (1) -Uses (3) -SEs (2) |
MOA
-Reversible ChE-I -Does not enter CNS Effects -Stimulates muscle contraction (greater effect than physostigmine) Uses -Myasthenia gravis -Anesthesia adjunct to reverse NMJ block -Urinary retention -Paralytic ileus SEs -Bradycardia -GI problems (nausea, vomiting, cramps and diarrhea) |
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Edrophonium
-MOA? -Uses (1) |
MOA
-Reversible ChE-I -Competitive inhibitor -Very short acting Use -Used to differentiate myasthenia gravis from cholinergic crisis -In myasthenia gravis will reduce muscle tension due to lack of stimulation of NMJ -In cholinergic crisis a person has too much neuromuscular stimulation and this will make it worse by inducing a depolarizing block |
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Organophospates
-MOA? -Examples (2) |
MOA
-Irreversible ChE-I -Long lasting effects Examples -Nerve gases -Agricultural insecticides |
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Nerve Gases
-MOA? -Treatment? (2) |
MOA
-Organophosphate -Irreversible ChE-I -Volatile and lipid soluble Treatment -Atropine for a muscarinic blockade -Pralidoxime for enzyme regeneration |
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Pralidoxime (2PAM)
-MOA? -Use (1) |
-MOA
-Regenerates AchE to function properly -AchE reactivator -Oxime takes phosphate off Use -Treatment for organophosphate poisoning (must be used quickly) |
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Diisopropyl Fluorophosphate (DFP)
-MOA? -Toxicity? |
MOA
-Irreversible ChE-I Toxicity -Potent neurotoxin -Ach accumulates and nerve impulses cannot be stopped causing prolonged contraction -Paralysis occurs and death can occur due to paralysis of respiratory muscles |
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Echothiophate
-MOA? -Uses (1) -SEs (1 main) |
MOA
-Irreversible ChE-I -No CNS effects Use -Used as ocular antihypertensive in treatment of chronic glaucoma -Slow rate of hydrolysis so it's effects can last a week or more SEs -Muscle spasm -Other systemic effects |
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Phenoxybenzamine
-MOA? -Uses (2) -SE (1) |
MOA
-Non-selective alpha antagonist (A1 > A2) -Biphasic -First reversible competitive inhibitor -Second irreversible non-competitive inhibitor SE -Reflex tachycardia (block alpha2A) Uses -Management of pheochromocytoma -Peripheral vascular disease (Reynaud's disease) |
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Carvedilol
-MOA? -Uses (1) -Side effect (1) |
MOA
-Alpha 1 and non-seletive beta inhibitor -Reduce peripheral resistance -Reduce stimulation of the heart Use -Used for Congestive Heart Failure SE -Hypotension |
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Summary of alpha-1 selective inhibitors
-Uses (3) -Favorable effects? (2) |
-Preserve alpha2A negative feedback (less cardiac effects)
-Treat congestive heart failure (low risk of tachycardia) -Treat hypertension -Fluid retention -Treat BPH if high selectivity for alpha1A receptor -Increase HDL/LDL ratio -Decrease serum lipids |
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Prazosin
-MOA? -Uses (4) -SE (1) |
MOA
-Alpha 1 selective antagonist -High bioavailability (70%) Uses -BPH -Hypertension (NOT for emergencies) -Congestive heart failure -Peripheral vascular disease (Reynaud's disease) SEs -Sycope |
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Terazosin
-MOA? -Uses (2) -SE (1) |
MOA
-Selective alpha-1 antagonist -Small 1st pass effect -Long half life (12hours) Use -Hypertension (NOT for emergencies) -Congestive heart failure -Small risk of tachycardia SE -Syncope |
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Tamsulosin
(Flomax) -MOA? -Uses (1) -SEs (2) |
MOA
-Specific alpha1A and 1D antagonist -More specific for alpha1 receptors in urinary system Use -BPH -Good for pt with BPH but no hypertension SEs -Male sexual dysfunction -Orthostatic hypotension (dose dependent) -Lower incidence of hypotension |
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Alfuzosin
-MOA? -Uses (1) -Side effects (3) |
MOA
-Selective alpha-1A antagonist -More specific for urinary tract receptors -Highly metabolized (60% bioavailability) Use -BPH SE -Muscle weakness or psychogenic weakness -Male sexual dysfunction -Orthostatic hypotension |
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Yohimbine
-MOA? -Uses (1) -Side effect (1) -Possible future uses? (1) |
MOA
-Alpha 2 selective antagonist -Blocks serotonin and DA receptors -Increase ADH release Use -Originally for sexual enhancement but uneffective SE -Nausea -Want to use an alpha-2 drug to treat diabetes |
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Phentolamine
-MOA? -Uses (1) |
MOA
-Non-selective alpha antagonist Use -Pheochromocytoma |
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General Beta-Blocker Activity
(4) |
-Decrease CO
-Inhibit renin release from juxtaglomerular cells (decrease peripheral resistance) -Decrease central sympathetic outflow (Reduced NE release) -Resetting of baroreceptor |
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General Clinical Uses for Beta-Blockers (11)
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-Coronary artery disease
-Hypertension -Arrhythmias -Congestive heart failure -Hypertophic obstructive cardiomyopathy -Pheochromocytoma -Hyperthyroidism -Migraine (prophylaxis with ISA) -Essential tumor -Anxiety (stage freight) -Glaucoma (topical) |
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Propranolol
-MOA? -Uses? (6) -Do not give to? (3) |
MOA
-Non-selective Beta antagonist -Lipid soluble and fast acting (short half life) -First pass effect Uses -Low dose for stage anxiety -Hypertension -Arrhythmias -Essential tremor -Migraine -Glaucoma Contraindications -Asthmatic pt -Do not drink --> nausea and vomiting -Cimetidine --> increases bioavailability (inhibit CYP 450) |
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Metoprolol
-MOA? -Uses (2 main) |
MOA
-Selective beta-1 blocker -Cardioselective -Moderate lipid solubility -1st pass effect Uses -Hypertension -Several diseases of the cardiovascular system (congestive heart failure, etc...) |
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Atenolol
-MOA? -Uses (1 main) |
MOA
-Selective beta-1 blocker -Cardioselective Use -Elderly with systolic hypertension |
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Bisoprolol
-MOA? -Uses? (2 main) |
MOA
-Selective beta-1 blocker -Cardioselective -Well tolerated but no ISA (fatigue SE) Uses -Hypertension -Cardiovascular disease |
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Pindolol
-MOA? -Uses? (1 main) -Additional advantages? (2) |
MOA
-Non selective beta blocker -Partial agonist (ISA)* --> CO and HR stay higher Use -Hypertensive pts with bradycardia or exercise intolerance Advantages -Less effect on lipid increase SE -Less bradycardia while controlling hypertension |
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Acebutolol
-MOA? -Additional advantages? (2) -Uses (1 main) |
MOA
-Beta-1 Selective blocker -Partial agonist (ISA)* Use -Good for hypertensive pts with bradycardia or exercise intolerance Advantages -Less negative effects on elevated serum lipids -Less bradycardia while controlling hypertension |
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Labetalol
-MOA? -Receptor selectivity? -Uses (1 main) |
MOA
-Alpha and beta blocker -B-1 = B2 >(or equal to) A1 > A2 Uses -Potent anti-hypertensive -Used during emergencies |
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Esmolol
-MOA? -Uses (4) |
MOA
-Beta-1 selective blocker -Rapid onset and short duration of action -Cardioselective Uses -Anti-arrhythmic -Prevent or treat tachycardia -Acute supra ventricular tachycardia -Drug of choice when aortic dissection is suspected |
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Doxazosin
-MOA? -Uses (2) |
MOA
-Alpha-1 specific antagonist Uses -Hypertension -BPH |
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Beta-Blocker Side Effects
(8) |
-Withdrawal syndrome (due to unregulated receptors) --> can lead to tachycardia, angina or MI
-Cardiac depression (rare) -Airway toxicity (bronchoconstriction) --> should not be use in asthma pts -Caution in pts w/ vasospastic disorders -Augments hypoglycemia --can mask tachycardia associated with hypoglycemia and can slip into diabetic coma** -Elevates serum lipids -Some CNS (depression, nightmares) -Fatigue (ISA improves this) |
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Tubocurarine
-MOA? -Uses (4) -Onset? -Duration of action? -Administration? -Drug Interactions (2) |
-Competitive NMJ blocker (surmountable)
-Decreased freq of channel opening -Prevent Ach induced muscle contraction -Longer duration of action (kidney eliminated) -Longer latency of onset (2-5mins) -Muscle maintains sensitivity -Uses --Muscle relaxation for surgical procedures --Intubations --ECT --Orthopedic procedures (dislocations) -IV administration -SEs --Histamine release (decrease BP --> reflex tachycardia) --Ganglionic activity --Post-op apnea or respiratory paralysis -Effects --Rapid muscle weakening --> flaccid paralysis --Order of paralysis (fine motor, large muscle groups, muscles of respiration) --Recovery follows reverse order -Drug Interactions (are Ca++ chelators and reduce ACh release so delay recovery) --Aminoglycoside antibiotics --Tetracyclines |
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Atracurium
-MOA? -Uses (4) -Onset? -Duration of action? -Administration? -Drug Interactions (2) |
-Competitive NMJ blocker (surmountable)
-Decreased freq of channel opening -Prevent Ach induced muscle contraction -Longer duration of action (kidney eliminated) -Longer latency of onset (2-5mins) -Muscle maintains sensitivity -Uses --Muscle relaxation for surgical procedures --Intubations --ECT --Orthopedic procedures (dislocations) -IV administration -SEs --Histamine release (decrease BP --> reflex tachycardia) --Ganglionic activity --Post-op apnea or respiratory paralysis -Effects --Rapid muscle weakening --> flaccid paralysis --Order of paralysis (fine motor, large muscle groups, muscles of respiration) --Recovery follows reverse order -Drug Interactions (are Ca++ chelators and reduce ACh release so delay recovery) --Aminoglycoside antibiotics --Tetracyclines |
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Mivacurium
-MOA? -Uses (4) -Onset? -Duration of action? -Administration? -Drug Interaction? (2) |
-Competitive NMJ blocker (surmountable)
-Decreased freq of channel opening -Prevent Ach induced muscle contraction -Short* duration of action (liver eliminated) -Shoter* latency of onset (1-1.5mins) -Muscle maintains sensitivity -Uses --Muscle relaxation for surgical procedures --Intubations --ECT --Orthopedic procedures (dislocations) -IV administration -SEs --Histamine release (decrease BP --> reflex tachycardia) --Ganglionic activity --Post-op apnea or respiratory paralysis -Effects --Rapid muscle weakening --> flaccid paralysis --Order of paralysis (fine motor, large muscle groups, muscles of respiration) --Recovery follows reverse order -Drug Interactions (are Ca++ chelators and reduce ACh release so delay recovery) --Aminoglycoside antibiotics --Tetracyclines |
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Vecuronium
-MOA? -Uses (4) -Administration? -Drug Interactions? (2) |
-Competitive NMJ blocker (surmountable)
-Decreased freq of channel opening -Prevent Ach induced muscle contraction -Muscle maintains sensitivity -Uses --Muscle relaxation for surgical procedures --Intubations --ECT --Orthopedic procedures (dislocations) -IV administration -SEs --Histamine release (decrease BP --> reflex tachycardia) --Ganglionic activity --Post-op apnea or respiratory paralysis -Effects --Rapid muscle weakening --> flaccid paralysis --Order of paralysis (fine motor, large muscle groups, muscles of respiration) --Recovery follows reverse order -Drug Interactions (are Ca++ chelators and reduce ACh release so delay recovery) --Aminoglycoside antibiotics --Tetracyclines |
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Succinylcholine
-MOA? -Duration of action? -Metabolized by? -SEs (5) -Caution in which patients? (7) -Drug Interactions (1) -Adminstration -Uses (4) |
-Depolarizing (insurmountable antagonism)
-Muscle refractory to all stimulation -AchE-I will enhance the block -Rapid onset and fast offset -Metabolized by serum* ChE -SEs --Little cardiac effect but may have ganglionic stimulations (increase HR and increase BP) --Slight histamine release --Increased intraocular and intragastric pressure (concern for aspiration of food) --Muscle fasciculations --Malignant hyperpyrexia; Succinylcholine + general anesthetic (abnormal ryanodine receptor) -Caution in pts with: --Burns, soft tissue damage, cardiac issues, nerve damage (increased K+ --> cardiac arrest) --Children --Pts w/ atypical serum ChE (prolonged effect) --Pts w/ rhabdomyolysis (muscle breakdown) --Body builders (increased muscle mass --> increased K+) -Drug interactions --ChE-I (enhanced effect) -IV administration -Uses --Muscle relaxation for surgical procedures --Intubations --ECT --Orthopedic procedures |
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Nicotine
-MOA? -OD? |
MOA
-Nm and Nn agonist -Produce depolarization in toxic doses OD -Patch + gum + snuck smoke -Respiratiory stimulation leading to arrest, convulsions, nausea -Highly addicting |
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Varenicline
-MOA? -Uses? (1) -Concerns -SE (1) |
MOA
-Partial nicotine receptor agonist -Does not have full efficacy --> little stimulation but reduces the additional rewarding aspect of smoking -Oral availability -Long half life (17-24 hours) Uses -Smoking cessation Concerns -Increased suicide SE -Weight gain |
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Allopurinol
MOA 5 Pharmacokinetics 3 |
MOA
-Converted to Oxipurinal -Decrease Uric Acid Syn by competitive inhibition of xanthine oxidase -Depletes stores of 5-PRPP -Inhibition of 5-PRPP aminotransferase -Reduces purine syn Pharm - Metabolized to Oxipurinol, an active longer lasting inhibitor of xanthine oxidase - 1 pill/day - Oral Half-life 1-2h |
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Allopurinol
Uses 8 Doses 3 |
- Initial urate-lowering drug w/ Colchicine
-Colchicine stopped when serum UA < 6mg or steady-state Treats: -Hyperuricemia caused by UA overproduction -Chronic Tophaceous gout, NOT acute -Especially useful in patients with renal insufficiency or calculi -NOT antagonized by salicylates -Inhibits reperfusion injury (free radicals) during transplants -Days to 2 weeks to work Doses - 100mg/day - Increased until UA < 6mg/dL -Intially given w/ Colchicine or NSAID to prevent gout episodes |
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Allopurinol
Toxicity 6 Drug interactions 3 |
Toxicity:
-GI* -Peripheral neuritis* -Necrotizing vasculitis* -Aplastic anemia -Hepatic toxicity - 3% get allergic skin reaaction(Pruritic Maculopapular lesions) Drug interactions - inhibit oxidation of mercaptopurines - increase toxicity of cytotoxic drugs (cyclophosphamide) - increased t1/2 of probenecid and thus excretion rate of oxipurinol |
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Febuxostate
-Metabolism (3) -Use(3) -Toxicity (2) |
Metabolism:
-Rapid oral absorbtion, Peak level in 1h -Liver metabolized, Kidney excreted -No dosage adjustments needed w/ impared renal function Use: -Alternative to Allopurinol -Treats chronic gout regardless of pathophys -NSAIDS and Cholchicine prophylacticly Toxicity: -GI* -Hepatic Function changes |
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Probenecid
-Type -MOA -Use (4) -Toxcitity -Drug interactions |
Uricosuric Agents
MOA -Inhibits middle (S2) part of proximal tubule active reabsorption of UA Use: -Hyperuricemia -Not acute gout -Not patients w/ renal insuficiency, or ppl already secreteing lots of UA -Colchicine prophylaxticly |
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Probenecid
-Type -Toxicity (4) -Drug interactions (2) |
Uricosuric Agents
Toxicity -Must maintain large urine volume and alkalized urine -GI* -Dermatitis -Nephrotic syndrome (rare) Drug Interactions: -Decreases renal secretion of acidic compounds -Increases renal excretion rate of oxipurinol (allopurinol) |
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Probenecid
Pharmacokinetics |
Probenecid:
-Actively secreted in prox tubule and completely reabsorbed by renal tubules -Plasma Protein bound -Oral admin -Slowly metabolized, half-life 6-12h |
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Colchicine
-MOA (3) -Pharmacokinetics (4) |
MOA:
-Binds/blocks microtubule formation -Stops leukocyte migration and Urate crystal phagocytosis -Inhibits B4 sythesis Pharmacokinetics: -Rapid oral absorption -Accumulates in luekocytes -Peak level in 2h, half-life 9h -Eliminated feces/urine |
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Colchicine
-Use (3) -Toxicity (2) -Overdose (5) |
Use:
-More specific than NSAIDs -Replaced by NSAIDs due to GI SFX -Prophylaxis of gout attacks and Mediterranean fever only Toxicity: -GI, diarrhea* (80%) -N/V/Ab pain Overdose: -Shock -Hematuria -Oliguria -CNS depress -GI |
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Indomethacin
MOA Use Dose |
MOA
Inhibit urate cyrstal phagocytosis and prostaglandin synthase Use NSAID prefered to colchicine, for acute attacks Dose 50mg x 3/day and continued 25mg x3/day for a week |
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Rasburicase
-Type -MOA -Use (3) -Adminstered (2) -Toxicity (3) |
Recombinant urate-oxidase
MOA -Catlyzes UA conversion to soluble Allatoin Use: -Increase UA degradation -More effective than Allopurinol in lowering urate levels -Pediatric hyperuricemia w/ chemo caused increased UA Administered: -IV 0.15mg/kg/day x 5 days -Chemo started a few hours after first dose Toxicity: -Antibody production/Anaphylaxis -Acute renal failure -GI |
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Cholchicine vs. NSAIDs
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Cholchicine is second to NSAIDS for treatment of acute gout episodes
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Teriparatide Acetate
-Uses (2) -MOA? -Administration? |
MOA
-Analog of PTH -Daily intermittent administration increases # and activity of osteoblasts -Does not produce bone resorption -Increase new bone formation -Decrease fracture risk -Possibly involves inhibition of osteoblast apoptosis Uses -Osteoporosis in men and postmenopausal women at high risk for fracture -Challenge test for pseudohypoparathyroidism --Urinary cAMP should increase if sensitivity to PTH is normal Administration -***Intermittent administration is key (SubQ) |
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Teriparatide Acetate
-SEs? -Contraindications? (6) |
SEs
-Possible increase in osteosarcoma --Black box warning Contraindications -Paget's disease of bone -Pediatric populations -Pts w/ prior radiation therapy involving the skeleton -History of bone metastases or skeletal malignancies -Metabolic bone disease other than osteoporosis -Pre-existing hypercalcemia |
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Calcitonin
-MOA? -Made from? (2) -Role significant in? (4) |
MOA
-Specific G-protein coupled membrane receptor -Inhibits osteoclast-mediated Ca2+ mobilization Preparations -Synthetic human CT -Synthetic salmon CT (more potent and cleared slower) Use -Role is only significant under conditions that stress Ca2+ homeostasis --Growth --Pregnancy --Lactation --High Ca2+ intake |
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Calcitonin
-Uses? (4) -Which type of CT used? |
Uses
-Treatment of severe hypercalcemia --Synthetic salmon CT -Symptomatic treatment of dehydration -Osteoporosis --Salmon CT as intranasal spray --Used in postmenopausal osteoporosis when hormone replacement therapy is contraindicated -Paget's disease --Salmon CT -Less effective than hormone replacement therapy or bisphosphonates |
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Calcitonin
Adverse effects? (6) |
SEs
-Nausea -Facial flushing -Swelling of the hands -Inflammatory rxns at injection sites -Urticaria -Up to 20% of pts with salmon calcitonin develop resistance --Alleviated by switching to hCT (human) |
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Calcitrol
-MOA? -Actions? (5) |
MOA
-Active metabolite of vitamin D -Intracellular receptor (nuclear hormone receptor family) -Hormone receptor complex regulates transcription -Forms heterodimer with retinoic acid receptor Actions -Facilitation of intestinal Ca2+ absorption -Increases expression of calbinins (binding protein of brush border) -Stimulates Ca2+ efflux into the blood -Stimulates synthesis of osteocalcin (bone matrix protein) -Enhances Ca2+ mobilization from bone |
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Calcitrol (Vitamin D)
Uses? (4) Adverse effects? (1) |
Uses
-Hypoparathyroidism -Pseudohypoparathyroidism -Osteoporosis (with calcium) -Rickets and osteomalacia --Prophylactic use in infants --Nutritional rickets --Metabolic rickets Adverse effects -Hypervitaminosis D which results in hypercalcemia |
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Dihydrotachysterol (DHT)
-MOA? |
MOA
-Synthetic vitamin D analog -Activated in liver and does NOT require renal hydroxylation like vitamin D2 and D3 -Rapid onset of action |
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DHT
-Uses? (4) -Adverse effects (1) |
Uses
-Hypoparathyroidism -Pseudohypoparathyroidism -Osteoporosis (with Ca2+) -Rickets and osteomalacia Adverse effects -Hypervitaminosis D |
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Alendronate
-MOA? -Availability? -Administration? |
MOA
-Bisphosphonate -Nonhormonal agent for hypercacemia -Analog of pyrophosphate -Incapacitates osteoclasts and inhibits bone resorption Availability -Poorly absorbed from intestine Administration -For oral admin taken w/ water only |
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Alendronate
-Uses? (4) -SEs? (5) |
Uses
-Osteoporosis in postmenopausal women -Preservation of bone density during glucocorticoid therapy -Paget's disease -Hypercalcemia associated w/ malignancy SEs -Osteomalacia -Hypocalcemia -Hypophosphatemia -Local irritation of upper GI mucosa* -Osteonecrosis of jaw |
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Ibandronate
-MOA? -Availability? -Administration? |
MOA
-Bisphosphonate -Nonhormonal agent for hypercacemia -Analog of pyrophosphate -Incapacitates osteoclasts and inhibits bone resorption Availability -Poorly absorbed from intestine Administration -For oral admin taken w/ water only |
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Ibandronate
-Uses? (4) -SEs? (5) |
Uses
-Osteoporosis in postmenopausal women -Preservation of bone density during glucocorticoid therapy -Paget's disease -Hypercalcemia associated w/ malignancy SEs -Osteomalacia -Hypocalcemia -Hypophosphatemia -Local irritation of upper GI mucosa* -Osteonecrosis of jaw |
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Zoledronic acid
-MOA? -Availability? -Administration? |
MOA
-Bisphosphonate -Nonhormonal agent for hypercacemia -Analog of pyrophosphate -Incapacitates osteoclasts and inhibits bone resorption Availability -Poorly absorbed from intestine Administration -For oral admin taken w/ water only |
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Zoledronic acid
-Uses? (4) -SEs? (5) |
Uses
-Osteoporosis in postmenopausal women -Preservation of bone density during glucocorticoid therapy -Paget's disease -Hypercalcemia associated w/ malignancy SEs -Osteomalacia -Hypocalcemia -Hypophosphatemia -Local irritation of upper GI mucosa* -Osteonecrosis of jaw |
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Osteoporosis
-Treatments (6) |
Treatments
-Increased dietary Ca2+ and vitamin D -Weight bearing exercise -Estrogen replacement --Increase production of OPG --Blocks osteoclast differentiation --Conjugated estrogens, estradiol patch or SERMs -Calcitonin -Bisphosphonate -Teriparatide acetate (intermittent) --Reserved for severe cases |
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Amitriptyline
Class MOA Other Effects 3 |
Class - TCA
MOA - mixed 5-HT and NE uptake inhibitors Other Effects - block alpha-1, muscarinic, histamine receptors Other Effects - histaminic: sedation - muscarinic: accommodation, mydriasis, dry mouth, constipation, urinary retention - a1 blockade: orthostatic hypotension |
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Amitriptyline
Cardiac Side Effects 6 Other Side Effects 3 |
- reflex sympathetic activation,
- NE uptake block - less release inhibition (alpha-2 down-reg) - strong NE activation of heart (beta-1) - tachycardia, arrhythmia, fibrillation, infarct - overdose can be fatal (careful w/ suicidal pts) Other SE - transition to hypomania - skin problems: rash, photosensitivity - sexual dysfunction |
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Phenelzine
MOA? Length of action? Problems? Effects seen in? SEs? (4) OD effect? (2) |
MOA
-Non-selective MAO-I -Binds irreversibly -Increase NE, 5-HT levels w/in 1-2 days Length of effects -2-3 weeks -Problem with dosage adjustment -OD management difficult -Mood elevation in depressed AND normal individuals SEs -Transition from depression to hypomania -Decrease in BP -Headache -Sexual dysfunction OD -Hypo or hypertension |
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Phenelzine
Interactions? (4) |
Interactions
-With tyramine from food* --Promotes release of NE stores --> can cause dangerous hypertension --Pt needs to be on tyramine-free diet -TCAs -SSRIs -Other sympathomimetics (cocaine, amphetamine, OTC drugs like pseudo ephedrine) |
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Selegiline
MOA? Uses? (2) SEs (4) OD effects? |
MOA
-MOA-I -Relatively selective for MAO-B -Increase DA levels w/in 1-2 days Uses -PD -Major depression SEs -Transition from depression to hypomania -Decrease in BP -Headache -Sexual Dysfunction OD -Hypo or hypertension |
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Selegiline
Interactions (4) |
Interactions
-With tyramine from food* --Promotes release of NE stores --> can cause dangerous hypertension --Pt needs to be on tyramine-free diet -TCAs -SSRIs -Other sympathomimetics (cocaine, amphetamine, OTC drugs like pseudo ephedrine) |
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Midazolam
MOA? Uses (6) |
MOA
-Benzodiazepine -Increase frequency of GABA-induced opening of Cl- channel leading to hyperpolarization and decreased neuronal firing -H2O soluble -Steep dose/response curve -2-4 hours half life Uses -Anti-anxiety -Sedation -Hypnosis -Anesthesia* (IV adjunct --> decreased anxiety, faster onset of anesthesia, amnesia for event -Muscle relaxant -Alcohol and barbiturate withdrawal |
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Midazolam
SEs? (10) |
SEs
-Tolerance -Dependence -Psychological Dependence (addictive) -Severe with extreme CNS excitability leading to convulsions (life threatening) -Withdrawal Syndrome -Paradoxical Hostility -Anterograde Amnesia -CNA depression in newborn (crosses placenta) -Sedation -Elderly or decrease liver function |
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Zolpidem (Ambien)
MOA? Use (1) Advantages? (3) Disadvantages? (1) |
MOA
-BZ-1 selective agents -Enhance Cl- influx -Latency but shorter duration Use -Effective hypnotic -Approved for short-term use but effective long-term as well Advantages -Less likely to produce tolerance and dependence -Superior to benzos and barbs -Flumazenil reversible Disadvantages -Not an effective anti-convulsant or muscle relaxant |
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Secobarbital
MOA? Metabolism? SEs? (6) Interactions (1) |
MOA
-Barbiturate -Short to intermediate duration of action -Prolong opening of Cl- channel following GABAergic activation Metabolism -Liver metabolism w/ induction of own enzymes and enhanced metabolism of self and other drugs SEs -Sedation -Pharmacodynamic tolerance -Physical dependence -Ataxia -Respiratory depression/arrest (narrow therapeutic index) -Induction of aminoevulinic acid synthase --> increase porphyrin synthesis and acute intermittent porphyria Interactions -Other CNS depressants --Narcotic analgesics --Benzos --Alcohol |
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Secobarbital
Uses? |
Uses
-Anesthesia adjunct -Anticonvulsants (but a lot of SEs) -Anxiolytic and seed/hypnosis when other agents not tolerated |
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Pentobarbital
MOA? Metabolism? SEs? (6) Interactions (1) |
MOA
-Barbiturate -Short to intermediate duration of action -Prolong opening of Cl- channel following GABAergic activation Metabolism -Liver metabolism w/ induction of own enzymes and enhanced metabolism of self and other drugs SEs -Sedation -Pharmacodynamic tolerance -Physical dependence -Ataxia -Respiratory depression/arrest (narrow therapeutic index) -Induction of aminoevulinic acid synthase --> increase porphyrin synthesis and acute intermittent porphyria Interactions -Other CNS depressants --Narcotic analgesics --Benzos --Alcohol |
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Pentobarbital
-Uses? (3) |
Uses
-Anesthesia adjunct -Anticonvulsants (but a lot of SEs) -Anxiolytic and seed/hypnosis when other agents not tolerated |
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Thiopental
MOA? Metabolism? SEs (6) Interactions (1) |
MOA
-Barbiturate -Ultra-short* duration of action -Prolong opening of Cl- channel following GABAergic activation Metabolism -Liver metabolism w/ induction of own enzymes and enhanced metabolism of self and other drugs SEs -Sedation -Pharmacodynamic tolerance -Physical dependence -Ataxia -Respiratory depression/arrest (narrow therapeutic index) -Induction of aminoevulinic acid synthase --> increase porphyrin synthesis and acute intermittent porphyria Interactions -Other CNS depressants --Narcotic analgesics --Benzos --Alcohol |
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Thiopental
-Uses (3) |
Uses
-Anesthesia adjunct -Anticonvulsants (but a lot of SEs) -Anxiolytic and seed/hypnosis when other agents not tolerated |
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Ramelteon
MOA? (1) Uses? (1) Effectiveness? |
MOA
-Melatonin 1 and 2 agonist Use -Approved for insomnia w/ sleep onset disturbance (not for early awakening) Effectiveness -Minimal effectiveness -Decrease sleep onset 8-16 mins -Small effect on total sleep time |
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Amitriptyline
Interactions 3 Issues |
Interactions
- MAO inhibitors cause enhanced effects due to complementary actions and increased cardiotoxicity - CNS depressants (e.g., alcohol, narcotics, barbiturates) - with sympathomimetics (enhanced effects) Issues - reasonably effective ADs - side effects - delay in therapeutic response - don’t work in all patients |
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Imipramine
Class MOA Other Effects 3 |
Class - TCA
MOA - mixed 5-HT and NE uptake inhibitors Other Effects - block alpha-1, muscarinic, histamine receptors Other Effects - histaminic: sedation - muscarinic: accommodation, mydriasis, dry mouth, constipation, urinary retention - a1 blockade: orthostatic hypotension |
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Imipramine
Cardiac Side Effects 6 Other Side Effects 3 |
- reflex sympathetic activation,
- NE uptake block - less release inhibition (alpha-2 down-reg) - strong NE activation of heart (beta-1) - tachycardia, arrhythmia, fibrillation, infarct - overdose can be fatal (careful w/ suicidal pts) Other SE - transition to hypomania - skin problems: rash, photosensitivity - sexual dysfunction |
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Imipramine
Interactions 3 Issues |
Interactions
- MAO inhibitors cause enhanced effects due to complementary actions and increased cardiotoxicity - CNS depressants (e.g., alcohol, narcotics, barbiturates) - with sympathomimetics (enhanced effects) Issues - reasonably effective ADs - side effects - delay in therapeutic response - don’t work in all patients |
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Nortriptyline
Class MOA Other Effects 3 |
Class - TCA
MOA - mixed 5-HT and NE uptake inhibitors Other Effects - block alpha-1, muscarinic, histamine receptors Other Effects - histaminic: sedation - muscarinic: accommodation, mydriasis, dry mouth, constipation, urinary retention - a1 blockade: orthostatic hypotension |
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Nortriptyline
Cardiac Side Effects 6 Other Side Effects 3 |
- reflex sympathetic activation,
- NE uptake block - less release inhibition (alpha-2 down-reg) - strong NE activation of heart (beta-1) - tachycardia, arrhythmia, fibrillation, infarct - overdose can be fatal (careful w/ suicidal pts) Other SE - transition to hypomania - skin problems: rash, photosensitivity - sexual dysfunction |
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Nortriptyline
Interactions 3 Issues |
Interactions
- MAO inhibitors cause enhanced effects due to complementary actions and increased cardiotoxicity - CNS depressants (e.g., alcohol, narcotics, barbiturates) - with sympathomimetics (enhanced effects) Issues - reasonably effective ADs - side effects - delay in therapeutic response - don’t work in all patients |
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Clomipramine
Class MOA Other Effects 3 |
Class - TCA
MOA - mixed 5-HT and NE uptake inhibitors Other Effects - block alpha-1, muscarinic, histamine receptors Other Effects - histaminic: sedation - muscarinic: accommodation, mydriasis, dry mouth, constipation, urinary retention - a1 blockade: orthostatic hypotension |
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Clomipramine
Cardiac Side Effects 6 Other Side Effects 3 |
- reflex sympathetic activation,
- NE uptake block - less release inhibition (alpha-2 down-reg) - strong NE activation of heart (beta-1) - tachycardia, arrhythmia, fibrillation, infarct - overdose can be fatal (careful w/ suicidal pts) Other SE - transition to hypomania - skin problems: rash, photosensitivity - sexual dysfunction |
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Clomipramine
Interactions 3 Issues |
Interactions
- MAO inhibitors cause enhanced effects due to complementary actions and increased cardiotoxicity - CNS depressants (e.g., alcohol, narcotics, barbiturates) - with sympathomimetics (enhanced effects) Issues - reasonably effective ADs - side effects - delay in therapeutic response - don’t work in all patients |
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Desipramine
Class MOA Other Effects 3 |
Class - TCA
MOA - mixed 5-HT and NE uptake inhibitors Other Effects - block alpha-1, muscarinic, histamine receptors Other Effects - histaminic: sedation - muscarinic: accommodation, mydriasis, dry mouth, constipation, urinary retention - a1 blockade: orthostatic hypotension |
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Desipramine
Cardiac Side Effects 6 Other Side Effects 3 |
- reflex sympathetic activation,
- NE uptake block - less release inhibition (alpha-2 down-reg) - strong NE activation of heart (beta-1) - tachycardia, arrhythmia, fibrillation, infarct - overdose can be fatal (careful w/ suicidal pts) Other SE - transition to hypomania - skin problems: rash, photosensitivity - sexual dysfunction |
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Desipramine
Interactions 3 Issues |
Interactions
- MAO inhibitors cause enhanced effects due to complementary actions and increased cardiotoxicity - CNS depressants (e.g., alcohol, narcotics, barbiturates) - with sympathomimetics (enhanced effects) Issues - reasonably effective ADs - side effects - delay in therapeutic response - don’t work in all patients |
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Bupropion
-MOA? -Other effects (1) -SEs? (1 main) -Decrease in which side effects (2) -Other clinical use? (1) |
-2nd generation AD
-MOA unclear -Some DA, few 5-HT/NE effects -Psychomotor activation (+ for hypoactive pts) -Fewer CV effects* -Fewer sexual complications* than TCAs SEs -Dose-related effect on the seizure threshold (high dose can precipitate seizures) -Also used as adjunct in nicotine withdrawal programs |
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Trazodone
-Structurally similar to? -Efficacy? -SEs (1 main) -Other uses (2) |
-Similar to Nefazodone
-Heavily promoted -Poor AD -Few side effects (1 severe though) --Can produce priapism -Sedation (sometimes given with MAO-I as sleep aide) -Good hypnotic |
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Mirtazapine
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- 3rd generation AD
- inhibits 5-HT + NE reuptake - rel. free of cardiotoxicity |
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Fluoxetine
(Prozac) -MOA? -Does NOT block which receptors? -Efficacy? -SEs? (5) |
-Prototypical SSRI
-Selective 5-HT reuptake blocker -NO anti-muscarinic or alpha-1 receptor blocking effects -Good efficacy (delay in AD effect possible) -Non-sedating, even behaviorally activating -Minor SEs --Low cardiac toxicity* --Activation: nervousness, insomnia, restlessness, motor activity (increased risk for suicide**) --GI effects (nausea, decrease food intake --> initial weight loss*) --Headache --Sexual dysfunction (most common complaint) which leads to problems w/ compliance |
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Fluoxetine
(Prozac) -Interactions? (1) -Half life? |
-Inhibits liver enzymes (P450 system) -> interactions with other drugs
-Long acting drug* --Metabolized to active metabolite with very long half life (200hrs) --Can interact with other drugs metabolized by P-450 system |
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Fluoxetine
(prozac) -Other uses? (1) |
-Obsessive Compulsive Disorder (OCD)
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Sertraline
-MOA? -Differences from fluoxetine? (3) |
-SSRI
-Newer -Less akathisia (inner restlessness) -NO inhibition of P-450 system -Shorter half life* |
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Paroxetine
-MOA? -Inhibition of? -Half life? |
-SSRI
-Similar to Sertraline -SOME inhibition of p-450 system -Short half-life |
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Fluvoxamine
-MOA? -Inhibition of? -Half life? |
-SSRI
-Similar to Sertraline -Some inhibition of p-450 system -Short half life |
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Citalopram
-MOA? -Selectivity? -Use? |
-SSRI
-Similar to Sertraline -Most selective -Widely used |
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Venlafaxine
-MOA? -Compared to TCAs? -SEs (1) |
-3rd generation
-Inhibits 5-HT and NE reuptake -Good AD --> equal in efficacy compared to TCAs -Relatively free of cardiotoxicity* -Well tolerated SEs -High doses produce increase in diastolic BP |
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Lithium
MOA 4 Pharmacokinetics 5 |
MOA
- increase rate of inactivation of biogenic amine neurotransmitters (opp. of antidepressants) - reduces release of neurotransmitters producing decreased neural activity - replace Na and Mg in electrolyte pool affecting neural activity and second messanger funtions - inhibitory second messager effects on IP3-DAG and adenyl cyclase Pharmacokinetics - administered orally and reaches peak conc in 1-3 hrs (some GI irrit.) - eliminated by kidneys (indep. of liver) - excretion influenced by Na levels (NSAIDS and ACEI's increase lithium) - narrow therapeutic window and low margin of safety - acute treatment levels 0.8-0.9 to 1.3-1.4 mEq/L (even toxic range) |
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Lithium
Acute Toxicities 6 Chronic Toxicities 8 |
Acute Toxicities
- toxic level is 2.0 mEq/L - first signs are fatigue, muscle weakness, and muscle tremor - then nausea, vomiting, and diarrhea - eventually coma and death - due to replacement of Na and Mg in excitable tissue - NSAIDs and ACE I's increase lithium levels Chronic Toxicities - uncommon but due to 2nd messenger effects - decreased TSH response, less T3/T4 feedback so high TSH and goiter - polydipsia and polyuria b/c less response to ADH -> nephrogenic diabetes insipidus - diabetes responds to amiloride but not vasopressin - chronic interstitial nephritis - minimal change glomerulopathy - edema - cardiac effects unclear but dont use w/ sick sinus syndrome (bradycardia-tachycardia) |
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Lithium
Toxicity Treatment 5 Sodium Intake Caution 3 |
Toxicity Treatment
- office serum test = finger stick, $11, 2-5 minutes - saline drip dilutes lithium and increases excretion - osmotic diuretics (mannitol) increase excretion - do not use loop or thiazide diuretics b/c enhance Na excretion and lithium retention - dialysis in severe cases but be careful of redistribution phenomenon after stopping Sodium - increased dietary Na decreases lithium - may lose effects - reversal in Na intake may cause high lithium levels |
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Lithium in Pregnancy
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- lithium clearance increases and then decreases post-partum
- watch for post-partum toxicity - transferred through milk (1/3-1/2 serum levels) - Ebsteins anomaly and malformed tricuspid w/ septal defects in newborns higher than in population - alternatives cause spina bifida - possibly discont. in preg. until symptoms appear or try ECT |
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Valproate
MOA 1 Uses 3 |
MOA: anti-convulsant
Uses: - early phase of mania - as effective as lithium w/ greater margin of safety - combined w/ lithium if no response seen |
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Carbamazepine
MOA 1 Uses 2 Administration 2 |
MOA: anti-convulsant
Uses - acutely and prophylactically for mania - less effective than lithium Administration - only drug available as extended release - immediate release just as effective |
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Lamotrigine
MOA 1 Use 1 |
MOA: anti-convulsant
Uses - w/ lithium for improved results in maintaining mood stabilization in mania |
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Clonazepam
MOA Use 1 SE 5 |
MOA: anti-convulsant benodiazepine
Use - acute mania Side Effects - anterograde amnesia - tolerance - physical dependence - abuse potential - sedation |
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Atypical Antipsychotics for Mania
|
- approved for long term maintainance
- lots of side effects - used as adjuncts when other agents not effective or alternatives can not be used |
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Alprazolam
-Trade name -Usual Dose (2) -Use (2) -Peak time -Half life |
Xanax
Dose: - 0.25-0.5mg, 2-3 times daily - 1-2mg, 2-3 times daily Use: -Anxiety -Depression Peak time: - 1.0-2.0h Half Life: - 12-15h |
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Benzodiazapine
-Structure -MOA (2) - CNS Effects 7 |
MOA:
Change GABA-A receptors, to increase frequency of GABA to Recptor interaction, Increasing chloride conductance, Hyperpolarizing membranes, Decreasing neuronal activity Don't work on their own, need GABA CNS Effects -Anxiolytic-sedative effects -Anesthesia -Alcohol withdrawal -Anti convulsant -Hypnotic effects -Muscle relaxtion -Tolerance and Dependence |
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Benzodiazapine
Anxiolytic-sedative effects 4 Hypnotic Effects 4 Muscle Relaxation |
Anxiolytic-Sedative Effects
-Drug of Choice for Anxiety -Always causes some sedation (dose dependent) -Rarely causes Respiratory depression -Impares Alertness (driving, complex motor activity) Hypnotic Effects -Induce or prolong sleep (at higher doses!) -Increases stage 2 of non-REM sleep -Decreases slow wave sleep -Longer acting agents can produce a hangover effects Muscle Relaxation - all agents that produce sedation can produce muscle relaxation |
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Benzodiazapine
Anesthesia 5 Anticonvulsant Effects 2 Alcohol withdrawl 2 |
Anesthesia
-During induction of anesthesia, produce loss of conciousness -Produce anterograde amnesia -Not complete anesthetics by themselves, don't block pain -Shorter acting agents are usually cause less drug interactions and are preffered to long acting agents -long acting agents prolong post-surg respiratory depression Anticonvulsant -Adjuncts to other anticonvulsant medications in poorly controlled seizures -Have specific uses ins selected siezure disorders (Diazepam for status epilepticus) Alcohol - Used in the detoxification process of chronic alcoholism - Ameliorate the intense withdrawal signs |
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Benzodiazapine
Tolerance and Dependence 4 Resp and CV effects 4 |
Tolerance
-Chronic use leads to tolerance and physical dependence -Tolerance is pharmacodynamic (not metablic) due to the down-reg of receptors, requires higher doses -Withdrawal syndrome upon abrupt stoppage leads to life threatening convulsions -Short acting agents are more susceptible and cause a faster onset! Resp/CV -No peripheral side effects -Very hard to produce Resp failure w/ high doses of Benzo's alone (usually need co-admin of Barb/EtOH) -Few CV effects but can cause problems in CHF, Hypovolemia, or compromised cardiac function -CV problems are worsened when given IV |
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Benzodiazapine
Pharmacokinetics 5 Metabolites are? Drug Interactions 2 |
-Different duration of actions between agents, absorbed at different rates
-Metabolized in liver by Microsomal Drug Oxidizing System (MDOS) -Don't induce their own enzymes of metabolism -Are all lipid solulbe to differing degrees -Protein bound in blood - metabolites are active Interactions - other CNS depressants including alcohol - Benzo's enhance depressant effects, such as respiratory depression |
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Benzodiazapine
Anxiety treatment 3 Treatment of sleep disorders 5 |
Anxiety
- Most effect in non psychotic anxious patients w/ high emotional and somatic symptoms - with low levels of depression and interpersonal problems - Can treat anxiety associated w/ depression but should also treat the underlying cause Sleep Disorders Safer than barbituates: -Produce less REM supression -Don't induce liver enzymes - Very Rare Resp depression - Can produce hangerover - Some REM supression does happen so REM rebound on discontinuation - Tolerance |
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Benzodiazapine
Anticonvulsant Treatment 3 Medical procedures 2 Unexpected Effects 2 |
Anticonvulsant
-Adjuncts to other medications or for short-term effects -Longer duration agents are used but produce sedation, interferes w/ daily activities -Diazepam treats Status Epilepticus!! Procedures -Hypnotic use for mildly discomforting procedures (intubation, colonoscopy) -Midazolam (versed) is drug of choice for this (IV admin), short acting Unexpected Effects -Anterograde Amnesia - Less recall of surgical event -Hostility - From loss of social inhibition due to reduced anxiety from drug |
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Benzodiazapine
CNS side effects 6 Overdose Treatment 2 |
CNS SE
At all doses: -Sedation -Lethargy -Fatigue -Mental clouding Higher (toxic) doses: -Fine motor incoordination -Ataxia OD -Mostly just reversal of CNS effects -Flumazenil!! |
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Benzodiazapine
Drug List 6 |
Alprazolam
Chlordiazepoxide Clonazepam Diazepam (long) Flurazepam (long) Triazolam (short) |
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Flumazenil
8 |
- BZ-1 & -2 antagonist
- Good reversal of sedation - Respiratory reversal is unreliable - Not effective with other agents, e.g., barbs, ethanol etc - Short acting (0.7 -1.3h) - IV - Multiple injections - Can produce precipitated withdrawal in physically dependent |
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Buspirone
Type Use 1 Does NOT 6 Toxicity 4 |
- NON- Benzodiazepine
Use - Anxiolytic, comparable to diazepam It does NOT: -An effective sedative -A muscle relaxant -Anticonvulsant -A hypnotic -Produce tolerance or physical dependence -Not a drug of abuse. Toxicity Cardio: -Palpitations/Tachycardia -Increased BP Eye: -Pupillary constriction GI distress |
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Anti-histamines for Anxiety
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used for sedation
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Triazolam
-Trade name -Usual Dose -Use -Peak Time -Half Life |
Halcion
Dose: 0.25-0.5mg, before bed Use: -Insomnia Peak Time: - 1.5-20h Half Life - 3-5 |
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Dantrolene
MOA? Uses? (2) SEs? (3) |
MOA
-Prevents release of Ca2+ from SR (binds ryanodine receptor) -Thus inhibits muscle contraction -Orally available -Half life = 8 hours Uses -General (muscle) relaxant with less sedation -Malignant hyperthermia SEs -Muscle weakness -Sedation -Hepatitis (rare) |
