step_1_pharm_20140606001619 Flashcards
Epinephrine
alpha-agonistdecrease aqueous humor synthesis via vasoconstrictionSE: mydriasis, not for closed-angle glaucoma
Brimonidine
alpha-agonist (alpha 2)decrease aqueous humor synthesisSE: blurry vision, ocular, hyperemia, foreign body sensation, ocular allergic reaction
Timolol, bextaolol, carteolol
decrease aqueous humor synthesisSE: none
Acetazolamide
diureticsdecrease aqueous humor synthesis via inhibition of carbonic anhydraseSE: none
Pilocarpine
direct cholinomimeticsincrease outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshworkSE: Miosis and cyclospasm (contraction of ciliary muscle)Use in emergencies - very effective at opening meshwork into canal of Schlemm
Carbachol
direct cholinomimeticsincrease outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshworkSE: Miosis and cyclospasm (contraction of ciliary muscle)
Physostigmine, echothiophate
indirect cholinomimeticsincrease outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshworkSE: Miosis and cyclospasm (contraction of ciliary muscle)
Latanoprost (PGF2alpha)
prostaglandinincrease outflow of aqueous humorSE: darkens color of iris
Morphine, fentanyl, codeine, heroin, methadone, dextromethorphan, diphenoxylate
opioid analgesicsagonist at opioid receptors (mu = morphine, delta = enkephalin, kappa = dynorphin) to modulate synaptic transmission. Inhibit release of Ach, NE, 5-HT, glutamate, substance PSE: addiction, respiratory depression, constipation, miosis (pinpoint pupil)Toxicity treated by naloxone or naltrexone (opioid receptor antagonist)
Butorphanol
mu-opioid receptor parital agonist and kappa receptor agonistUses: severe pain (migtaine, labor)Causes less respiratory depression than full agonistCan cause opioid withdrawal symptoms if patient is also taking full opioid agonist
Tramadol
very weak opioid agonist; also inhibits serotonin and NE reuptakeUses: chronic painSE: similar to opioids. decreases seizure threshold
Phenytoin
simple, comlpex, tonic-clonic (1st line), status epilepticus (1st line for prophylaxis)use-dependent blockade of Na channels; inhibition of glutamate release from excitatory presynaptic neuronfosphenytoin for parenteral useSE: nystagmus, diplopia, ataxia, sedation, gingival, hyperplasia, hirsutism, megaloblastic anemia (decreased folate), fetal hydantoin syndrome, SLE-like syndrome, induction of P-450, lymphadenopathy, Steven-Johnson syndrome, osteopenia
Carbamazepine
simple, complex, tonic-clonic, trigeminal neuralgia (1st line for all)increase Na channel inactivationSE: diplopia, ataxia, blood dyscrasias, liver toxicity, teratogenesis, induction of P-450, Steven-Johnson syndrome
Lamotrigine
simple, complex, tonic-clonicblocks VG-Na channelsSE: Steven-Johnson syndrome
Gabapentin
simple, complex, tonic-clonic, peripheral neuropathy, postherpetic neuralgia, migraines prophylaxis, bipolar disorderdesigned as GABA analog, but primarily inhibits high-voltage-activated Ca channelsSE: sedation, ataxia
Topiramate
simple, complex, tonic-clonic, migraine preventionblocks Na channels, increase GABA actionSE: sedation, mental dulling, kidney stones, weight loss
Phenobarbital
simple, complex, tonic-clonic (1st line in children)increase GABAa actionSE: sedation, tolerance, dependence, induction of P-450
Ethosuximide
1st line for absenceblocks thalamic T-type Ca channelsSE: GI distress, fatigue, headache, urticaria, Steven-Johnson syndromeEFGH - Etho, Fatigue, GI, Headache
Benzodiazepines
diazepam, lorazepam, triazolam, oxazepam, midazolamUses: 1st line for acute status epilepticus (diaz-, loraz-), seizures of eclampsia, anxiety, spasticity, detox (alcohol withdrawal), night terrors, sleepwalking, anesthetic (muscle relaxation), hypnoticMOA: facilitate GABAa action by increased frequency of Cl channel opening, decrease REM sleepSE: dependence, addictive CNS depression effects with alcohol. less risk of respiratory depression and coma than with barbituratesTreat overdose with flumazenil (competative antagonist)Most have long half-lives and active metabolites except triazolam, oxazepam, and midazolam - higher addictive potential
Barbiturates
phenobarbital, pentobarbital, thiopental, secobarbitalfacilitate GABAa action by increased duration of Cl channel opening, thus decrease neuron firingcontraindicated in porphyriaUses: sedative for anxiety, seizures, insomnia, induction, of anesthesia (thiopental)SE: respiratory and cardiovascular depression, CNS depression (with alcohol), dependence, induces P-450overdose treatment is supportive (assist respiration and maintian BP)
Valproic acid
simple, complex, tonic-clonic (1st line), absence, myoclonicincrease Na channel inactivation, increase GABAconcentraitonSE: GI distress, rare but fatal hepatotoxicity, nueral tube defects in fetal (spina bifida), tremor, weight gainContraindicated in pregnancy
Non-benzo hypnotics
zolpidem, zaleplon, eszopicloneact via BZ1 subunit of the GABA receptorreversed by flumazenilUse: insomniaSE: ataxia, headaches, confusionrapid metabolism by liver enzymes, only modest day-after psychomotor depression, lower dependence risk
Inhaled anesthetics
halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, NOEffects: myocardial depression, repiratory depression, nausea/emesis, increased cerebral blood flow (decreased cerebral metabolic demand)SE: hepatotoxicity (halothane), nephrotoxicity (mehoxyflurane), proconvulsant (enflurane), malignant hyperthermia (all but NO), expansion of trapped gas in a body cavity (NO)
Thiopental
IV anesthetics - barbiturateshigh potency, high lipid solubility, rapid entry into brainUse: induction of anesthesia and short surgical proceduresterminated by rapid redistribution into tissue and fatdecrease cerebral blood flow
Midazolam
IV anesthetic - benzodiazepineUse: endoscopy; used adjunctively with gaseous anesthetic and narcoticsSE: postop respiratory depression, decreased BP (treat with flumazenil), amnesia
Arylcyclohexylamines (ketamine)
IV anesthetic - PCP analogblock NMDA receptors, cardiovascular stimulantSE: disorientation, hallucination, and bad dreamsincrease cerebral blood flow
Propofol
IV anesthesticpotentiates GABAaUse: sedation in ICU, rapid anesthesia induction, and short proceduresless postop nausea than thiopental
Local anesthetics
Esters - procaine, cocaine, tetracaineAmides - lidocaine, mepivacaine, bupivacaine (2 i’s)block Na channels by binding specific receptors on inner portion of channel; preferentially bind to activated Na channels (rapid firing neurons)tertiary amine - penetrate membrane in uncharged form then bind ion channels as charged formcan be given with vasoconstrictors to enhance local actionin infected tissue (acidic), alkaline anesthetics are charged and cannot penetrate membrane –> increase doseOrder of blockage: small myl > small unmyl > large myl > larger unmylOrder of loss: pain, temp, touch, pressureUse: minor surgical procedures, spinal anesthesiaSE: CNS excitation, severe CV toxicity (bupivacaine), HTN, hypotension, arrhythmias (cocaine)
Succinylcholine
depolarizing NMBAch receptor agonist –> sustained muscle depolarization and prevents muscle contractionPhase I (prolonged depolarization) - no antidotes (potentiated by AchE inhibitors)Phase II (repolarized but blocked) - antidote is neostigmineSE: hypercalcemia, hyper kalemia, and malignant hyperthermia
Nondepolarizing NMB
tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuroniumcompetitive antagonists - compete with Ach for receptorReversal of block - neostigmine, edrophonium
Dantrolene
prevents release of Ca from SR of skeletal muscleUse: malignant hyperthermia, neuroleptic malignant syndrome
Dopamine agonists
bromocriptine (ergot), pramipexole, ropinirole (non-ergot)non-ergot preferred
Increase dopamine
amantadine - increase dopamine release (also for influenza A and rubella) SE: ataxiaL-dopa/carbidopa (converted to dopamine in CNS)
Prevent dopamine breakdown
selegiline - MAO type B inhibitorentacapone, tolcapone - COMT inhibitors – prevent L-dopa peripheral degradation, thereby increasing availability
L-dopa/carbidopa
increase levels of dopamine in brainSE: arrhythmias from increased peripheral formation of catecholamines; long term use dyskinesia following administration, akinesia between doses
Selegiline
MAO-B inhibitor, which preferentially metabolizes dopamine over NE and 5-HTUse: adjunctive agent to L-dopa in treatment of Parkinson’s diseaseSE: enhance SE of L-dopa
Memantine
NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca)Use: Alzheimer’sSE: dizziness, confusion, hallucinations
Donepezil, galantamine, rivastigmine
acethylcolinesterase inhibitorsUse: Alzheimer’sSE: nausea, dizziness, insomnia
Sumatriptan
5-HT 1B/1D agonistinhibits trigeminal nerve activation; prevents vasoactive peptide release –> vasoconstrictionUse: acute migraine, cluster headache attacksSE: coronary vasospasm (contraindicated in CAD and Prinzmetal’s angina), mild tingling
H2 blockers
cimetidine, ranitidine, famotidine, nizatidine (-tidine)Reversible block of H2-receptor –> decreased H+ secretion by parietal cellsUses: peptic ulcer, gastritis, mild esophageal refluxSE: cimetidine is a potent inhibitor of P-450; antiandrogenic effects (prolactin release, gynecomastia, impotence); can cross blood-brain barrier (confusion, dizziness, headaches) and placenta; cimetidine and ranitidine decrease renal excretion of creatinine
PPI
omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazoleirreversibly inhibit H+/K+ ATPase in stomach parietal cellsUses: peptic ulcer, gastritis, esophageal reflux, ZE syndromeSE: increased risk of C. difficle infection, pneumonia. hip fractures, decreased serum Mg with long term use
Bismuth, sucralfate
bind to ulcer base, providing physical protection and allowing HCO- secretion to reestablish pH gradient in the mucous layerUses: increased ulcer healing, traveler’s diarrhea
Misoprostol
PGE1 analog. increase production and secretion of gastric mucous barrier; decreased acid productionUses: prevention of NSAID-induced peptic ulcers; maintenance of PDA, induce laborSE: diarrhea, contraindicated in women of childbearing potential
Octreotide
Long-acting somatostain analogUses: acute variceal bleeds, acromegaly, VIPoma, and carcinoid tumorsSE: nausea, cramps, steatorrhea
Aluminum hydroxide
SE: hypokalemia, constipation and hypophosphatemia, proximal muscle weakness, osteodystrophy, seizuresAluminimum amount of feces
Magnesium hydrozide
SE: hypokalemia, diarrhea, hyporeflexia, hypotension, cardiac arrestMg = must go to the bathroom
Calcium carbonate
SE: hyperkalemia, hypercalcemia, rebound acid increase; can chelate and decrease effectiveness of other drugs (tetracycline)
Osmotic laxatives
magnesium hyroxide, magnesium citrate, polyethylene gycol, lactuloseprovide osmotic load to draw water outlactulose also treats hepatic encephalopathy since gut flora degrade it into metabolites (lactic acid and acetic acid) that promote nitrogen excretion as NH4Uses: constipationSE: diarrhea, dehydration
Inflizimab
monoclonal antibody to TNF-alphaCrohn’s disease, UC, RASE: infection (including reactivation of latent TB), fever, hypotension
Sulfasalazine
combination of sulfapyridine (antibacterial) and 5-aminosalicyclic acid (anti-inflammatory); activated by colonic bacteriaUse: UC, Crohn’s diseaseSE: malaise, nausea, sulfonamide toxicity, reversible oligospermia
Ondansetron
5-HT3 antagonist. powerful central-acting antiemeticUses: control vomiting postoperatively and in patients undergoing cancer chemotherapySE: headache, constipation
Metoclopramide
D2 receptor antagonist. increased resting tone, contractility, LES tone, motility. does not influence colon transport timeUses: diabetic and post-surgery gastroparesis, antiemeticSE: increased parkinsoniam effects. Restlessness, drowsiness, depression, nausea, diarrhea. drug interaction with digoxin and diabetic agentscontraindicated in patient with small bowel obstruction or Parkinson’s disease
CNS stimulants
methylphenidate, dextroamphetamine, methamphetamineincreases catecholamines at the synaptic cleft, especially NE and dopamineUses: ADHD, narcolepsy, appetite control
Antipsychotics (neuroleptics)
haloperidol, trifluoperazone, fluphenazine, thioridazine, chlorpromazine (-azines)block D2 receptors (increase cAMP)Uses: schizophrenia (positive symptoms), psychosis, acute mania, Tourette’sSE: lipid soluble and stored in body fat, hyperprolactin, High potency: Try to Fly High (TFH) - extrapyramidal symptoms SE: NMS (rigidity, myoglobinuria, autonomic instability, hyperpyrexia), tardive dyskinesia (stereotypic oral-facial movements as a result of long-term antipsychotic use)NMS - Fever, Enchephalopathy, Vital insability, Elevated enzymes, Rigidity of muscles (FEVER)Low potency: Cheating Thieves are low (CT) - non-neurologic SE: blocking muscarinic, alpha 1 and histamine receptorsC - corneal deposits; T - retinal deposits
Atypical antipsychotics
olanzopine, clozapine, quetiapine, risperidone, aripiprazole, ziprasidonevaried effects on 5-HT, dopamine, and alpha and H1 receptorsUses: schizophrenia (both positive and negative), bipolar, OCD, anxiety disorder, depression, mania, Tourette’sSE: fewer extrapyramidal and anticholinergic SEolan/cloza - weight gaincloza - agranulocytosis (monitor WBC weekly) and seizureZipra - may prolong QT
Lithium
Possibly related to inhibition of phosphoinositol cascadeUses: mood stabilizer for bipolar disorder; blocks relapse and acute manic events, SIADHSE: tremor, sedation, edema, heart block, hypothyroidism, polyuria, teratogenesis, Ebstein anomaly and malformation of great vesselsnarrow therapeutic window, exclusively secreted by kindeys; most is reabsorbed at proximal convoluted tubule following Na
Buspirone
stimulates 5-HT1A receptorsUses: GAD, requires 1-2 weeks to see effects
SSRIs
fluoxetine, paroxetine, setraline, citalopramUses: depression, GAD, panic disorder, OCD, bulimia, social phobias, PTSDSE: GI distress, sexual dysfunciton, serotonin syndrome (treat with cyproheptadine)
SNRIs
venlafaxine, duloxetine (greater effect on NE)inhibit serotonin and NE reuptakeUses: depression; V - also for GAD; D - diabetic peripheral neuropathySE: increased BP, nausea, sedation
Tricyclic antidepressants
amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, doxepin, amoxopine (-iptyline or -ipramine)block reuptake of NE and serotoninUses: major depression, betwetting (im-), OCD (clom-), fibromyalgiaSE: sedation, alpha1 blocking effects (postural hypotension), atropine-like, convulsions, coma, cardiotoxicity (treat with NaHCO3), respiratory depression, hypersyrexianortriptyline in elderly with anticholenergic SE
MAO inhibitors
tranylcypromin, phenelzine, isocarboxazid, selegiline (MAO-B selective)nonselective MAO inhibition increases levels of amine NT (NE, serotonin, dopamine)Uses: atypical depression, anxiety, hypochondriasisSE: HTN crisis, CNS stimulationcontraindicated with SSRIs, TCAs, St. John’s Wort, meperidine, and dextromethorphan
Bupropion
atypical anti-depressantincrease NE and dopamine via unknown mechanismSE: stimulant effects, headache, seizure in bulimic patientsalso used for smoking cessation
Mirtazapine
atypical anti-depressantalpha2-antagonist (increase release of NE and serotonin) and potent 5-HT2 and 5-HT3 receptorSE: sedation (desirable for insomnia), increased appetite, weight gain (desirable for elderly), dry mouth
Maprotiline
atypical anti-depressantblocks NE reuptakeSE: sedation, orthostatic hypotension
Trazodone
atypical anti-depressantinhibits serotonin reuptakeUses: insomnia, high dose for antidepressant effectSE: sedation, nausea, priapism, postural hypotension
Alcohol withdrawal
benzodiazepines
Anxiety
SSRIs, SNRIs, buspirone
ADHD
methylphenidate, amphetamines
Bipolar disorder
lithium, valproate, carbamazepine, atypical antiphyschotics
Bulimia
SSRIs
Depression
SSRIs, SNRIs, TCAs, buspirone, mirtazapine (especially with insomnia)
OCD
SSRIs, clomipramine
Panic disorder
SSRIs, venlafaxine, benzodiazepines
PTSD
SSRIs
Schizophrenia
Antipsychotics
Social phobias
SSRIs
Tourette’s syndrome
antipsychotics
Insulin
Rapid acting: Lispro, Aspart, GlulisineShort-acting: regularIntermediate: NPHLong-acting: Glargine, Detemirbind insulin receptor (tyrosine kinase activity)Liver: increase glucose stored as glycogenMuscle: increased glycogen and protein synthesis, K uptakeFat: aids TG storageUses: DM 1 & 2, gestational diabetes, life-threatening hyperkalemia, stress-induced hyperglycemiaSE: hypoglycemia, very rarely hypersensitivity reactions
Biguanides
Metformindecreases gluconeogenesis, increases glycolysis, increases peripheral glucose uptakeUses: oral - 1st line for DM2SE: GI upset, lactic acidosis (contraindicated in patients with renal failure)
Sulfonylureas
1st gen: tolbutamide, chlorpropamide2nd gen: glybutide, glimepriride, glipizideclose K+ channel in beta-cell membrane, so depolarizes –> triggering insulin release via Ca influxUses: DM2, requires some islet functionSE: 1st - disulfiram-like effects; 2nd - hypoglycemia
Glitazones/thiazolidinediones
pioglitazone, rosiglitazoneincrease insulin sensitivity in peripheral tissues. bind PPAR-gamma nuclear transcription regulator (activate fatty acid storage and glucose metabolism)Use: monotherapy in DM2 or combinedSE: weight gain, edema, hepatotoxicity, HF
Alpha-glucosidase inhibitors
acarbose, miglitolinhibit intestinal brush-border alpha-glucosidases, delayed sugar hydrolysis and glucose absorption –> decreased postprandial hyperglycemiaUse: montherapy for DM2 or conbinedSE: GI disturbances
Amylin analongs
pramlintidedecreased glucagonUses: DM 1 & 2SE: hypoglycemia, nausea, diarrhea
GLP-1 analogs
exenatide, liraglutideincreases insulin, decreases glucagon releaseUse: DM2SE: nausea, vomiting, pancreatitis
DPP-4 inhibitors
linagliptin, saxagliptin, sitagliptinincrease insulin, decrease glucagon releaseUse: DM2SE: mild urinary or respiratory infections
PTU
block peroxidase (organification of iodide and coupling), blocks 5’-deiodinase (decreases peripheral conversion of T4 to T3)Use: hyperthyroidSE: skin rash, agranulocytosis, aplastic anemia, hepatotoxicity
Methimazole
block peroxidase (organification of iodide and coupling)Use: hyperthyroidSE: skin rash, agranulocytosis, aplastic anemia, teratogen
Levothyroxine, triiodothyronine
thyroxine replacementUse: hypothyroidism, myxedemaSE: tachycardia, heat intolerance, tremors, arrhythmias
GH
GH deficiency, Turner syndrome
Somatostatin
octreotideacromegaly, carcinoid, gastrinoma, glucagonoma, esophageal varices
Oxytocin
stimulates labor, uterine contractions, milk let-down; control uterine hemorrhage
Demeclocycline
ADH antagonistUse: SIADHSE: nephrogenic DI, photosensitivity, abnormalities of bone and teeth
Glucocorticoids
hydrocortisone, prednisone, triamcinolone, dexamethasone, beclomethasonedecrease the production of leukotrienes and prostaglandins by inhibiting phospholipase A2 and expression of COX-2Uses: Addision’s disease, inflammation, immune suppressio, asthmaSE: iatrogenic Cushing’s, adrenal insufficiency when drug stopped abruptly after chronic use
Mannitol
osmotic diureticincrease tubular fluid osmolarity; producing increased urine flow, decrease intracranial/intraocular pressureUses: drug overdose, elevated intraocular/intracranial pressureSE: pulmonary edema, dehydrationContraindicated in anuria, CHF
Acetacolamide
CA inhibitorcauses self-limited NaHCO3 diuresis and reduction in total-body HCO3-Uses: glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness, pseudotumor cerebriSE: hyperchloremic metabolic acidosis, paresthesias, NH3 toxicity, sulfa allergy
Furosemide
sulfonamide loop diureticinhibits cotransport system (Na, K, Cl) of TAL of Henle; abolishes hypertonicityof medulla, preventing concentration of urinestimulate PGE release (vasodilatory effect on afferent arteriole); increase Ca excretion (Loops Lose Ca)SE: Ototoxicity, Hypokalemia, Dehydration, Allergy, Nephritis (interstitial), Gout (OH DANG)
Ethacrynic acid
loop diureticphenoxyacetic acid derivative; same action as furosemideSE: similar to furosemide; can cause hyperuricemia
Hydrochlorothiazide
thiazide diureticinhibits NaCl reabsorption in early distal tubule, reducing capacity of the nephron, decrease Ca excretionUse: HTN, CHF, idiopathic hypercalciuria, nephrogenic DISE: hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, and hypercalcemia, sulfa allergy (HyperGLUC)
K sparing diuretics
spironolactone, eplerenonecompetitive aldosterone receptor antagonists in the cortical collecting tubuletriamterene, amilorideact on cortical collecting tubule by blocking Na channelsUse: hyperaldosteronism, K+ depletion, CHFSE: hyperkalemia (arrhythmia), endocrine effect with spironolactone (gynecomastia, antiandrogen effects)
ACE inhibitors
captopril, enalapril, lisinoprilinhibit ACE –> decreases angiotensin II –> decreases GFR by preventing constriction of the efferent arterioles; also prevents inactivation of of bradykinin, a potent vasodilatorUse: HTN, CHF, proteinuria, diabetic renal disease; prevent unfavorable heart remodeling as a result of chronic hypertensionSE: cough, angioedema, teratogen (fetal renal malformation), creatinine increase, hyperkalemia, hypotensionAvoid in bilateral renal artery stenosis because ACE inhibitors will further decrease GFR –> renal failure
Penicillin
penicillin G (IV and IM form), penicillin V (oral)beta-lactambind penicillin-binding proteins; block transpeptidase cross-linking of peptidoglycan; activate autolytic enzymesUses: gram-positive organisms (S. pnuemoniae, S. pyogenes, Actinomyces); N. meningitidis Treponema pallidum, syphilisbactericidal for gram-positive cocci, gram-positive rods, gram-negative cocci, and spirochetesnot penicillinase resistantSE: hypersensitivity reaction, hemolytic anemiaResistance: beta-lactamases cleave beta-lactam ring
Oxacillin, nafcillin, dicloxacillin
penicillinase-resistant penicillinssame as penicillin; resistant because bulky R group blocks accessUses: S. aureus (except MRSA; resistant because altered penicillin-binding protein target site)SE: hypersensitivity reactions; interstital nephritis
Ampicillin, amoxicillin
aminopenicillinssame as penicillin; wider spectrum, penicillinase sensitive; combine with clavulanic acid to protect against beta-lactamaseamoxicillin has greater oral bioavailablityUses: H. influenzae, E. coli, Listeria, Proteus, Salmonella, Shigella, enterococci (HELPSS)SE: hypersensitivity reactions; ampicillin rash; pseudomembranous colitisResistance: beat-lactamase cleaves beta-lactam ring
Ticarcillin, piperacillin
antipseudomonalssame as penicilinUses: Psudomonas spp., gram-negative rods; susceptible to penicillinase; use with clavulanic acidSE: hypersensitivity reaction
Beta-lactamase inhibitors
clavulanic acidsulbactamtazobactum
Cephalosporins
beta-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicilinases; bactericidal1st gen (cefazolin, cephalexin) - gram-positive cocci, Proteus, E. coli, Klebsiella (PEcK)cefazolin used prior to surgery to prevent S. aureus wound infections2nd gen (cefoxitin, cefaclor, cefuroxime) - gram-positive cocci, H. influenzae, Enterobacter aerogenes, Neiseria spp., Proteus, E. coli, Klebsiella, Serratia (HEN PEcKS)3rd gen (ceftriaxone, cefotaxime, ceftazidime) - serious gram-negative infections resistant to other beta-Ceftriaxone - meningitis and gonorrheaCeftazidime - Pseudomonas4th gen (cefepime) - increase activity against Pseudomonas and gram-positive organismsSE: HSR, vitamin K deficiency, increase nephrotoxicity of aminoglycosides
Aztreonam
monobactam resistant to beta-lactamases; prevent cross-linking by binding to PBP3synergistic with aminoglycosidesUses: gram-negative rods onlyfor penicillin-allergic patients and those with renal insufficiency who can’t tolerate aminoglycosidesSE: nontoxic; GI upset
Imipenem/cilastatin, meropenem
imipenem - broad spectrum beta-lactamase-resistant carbapenemalways administered with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubulesUse: gram-positive cocci, gram-negative rods and anarodes; SE limit effects use to life-threatening infectionsSE: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels
Vancomycin
inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursorsUse: gram-positive only - serious, multidrug-resistant organisms, including MRSA, enterococci, and C. difficileSE: Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing - red man syndrome (prevented by pretreatment with anti-histamines and slow infusion rates)Resistance: amino acid change of D-ala D-ala to D-ala D-lac
Aminoglycosides
gentamicin, neomycin, amikacin, tobramycin, strptomycinbactericidal; inhibit formation of initiation complex and cause misreading mRNA; block translation; require O2 uptake - ineffective against anaerobesUse: severe gram-negative rod infections; bowel surgery (neomycin)synergistic with beta-lactam antibioticsSE: Nephrotoxicity (especially when used with cephalosporins), Neuromuscular blockage, Ototoxicity (with loop diuretics); tertogen
Tetracyclines
tetracycline, doxycycline, demeclocycline, minocyclinebacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA; limited CNS penetrationdoxycycline - fecally eliminated; can be used in patients with renal failuredo not take with milk, antacid, or iron-containg preparations because divalent cations inhibit its absorption in the gutUse: Borrelia burgdorferi, M. peneumoniae; Rickettsia and Chlamydia (accumulates intracellularly)SE: GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivitycontraindicated in pregnancyResistance: decreased uptake into cells or increased efflux out of cell by plasmid-encoded transport pumps
Macrolides
azithromycin, clarithromycin, erythromycininhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit; bacteriostaticUse: atypical pneumonias (mycoplasma, chlamydia, legionella), STDs (chlamydia), gram-positive cocci (strep in patient allergic to penicillin)SE: Motility issues, Arrhythmia caused by prolonged QT, acute Cholestatic hepatic hepatitis, Rash eOsinophilia (MACRO); increased concentration of throphyllines, oral anticoagulantsResistance: methylation of 23S rRNA binding site
Chloramphenicol
blocks peptidyltransferase at 50S ribosomal subunit; bacteriostaticUse: Meningitis (Hib, N. meningitidis, S. pntumoniae)SE: anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (premature infants b/c of lack of UDP-glucuronyl tranferase)Resistance: plasmid-encoded acetyltransferase that inactiavtes drug
Clindamycin
blocks peptide transfer at 50S ribosomal subunit; bacteriostaticUse: anaerobic infections in aspiration pneumonia; oral infections with mouth anaerobes; anaerobes above the diaphragmSE: pseudomembranous colitis (C. diff), fever, diarrhea
Sulfonamides
sulfamethoxazole, sulfisoxazole, sulfadiazinePABA antimetabolites inhibit dihydropteroate synthase; bacteriostaticUse: gram-positive, gram-negative, Nocardia, Chlamydia, UTISE: hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drigs from albuminResistance: altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or increased PABA synthesis
Trimethoprim
inhibits bacterial dihydrofolate reductase; bacteriostaticUse: combo with SMX - UTIs, Shigella, Salmonella, Pneumocystis pneumonia (treatment and prophylaxis)SE: megaloblastic anemia, leukopenia, granulocytopeniaTMP: Treats Marrow Poorly
Fluoroquinolones
ciprofloxacin, norfloxacin, enoxacin, nalidicic acidinhibit DNA gyrase (topo II) and topo IV; bacteriocidal; don’t take with antacidsUse: gram-negative rods of urinary and GI tracts (Pseusomonas), Neisseria, some gram-positive organismsSE: GI upset, superinfections, skin rashes, headache, dizziness, less common - tendonitis, tendon rupture (> 60 or taking prednisone), leg cramps, myalgias; prolonged QTcontraindicated in pregnant women and in children because cartilage damageResistance: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps
Metronidazole
forms free radical toxic metabolites in the bacterial cell that damage DNA; bacteriocidal, antiprotozoalUse: Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes, H. pylori (with PPI and clarithromycin) (GET GAP)SE: disulfiram-like reaction with alcohol; headache, metallic taste
Isoniazid
decrease synthesis of mycolic acids; bacterial catalase-peroxidase needed to convert INH to active metaboliteUse: Mycobacterium tuberculosis prophylaxisdifferent half-lives in fast vs. slow acetylatorsSE: neurotoxicity, hepatotoxicity. Vit B6 can prevent neurotoxicity, lupus
Rifampin
inhibits DNA-dept RNA-polymeraseUse: Mycobacterium tuberculosis; delays resistance to dapsone when used in leprosy; meningococcal prophylaxis and chemoprophylaxis in contacts of children with HibSE: minor hepatotoxicity and drug interaction (increase P450), orange body fluids, rapid resistance if used alone
Pyrazinamide
thought to acidify intracellular environment via conversion to pyrazinoic acidUse: TBSE: hyperuricemia, hepatotoxicity
Ethambutol
decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltarnsferaseUse: TBSE: optic neuropathy (red-green cold blindness)
Amphotericin B
binds ergosterol (unique to fungi); form membrane pores that allow leakage of electrolytesUse: serious, systemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Candida, Mucorsupplement K and Mg because of altered renal tubule permeabilitySE: fever/chills, hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis
Nystatin
binds ergosterol (unique to fungi); form membrane pores that allow leakage of electrolytes; topical b/c too toxic for systemic useUse: “swish and shallow” for oral candidiasis, topical for diaper rash or vaginal candidiasis
Azoles
fluconazole, ketoconazole, clotrimazole, miconazole (-nazole)inhibit fungal sterol synthesis, by inhibiting P-450 enzyme that converts lanosterol to ergosterolUse: local and less serious systemic mycosesfluconazole - cryptococcal meningitis in AIDSitraconazole - Blastomyces, Coccidioides, HistoplasmaSE: testosterone synthesis inhibition (gynecomastia), liver dysfunction (inhibit P450)
Flucytosine
inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminaseUse: systemic fungal infections (Crypto) in combo with amphotericin BSE: bone marrow suppression
Caspofungin, micafungin
inhibits cell wall synthesis by inhibiting synthesis of beta-glucanUse: invasive aspergillosis, CandidaSE: GI upset, flushing (by histamine release)
Terbinafine
inhibits the fungal enzyme squalene epozidaseUse: dermatophytoses (onchomycosis - fungal infection of finger or toe nails)SE: abnormal LFTs, visual disturbances
Griseofluvin
interferes with microtubule function; disrupts mitosis; deposits in keratin-containing tissuesUse: oral treatment of superficial infections, inhibits growth of dermatophytes (tinea, ringworm)SE: teratogenic, carcinogenic, confusion, headache, increase P450 and warfarin metabolism
Chloroquine
blocks detoxification of heme into hemozoin; heme accumulates and is toxic to plasmodiaUse: plasmodial species other than P. falciparum (resistance due to membrane pump that decreases intracellular concentration)SE: retinopathy
Zanamivir, oseltamivir
inhibit influenza neuraminidase, decreasing the release of progeny virusUse: treatment and prevention of influenza A and B
Ribavirin
inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenaseUse: RSV, chronic hepatitis CSE: hemolytic anemia, severe teratogen
Acyclovir
monophosphotylated by HSV/VZV thymidine kinase; guanosine analog; triphosphate formed by cellular enzymes; preferentially inhibits viral DNA polymerase by chain terminationUse: HSV and VZV; weak against EBV; no activity against CMV; prophylaxis in immunocompromisedfor herpes zoster - famciclovirSE: noneResistance: mutated viral thymidine kinase
Ganciclovir
5’-monophosphate formed by a CMV viral kinase; guanosine analog; triphosphate formed by cellular kinases; preferentially inhibits viral DNA polymeraseUse: CMV, especially in immunocompromisedvalganciclovir (prodrug) - better oral bioavailabilitySE: leukopenia, neutropenia, thrombocytopenia, reanl toxicityResistance: mutated CMV DNA polymerase or lack of viral kinase
Foscarnet
viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzymedoesn’t require activation by viral kinaseUse: CMV retinitis in immunocompromised when ganciclover fails; acyclovir-resistant HSVSE: nephrotoxicityResistance: mutated DNA polymerase
Cidofvir
preferentially inhibit viral DNA polymerasedoesn’t require phosphorylation by viral kinaseUse: CMV retinitis in immunocompromised; acyclovir-resistant HSVlong half-lifeSE: nephrotoxicity (coadminister with probenecid and IV saline to reduce toxicity)
1st gen H1 blockers
diphenhydramine, dimenhydrinate, chlorpheniraminereversible inhibitors of H1 histamine receptorsUse: allergy, motion sickness, sleep aidSE: sedation, antimuscarinic, anti-alpha-adrenergic
2nd gen H1 blockers
loratadine, fexofenadine, desloratadine, cetirizine (-adine)Use: allergySE: less sedating then 1st gen because of decreased entry into CNS
Albuterol
beta 2 agonistrelaxes bronchial smooth muscle (increase cAMP)Use: acute asthma exacerbation
Salmerterol, formoterol
beta 2 agonist (increase cAMP)Use: long-acting agents for prophylaxisSE: tremor, arrhythmia
Theophylline
methylxanthinecauses bronchodilation by inhibiting phosphodiesterase, thereby resulting in increased cAMP due to decreased cAMP hydrolysis; blocks action of adenosine (which promotes bronchoconstriction)Use: asthma, but limited because of narrow TISE: cardiotoxicity, neurotoxicity, blocks action of adenosine; metabolized by P450
Ipratropium
muscarinic antagonistcompetitive block of muscarinic receptors, preventing bronchoconstrictionUse: asthma, COPDtiotropium = long acting
Beclomethasone, fluticasone
corticosteroidsinhibit the synthesis of virtually all cytokines; inactivate NF-kB (transcription factor that induces production of TNF-alpha)Use: 1st line for chronic asthma
Monrelukast, zafirlukast
anti-leukotrieneblock leukotriene receptorsUse: especially good for aspirin-induced asthma
Zileuton
anti-leukotriene5-lipoxygenase pathway inhibitor; block conversion of arachidonic acid to leukotrienes Use: asthma
Omalizumab
monoclonal anti-IgE antibodybind mostly unbound antibodiesUse: allergic asthma resistant to inhaled steroids and long-acting beta 2 agonists
Bosentan
competitively antagonizes endothelin-1 receptors, deceasing pulmonary vascular resistanceUse: pulmonary HTN
Dextromethorphan
antitussiveantagonizes NMDA glutamate receptors; synthetic codeine analog - mild opioid effect when used in excessnaloxone used for overdoes
Pseudoephedrine, phenylephrine
sympathomimetic alpha agonist - non-prescription nasal decongestantUse: reduce hyperemia, edema, nasal congestion; open obstructed eustachian tubesSE: HTN; CNS stimulation/anxiety (pseudoephedrine)
Ca channel blockers
nifedipine, verapamil, diltiazem, amlodipineblock VG L-type Ca channels of cardiac and smooth muscle and thereby reduce muscle contractilityvascular smooth muscle - amlodipine = nifedipine > diltiazem > verapamilheart - verapamil > diltiazem > amlodipine = nifedipineUse: HTN, angina, arrhythmias (not nifedipine), Prinzmetal’s angina, Raynaud’sSE: cardiac depression, AV block, peripheral edema, flushing, dizziness, and constipation
Hydralazine
increase cGMP –> smooth muscle relaxationvasodilates arterioles > veins; afterload reductionUse: severe HTN (1st line in pregnancy w/ methyldopa), CHFfrequently administered with a beta-blocker to prevent reflex tachycardiaSE: compensatory tachycardia (contraindicated in angina/CAD), fluid retention, nausea, headache, angina, lupus-like syndrome
Nitroprusside
short acting; increased cGMP via direct release of NOUse: malignant HTNSE: cyanide toxicity (releases cyanide)
Fenoldopam
D1 receptor agonist - coronary, peripheral, renal, splanchnic vasodilationreduce BP, increase natriuresisUse: malignant HTN
Nitroglycerin, isosorbide dinitrate
vasodilate by releasing nitric oxide in smooth muscle, causing increase in cGMP and smooth muscle relaxationdilate veins»_space; arteries; decrease preloadUse: angina, pulmonary edemaSE: reflex tachycardia, hypotension, flushing, headache, “Monday disease” in industrial exposure
HMG-CoA reductase inhibitors
statins(3) decreases LDL, (1) increase HDL, (1) decrease TGsinhibit conversion of HMG-CoA to mevalonate, a cholesterol precursor; increased LDLRSE: hepatotoxicity (increased LFTs), rhabdomyolysis
Niacin
vitamin B3(2) decrease LDL, (2) increase HDL, (1) decrease TGinhibits lipolysis in adipose tissue; reduces hepatic VLDL secretion into circulation; vasodilatory effectSE: red, flushed face (decreased by aspirin or long-term use), hyperglycemia (acanthosis nigricans), hyperuricemia (gout)
Bile acid resins
cholestryamine, colestipol, colesevelam (coles-)(2) decrease LDLprevents intestinal reabsorptoin of bile acids; liver must use cholesterol to make moreSE: tastes bad and causes GI discomfort, decreased absorption of fat-soluble vitamins; cholesterol gallstones
Cholesterol absorption blockers
ezetimibe(2) decrease LDLprevent cholestrol reabsorption at small intestine brush borderSE: rare, increased LFTs, diarrhea
Fibrates
gemfibrozil, clofibrate, bezafibrate, fenofibrate(1) decrease LDL, (1) increase HDL, (3) decrease TGupregulate LPL –> increase TG clearanceSE: myositis, hepatotoxicity (increased LFTs), cholesterol gallstones
Digoxin
cardiac glycosidedirect inhibition of Na/K ATPase leads to indirect inhibition of Na/Ca exchanger/antiport; increased intracellular Ca concentration –> positive inotropystimulates vagus nerve –> decreased HRUse: CHF (increased contractility); atrial fibrillarion (decreased conduction at AV node and depression of SA node)SE:cholinergic - nausea, vomiting, diarrhea, blurry yellow visionECG - increased PR, decreased QT, ST scooping, T-wave inversion, arrhythmia, AV blockcan lead to hyperkalemia, poor prognostic indicatorfactors predisposing to toxicity - renal failure (decreased excretion), hypokalemia, quinidine (decreased clearance)Antidote: slowly normalize K, lidocaine, cardiac pacer, anti-digoxin Fab fragments, Mg75% bioavailability, 20-40% protein bound, half-life: 40 hours, urinary excretion
Class I General
Na channel blockerslocal anestheticsslow or block conduction; decreases slope of phase 0 depolarization and increase threshold for firing in abnormal pacemaker cellsstate dependent - selectively depress tissue that is frequently depolarizedhyperkalemia causes increased toxicity for all class I
Class IA
quinidine, procainamide, disopyramideincrease AP duration, increase effective refractory period, increase QT interval affect both atrial and ventricular arrhythmias; reentrant and ectopic supraventricular and venricular tachycardiaSE: thrombocytopenia, torsades de pointes due to increased QT intervalquinidine - cinchonism = headache, tinnitusprocainamide - reversible SLE-like syndromedisopyramide - HF
Class IB
lidocaine, mexiletine, tocainide (maybe phenytoin)decrease AP duration; preferentially affect ischemic or depolarized Purkinje and ventricular tissueUse: acute ventricular arrhythmias (especially post-MI), digitalis-induced arrhythmiasSE: local anesthetic, CNS stimulation/depression, CV depression
Class IC
flecainide, propafenoneno effect on AP durationUse: ventricular tachycardias that progress to VF and in intractable SVT; usually only last resort in refractory tachyarrhythmiascontraindicated in structural heart disease and post-MISE: proarrhythmic, especially post-MI (contraindicated); significantly prolongs refractory period in AV node
Class II
beta-blocker: metroprolol, propranolol, esmolol, atenolol, timololdecreases SA and AV nodal activity by decreasing cAMP, decreased Ca currents; suppress abnormal pacemakers by decreasing slope of phase 4Use: ventricular tachycardia, SVT, slowing ventricular rate during atrial fibrillation and atrial flutterSE: impotence, exacerbation of asthma, CV effects (bradycardia, AV block, CHF), CNS effects (sedation sleep alteration)may mask signs of hypoglycemiametoprolol can cause dyslipidemia; treat overdose with glucagonpropranolol - exacerbate vasospasm in Prinzmetal’s angina
Class III
K channel blocker: amiodarone, ibutilide, dofetilide sotalolincrease AP duration, increase ERP, increase QT intervalUse: when other antirrhythmics failSE:sotalol - torsades de pointes, excessive beta blockibutilide - torsadesamiodarone - pulmonary fibrosis, hepatotoxicity, hypo/hyperthyroid (check PFTs, LFTs, TFTs), corneal and skin (blue/gray) deposits, neurological effects, constipation, CV effects (bradycardia, heart block, CHF)
Class IV
Ca channel blockers - verapamil, diltiazemdecrease conduction velocity, increase ERP, increase PR intervalUse: prevention of nodal arrhythmias (SVT)SE: constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression)
Adenosine
increase K out of cell –> hyperpolarizing the cell and decreasing CaUse: 1st line for diagnosing and abolishing supraventricular tachycardiavery short acting (~15 sec)SE: flushing, hypotension, chest paineffects blocked by caffeine and theophylline
Mg
effective in torsades de pointes and digoxin toxicity
Aspirin
NSAIDirreversibly inhibit COX-1 and COX-2 by acetylation, which decreases synthesis of both TXA2 and prostagladinsincreases bleeding time; no effect on PT, PTTUse: low dose (< 300 mg/day) - decrease platelet aggregationintermediate dose (300-2400) - antipyretic and analgesichigh dose (2400-4000): anti-inflammatorySE: gastric ulceration, tinnitus (CN VIII), acute renal failure (chronic use), interstitial nephritis, upper GI bleeding, Reye’s syndrome; respiratory alkalosis
NSAIDs
ibuprofen, naproxen, idomethacin, ketorolac, diclofenacreversibly inhibit COX-1 and COX-2 –> block PG synthesisUse: antipyretic, analgesic, anti-inflammatory; indomethacin to close PDASE: interstitial nephritis, gastric ulcer, renal ischemia
Celecoxib
COX-2 inhibitorsreversibly inhibit COX-2 (spares COX-1 = maintains gastric mucosa and spares platelet function)Use: RA, osteoarthritis; patients with gastritis or ulcersSE: increases risk of thrombosis, sulfa allergy
Acetaminophen
reversibly inhibits COX, mostly in CNS; inactivated peripherallyUse: antipyretic, analgesic, but not anti-inflammatory, use instead of aspirin in childrenSE: overdose produces hepatic necrosis; depletes glutathioneN-acetylcysteine is antidote - regenerates glutathione
Bisphosphaonates
alendronate (-dronates)pyrophosphate analongs; bind hydroxyapatite in bone, inhibiting osteoclast activityUse: osteoporosis, hypercalcemia, Paget’s disease of boneSE: corrosive esophagitis, osteonecrosis of the jaw
Allopurinol
inhibits xanthine oxidase, decrease conversion of xanthine to uric acidUse: chronic gout, tumor lysis syndromeincreases concentrations of azathioprine and 6-MPdo not give salicylates
Febuxostat
inhibits xanthine oxidaseUse: chronic gout
Probenecid
inhibits reabsorption of uric acid in PCTUse: chronic goutalso inhibits secretion of penicillin
Colchicine
binds and stabilizes tubulin to inhibit polymerization, impairing leukocyte chemotaxis and degranulationUse: chronic goutSE: GI; avoid in elderly or renal problems
Etanercept
fusion protein (receptor for TNF-alpha + IgG Fc), produced by recombinant DNATNF decoy receptorUse: RA, psoriasis, ankylosing spondylitisSE: reactivation of latent TB
Infliximab, adalimumab
anti-TNF-alpha monoclonal antibodyUse: Crohn’s disease, RA, ankylosing spondylitis, psoriasisSE: reactivation of latent TB
Rasburicase
recombinant version of urate oxidaseUse: tumor lysis syndrome
Haparin
cofactor for the activation of antithrombin, decrease thrombin, decrease factor Xa. short half-lifeUse: immediate anticogulation for pulmonary embolism, acute coronary syndrome, MI, DVTused during pregnancy (doesn’t cross placenta); follow PTTSE: bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactionsrapid reversal with proamine sulfate (positive charged molecule that binds negatively charged heparin)LMW haparins act more on Factor Xa, longer actingHIT - development of IgG antibodies against haparin bound platelet factor 4 –> complex activates platelets
Lepirudin, bivalirudin
derivatives of hirudin, anticoagulant used by leechesinhibit thrombinused as alternative to haparin for patients with HIT
Warfarin (coumadin)
interferes with normal synthesis and gamma-carboxylation of vitamin K-dependent clotting factors II, VII, IX, and X, protein C and Smetabolized by P450; monitor PT; long half-lifeUse: chronic anticoagulant (after STEMI, venous thromboembolism prophylaxis, prevention of stroke in atrial fibrillation)don’t use in pregnant womenSE: bleeding, teratogenic, skin/tissues necrosis, drug-drug interactionsreversal - vitamin K; rapid - fresh frozen plasma
Thromobolytics
alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA) = fibrin specificstreptokinase = non-specificdirectly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots; increases PT, PTT, no change in platelet countUse: early MI, early ischemic stroke, direct thrombolysis of PESE: bleedingcontraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diathesis, severe HTNtreat toxicity with aminocaproic acid (inhibitor of fibrinolysis)
ADP receptor inhibitor
clopidogrel, ticlopidine, prasugrel, ticagrelorinhibit platelet aggregation by irreversible blocking ADP receptor; inhibit fibrinogen binding by preeventing glycoprotein IIb/IIIa from binding fibrinogenUse: acute coronary syndrome, coronary stenting, decreased, decreased incidence of recurrence of thrombotic strokeSE: neutropenia (ticlopidine)
Cliostazol, dipyridamole
prosphodiesterase II inhibitor; increase cAMP in platelets, thus inhibiting platelet aggregation; vasodilationUse: intermittent claudication, coronary vasodilation, prevention of stroke or TIA (combined with aspirin), angina prophylaxisSE: nausea, headache, facial flushing, hypotension, abdominal pain
GP IIb/IIIa inhibitors
abciximab, eptifibatide, tirofibanbind to glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregationUse: acute coronary syndromes, percutaneous transluminal coronary angioplastySE: bleeding, thrombocytopenia
Methotrexate (MTX)
antimetabolite (S phase specific)folic acid analog that inhibits dihydrofolate reductase –> decreased dTMP –> decreased DNA and protein synthesisUse: luekemias, lymphomas, choriocarcinoma, sarcomas, abortion, ectopic pregnancy, RA, psoriasisSE: myelosuppression (reversible with leucovorin (folinic acid)); macrovesicular fatty change in liver; mucositis, teratogenic
5-fluorouracil (5-FU)
pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid; complex inhibits thymidylate synthase –> decreases dTMP –> decreased DNA and protein synthesisUse: colon cancer, basal cell carcinoma (topical)SE: myelosuppression (rescue with thymidine), photosensitivity
Cytarabine (arabinofuranosyl cytidine)
pyrimidine analog –> inhibition of DNA polymeraseUse: leukemia, lymphomasSE: leukopenia, thrombocytopenia, megaloblastic anemia
Azathioprine, 6-mercaptopurine (6-MP), 6 thioguanine (6-TG)
purine (thiol) analogs –> decreased de novo purine synthesis; activated by HGPRTUse: leukemiasSE: bone marrow, GI, liver, increased toxicity with allopurinol (metabolized by xanthine oxidase)
Dactinomycin
intercalates in DNAUse: Wilm’s tumor, Ewing’s sarcoma, rhabdomyosarcoma; childhood tumorsSE: myelosuppression
Doxorubicin, daunorubicin
generate free radicals; noncovalently intercalate in DNA –> breaks in DNA –> decreased replicationUse: solid tumors, leukemias, lymphomasSE: cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia; toxic after extravasationuse dexrazoxane (iron chelating agent), used to prevent cardiotoxicity
Bleomycin
induces free radical formation, which causes breaks in DNA strands (act in G2)Use: testicular cancer, Hodgkin’s lymphomaSE: pulmonary fibrosis, skin changes, minimal myelosuppression
Cyclophosphamide, ifosfamide
alkylating agentscovalently X-linked (interstrand) DNA at guanine N-7; reactivated by liverUse: solid tumors, leukemia, lymphomas, and some brain cancersSE: myelosuppression; hemorrhagic cystitis (prevented by mensa - thiol group binds toxic metabolite)
Nitrosoureas
carmustine, lomustine, semustine, streptozocin (-stine)alkylating agentsrequires bioactivation; cross BBB –> CNSUse: brian tumors (GBM)SE: CNS toxicity (dizziness, ataxia)
Busulfan
alkylates DNAUse: CML, also used to ablate patient’s bone marrow before bone marrow transplantationSE: pulmonary fibrosis, hyperpigmentation
Vincristine, vinblastine
alkaloids that bind to tubulin in M phase and block polymerization of microtubules so that mitotic spindle cannot form (work in M phase)Use: solid tumors, leukemias, lymphomasSE: vincristine - neurotoxicity, paralytic ileusvinblastine - blast bone marrow (suppression)
Paclitaxel, other taxols
hyperstabilizes polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cant occur)Use: ovarian, breast carcinomasSE: myelosuppression, hypersensitivity
Cisplatin, carboplatin
cross-link DNAUse: testicular, bladder, ovary and lung carcinomasSE: nephrotocity, acoustic nerve damage (prevent with amifostine - free radical scavenger - and chloride diuresis
Etoposide, teniposide
inhibit topoisomerase II –> increased DNA degradationact in S, G2Use: solid tumors, leukemias, lymphomasSE: myelosuppression, GI irritation, alopecia
Hydroxyrea
inhibits ribonucleotide reductase –> decreases DNA synthesis (S-phase specific)Use: melanoma, CML, sickle cell disease (increase HbF)SE: bone marrow suppression, GI upset
Prednisone, prednisolone
may trigger apoptosis; may even work on nondividing cellsUse: CLL, non-Hodgkin’s lymphoma (part of combination therapy), immmunosuppresionSE: Cushing-like symptoms; immunosuppression, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis
Tamoxifen, raloxifene
SERMs - receptor antagonists in breast and agonist in bone; block the binding of estrogen to estrogen receptor-positive cellsUse: breast cancer treatment and prevention; prevent osteoporosisSE:tamoxifen - partial agonist in endometrium, which increases the risk of endometrial cancer; “hot flashes”ralozifene - no increase in endometrial carcinoma b/c is an endometrial antagonist
Trastuzumab (herceptin)
monoclonal antibody against HER-2 (tyrosine kinase); antibody-dependent cytotoxicityUse: HER-2-positive breast cancerSE: cardiotoxicity
Imatinib (gleevec)
Philadelphia chromosome bcr-abl tyrosine kinase inhibitorUse: CML, GI stromal tumorsSE: fluid retention
Rituximab
monoclonal antibody against CD20, which is found on most B-cell neoplasmsUse: non-Hodgkin’s lymphoma, RA (with MTX)
Vemurafenib
small molecule inhibitor of forms of B-Raf kinase with the V600E mutationUse: metastaic melanoma
Bevacizumab
monoclonal antibody against VEGF; inhibits angiogenesisUse: solid tumors
Leuprolide
GnRH analog with agonist properties when used in pulsatile fashionantagonist properties when used in continuous fashionUse: infertility (pulsatile), prostate cancer (continuous with flutamide), uterine fibroids (continuous), precocious puberty (continuous)SE: antiandrogen, nausea, vomiting
Testosterone, methyltestosterone
agonist at androgen receptorsUse: treats hypogonadism and promotes development of secondary sex characteristics; stimulation of anabolism to promote recovery after burn or injurySE: cause masculinization in females; reduces intratesticular testosterone in males by inhibiting release of LH (gonadal atrophy); premature closure of epiphyseal plate; increase LDL, decrease HDL
Finasteride
antiandrogen5alpha-reductase inhibitorUse: BPH; male pattern baldness
Flutamide
antiandrogennonsteroidal competitive inhibitor of androgens at the testosterone receptorUse: prostate carcinoma
Ketoconazole
antiandrogeninhibits steroid synthesis (inhibits 17,20-desmolase)Use: PCOS - to prevent hirsutismSE: gynecomastia, amenorrhea
Spironolactone
antiandrogeninhibits steroid bindingUse: PCOS - to prevent hirsutismSE: gynecomastia, amenorrhea
Estrogens
ethyl estradiol, DES, mestranolbind estrogen receptorsUse: hypogonadism or ovarian failure, mentral abnormalities, HRT in postmenopausal women; use in men with andeogen-dependent prostate cancerSE: increase risk of endometrial cancer, bleeding in postmenopausal women, clear cell adenocarcinoma of vagina (DES), increase risk of thrombicontraindication - ER-postive breast cancer, history of DVTs
Clomiphene
SERMpartial agonist at estrogen receptors in hypothalamus; prevent normal feedback inhibition and increase release of LH and FSH –> ovulationUse: infertility, PCOSSE: hot flashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances
Tamoxifen
SERMantagonist on breast tissueUse: treat and prevent recurrence of ER-positive breast cancer
Raloxifene
SERMagonist on bone; reduces resorption of boneUse: osteoporosis
HRT
Use: relief or prevention of menopausal symptoms and osteoporosisunopposed ERT increases the risk of endometrial cancer, so progesterone is addedpossible increased CV risk
Anastrozole/exemestane
aromatase inhibitors used in postmenopausal women with breast cancer
Progestins
bind progesterone receptors, reduce growth and increase vascularization of endometriumUse: oral contraceptives; endometrial cancer, abnormal uterine bleeding
Mifepristone
competitive inhibitor of progestins at progesterone receptorsUse: termination of pregnancy; administered with misoprostolSE: heavy bleeding, GI effects, abdominal pain
Oral contraception
FILL IN
Terbutaline
beta 2 agonist that relaxes the uterus; reduces premature uterine contractions
Tamsulosin
alpha 1 antagonist (selective for 1A,D in prostate vs 1B vascular)inhibit smooth muscle contractionUse: BPH
Silenafil, vardenafil
inhibit phosphodiesterase 5, causing increase cGMP, smooth muscle relaxation in corpus cavernosum, increased blood flow and penile erectionUse: EDSE: headache, flushing, dyspepsia, impaired blue-green color visionrisk of life-threatening hypotension in patients taking nitrates
Danazol
synthetic androgen that acts as partial agonist at androgen receptorsUse: endometriosis and hereditary angioendemaSE: weight gain, edema acne, hirsutism, masculinization, decreased HDL levels, hepatotoxicity
