Drugs 0603 Flashcards
Leucovorin
Folinic acid. Tx methotrexate overdose.
Filgrastim
G-CSF analog used to stimulate proliferation and differentiation of granulocytes in patients with neutropenia post-chemo.
Cyclophosphamide toxicity
Hemorrhagic cystitis–use mesna to bind acrolein in urine.
What are the following types of biological agents?
Rituximab, infliximab, certolizumab, imatinib, etanercept?
Rituximab: CD20 blocker for CD20+ non-Hodgkin’s lymphoma
Infliximab: TNF-a blocker for autoimmune diseases (Crohn’s, RA)
Certolizumab: pegylated humanized monoclonal Ab that targets TNF-a. Lacks Fc region (prevents complement and cell-mediated toxicity), treats autoimmune d/o associated with TNF-a
Imatinib: philadelphia chromosome + CML and kit-positive GI stromal tumors. Small-molecule tyrosine kinase receptor inhibitor.
Etanercept: TNFa inhibitor added to methotrexate for RA. Fusion protein linking soluble TNFa receptor to Fc part of human IgG1. DECOY.
Rituximab
Rituximab: CD20 blocker for CD20+ non-Hodgkin’s lymphoma
Infliximab
Infliximab: TNF-a blocker for autoimmune diseases (Crohn’s, RA)
Certolizumab
Certolizumab: pegylated humanized monoclonal Ab that targets TNF-a. Lacks Fc region (prevents complement and cell-mediated toxicity), treats autoimmune d/o associated with TNF-a
Imatinib
Imatinib: philadelphia chromosome + CML and kit-positive GI stromal tumors. Small-molecule tyrosine kinase receptor inhibitor.
Etanercept
Etanercept: TNFa inhibitor added to methotrexate for RA. Fusion protein linking soluble TNFa receptor to Fc part of human IgG1. DECOY.
Which drugs have 0-order elimination?
PEA (round, 0): phenytoin, ethanol, aspirin
How do you treat salicylate and amphetamine OD?
- Acidic drug OD (salicylate): NaHCO3 to trap acidic drug in basic urine
- Basic drug OD (amphetamines): Na4Cl to trap basic drug in acidic urine
Chlorpropamide, tolbutamide
First gen sulfonylureas. Close K+ channel in b-cell membrane –> insulin release via calcium influx. SE: disulfiram effects.
Glimepiride, glipizide, glyburide
2nd gen sulfonylureas. SE: hypoglycemia
Pioglitazone, rosiglitazone
Glitazones/thiazolidinedions. Increase insulin sensitivity in peripheral tissue. Binds to PPAR-g nuclear transcription regulator. SE: weight gain, edema, hepatotoxicity, HF, increase risk of fractures.
Adiponectins.
Exenatide, liraglutide
GLP-1 analogs. Increase insulin, decrease glucagon release. SE: N/V, pancreatitis.
Linagliptin, saxagliptin, sitagliptin
DPP-4 inhibitors. Increase insulin, decrease glucagon release. Mild urinary or respiratory infections.
Pramlintide
Amylin analogs. Decrease gastric emptying, decrease glucagon. Type 1 and type 2 DM. SE: hypoglycemia, N/D.
Canagliflozin
SGLT-2 inhibitors. Block reabs of glucose in PCT. Type 2 DM. SE: Glucosuria, UTIs, vaginal yeast infections.
Acarbose, miglitol
a-glucosidase inhibitors. Inhibit intestinal brush-border a-glucosidases. Delayed carb hydrolysis and glucose abs, decreases post prandial hyperglycemia. SE: GI.
Nimodipine
Subarachnoid hemorrhage (prevents cerebral vasospasm)
Clevidipine
HTN urgency or emergency
Nitroprusside
Releases NO, which generated cGMP in smooth muscle of arteries and veins. Reduces preload and afterload.
Use: HTN emergency, given by IV infusion
SE: rebound HTN, cyanide toxicity (co-admin with nitrates and thiosulfate to decr toxicity).
Hydralazine
Acts directly on arterioles (increase cGMP), resulting in decreased resistance (esp in coronary, renal and cerebral beds). Reduces afterload.
Use: severe HTN, HF, safe in pregnancy.
SE: compensatory tachycardia, HA, flushing, sweating, fluid retention, reflex tachy, lupus-like syndrome in slow acetylators.
*Treat with diuretics to counteract fluid retention and b-blockers to prevent tachy.
Fenoldopam
Dopamine D1 receptor agonist: coronary, peripheral, renal, and splanchnic vasodilation.
Decrease BP, increase natriuresis.
Nitrates
Vasodilate by increasing NO in vascular smooth muscle –> increased cGMP in smooth muscle relaxation. Decreases preload.
Increased cGMP, decrased intracellular Ca, myosin dephosphorylation.
Use: angina, acute coronary syndrome, pulmonary edema.
SE: reflex tachy (tx with b-blocker), hypotension, flushing, HA, Monday disease (tolerance during week and loss of tolerance on weekend –> tachy, dizzy, HA on reexposure).
HMG-CoA reductase inhibitors
Hepatotoxicity (LFTs), myopathy (esp with fibrates or niacin)
CI: liver dz, pregnancy
Cholestyramine, colestipol, colesevelam
Bile acid resins. Decrease LDL, increase HDL slightly, increase TG slightly
Prevent intestinal reabs of bile acids; liver must use cholesterol to make more.
SE: GI upset, decr abs of other drugs and fat-soluble vitamins, cholesterol gallstones
Ezetimibe
Decrease LDL.
Prevent cholesterol abs at small intestine brush border (block NPC1L1).
SE: rare increase LFTs, diarrhea.
Gemfibrozil, clofibrate, bezafibrate, fenofibrate
Decrease TGs!
Upregulate LPL –> increase TG clearance. Activates PPAR-a to induce HDL synthesis.
SE: myopathy (increase risk with statins), cholesterol gallstones, rash, ED, GI
Niacin (B3)
Increase HDLs. Inhibits lipolysis in adipose tissue; reduces hepatic VLDL synthesis.
SE: red, flushed face (d/t PGs, pre-tx with NSAIDs), hyperglycemia, hyperuricemia.
Adenosine
Increase K+ out of cells –> hyperpolarizing cell and decrease Ica. Drug of choice to abolish supraventricular tachycardia.
Effect blunted by theophylline and caffeine.
SE: flushing, hypotension, chest pain, sense of impending doom, bronchospasm.
Clozapine
D4 receptors? (atypical)
Use: tx-resistant schizophrenic, for positive and negative sx.
SE: agranulocytosis. Must monitor WBC. Seizures.Hypersalivation, myocarditis, weight gain.
*Must watch CLOZely
Mifepristone
Abortifacient up to 49 days after conception.
Progesterone antagonist – decidual necrosis and expulsion of products of conception. Stimulate release of endogenous PGs, sensitize myometrium to effects of hormone.
High potency antipsychotics/neuroleptics
Try Fly High: Trifuoperazine, fluphenazine, haloperidol
Block D2 (increase cAMP in CNS)
Uses: Schizo (for + sx), psychosis, acute mania, Tourette’s
Neurologic SE: Huntington, delirium, EPS symptoms
Haloperidol: NMS, tardive dyskinesia.
NMS–Neuroleptic malignant syndrome
FEVER: fever, encephalopathy, vitals unstable, elevated enzymes, rigidity of muscles.
Rigidity, myoglobinuria, autonomic instability, hyperpyrexia.
Ts: Dantrolene, D2 agonists–bromocriptine
Anti-psychotic SE
Highly lipid soluble and stored in body fat, slow to be removed.
EPS: dyskinesia, neuroleptic malignant syndrome. Tx with benztropine or diphenhydramine.
Endocrine SE: dopamine receptor antagonism –> hyperprolactinemia (galactorrhea).
Anti-muscarinic: dry mouth, constipation
Block A1: hypotension
Block Histamine: sedation
QT prolongation
Low potency antipsychotics/neuroleptics
Cheating Thieves are low: Chlorpromazine, thioridazine
Non-neurologic SE: anticholinergic, antihistamine, a-blockade effects
Chlorpromazine: Corneal deposits
Thioridazine: reTinal deposits
Evolution of EPS SE
4 hr acute dystonia (muscle spasm, stiffness, oculogyric crisis)–Tx = benztropine or diphenhydramine
4 day akathisia (restlessness, fidgetiness)–Tx = propranolol, benzodiazepines, benztropine
4 wk bradykinesia (parkinsonism)
4 mo tardive dyskinesia (involuntary writhing, mouth, tongue)–Likely due to compensatory hypersensitivity of DA receptors after long-term administration.
Atypical antipsychotics
Olanzapine, clozapine, quetiapine, risperidone, aripiprazole, aiprasidone
Effects on 5HT2, DA, and a and H1 receptors
Fewer extrapyramidal/anticholinergic SE.
Olanzapine: OCD
Toxicities:
Olanzapine/clozapine: weight gain
Clozapine: agranulocytosis (WBC monitoring) and seizure
RIsperidone: increase prolactin – decrease GnRH, LH, and FSH (irr menstruation and fertility)
Ziprasidone: prolong QT (the most)
Quetiapine: cataracts–periodic slit lamp exam!
All prolong QT.
Lithium
Related to inhibition of phosphoinositol cascade.
Use: Mood stabilizer and SIADH.
Toxicity: tremor, hypothyroidism, polyuria (DI), teratogenesis (Ebstein anomaly).
Excreted by kidneys. Reabsorbed at PCT with Na+.
Thiazide use makes it worse!!!
Buspirone
Stimulates 5-HT1A receptors
GAD. Does not cause sedation, addiction, or tolerance. Takes 1-2 weeks. Does not interact with alcohol.
SSRI
Fuoxetine, paroxetine, sertraline, citalopram
5HT specific reuptake inhibitors
SIADH, sexual dysfunction
Serotonin syndrome: hyperthermia, confusion, myoclonus, CV instability, flushing, diarrhea, seizures
Tx: cyproheptadine (5HT2 receptor antagonist)
SNRI
Venlafaxine, duloxetine
Inhibit 5HT and NE reuptake
Depression, GAD, panic d/o, PTSD. Duloxetine for DM peripheral neuropathy
Toxicity: increased BP, stimulant effects, sedation, N
TCA
Amitriptyline, nortriptyline, imipramine, desipramine, clomipramine (OCD), doxepin, amoxapine
Block NE and 5HT.
SE: sedation, a1-blocking effects (postural hypotension), atropine like SE (tachy, urinary retention, dry mouth). Can prolong QT.
Tri-C’s = Convulsions, Coma, Cardiotoxicity (arrhythmias). Also respiratory depression, hyperpyrexia. Confusion and hallucinations in elderly due to anticholinergic SE (use nortriptyline). Tx: NaHCO3.
MAOI
Trancylcypromine, phenelzine, isocarboxazid, selegiline (selective MAOB)
MAO Takes Pride In Shainghai.
Increase amine NTs (NE, 5HT, DA)
Atypical depression, anxiety.
Toxicity: hypertensive crisis (tyramine foods), CNS stimulation.
CI: SSRIs, TCAs, St. John’s worrt, meperidine, dextromethorphan (serotonin syndrome).
Bupropion
Atypical antidepressant, smoking sensation.
Increase NE and DA.
Toxicity: stimulant effects (tachy, insomnia), HA, seizures in anorexic/bulimic. No sexual SE.
Mirtazapine
A2 antagonist (release NE and 5HT) and potent 5HT2 and 5HT3 receptor antagonist.
Toxicity: sedation (maybe good in depressed with insomnia), increased appetite, weight gain (for anorexics), dry mouth.
Trazadone
Block 5HT2 and a1-adrenergic. For insomia.
Toxicity: sedation, N, priapism, postural hypotnesion.
H2 blockeres
Cimetidine, ranitidine, famotidine, nizatidine.
MOA: Decrease H+ decrease by parietal cells.
Use: peptic ulcer, gastritis, mild esophageal reflux.
Toxicity: Cimetidine inhibits P450 and has natiandrogenic effects. Can cross BBB (HA, confusion, dizzy), placenta. Cimetidine + ranitidine decrease renal excretion of creatinine.
PPI
Omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole.
MOA: Irr. Block H+/K+ ATPase on parietal cells.
Use: Peptic ulcer, gastritic, esophageal reflux, Zollinger-Ellison
Toxicity: risk of C. difficile, pneumonia. Decrease serum Mg2+ in long term.
Bismuth, sucralfate
MOA: Bind to ulcer base, physicial protection, allows bicarb secretion to reestablish pH in mucous layer.
Use: ulcer healing and travers’ diarrhea.
Misoprostol
MOA: PGE1 analog. Increase secretion of gastric mucous barrier, decrease acid production.
Use: prevent NSAID induced peptic ulcers, maintain PDA, ripens cervix.
Toxicity: diarrhea, abortifacient (CI in childbearing age W)
Octreotide
MOA: long-acting somatostatin analog, inhibig splanchnic vasoconstriction homrones.
Use: acute variceal bleeds, acromegaly, VIPoma, carcinoid tumors
Toxicity: N, cramps, steatorrhea.
Antacid use
All: can affect absorption, bioavailability, or urinary excretion of other drugs by changing gastric and urinary pH or delay gastric emptying. Hypokalemia.
1. Aluminum hydroxide: constipation, hypophosphatemia, proximal muscle weakness, osteodystrophy, seizures.
2. Calcium carbonate: hypercalcemia (increases gastrin), rebound acid increases. Can chelate and decr effectives of other drugs (tetracycline).
3. Magnesium hydroxide: diarrhea, hyporeflexia, hypotension, cardiac arrest (MG is a smooth muscle relaxer). MG=must go to bathroom.
Osmotic laxatives
Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose
MOA: osmotic load to draw water
Use: constipation. Lactulose: hepatic enceph since gut flora degrades it into metabolites (lactic acid and acetic acid) that promote nitrogen excretion as NH4+.
Toxicity: diarrhea, dehydration, abused by bulimics.
Sulfasalazine
MOA: combo of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory). Activated by colonic bacteria.
Use: UC, Crohns (colitis part)
Toxicity: malaise, nausea, sulfonamide toxicity, reversible oligospermia. Blocks IL-1, TNF, lipooxygenase, free radical scavaging.
Ondansetron
MOA: 5HT3 blocker, decrease vagal stimulation, powerful central-acting antiemetic.
Use: Control vomiting postop and in chemo
Toxicity: HA, constpiation, QT prolongation.
* Too much serotonin – diarrhea, not enough serotonin – constipation!
Metoclopramide
MOA: D2 receptor blocker. Increases resting tone, contractility, LES tone, motility. Does not influence colon trasnport time.
Use: Diabetic and postsurgery gastroparesis, antiemetic, GERD
Toxicity: Increase Parkinsonian effects, tardive dyskinesia, restlessness, drowsiness, fatigue, depression, diarrhea. Drug intxn with digoxin and diabetic agents.
CI: patients with SBO or Parkinson disease (D1 receptor blockage)–seizrue
Orlistat
MOA: inhibit gastric and pancreatic lipase – decrease breakdown and absorption of dietary fats.
Use: weight loss
Toxicity: steatorrhea, decrease absorption of fat-soluble vitamins.
Heparin
MOA: Activates AT, decr thrombin and factor Xa. Short half-life. PTT*
Use: PE, acute coronary syndrome, MI, DVT. PREGNANCY.
Toxicity: Bleeding, HIT, osteoporosis, drug-drug intxn.
Antidote: protamine sulfate (+ charged)
HIT
IgG abs against heparin-bound platelet factor 4 (PF4). Ab-heparin-PF4 complex activates platelets –> thrombosis and thrombocytopenia.
*Switch to direct thrombin inhibitors! Argatroban, bivalirudin, dabigatran
Low molecular-weight heparins
Enoxaparin, dalteparin, fondaparinaux (indirect, best for hepatic dysfxn)
More on factor Xa, better bioavailability, 2-4x longer half-life, SQ and no monitoring. Not easily reversible.
Argatroban, bivalirudin, dabigatran
Bivalirudin–related to hirudin (leeches)
Inhibit thrombin directly. Alternative for HIT.
Warfarin
MOA: blocks g-carboxylation of vitamin K (factors, 2, 7, 9, 10, proteins C, S). Metabolism affected by polymorphisms of gene for vitamin K epoxide reductase complex (VKORC1). Affects extrinsic pw and PT. Long half-life.
Use: chronic anti-coag (DVT prophylaxis, prevent stroke in afib). Not for pregnant wome.
Toxicity: Bleeding, teratogenic, skin/tissue necrosis, drug-drug intxn. Protein C/S have shorter half-lives–start tx with heparin!
*Skin/tissue necrosis: due to small vessel microtromboses.
Reversal: vitamin K or FFP (rapid).
Direct factor Xa inhibitors
Apixaban, rivaroxaban
MOA: bind to/directly block factor Xa.
Use: Tx and proph for DT and PE (rivaroxaban); stroke prophylaxis in afib. No monitoring.
Toxicity: bleeding, no reversal agent
Thrombolytics
Alteplase (tPA), reteplase, streptokinase, tenecteplase
MOA: directly or indirectly convert plasminogen to plasmin, which cleaves thrombin and fibrin clots. **Increases PT, PTT, no change in platelets.
Use: Early MI or stroke, direct thrombolysis of severe PE.
Toxicity: Bleeding. CI in active bleeding, hx of intracranial bleeding, recent surgery, known bleeding diatheses, or severe HTN.
Reversal: aminocaproic acid (blocks fibrinolysis), FFP, and cryoprecipitate to replace factors.
Asprin
MOA: irr blocks COX1+2 by covalent acetylation. Lasts until new platelet is produced. Increases bleedint time, decreases TXA2 and PGs, no effect on PT/PTT.
Use: antipyretic, analgesic, anti-inflammatory, antiplatelet
Toxicity: GI ulceration, tinnitus (CN8), acute renal failure, interstitial nephritis, upper GI bleeding, Reye syndrome.
Overdose: hyperventilation but becomes mixed metabolic acidosis-resp alkalosis.
ADP receptor inhibitors
Clopidogrel, prasugrel, ticagrelor (reversible), ticlopidine.
MOA: block platlet aggregation by irr. Blocking ADP receptors. Prevents expression of glycoproteins Iib/IIIa on platelet surface.
Use: Acute coronary sydnrome, coronary stenting, decreases incidence or recurrent of thrombotic stroke.
Toxicity: Neutropenia (ticlopidine), TTP
PDEIII Inhibitors
Cilostazol, dipyridamole
MOA: increase cAMP in platelets, inhibits platelet aggregation, vasodilators.
Use: intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (with aspirin), angina proph
Toxicity: N/HA, facial flushing, hypotension, abd pain
GPIIb/IIIa Inhibitors
Abciximab, eptifibatide, tirofiban
MOA: Bind to Iib/IIIa on activated platelets, prevent agg. Abciximab is made from monoclonal ab Fab fragments.
Use: unstable angina, percutaneous transluminal coronary angioplasty.
Toxicity: Bleeding, thrombocytopenia
Azathioprine, 6MP, 6TG
MOA: Purine analogs–decerase de novo purine synthesis. Activated by HGPRT. Azathioprine –> 6MP.
Use: Prevent organ rejection, RA, IBD, SLE, wean pt off steroids
Toxicity: Myelosuppression, GI, liver.
*Azothioprine and 6MP: metabolized by XO. Allopurinol/feboxustat incr toxicity.
Cladribine (2CDA)
MOA: Purine analog–inhibtion of DNA pol, DNA strand breaks
Use: Hairy cell leukemia
Toxicity: Myelosuppresion, nephrotoxicity, neurotoxicity
Cytarabine (arabinofuranosyl cytidine)
MOA: Pyrimidine analog–blocks DNA pol
USE: Leukemias (AML), lymphomas
Toxicity: Leukopenia, thrombocytopenia, megaloblastic anemia.
*CYTarabine causes panCYTopenia
5-FU
MOA: Pyrimidine analog bioactivated to 5F-dUMP–covalently complexes folic acid. Inhibits thymidylate synthase –> decr dTMP, DNA synth.
Use: Colon cancer, pancreatic cancer, basal cell carcinoma (topical)
Toxicity: Myelosuppression (not reversible with leucovorin)
MTX
MOA: folic acid analog that competitively inhibits dihydrofolate reductase –> decr dTMP, DNA synth.
Use: 1. Cancers: leukemias (ALL), lymphomas, choriocarcinoma, sarcomas. 2. Non-neoplastic: ectopic pregnancy, medical aborption (w misoprostol), RA, psoriasis, IBD, vasculitis.
Toxicity: Myelosuppresion (rev with leucovorin), hepatotoxicity, mucositis (mouth ulcers), pulmonary fibrosis.
Bleomycin (antitumor)
MOA: free radical formation, DNA strand breaks
Use: Testicular cancer, Hodgkin lymphoma
Toxicity: Pulmonary fibrosis, skin hyperpigmentation, mucositis, minimal myelosuppresion.
Dactinomycin/actinomycin D (antitumor)
MOA: Intercalates in DNA.
Use: Wilms tumor, Ewing sarcoma, rhabdomyosarcoma. Childhood tumors. Children’s ACT out.
Toxicity: Myelosuppression.
Doxorubicin, daunorubicin (antitumor)
MOA: Generates free radicals. Intercalates in DNA, DNA breaks, decr replication.
Use: Solid tumors, leukemias, lymphomas.
Toxicity: Cardiotoxicity (dilated), myelosuppression, alopecia. Toxic to tissues following extravasation. Dexrazoxane (iron chelating agent) used to prevent cardiotoxicity.
Busulfan (alkylating agent)
MOA: Cross-links DNA.
Use: CML. Used to ablate bone marrow before transplant.
Toxicity: Severe myelosuppression, pulmonary fibrosis, hyperpigmentation.
Cyclophosphamide, ifosfamide (alkylating agent)
MOA: Cross links DNA at guanine N7. Requires bioactivation by liver.
Use: Solid tumors, leukemia, lymphomas.
Toxicity: Myelosuppression, hemorrhagic cystitis, partially prevented with mesna (thiol group of mesna binds toxic metabolites).
Nitrosoureas (carmustine, lomustine, semustine, streptozocin) (alkylating agents)
MOA: requires bioactivation. Crosses BBB – CNS. Cross links DNA.
Use: Brain tumors (including glioblastoma multiforme).
Toxicity: CNS toxicity (convulsions, dizziness, ataxia).
Paclitaxel (MT inhib)
MOA: Hyperstabilize polyermized MTs in M phase, mitotic spindle can’t break down (no anaphase)
*Taxing to stay polymerized!
Use: Ovarian and breast carcinomas
Toxicity: Myelosuppression, alopecia, HSN, peripheral neuropathy
Vincristine, vinblastine (MT inhib)
MOA: Vinca alkaloids, bind b-tubulin and block polymerization into MT, prevent mitotic spindle formation, M-phase arrest.
Use: Solid tumors, leukemias, Hodgkin (vinblastine), and nonhodgkin (vincristine). Also Wilms, Ewing, choriocarinoma.
Toxicity: Neurotoxicity (areflexia, peripheral neuritis), paralytic ileus
*Vinblastine blasts bones (suppression).
Cisplatin, carboplatin
MOA: Cross-link DNA (platinum coord complex)
Use: Testicular, bladder, ovary, lung carcinomas
Toxicity: Nephrotoxicity, ototoxicity. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride (saline) diuresis.
Etoposide, teniposide
MOA: Etoposide inhibits topoisomerase II – increase DNA degradation
Use: Solid tumors (testicular and small cell lung), leukemias, lymphomas
Toxicity: Myelosuppression, GI upset, alopecia
Irinotecan, topotecan
MOA: Inhibit topoisomerase I and block DNA unwinding and rep.
Use: Colon cancer (irinotecan), ovarian, small cell lung cancer (topotecan)
Toxicity: Severe myelosuppression, diarrhea.
Hydroxyurea
MOA: Block rionucleotide reductase –> decrease DNA synthesis (S-specific).
Use: Melanoma, CML, sickle cell disease (increase HbF)
Toxicity: Severe myelosuppression, GI upset.
Eradicate ball cancer
Etoposide, bleomycin (or ifosfamide), cisplatin
Predisone, prednisolone
MOA: bind intracytoplasmic receptor, alter gene transcription
Use: MC used glucocorticoids in chemo. CLL, non-Hodgkin lymphoma, immunosuppression
Toxicity: Cushing
Bevacizumab
MOA: monoclonal ab against VEGF, block angiogenesis
Use: Solid tumors (colorectal cancer, RCC)
Toxicity: Hemorrhage, blood clots, imparied wound healing
Erlotinib
MOA: EGFR tyrosine kinase inhibitor
Use: Non-small cell lung carcinoma
Toxicity: Rash
Imatinib
MOA: Tyrosine kinase inhibitor of BCR-ABL and c-kit (common in Gi stromal tumors).
Use: CML, GI stromal tumors
Toxicity: Fluid retention
Rituximab
MOA: monoclonal ab against CD20 (most B cell neoplasms)
Use: Non-hodgkin lymphoma, CLL, IBD, rheumatoid arthritis
Toxicity: Increase risk of progressive multifocal leukoencephaloapthy
Tamoxifen, raloxifene
MOA: SERMs–antagonists in breast and agonists in bone. Block binding of estrogen to ER+ cells.
Use: Breast cancer (tamoxifen only) and prevention. Raloxifene useful to prevent ostoeporosis
Toxicity: Tamoxifen–partial agonist in endometrium (increase cancer risk), hot flashes. Raloxifen: no incr in endometrial CA, partial antagonist in endometrial tissue.
Trastuzumab (herceptin)
MOA: Monoclonal ab against HER-2 (c-erbB2), tyrosine kinase receptor. Helps kill cancer cells that overexpress HER-2, through inhibition of HER2-initiated cellular signaling and ab-depedent cytotoxicity.
Use: HER-2+ breast cancer and gastric cancer (tras2zumab)
Toxicity: Cardiotoxicity–heartceptin
Vemurafenib
MOA: small molecule inhibitor of BRAF oncogene + melanoma
Use: Mets melanoma
Interferons
MOA: Glycoproteins normally made by virus-infected cells, exhibit wide range of antiviral and antitumor properties.
IFNa: chronic hep B and C, kaposi, hairy cell leukemia, condyloma acuminatum, RCC, malignant melanoma
IFNb: multiple sclerosis
IFNg: chronic granulomatous disease
Toxicity:
Hep C therapy
Ribavirin: block guanine nucleotides by inhibiting IMP dehydrogenase. Chronic HCV, RSV (palivizumab for kids). Toxicity: hemolytic anemia, severe teratogen
Simeprevir: HCV protease inhibitor, prevents viral replication. Chronic HCV in combo wtih ribavirin and peginterferon-a. NOT monotherapy. Toxicity: photosensitivity, rash
Sofosbuvir: inhibitos HCV RNA-dep RNA pol, chain terminator. Chronic HCV via combo with ribavirin and pegifnA. NOT monotherpay. Toxicity: fatigue, HA, nausea
Abx to avoid in pregnancy
Sulfonamides: kernicterus
Aminoglycosides: ototoxicity
FQ: cartilage damage
Clarithromycin: embryotoxic
Tetracyclines: discolored teeth, inhibition of bone growth
Ribavirin (antiviral): teratogenic
Griseofulvin (antifungal): teratogenic
Chloramphenicol: Gray baby
Epinephrine, brimonidine
Glaucoma drugs
Epinephrine (a1): decrease aqueous humor synthesis via vasoconstriction. *This causes mydriasis–DO NOT use in closed angle
Brimonidine (a2): decrease aqueous humor synthesis
*Both can cause blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, ocular pruritis
Timilol, betaxolol, carteolol
Glucoma drugs
Decrease aqueous humor synthesis, no pupillary or vision changes
Acetazolamide
Glucoma drugs
Decrease aqueous humor synthesis via inhibition of CA. No pupillary or vision changes.
Pilocarpine, carbachol
Glucoma drugs, Direct cholinomimetics
Increase outflow of aquous humor via contraction of ciliary muscle and opening of trabecular meshwork. Use pilocarpine in emergencies–opens meshwork into canal
*Miosis and cyclospasm (contraction of ciliary muscle).
Physostigmine, echothiophate
Glucoma drugs, Indirect cholinomimetics
*Miosis and cyclospasm (contraction of ciliary muscle).
Latanoprost
Glucoma drugs, PGF2a
Increase outflow of aqueous humor
*Darkens color of iris (browning)
Pentazocine
Partial opioid, lower abuse potential. Can cause withdrawal sx if using full opioid agonist.
Tramadol
Weak opioid, also inhibits 5HT and NE reuptake. “tram it all”–works on multiple NTs.
Use: chornic pain.
*Decreases seizure threshold, serotonin syndrome.
Local anesthetics–Esters
Procaine, cocaine, tetracaine
Local anesthetics–Amides
All have 2 I’s
Lidocaine, mepivacain, bupivacaine (cardiovascular toxicity)
Order of nerve blockade (local anesthetic)
Small-diameter fibers > large
Myelinated fibers > unmyelinated fibers
Order of nerve sensation loss (local anesthetic)
Pain, temp, touch, pressure
Local anesthetics
Block Na+ channels, bind to inner part of channel when it’s activated (most effective in rapidly firing neurons).
Depolarizing NM blocking drugs
Succinylcholine: strong Ach receptor agonist, produces sustained depolarization and prevents muscle contraction.
Reversal of blockage: Phase I–prolonged depolarization/NO ANTIDOTE. Block potentiated by cholinesterase inhibitors. Phase II–repolarized but blocked/ACh receptors are available, but desensitized. Antidote: cholinesterase inhibitors.
Complications: hypercalcemia, hyperkalemia, malignant hyperthermia
Nondepolarizing NM blocking drugs
Tubocurarine, atracurium, mivacurium, pancuronium: all are competitive antagonists and compete with ACh for receptors. *Can release histamine and cause fall in BP, flushing, bronchoconsriction.
Reversal of blockage: neostigmine (must be given with atropine to prevent muscarinic effects like bradycardia), edrophonium, other cholinesterase inhibitors.
Zolpiedem, zaleplon, eszopiclone
BZ1 subtype of GABA receptor, reversed by flumazenil
Use: insomnia
SE: ataxia, HA, confusion. Short duration because of rapid metabolism by liver. Only modest day-after psychomotor depression and few amnestic effects. Less dependence.
Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, N2O
Effects: myocardial depression, respiratory depression, N/emesis, increased cerebral blood flow (decreased cerebral metabolic demand).
Toxicity: hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), expansion of trapped gas in body (N2O).
Can cause malignant hyperthermia–inhaled anesthetics (except N2O) and succinylcholine induce fever and severe muscle contractions. Tx with dantrolene.
Midazolam
MC drug used for endoscopy. Short acting benzo. Can cause severe post op resp depression, decrease in BP, anterograde amnesia
Ketamine
PCP analogs that act as dissociative anesthetics. Block NMDA receptors. CV stimulants. Cause disorientation, hallucination, bad dreams, increases cerebral blood flow.
Propofol
Sedation in ICU, rapid anesthesia induction, short procedures. Less postop N than thiopental. Potentiates GABAa.
Baclofen
Inhibits GABAb receptors at the spinal cord level, inducing skeletal muscle relxation.
Use: muscle spasms
Cyclobenzprine
Centrally acting skeletal muscle relaxant. Structurally related to TCAs, similar anticholinergic side effets.
Use: muscle spasms
Parkinson drugs
BALSA
-Bromocriptine: ergot, DA agonist
-Amantadine: incr DA release and decr reuptake, also antiviral for influenza A and rubella. Toxicity = ataxia, livedo reticularis.
-L-dopa/carbidopa: carbidopa blocks peripheral conversion to dopamine by blocking DOPA decarboxylase. Reduces SE of peripheral L-dopa conversion too (N/V). Also entacapone/tolcapone block COMT.
-Selegiline (and COMT inhibitors): blocks breakdown centrally to increase DA. Selegiline blocks MAO-B, Tolcapone blocks COMT.
-Antimuscarinics: Benztropine–improves tremor and rrigidity but little effect on bradykinesia.
Alzheimer drugs
Memantine: NMDA receptor antagonist, prevent excitotoxicity (Ca). SE: Dizziness, confusion, hallucinations.
Donepezil, galantamine, rivastigmine, tacrine: AChE inhibitors. SE: N/dizziness, insomnia
Huntington disease drugs
NT changes in Huntington: decr GABA, Ach, incr DA
Tetrabenazine and reserpine: inhibit VMAT
Haloperidol: D2 receptor blocker
