Pharmacology High Yields Flashcards
Azathioprine, 6-MP, G-TG
Mechanism: purine analog; activated by HGPRT; AZ –> 6-MP
Use: preventing organ rejection, RA, IBD, SLE, ALL
Toxicity: Myelosuppression, GI, liver (Jaundice)
AZ and 6-MP are metabolized by xanthine oxidase (and TPMT in liver), thus both have increased toxicity with allopurinol or febuxostat
Works during S phase
Cladribine (2-CDA)
Mechanism: purine analog; resistant to degradation by adenosine deaminase
Use: Hairy cell leukemia
Toxicity: myelosuppression, nephrotoxicity and neurotoxicity
Cytarabine (arabinofuranosyl cytidine)
Mechanism: pyrimidine analog –> inhibition of DNA polymerase
Uses: AML, lymphomas
Toxicity: leukopenia, thrombocytopenia, megaloblastic anemia
“CYTarabine causes panCYTopenia”
5-FU
Mechanism: pyrimidine analogue, bioactivated to 5F-dUMP, which covalently complexed with folic acid and inhibits thymidylate synthase -> decreased DNA synthesis
Uses: colon cancer, pancreatic cancer, basal cell carcinoma
Toxicity: mylosuppression NOT reversed by leucovorin (folinic acid)
MTX
Mechanism: Folic acid analog that competitively inhibits dihydrofolate reductase –> decreased DNA synthesis
Uses: ALL, lymphoma, ectopic pregnancy, medical abortion, RA, psoriasis, IBD, vasculitis
Toxicity: myelosuppression which IS reversible with leucovorin “rescue” ; hepatoxocity, mucositis (mouth ulcers), pulmonary fibrosis, teratogen, nephrotoxicity
Bleomycin
Mechanism: Induces free radical formation –> breaks in DNA strands
Use: testicular cancer, Hodgkin lymphoma
Toxicity: pulmonary fibrosis, skin hyperpigmentation, mucositis, minimal myelosuppression
Acts during G2 phase
Dactinomycin
Mechanism: intercalates in DNA –> inhibition of DNA-dep. RNA pol.
Use: Wilms tumor, Ewing sarcoma, rhabdomyosarcoma - tumors of childhood (“children ACT out”)
Toxicity: myelosuppression, radiation recall
Doxorubicin/Daunorubicin
Mechanism: generate free radicals; intercalate in DNA –> breaks in DNA
Use: solid tumors, leukemia, lymphoma
Toxicity: dilated cardiomyopathy, myelosuppression, alopecia
Dexrazoxane
Iron chelating agent used to prevent cardio toxicity from doxorubicin and daunorubicin
Leucovorin
Folinic acid - N5-formyl-THF; used to overcome myelosuppression in Methotrexate usage NOT 5-FU usage
Busulfan
Mechanism: cross-links DNA
Use: CML, bone marrow ablation
Toxicity: myelosuppression severe, pulmonary fibrosis, hyperpigmentation, seizures
Cyclophosphamide/Ifosfamide
Mechanism: Cross-link DNA at guanine N-7; requires bioactivation by P450 in liver
Use: Solid tumors, leukemia, lymphoma, immunosuppression
Toxicity: hemorrhagic cystitis (partially prevented with MESNA)
MESNA
thiol group of mesna binds toxic metabolites and helps to reduce hemorrhagic cystitis when using cyclophosphamide
Nitrosoureas
Carmustine, Lomustine, Semustine, Streptozocin
Mechanism: requires bioactivation; cross blood brain barrier (lipid soluble); cross link DNA; effective in CNS
Use: brain tumors
Toxicity: CNS - convulsions, dizziness, ataxia, nephrotoxicity
Paclitaxel/Taxols
Mechanism: hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down and anaphase cannot occur
Use: Ovarian and breast cancer; coat stents
Toxicity: myelosuppression, alopecia, hypersensitivity
Vincristine/Vinblastine
Mechanism: vinca alkaloids that bind beta-tubulin and inhibit polymerazation into microtubules –> prevent mitotic spindle formation (M phase)
Use: solid tumors - testicular breast - NSCLC - Hodgkin (vinblastine) and non-Hodgkin (vincristine), ALL
Toxicity: Neurotoxicity - peripheral neuritis (Vincristine), paralytic ileus (Vincristine), Marros suppression (Vinblastin - Blasts bone)
Cisplatin/Carboplatin
Mechanism: cross-link DNA
Use: testicular, bladder, ovary and lung carcinoma
Toxicity: nephrotoxicity (prevent with amifostine and chloride diuresis), ototoxicity
Amifostine
Free radical scavenger used to treat cisplatin nephrotoxicity
Etoposide/Teniposide
Mechanism: inhibit topoisomerase II –> DNA degradation
*S–>G2 phase
Use: solid tumors - testicular and SCLC - leukemia, lymphoma
Toxicity: myelosuppression, GI upset alopecia
Irinotecan/Topotecan
Mechanism: inhibit topoisomerase I and prevent DNA unwinding and replication
*S –> G2 phase
Use: colon cancer, ovarian and SCLC
Toxicity: myelosuppression, diarrhea
Hydroxyurea
Mechanism: inhibit ribonucleotide reductase –> decreased DNA synthesis (S phase specific)
Use: melanoma, CML, sickle cell (increases HbF)
Toxicity: severe myelosuppression, GI upset
Bevacizumab
Mechanism: monoclonal antibody against VEGF –> inhibit angiogenesis
Use: solid tumors - colorectal and renal cell
Toxicity: hemorrhage, blood clots, impaired wound healing
Erlotinib
Mechanism: EGFR tyrosine kinase inhibitor
Use: NSCLC
Toxicity: rash
Imatinib
Mechanism: tyrosine kinase inhibitor of BCR-ABL and c-kit
Use: CML, GI stromal tumors
Toxicity: fluid retention, heart failure
Rituximab
Mechanism: monoclonal antibody against CD20, found on most B cell neoplasms
Use: Non-Hodgkins, CLL, IBD, RA
Toxicity: increased risk of progressive multifocal leukoencephalopathy, infusion rxn, tumor lysis sydrome
Tamoxifen/ Raloxifene
Mechanism: selective estrogen receptor modulator (SERM) - block the bind of estrogen to ER+ cells
Use: breast cancer (Tamoxifen) Osteoporosis prevention (Raloxifen)
Toxicity: increased risk of endometrial cancer; hot flashes (tamoxifen)
Trastuzumab (Herceptin)
Mechanism: monoclonal antibody against HER-2 (c-erbB2) - a tyrosine kinase inhibitor; through inhibition of HER-2-initiated cellular signaling and antibody-dependent cytotoxicity
Use: Her2+ breast canse and gastric cancer
Toxicity: cardiotoxicity - “HEARTceptin”
Vemurafenib
Mechanism: small molecule inhibitor of BRAF oncogene + melanoma
Use: metastatic melanoma
Vemurafenib
Mechanism: small molecule inhibitor of BRAF oncogene + melanoma
Use: metastatic melanoma
Alpha 1
Gq
Gq
PLC –> DAG/IPS –> Ca2+/Calmodulin/PKC –> Phosphorylation
Gs
ATP–> cAMP –> PKA
Alpha 2
Gi
Beta1 & Beta2
Gs
M1 & M3
Gq
M2
Gi
D1
Gs
D2
Gi
H1
Gq
H2
Gs
V1
Gq
V2
Gs
Bethanechol
Muscarinic agonist; Tx of Ileus and urinary retention (resistant to esterase)
Carbachol
Muscarinic/nicotinic agonist; Causes contraction of ciliary muscle for open-angle glaucoma; constricts pupil
Pilocarpine
Muscarinic agonist; stimulates tears, sweat and saliva; Constricts pupil and ciliary muscle - acute glaucoma tx.
Clonidine
Agonist of central alpha2 adrenergic receptors –> decreased sympathetic outflow
Nonselective Alpha Blockers
Phenoxybenzamine (irreversible)
Phentolamine (reversible)
Alpha 1 Selective Blockers
Prazosin, Terazosin, Doxazosin (longest acting)
Tx. of HTN and BPH; may cause orthostatic hypotension so take at bedtime
Alpha 2 Selective Blockers
Mirtazapine - treatment of depression; can cause sedation, increased cholesterol and increased appetite
Alpha 2 Selective Blockers
Mirtazapine - treatment of depression; can cause sedation, increased cholesterol and increased appetite
Mixed Alpha and Beta Blockers
Carvedilol
Labetalol
Partial Beta Agonists
Pindolol
Acebutolol
Acetaminophen Antidote
N-acetylcysteine helps regenerate glutathione
Salicylates Antidote
sodium bicarb to alkalinize urine; dialysis
Anticholinesterases
Organophosphate Toxicity Antidote
Atropine; 2-PAM
Anticholinergics Antidote (eg. Scopolamine, Atropine)
Physostigmine
Beta Blocker Antidote
Glucagon to increase inotropy and chronotrophy
Digitalis Antidote
Anti-digitalis Fab fragments; Normalize serum electrolytes, esp. K+; then lidocaine, magnesium
Iron Antidote
Deferoxamine
Lead Antidote
Ca-EDTA; Dimercaprol, Succimer, Penicillamine
Arsenic, Mercury, Gold Antidote
Dimercaperol, Succimer
Copper, Arsenic, Gold Antidote
Penicillamine
Cyanide Antidote
Nitrite, Hydroxocobalamin, Thiosulfate
Methemoglobin Antidote
Methylene Blue, Vit. C
Heparin Antidote
Protamine
tPA, Streptokinase Antidote
Aminocaproic acid
Theophylline Antidote
Beta-blocker
Atropine-Like (anticholinergic) SE
TCAs, Anti-histamines
Dilated Cardiomyopathy SE
Doxorubicin, Danorubicin
Coronary Vasospasm SE
Cocaine, Sumitriptan
Cutaneous Flushing SE
Vancomycin, Adenosine, Niacin, Ca-channel blockers
Torsades De Pointes SE
Class III (sotalol), Class IA (quinidine), Cispride; Tx. with magnesium
Agranulocytosis SE
Clozapine, Carbamazepine, Colchicine, Propylthiouracil, Dapsone, Methimazole
Aplastic Anemia SE
Cholramphenicol, Benzene, NSAIDs, Felbamate
Hemolytic Anemia (Coombs +) SE
Methyldopa
G-6-PD deficiency Hemolytic Anemia
Isoniazid, Sulfa drugs, Asprin, Ibuprofen, Nitrofurantoin, Primaquin
Megaloblastic Anemia SE
Methotrexate, Sulfa Drugs, Phenytoin
Thrombosis SE
OCPs
Thrombosis SE
OCPs
Pulmonary Fibrosis SE
Bleomycin, Amiodarone, Busulfan
Pulmonary Fibrosis SE
Bleomycin, Amiodarone, Busulfan
Hepatitis SE
Isoniazid
Cholestatic Hepatitis SE
Macrolides (azithro, clarithro)
Hepatic Necrosis SE
Halothane, Valproic Acid, Acetaminophen, Amanita phalloides (mushroom)
Pseudomembranous Colitis SE
Clindamycin, Ampicillin, Cephalosporins
Pancreatitis SE
Azathioprine, Sulfonamides, Valproic acid, methyldopa, furosemide, corticosteroids, sulindac, tetracycline, didanosine, estrogens, 6-MP, pentamide, 5-ASA, Ocreotide
Adrenocortical Insufficiency SE
Glucocorticoid withdrawal, Etomidate
Gynecomastia SE
Spironolactone, Digitalis, Cimetidine, Alcohol, Estrogens, Ketoconazole
Hot Flashes SE
Tamixoifen, Clomiphene
Hypothyroidism SE
Lithium, Amiodarone
Gingival Hyperplasia SE
Phenytoin
Gout SE
Furosemide, Thiazides
Osteoporosis SE
Corticosteroids, Heparin, H2 Blockers
Photosensitivity SE
Sulfonamides, Amiodarone, Tetracytlines, Fluoroquinolones
Rash (steven-johnson)
Sulfa Drugs, Penicillin, Carbamazepine, Allopurinol
Tendon Rupture SE
Fluoroquinolones
Lupus-Like Syndrome SE
Hydralazine, INH, Procainamide, Phenytoin
Fanconi’s Syndrome SE
Expired tetracylcines
Interstitial Nephritis SE
Methicillin, NSAIDs
Hemorrhagic Cystitis SE
Cyclophosphamide
Cinchonism SE
Quinidine, Quinine
Diabetes Insipidus SE
Lithium, Demeclocycline (tx. for SIADH)
Seizures SE
Buproprion, Imipenem/Cilastatin, INH
Parkinson-Like Syndrome SE
Haloperidol, Chlorpromazine, Reserpine, Metoclopramide
Tardive Dyskinesia SE
Typical antipsychotics
Disulfiram-Like Reaction
Metro, Procarbazine, Sulfonylureas, Cephalosporins
Nephrotoxicity/Neurotoxicity
Polymxyins
Nephrotoxicity/Ototoxicity
Aminoglycosides, Vanco, Loop diuretics, Cisplatin
P450 Inducers
Chronic Alcohol Modafinil St. Johns Word Phenytoin Pehnobarbital Nevirapine Rifampin Griseofulvin Carbamazepine "Chronic Alcoholic Mona Steals Phen-Phen and Never Refuses Greasy Carbs"
P450 Inducers
Chronic Alcohol Modafinil St. Johns Word Phenytoin Pehnobarbital Nevirapine Rifampin Griseofulvin Carbamazepine "Chronic Alcoholic Mona Steals Phen-Phen and Never Refuses Greasy Carbs" Also Quinidine and Glucocorticoids
P450 Substrates
Anti-epileptics Antidepressants Antipsychotics Anesthetics Theophylline Warfarin Statins OCPs "Always, always, always, always think when starting others"
P450 Inhibitors
Acute alcohol abuse Gemfibrozil (fibrate) Ciprofloxacin Isoniazid Grapefruit juice Quinidine Amiodarone Ketoconazole Macrolides Sulfonamides Cimetidine Ritonavir "A cute gentleman 'cipped' iced grapefruit juice quickly and kept munching on soft cinnamon rolls"
Sulfa Drugs
Probenecid Furosemide Acetazolamide Celecoxib Thiazides Sulfonamides Sulfasalazine Sulfonylureas "Popular FACTSSS" May develop fever, UTI, Steven-Johnson, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria
Sulfa Drugs
Probenecid Furosemide Acetazolamide Celecoxib Thiazides Sulfonamides Sulfasalazine Sulfonylureas "Popular FACTSSS" May develop fever, UTI, Steven-Johnson, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria
Sulfa Drugs
Probenecid Furosemide Acetazolamide Celecoxib Thiazides Sulfonamides Sulfasalazine Sulfonylureas "Popular FACTSSS" May develop fever, UTI, Steven-Johnson, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria
Vd
= Total amount of drug in body / [drug] plasma
Clearance
= Rate of drug elimination / plasma drug concentration = Vd x Ke
Half Life
= 0.7 x Vd / Clearance 1 Half Life - 50% 2 Half Lives - 75% 3 Half Lives - 87.5% 4 Half Lives - 93.8% 5 Half Lives - 96.9%
Loading Dose
= Vd x blood plasm concentration / bioavailability
Maintenance Dose
= Clearance x Css / bioavailability
Bioavailability
= 1 for IV infusions
Low Vd
Mostly in blood
Mid Vd
Mostly in extracellular fluid
High Vd
In all tissues
Metformin SE
Lactic Acidosis
Prednisone Electrolyte Abnormalities
H2O retention, hypokalemia, hypernatremia, hypocalcemia, hyperglycemia
Therapeutic Index
= LD50/ ED50 = median dose that produces toxic effect / median does required to produce therapeutic effect
Priapism SE
Hydralazine, Prazosin, Chlorpromazine, Sildafil, Trazodone
Phenylephrine
Pupillary dilation
ACh
miosis
