1. antimicrobial

summary

2. Penicillin G, V Mechanism: D-Ala-D-Ala structural analog.

Bind penicillin-binding proteins

(transpeptidases).

- Block transpeptidase cross-linking of

peptidoglycan in cell wall.

- Activate autolytic enzymes.

CLINICAL USE: Mostly used for gram ⊕

organisms; Also used for gram ⊝ cocci

(mainly N meningitidis) and spirochetes

(namely T pallidum)

ADVERSE EFFECTS: Hypersensitivity

reactions, direct Coombs ⊕ hemolytic

anemia, drug-induced interstitial nephritis.

Resistance: β-lactamase cleaves the β-

lactam ring.

3. Metronidazole Mechanism: Forms toxic free radical

metabolites in the bacterial cell that damage

DNA. Bactericidal, antiprotozoal.

Treats: Giardia, Entamoeba, Trichomonas,

Gardnerella vaginalis, Anaerobes

(Bacteroides, C difficile). C

an be used in place of amoxicillin in H pylori

"triple therapy" in case of penicillin allergy.

adverse: Disulfiram-like reaction (severe

flushing, tachycardia, hypotension) with

alcohol; headache, metallic taste.

4. Penicillinase-

sensitive

penicillins

Amoxicillin, ampicillin; aminopenicillins

Mechanism: same as penicillin. combine

with clavulanic acid to protect against

destruction by β-lactamase.

Extended-spectrum penicillin — H

influenzae, H pylori, E coli, Listeria

monocytogenes, Proteus mirabilis,

Salmonella, Shigella, enterococci.

SNL + PES and H. flu

Adverse: Hypersensitivity reactions, rash,

pseudomembranous colitis

resistance: Penicillinase (a type of β-

lactamase) cleaves β-lactam ring.

5. Penicillinase-

resistant

penicillins

Dicloxacillin, nafcillin, oxacillin.

Same as penicillin. narrow spectrum;

penicillinase resistant because bulky R

group blocks access of β-lactamase to β-

lactam ring.

for S aureus (except MRSA).

- Naf for Staph

resistance: MRSA has altered penicillin-

binding protein target site

6. Antipseudomonal

penicillins

Piperacillin, ticarcillin.

Same as penicillin. Extended spectrum.

Penicillinase sensitive; use with β-

lactamase inhibitors

Pseudomonas spp. and gram ⊝ rods.

7. β-lactamase

inhibitors

Include Clavulanic acid, Avibactam,

Sulbactam, Tazobactam.

Often added to penicillin antibiotics to

protect the antibiotic from destruction by

β-lactamase (penicillinase).

Pharmacology summaryStudy online at quizlet.com/_4dcfce

8. Cephalosporins

- general

β-lactam drugs that inhibit cell wall

synthesis but are less susceptible to

penicillinases. Bactericidal

Organisms typically not covered by 1st-4th

generation cephalosporins are LAME:

- Listeria

- Atypicals (Chlamydia, Mycoplasma)

- MRSA

- Enterococci.

Hypersensitivity reactions, autoimmune

hemolytic anemia, disulfiram-like reaction,

vitamin K deficiency.

Low rate of cross- reactivity even in

penicillin-allergic patients. nephrotoxicity of

aminoglycosides.

resistance: Inactivated by

cephalosporinases (a type of β-lactamase).

Structural change in penicillin- binding

proteins (transpeptidases).

9. Cephalosporins

- First

generation

cefazolin, cephalexin

gram ⊕ cocci and Proteus mirabilis, E coli,

Klebsiella pneumoniae.

PEcK: Proteus, E coli, Klebsiella

used prior to surgery to prevent S aureus

wound infections.

10. Cephalosporins

-second

generation

cefaclor, cefoxitin, cefuroxime, cefotetan

- 2nd grader brought Fake Fur to Tea party

gram ⊕ cocci, H influenza, Enterobacter

aerogenes, Neisseria spp., Serratia

marcescens, Proteus mirabilis, E coli,

Klebsiella pneumoniae.

- 2nd generation—HENS PEcK.

11. Cephalosporins

- third

generation

ceftriaxone, cefotaxime, cefpodoxime,

ceftazidime

serious gram ⊝ infections resistant to other

β-lactams.

Can cross BBB

Ceftriaxone—meningitis, gonorrhea,

disseminated Lyme disease

Ceftazidime—Pseudomonas

12. Cephalosporins

- fourth

generation

cefepime

gram ⊝ organisms, with activity against

Pseudomonas and gram ⊕ organisms.

13. Cephalosporins

- fifth

generation

ceftaroline

broad gram ⊕ and gram ⊝ organism

coverage; unlike 1st-4th generation

cephalosporins, ceftaroline covers Listeria,

MRSA, and Enterococcus faecalis— does

not cover Pseudomonas.

14. Carbapenems Doripenem, Imipenem, Meropenem,

Ertapenem

broad-spectrum, β-lactamase- resistant

carbapenem.

Always administered with cilastatin

(inhibitor of renal dehydropeptidase I)

toinactivation of drug in renal tubules

Gram ⊕ cocci, gram ⊝ rods, and

anaerobes. Wide spectrum and significant

side effects limit use to life-threatening

infections or after other drugs have failed

Meropenem has a decreased risk of

seizures and is stable to

dehydropeptidase I

adverse: GI distress, rash, and CNS toxicity

(seizures) at high plasma levels

15. Monobactams Aztreonam

Less susceptible to β-lactamases. Prevents

peptidoglycan cross-linking by binding to

penicillin- binding protein

Synergistic with aminoglycosides. No

cross-allergenicity with penicillins.

Gram ⊝ rods only—no activity against

gram ⊕ rods or anaerobes.

For penicillin-allergic patients and those

with renal insufficiency who cannot

tolerate aminoglycosides.

Usually nontoxic; occasional GI upset.

16. Vancomycin Inhibits cell wall peptidoglycan formation by

binding D-Ala-D-Ala portion of cell wall

precursors.

Bactericidal against most bacteria

(bacteriostatic against C difficile).

Not susceptible to β-lactamases

Gram ⊕ bugs only—serious, multidrug-resistant

organisms, including MRSA, S epidermidis,

sensitive Enterococcus species, and

Clostridium difficile (oral dose for

pseudomembranous colitis).

NOT trouble free. Nephrotoxicity, Ototoxicity,

Thrombophlebitis

red man syndrome: (largely preventable by

pretreatment with antihistamines and slow

infusion rate), drug reaction with eosinophilia

and systemic symptoms (DRESS syndrome)

Resistance: Occurs in bacteria (eg,

Enterococcus) via amino acid modification of

D-Ala-D-Ala to D-Ala-D-Lac

17. Protein

synthesis

inhibitors -

summary

Specifically target smaller bacterial ribosome

(70S, made of 30S and 50S subunits),

leaving human ribosome (80S) unaffected.

All are bacteriostatic, except

aminoglycosides (bactericidal) and linezolid

(variable).

30S inhibitors

- Aminoglycosides

- Tetracyclines

50S inhibitors

- Chloramphenicol

- Clindamycin, Erythromycin (macrolides)

- Linezolid

buy AT 30, CCEL at 50

18. Aminoglycosides

Gentamicin, Neomycin, Amikacin,

Tobramycin, Streptomycin.

Bactericidal

irreversible inhibition of initiation

complex through binding of the 30S

subunit.

Can cause misreading of mRNA.

Also block translocation.

Require O2 for uptake; therefore

ineffective against anaerobes

Severe gram ⊝ rod infections. Synergistic

with β-lactam antibiotics.

Neomycin for bowel surgery.

Adverse: Nephrotoxicity, Neuromuscular

blockade, Ototoxicity (especially when

used with loop diuretics). Teratogen

Resistance: Bacterial transferase

enzymes inactivate the drug by

acetylation, phosphorylation, or

adenylation

19. Tetracyclines

Tetracycline, doxycycline, minocycline

Bacteriostatic

bind to 30S and prevent attachment of

aminoacyl-tRNA.

Limited CNS penetration.

Doxycycline is fecally eliminated and can

be used in patients with renal failure.

Do not take tetracyclines with milk (Ca2+),

antacids (Ca2+ or Mg2+), or iron-containing

preparations because divalent cations inhibit

drugs' absorption in the gut

Borrelia burgdorferi, M pneumoniae. Drugs'

ability to accumulate intracellularly makes

them very effective against Rickettsia and

Chlamydia.

Also used to treat acne. Doxycycline effective

against MRSA.

discoloration of teeth and inhibition of bone

growth in children, photosensitivity.

Contraindicated in pregnancy.

20. Glycylcyclines

Tigecycline.

Tetracycline derivative. Binds to 30S,

inhibiting protein synthesis. Generally

bacteriostatic

Broad-spectrum anaerobic, gram ⊝, and

gram ⊕ coverage. Multidrug-resistant

organisms (MRSA, VRE) or infections

requiring deep tissue penetration.

21. Chloramphenicol

Blocks peptidyltransferase at 50S

ribosomal subunit. Bacteriostatic.

Meningitis (Haemophilus influenzae,

Neisseria meningitidis, Streptococcus

pneumoniae) and rickettsial diseases (eg,

Rocky Mountain spotted fever

[Rickettsia rickettsii]).

Limited use due to toxicity but often still

used in developing countries because of

low cost.

Anemia (dose dependent), aplastic

anemia (dose independent), gray baby

syndrome (in premature infants

because they lack liver UDP-

glucuronosyltransferase)

22. Clindamycin

Blocks peptide transfer (translocation) at 50S

ribosomal subunit.

Bacteriostatic

Treats anaerobic infections above the

diaphragm vs metronidazole (anaerobic

infections below diaphragm)

Anaerobic infections (eg, Bacteroides spp.,

Clostridium perfringens) in aspiration

pneumonia, lung abscesses, and oral

infections.

Also effective against invasive group A

streptococcal infection.

adverse: Pseudomembranous colitis (C

difficile overgrowth), fever, diarrhea.

23. Oxazolidinones

Linezolid.

Inhibit protein synthesis by binding to 50S

subunit and preventing formation of the

initiation complex

Gram ⊕ species including MRSA and VRE

Bone marrow suppression (especially

thrombocytopenia), peripheral neuropathy,

serotonin syndrome.

resistance: Point mutation of ribosomal

RNA.

24. Macrolides Azithromycin, clarithromycin, erythromycin.

Inhibit protein synthesis by blocking

translocation ("macroslides"); bind to the

23S rRNA of the 50S ribosomal subunit.

Bacteriostatic.

Atypical pneumonias (Mycoplasma,

Chlamydia, Legionella), STIs (Chlamydia),

gram ⊕ cocci (streptococcal infections in

patients allergic to penicillin), and B

pertussis.

adverse: MACRO: Gastrointestinal Motility

issues, Arrhythmia caused by prolonged

QT interval, acute Cholestatic hepatitis,

Rash, eOsinophilia.

Increases serum concentration of

theophylline, oral anticoagulants

Clarithromycin and erythromycin inhibit

cytochrome P-450

resistance: Methylation of 23S rRNA-

binding site prevents binding of drug.

25. Sulfonamides

Sulfamethoxazole (SMX), sulfisoxazole,

sulfadiazine.

Inhibit dihydropteroate synthase, thus

inhibiting folate synthesis.

Bacteriostatic (bactericidal when combined

with trimethoprim).

Gram ⊕, gram ⊝, Nocardia.

TMP-SMX for simple UTI.

Hypersensitivity reactions, hemolysis if G6PD

deficient, nephrotoxicity (tubulointerstitial

nephritis), photosensitivity, Stevens-

Johnsonn syndrome, kernicterus in infants

displace other drugs from albumin (eg,

warfarin)

resistance: Altered enzyme (bacterial

dihydropteroate synthase), decreasedz

uptake, or increased PABA synthesis.

26. Dapsone

Similar to sulfonamides, but structurally

distinct agent.

Leprosy (lepromatous and tuberculoid),

Pneumocystis jirovecii prophylaxis

Hemolysis if G6PD deficient,

methemoglobinemia.

27. Trimethoprim

Inhibits bacterial dihydrofolate reductase.

Bacteriostatic.

Used in combination with sulfonamides

(trimethoprim-sulfamethoxazole [TMP- SMX]),

causing sequential block of folate synthesis.

Combination used for UTIs, Shigella,

Salmonella, Pneumocystis jirovecii

pneumonia treatment and prophylaxis,

toxoplasmosis prophylaxis

Megaloblastic anemia, leukopenia,

granulocytopenia, which may be avoided with

coadministration of folinic acid.

TMP Treats Marrow Poorly

28. Fluoroquinolones Ciprofloxacin, enoxacin, norfloxacin,

ofloxacin; respiratory fluoroquinolones—

gemifloxacin, levofloxacin,

moxifloxacin.

Inhibit prokaryotic enzymes

*topoisomerase

II (DNA gyrase) and topoisomerase IV.*

Bactericidal

Must not be taken with antacids

Gram ⊝ rods of urinary and GI tracts

(including Pseudomonas), some gram ⊕

organisms, otitis externa

Some may prolong QT interval.

May cause tendonitis or tendon

rupture in people > 60 years old and

in patients taking prednisone.

Ciprofloxacin inhibits cytochrome P-

450.

29. Daptomycin Lipopeptide that disrupts cell

membranes of gram ⊕ cocci by creating

transmembrane channels

S aureus skin infections (especially

MRSA), bacteremia, endocarditis, VRE

Not used for pneumonia (avidly binds

to and is inactivated by surfactant).

adverse: Myopathy, rhabdomyolysis.

30. Antimycobacterial

drugs

M tuberculosis: RIPE

M avium-intracellulare: Azithromycin,

rifabutin

M leprae - Long-term treatment with

dapsone and rifampin for tuberculoid

form. Add clofazimine for lepromatous

form.

31. Rifamycins

Rifampin, rifabutin.

Inhibit DNA-dependent RNA polymerase

Rifampin's 4 R's:

- RNA polymerase inhibitor

- Ramps up microsomal cytochrome P-450

- Red/orange body fluids

- Rapid resistance if used alone

32. Isoniazid

decreases synthesis of mycolic acids.

Bacterial catalase- peroxidase (encoded by

KatG) needed to convert INH to active

metabolite.

The only agent used as solo prophylaxis

against TB

INH Injures Neurons and Hepatocytes

- P-450 inhibition

Drug-induced SLE, anion gap metabolic

acidosis, vitamin B6 deficiency (peripheral

neuropathy, sideroblastic anemia). Administer

with pyridoxine (B6).

33. Pyrazinamide

Mechanism uncertain. Pyrazinamide is a

prodrug that is converted to the active

compound pyrazinoic acid.

Works best at acidic pH (eg, in host

phagolysosomes).

adverse: Hyperuricemia, hepatotoxicity.

34. Ethambutol

decrease carbohydrate polymerization of

mycobacterium cell wall by blocking

arabinosyltransferase.

Optic neuropathy (red-green color

blindness). Pronounce "eyethambutol."

35. Streptomycin Interferes with 30S component of

ribosome.

Tinnitus, vertigo, ataxia, nephrotoxicity.

Its an aminoglycoside rememeber

36. Antimicrobial

prophylaxis:

High risk for endocarditis and undergoing

surgical or dental procedures

- Amoxicillin

Exposure to gonorrhea

- Ceftriaxone

History of recurrent UTIs

- TMP-SMX

Exposure to meningococcal infection

- Ceftriaxone, ciprofloxacin, or rifampin

Pregnant woman carrying group B strep

- Intrapartum penicillin G or ampicillin

Prevention of gonococcal conjunctivitis in

newborn

- Erythromycin ointment on eyes

Prevention of postsurgical infection due to

S aureus

- Cefazolin

Prophylaxis of strep pharyngitis in child with

prior rheumatic fever

- Benzathine penicillin G or oral penicillin V

Exposure to syphilis

- Benzathine penicillin G

37. Prophylaxis

in HIV

patients

CD4 < 200 cells/mm3: TMP-SMX for PCP

CD4 < 100 cells/mm3: TMP-SMX for PCP

and toxo

CD4 < 50 cells/mm3: Azithro and Chlarithro

for MAC

38. MRSA

treatment

vancomycin, daptomycin, linezolid,

tigecycline, ceftaroline, doxycycline.

39. VRE tx linezolid and streptogramins (quinupristin,

dalfopristin).

40. Amphotericin

B

Binds ergosterol (unique to fungi); forms

membrane pores that allow leakage of

electrolytes.

- Amphotericin tears holes

Serious, systemic mycoses. Cryptococcus

(amphotericin B with/without flucytosine for

cryptococcal meningitis), Blastomyces,

Coccidioides, Histoplasma, Candida,

Mucor.

Intrathecally for fungal meningitis.

Supplement K+ and Mg2+ because of

altered renal tubule permeability

Adverse: Fever/chills ("shake and bake"),

hypotension, nephrotoxicity, arrhythmias,

anemia, IV phlebitis ("amphoterrible").

Hydration nephrotoxicity. Liposomal

amphotericin toxicity.

41. Nystatin Same as amphotericin B. Topical use only as

too toxic for systemic use.

"Swish and swallow" for oral candidiasis

(thrush); topical for diaper rash or vaginal

candidiasis.

42. Flucytosine Inhibits DNA and RNA biosynthesis by

conversion to 5-fluorouracil by cytosine

deaminase

- Flu by cytosine

Systemic fungal infections (especially

meningitis caused by Cryptococcus) in

combination with amphotericin B.

adverse: Bone marrow suppression.

43. Azoles Clotrimazole, fluconazole, isavuconazole,

itraconazole, ketoconazole, miconazole,

voriconazole.

Inhibit fungal sterol (ergosterol) synthesis

by inhibiting the cytochrome P-450

enzyme that converts lanosterol to

ergosterol.

Local and less serious systemic mycoses.

Fluconazole for chronic suppression of

cryptococcal meningitis in AIDS patients

and candidal infections of all types.

Itraconazole for Blastomyces,

Coccidioides, Histoplasma.

Clotrimazole and miconazole for topical

fungal infections.

Voriconazole for Aspergillus and some

Candida. Isavuconazole for serious

Aspergillus and Mucor infections.

44. Terbinafine Inhibits the fungal enzyme squalene

epoxidase.

Dermatophytoses (especially

onychomycosis—fungal infection of finger

or toe nails).

taste disturbance.

45. Echinocandins Anidulafungin, caspofungin, micafungin.

Inhibit cell wall synthesis by inhibiting

synthesis of β-glucan

for Invasive aspergillosis, Candida.

46. Griseofulvin Interferes with microtubule function;

disrupts mitosis. Deposits in keratin-

containing tissues (eg, nails).

Oral treatment of superficial infections;

inhibits growth of dermatophytes (tinea,

ringworm).

Teratogenic, carcinogenic, confusion,

headaches, disulfiram-like reaction, up

cytochrome P-450 and warfarin

metabolism.

47. Antiprotozoal

therapy

Pyrimethamine (toxoplasmosis)

- tax the pyramid

suramin and melarsoprol (Trypanosoma

brucei)

- Serum and soap

nifurtimox (T cruzi)

- Knee high fur

sodium stibogluconate (leishmaniasis).

48. Anti-

mite/louse

therapy

Permethrin (inhibits Na+ channel

deactivation neuronal membrane

depolarization)

malathion (acetylcholinesterase inhibitor)

lindane (blocks GABA channels

neurotoxicity).

Used to treat scabies (Sarcoptes scabiei) and

lice (Pediculus and Pthirus).

Treat PML (Pesty Mites and Lice) with PML

(Permethrin, Malathion, Lindane), because

they NAG you (Na, AChE, GABA blockade).

49. Chloroquine Blocks detoxification of heme into

hemozoin.

Heme accumulates and is toxic to

plasmodia.

adverse: Retinopathy; pruritus (especially

in dark-skinned individuals)

50. Oseltamivir,

zanamivir

Inhibit influenza neuraminidase: down

release of progeny virus.

Treatment and prevention of both influenza A

and B.

Beginning therapy within 48 hours of

symptom onset may shorten duration of

illness.

51. Acyclovir,

famciclovir,

valacyclovir

Guanosine analogs. Monophosphorylated by

HSV/VZV thymidine kinase and not

phosphorylated in uninfected cells -> few

adverse effects.

Triphosphate formed by cellular enzymes.

Preferentially inhibit viral DNA polymerase

by chain termination

HSV and VZV. Weak activity against EBV. No

activity against CMV

Valacyclovir, a prodrug of acyclovir, has

better oral bioavailability

adverse: Obstructive crystalline nephropathy

and acute renal failure if not adequately

hydrated.

Resistance: Mutated viral thymidine kinase

52. Ganciclovir 5′-monophosphate formed by a CMV viral

kinase.

Guanosine analog. Triphosphate formed by

cellular kinases. Preferentially inhibits viral

DNA polymerase.

Valganciclovir, a prodrug of ganciclovir, has

better oral bioavailability.

advrse: Bone marrow suppression

(leukopenia, neutropenia, thrombocytopenia),

renal toxicity. More toxic to host enzymes than

acyclovir.

Resistance: Mutated viral kinase.

53. Foscarnet Viral DNA/RNA polymerase inhibitor and

HIV reverse transcriptase inhibitor.

Binds to pyrophosphate-binding site of

enzyme.

Does not require any kinase activation.

for CMV retinitis in immunocompromised

patients when ganciclovir fails; acyclovir-

resistant HSV.

Nephrotoxicity, electrolyte abnormalities

(hypo- or hypercalcemia, hypo- or

hyperphosphatemia, hypokalemia,

hypomagnesemia) can lead to seizures.

resistance: Mutated DNA polymerase.

54. Cidofovir Preferentially inhibits viral DNA polymerase.

Does not require phosphorylation by viral kinase.

CMV retinitis in immunocompromised patients;

acyclovir-resistant HSV. Long half-life.

Nephrotoxicity (coadminister with probenecid

and IV saline to decrease totoxicity).

55. HIV

therapy

general

rules

Regimen consists of 3 drugs to prevent resistance:

- 2 NRTIs and preferably an integrase inhibitor.

56. NRTIs Abacavir (ABC) Didanosine (ddI) Emtricitabine

(FTC) Lamivudine (3TC) Stavudine (d4T) Tenofovir

(TDF) Zidovudine (ZDV, formerly AZT)

Competitively inhibit nucleotide binding to

reverse transcriptase and terminate the DNA

chain (lack a 3′ OH group).

Tenofovir is a nucleoTide; the others are

nucleosides.

All need to be phosphorylated to be active.

ZDV can be used for general prophylaxis and

during pregnancy to reduce risk of fetal

transmission.

Tox: Bone marrow suppression (can be reversed

with granulocyte colony-stimulating factor [G-

CSF] and erythropoietin), peripheral neuropathy,

lactic acidosis (nucleosides),

anemia (ZDV)

pancreatitis (didanosine).

Abacavir contraindicated if patient has HLA-B5701

mutation due torisk of hypersensitivity*.

57. NNRTIs Delavirdine, Efavirenz, Nevirapine

VIRE

Bind to reverse transcriptase at site different

from NRTIs.

Do not require phosphorylation to be active or

compete with nucleotides.

Rash and hepatotoxicity are common to all

NNRTIs.

Vivid dreams and CNS symptoms are common

with efavirenz.

Delavirdine and efavirenz are contraindicated in

pregnancy.

58. Protease

inhibitors

NAVIR - Navir Tease a Protease

Atazanavir Darunavir Fosamprenavir Indinavir

Lopinavir Ritonavir Saquinavir

Assembly of virions depends on HIV-1 protease

(pol gene), which cleaves the polypeptide

products of HIV mRNA into their functional

parts.

- Thus, protease inhibitors prevent maturation

of new viruses.

Ritonavir can "boost" other drug concentrations

by inhibiting cytochrome P-450

Hyperglycemia, GI intolerance (nausea,

diarrhea), lipodystrophy (Cushing-like

syndrome).

Nephropathy, hematuria, thrombocytopenia

(indinavir)

Rifampin (potent CYP/UGT inducer) reduces

protease inhibitor concentrations; use rifabutin

instead.

59. Integrase

inhibitors

TEGRA

Dolutegravir

Elvitegravir Raltegravir

*Inhibits HIV genome integration into host cell

chromosome by reversibly inhibiting HIV

integrase*

can increase CK

60. Fusion

inhibitors

Binds gp41, inhibiting viral entry.

- Enfuvirtide inhibits fusion.

Maraviroc

- Binds CCR-5 on surface of Tcells/monocytes,

inhibiting interaction with gp120.

- Maraviroc inhibits docking.

61. Interferons for Chronic HBV and HVC, Kaposi sarcoma,

hairy cell leukemia, condyloma acuminatum,

renal cell carcinoma, malignant melanoma,

multiple sclerosis, chronic granulomatous

disease.

Flu-like symptoms, depression, neutropenia,

myopathy.

62. Hep C

therapy

Has to be polytherapy: monotherapy not

approved

all are VIR

Ribavirin also used to treat RSV (palivizumab

preferred in children).

Ledipasvir: Viral phosphoprotein (NS5A)

inhibitor; NS5A plays important role in

replication.

Ribavirin: Inhibits synthesis of guanine

nucleotides by competitively inhibiting inosine

monophosphate dehydrogenase.

- Severe teratogen

Simeprevir: HCV protease (NS3/4A); prevents

viral replication.

Sofosbuvir: Inhibits HCV RNA-dependent

RNA polymerase (NS5B) acting as a chain

terminator.

63. Antimicrobials

to avoid in

pregnancy

Sulfonamides: Kernicterus

Aminoglycosides: ototoxicity

Flouroquinolones: Cartilage damage

Clarithromycin: Clarithromycin

Tetracycline: discolored teeth, inhibition of

bone growth

Ribavirin: Teratogenic

Griseofulvin: Teratogenic

Chloramphenicol: Gray baby syndrome

64. CNS and PNS

Pelvic splanchnic nerves and CN III, VII, IX

and X are part of the parasympathetic

nervous system.

Adrenal medulla is directly innervated by

preganglionic sympathetic fibers.

Sweat glands are part of the sympathetic

pathway but are innervated by cholinergic

fibers.

65. Acetylcholine

receptors

Nicotinic ACh receptors are ligand-gated

Na+/K+ channels. Two subtypes:

- NN (found in autonomic ganglia, adrenal

medulla)

- NM (found in neuromuscular junction of

skeletal muscle).

Muscarinic ACh receptors are G-protein-

coupled receptors that usually act through

2nd messengers. 5 subtypes:

- M1-5 found in heart, smooth muscle, brain,

exocrine glands, and on sweat glands

(cholinergic sympathetic).

66. α1

receptor

Gq PCR

up vascular smooth muscle contraction, up

pupillary dilator muscle contraction (mydriasis),

up intestinal and bladder sphincter muscle

contraction

67. α2

receptor

Gi PCR

decreased sympathetic (adrenergic) outflow, down

insulin release, down lipolysis, up platelet

aggregation, down aqueous humor production

68. β1

receptor

Gs PCR

Up: heart rate, contractility (one heart), renin

release, lipolysis

69. β2

receptor

Gs PCR

Vasodilation, bronchodilation (two lungs), up

lipolysis,up insulin release, up glycogenolysis,

down uterine tone (tocolysis), up aqueous

humor production, up cellular K+ uptake

70. β3

receptor

Gs PCR

up lipolysis, up thermogenesis in skeletal

muscle, up bladder relaxation

71. M1

receptor

Gq PCR

Mediates higher cognitive functions, stimulates

enteric nervous system

72. M2

receptor

Gi PCR

down heart rate and contractility of atria

73. M3

receptor

Gq PCR

UP: exocrine gland secretions (eg, lacrimal,

sweat, salivary, gastric acid), gut

peristalsis,bladder contraction,

bronchoconstriction, pupillary sphincter muscle

contraction (miosis), ciliary muscle contraction

(accommodation),insulin release

74. D1

receptor

Gs PCR

Relaxes renal vascular smooth muscle, activates

direct pathway of striatum

75. D2

receptor

Gi PCR

Modulates transmitter release, especially in brain,

inhibits indirect pathway of striatum

76. H1 receptor Gq PCR

up nasal and bronchial mucus

production,vascular permeability,

bronchoconstriction, pruritus, pain

77. H2 receptor Gs PCR

up gastric acid secretion

78. V1 receptor Gq PCR

vascular smooth muscle

contraction

79. V2 receptors Gs PCR

increased H2O permeability and

reabsorption via upregulating

aquaporin-2 in collecting

twobules (tubules) of kidney

80. Mnemonic for

remembering what

receptor's G protein in

CNS, PNS

after a QISSeS you get a QIQ out

of SIQ Super Qinky Sex

order: alpha 1,2 beta 1,2,3 M 1,2,3

Dop 1,2, H 1,2 Vaso 1,2

81. Gq receptors in CNS HAVe 1 M&M

H1, Alpha 1, V1

M1, M3

82. Gi receptors in CNS are the MAD2's

M2, Alpha 2, D2

83. Release of

norepinephrine from a

sympathetic nerve

ending is modulated

by

NE itself, acting on presynaptic α2-

autoreceptors -> negative

feedback.

84. Bethanechol Direct agonists cholinomimetic

Activates bowel and bladder

smooth muscle; resistant to AChE.

No nicotinic activity.

for: Postoperative ileus, neurogenic

ileus, urinary retention

85. Carbachol Direct agonists cholinomimetic

Carbon copy of acetylcholine (but

resistant to AChE).

Constricts pupil and relieves

intraocular pressure in open-

angle glaucoma

86. Methacholine Direct agonists cholinomimetic

Stimulates muscarinic receptors in airway

when inhaled.

Challenge test for diagnosis of asthma

87. Pilocarpine Direct agonists cholinomimetic

Contracts ciliary muscle of eye (open-

angle glaucoma), pupillary sphincter

(closed-angle glaucoma); resistant to AChE,

can cross blood- brain barrier (tertiary

amine).

"You cry, drool, and sweat on your 'pilow.' "

Potent stimulator of sweat, tears, and saliva

Open-angle and closed-angle glaucoma,

xerostomia (Sjögren syndrome)

88. Donepezil,

rivastigmine,

galantamine

Indirect agonists (anticholinesterases)

Alzheimer disease

89. Edrophonium Indirect agonists (anticholinesterases)

Historically used to diagnose myasthenia

gravis; replaced by anti-AChR Ab (anti-

acetylcholine receptor antibody) test.

90. Neostigmine Indirect agonists (anticholinesterases)

Neo CNS = No CNS penetration (quaternary

amine).

Postoperative and neurogenic ileus and

urinary retention, myasthenia gravis, reversal

of neuromuscular junction blockade

(postoperative).

91. Physostigmine Indirect agonists (anticholinesterases)

*Phreely (freely) crosses blood-brain

barrier* -> CNS (tertiary amine).

Antidote for anticholinergic toxicity;

physostigmine "phyxes" atropine overdose.

92. Pyridostigmine Indirect agonists (anticholinesterases)

Pyridostigmine gets rid of myasthenia

gravis.

does not penetrate CNS (quaternary amine).

93. Cholinesterase

inhibitor

poisoning

Antidote—atropine (competitive inhibitor) +

pralidoxime (regenerates AChE if given

early).

94. Benztropine,

trihexyphenidyl

Muscarinic antagonists

CNS

Parkinson disease ("park my Benz"). Acute

dystonia.

95. Glycopyrrolate Muscarinic antagonists

GI, respiratory

Parenteral: preoperative use to reduce

airway secretions.

Oral: drooling, peptic ulcer.

96. Ipratropium,

tiotropium

Muscarinic antagonists

COPD, asthma

97. Oxybutynin,

solifenacin,

tolterodine

Muscarinic antagonists

Genitourinary

Reduce bladder spasms and urge urinary

incontinence (overactive bladder).

98. Scopolamine Muscarinic antagonists

CNS

motion sickness

99. parasympathetic

meds side

effects

Hot as a hare

Dry as a bone

Red as a beet

Blind as a bat

Mad as a hatter

Full as a flask

100. Atropine Muscarinic antagonist. Used to treat

bradycardia and for ophthalmic

applications.

101. Albuterol,

salmeterol,

terbutaline

Direct sympathomimetics

β2 > β1

Albuterol for acute asthma or COPD.

Salmeterol for long-term asthma or

COPD management.

Terbutaline for acute bronchospasm in

asthma and tocolysis.

102. Dobutamine Direct sympathomimetic

β1 > β2, α

Heart failure (HF), cardiogenic shock

(inotropic > chronotropic), cardiac stress

testing.

103. Dopamine Direct sympathomimetic

D1 = D2> β > α

Unstable bradycardia, HF, shock; inotropic

and chronotropic effects at lower doses due

to β effects; vasoconstriction at high doses

due to α effects.

104. Epinephrine Direct sympathomimetic

β>α

Anaphylaxis, asthma, open-angle glaucoma;

α effects predominate at high doses.

Significantly stronger effect at β2-

receptor than norepinephrine

105. Fenoldopam Direct sympathomimetic

D1

Postoperative hypertension, hypertensive

crisis.

Vasodilator (coronary, peripheral, renal,

and splanchnic).

Promotes natriuresis. Can cause hypotension

and tachycardia.

106. Isoproterenol Direct sympathomimetic

β1 = β2

Electrophysiologic evaluation of

tachyarrhythmias. Can worsen ischemia.

Has negligible α effect.

107. Midodrine Direct sympathomimetic

α1

Autonomic insufficiency and postural

hypotension. May exacerbate supine

hypertension.

108. Mirabegron Direct sympathomimetic

β3

Urinary urge incontinence or overactive

bladder.

109. Norepinephrine Direct sympathomimetic

α1 > α2 >β1

Hypotension, septic shock.

110. Phenylephrine Direct sympathomimetic

α1 > α2

Hypotension (vasoconstrictor), ocular

procedures (mydriatic), rhinitis

(decongestant), ischemic priapism.

111. Amphetamine Indirect sympathomimetic

Indirect general agonist, reuptake inhibitor,

also releases stored catecholamines

112. Cocaine Indirect general agonist, reuptake inhibitor

Indirect sympathomimetic

Caution when giving β-blockers if cocaine

intoxication is suspected (unoposed

alpha)

113. Ephedrine Indirect sympathomimetic

Indirect general agonist, releases stored

catecholamines

Nasal decongestion (pseudoephedrine),

urinary incontinence, hypotension.

114. Norepinephrine

vs

isoproterenol

NE increase systolic and diastolic

pressures as a result of α1-mediated

vasoconstriction -> up mean arterial

pressure -> reflex bradycardia.

However, isoproterenol (rarely used) has

little α effect but causes β2-mediated

vasodilation, resulting in reduced mean

arterial pressure and increased heart

rate through β1 and reflex activity.

115. Clonidine,

guanfacine

Sympatholytic (α2-agonist)

Hypertensive urgency (limited

situations), ADHD, Tourette syndrome,

symptom control in opioid

withdrawal

adverse: CNS depression,

bradycardia, hypotension, respiratory

depression, miosis, rebound

hypertension with abrupt cessation

116. α-methyldopa Sympatholytic (α2-agonist)

Hypertension in pregnancy

Adverse: Direct Coombs ⊕

hemolysis, drug-induced lupus

117. Tizanidine Sympatholytic (α2-agonist)

Relief of spasticity

Adverse: Hypotension, weakness,

xerostomia

118. Phenoxybenzamine Non selective α-blocker

Irreversible. Pheochromocytoma (used

preoperatively) to prevent

catecholamine (hypertensive) crisis

Adverse: Orthostatic hypotension,

reflex tachycardia

119. Phentolamine Non selective α-blocker

Reversible. Give to patients on MAO

inhibitors who eat tyramine-

containing foods and for severe

cocaine-induced hypertension (2nd

line)

adverse: Orthostatic hypotension,

reflex tachycardia

120. Prazosin, terazosin,

doxazosin,

tamsulosin

α1 selective (-osin ending) blocker

Urinary symptoms of BPH; PTSD

(prazosin); hypertension (except

tamsulosin)

Adverse: 1st-dose orthostatic

hypotension, dizziness, headache

121. Mirtazapine α2 selective blocker

Depression

adverse: Sedation, up serum cholesterol, up

appetitex

122. beta blocker

use in

glaucoma

timolol

decreased production of aqueous humor

123. beta blocker

use in SVT

*reduce AV conduction velocity (class II

antiarrhythmic)*

Metoprolol, esmolol

124. beta blocker

selectivity

β1-selective antagonists (β1 > β2)—acebutolol

(partial agonist), atenolol, betaxolol,

bisoprolol, esmolol, metoprolol

- Selective antagonists mostly go from A to

M (β1 with 1st half of alphabet)

Nonselective antagonists (β1 = β2)—nadolol,

pindolol (partial agonist), propranolol,

timolol

- Nonselective antagonists mostly go from N

to Z (β2 with 2nd half of alphabet)

Nonselective α- and β-antagonists—

carvedilol, labetalol

- Nonselective α- and β-antagonists have

modified suffixes (instead of "-olol")

Nebivolol combines cardiac-selective β1-

adrenergic blockade with stimulation of β3-

receptors (activate nitric oxide synthase in

the vasculature and reduce SVR)

- Nebivolol increases NO

125. Histamine

(scombroid

poisoning)

Spoiled dark-meat fish such as tuna, mahi-

mahi, mackerel, and bonito.

Bacterial histidine decarboxylase converts

histidine to histamine.

Frequently misdiagnosed as fish allergy.

Mimics anaphylaxis

Antihistamines. Albuterol and epinephrine

if needed.

126. Tetrodotoxin Pufferfish.

Highly potent toxin; binds fast voltage-

gated Na+ channels in cardiac/nerve tissue,

preventing depolarization.

Tx: Supportive.

127. Ciguatoxin Reef fish such as barracuda, snapper,

and moray eel.

Opens Na+ channels, causing

depolarization

Nausea, vomiting, diarrhea; perioral

numbness;

reversal of hot and cold sensations;

bradycardia, heart block, hypotension.

Tx: Supportive.

128. Beers criteria Widely used criteria developed to

reduce potentially inappropriate

prescribing and harmful polypharmacy

in the geriatric population. Includes >

50 medications that should be avoided

in elderly patients due to decreased

efficacy and/or increased risk of

adverse evetns

- α-blockers (up risk of hypotension)

- Anticholinergics, antidepressants,

antihistamines, opioids (up risk of

delirium, sedation, falls,

constipation, urinary retention)

- Benzodiazepines (up risk of delirium,

sedation, falls)

- NSAIDs ( up risk of GI bleeding,

especially with concomitant

anticoagulation)

- PPIs ( risk of C difficile infection)

129. Acetaminophen

toxicity treatment

N-acetylcysteine (replenishes

glutathione)

130. AChE inhibitors,

organophosphates

toxicity treatment

Atropine > pralidoxime

131. Antimuscarinic,

anticholinergic

agents toxicity

treatment

Physostigmine, control hyperthermia

132. Arsenic toxicity

treatment

Dimercaprol, succimer

133. toxicity treatment

Benzodiazepines

Flumazenil

134. toxicity treatment

β-blockers

Atropine, glucagon

135. toxicity treatment

Copper

Penicillamine, trientine (Copper

penny)

136. toxicity treatment

Cyanide

Nitrite + thiosulfate,

hydroxocobalamin

137. toxicity treatment:

Digitalis (digoxin)

Anti-dig Fab fragments

138. toxicity treatment:

Heparin

Protamine sulfate

139. toxicity treatment: Iron Deferoxamine, deferasirox,

deferiprone

140. toxicity treatment:

Mercury

Dimercaprol, succimer

141. toxicity treatment:

Methanol, ethylene

glycol (antifreeze)

Fomepizole > ethanol, dialysis

142. toxicity treatment:

Methemoglobin

Methylene blue, vitamin C

(reducing agent)

143. toxicity treatment:

Salicylates

NaHCO3 (alkalinize urine),

dialysis

144. toxicity treatment: TCAs NaHCO3 (stabilizes cardiac cell

membrane)

145. toxicity treatment:

Warfarin

Vitamin K (delayed effect), fresh

frozen plasma (immediate)

146. drugs that cause

Coronary vasospasm

Cocaine, Amphetamines,

Sumatriptan, Ergot alkaloids

147. drugs that cause

Cutaneous flushing

Vancomycin, Adenosine, Niacin,

Ca2+ channel blockers,

Echinocandins, Nitrates

148. drugs that cause dilated

cardiomyopathy

Anthracyclines (eg,

Doxorubicin, Daunorubicin);

prevent with Dexrazoxane

149. Dexrazoxane to prevent dilated CM with

Anthracyclines (eg,

Doxorubicin, Daunorubicin)

150. drugs that cause

torsades

Agents that prolong QT interval

(ABCDE)

- antiArrhythmics (class IA, III)

- antiBiotics (eg, macrolides)

- anti"C"ychotics (eg,

haloperidol),

- antiDepressants (eg, TCAs)

- antiEmetics (eg, ondansetron)

151. drugs that cause

Diabetes insipidus

Lithium, demeclocycline

152. drugs that cause

Hyperglycemia

Tacrolimus, Protease inhibitors,

Niacin, HCTZ, Corticosteroids

153. drugs that cause

Hyperprolactinemia

Typical antipsychotics (eg,

haloperidol), atypical antipsychotics

(eg, quetiapine), metoclopramide,

methyldopa

Presents with hypogonadism (eg,

infertility, amenorrhea, erectile

dysfunction) and galactorrhea (more

common in men)

154. drugs that cause

Hyperthyroidism

Lithium, amiodarone

155. drugs that cause

Hypothyroidism

AMiodarone, SUlfonamides, Lithium

156. drugs that cause

SIADH

Carbamazepine, Cyclophosphamide,

SSRIs

157. drugs that cause

Acute cholestatic

hepatitis, jaundice

Macrolides (eg, erythromycin)

158. drugs that cause

Focal to massive

hepatic necrosis

Halothane, Amanita phalloides

(death cap mushroom), Valproic acid,

Acetaminophen

159. drugs that cause

Hepatitis

Rifampin, isoniazid, pyrazinamide,

statins, fibrates

160. drugs that cause

Pancreatitis

Didanosine, Corticosteroids, Alcohol,

Valproic acid, Azathioprine, Diuretics

(furosemide, HCTZ)

161. drugs that cause

Pill-induced

esophagitis

Bisphosphonates, ferrous sulfate,

NSAIDs, potassium chloride,

tetracyclines

162. drugs that cause

Pseudomembranous

colitis

Ampicillin, cephalosporins,

clindamycin, fluoroquinolones

163. drugs that cause

Agranulocytosis

Clozapine, Carbamazepine,

Propylthiouracil, Methimazole,

Colchicine, Ganciclovir

164. drugs that

causeAplastic

anemia

Carbamazepine, Methimazole,

NSAIDs, Benzene, Chloramphenicol,

Propylthiouracil

165. drugs that cause

Direct Coombs-

positive hemolytic

anemia

Penicillin, methylDopa,

Cephalosporins

P Diddy Coombs

166. drugs that cause

Drug reaction with

eosinophilia and

systemic

symptoms

(DRESS)

*Allopurinol, anticonvulsants,

antibiotics, sulfa

drugs*

DRESS is a potentially fatal delayed

hypersen- sitivity reaction. Latency

period (2-8 weeks) followed by fever,

morbilliform skin rash, and frequent

multiorgan involvement.

Treatment: withdrawal of offending

drug, corticosteroids.

167. drugs that cause

Gray baby

syndrome

Chloramphenicol

168. drugs that cause

Hemolysis in

G6PD deficiency

Isoniazid, Sulfonamides, Dapsone,

Primaquine,

Aspirin, Ibuprofen, Nitrofurantoin

169. drugs that cause

Megaloblastic

anemia

Hydroxyurea, Phenytoin,

Methotrexate, Sulfa drugs

170. drugs that cause

Thrombocytopenia

Heparin, Vancomycin, Linezolid

171. drugs that cause

Thrombotic

complications

Combined oral contraceptives,

hormone replacement therapy, SERMs

(eg, tamoxifen, raloxifene,

clomiphene)

172. drugs that cause

Fat redistribution

Protease inhibitors, Glucocorticoids

173. drugs that cause

Gingival

hyperplasia

Cyclosporine, Ca2+ channel blockers,

Phenytoin

174. drugs that cause

Hyperuricemia

(gout)

Pyrazinamide, Thiazides, Furosemide,

Niacin,

Cyclosporine

175. drugs that cause

Myopathy

Statins, fibrates, niacin, colchicine,

daptomycin, hydroxychloroquine,

interferon-α, penicillamine,

glucocorticoids

176. drugs that cause

Osteoporosis

Corticosteroids, depot

medroxyprogesterone acetate, GnRH

agonists, aromatase inhibitors,

anticonvulsants, heparin, PPIs

177. drugs that cause

Photosensitivity

Sulfonamides, Amiodarone,

Tetracyclines, 5-FU

178. drugs that cause

Rash (Stevens-

Johnson

syndrome)

Anti-epileptic drugs (especially

lamotrigine),

allopurinol, sulfa drugs, penicillin

179. drugs that cause

Teeth discoloration

Tetracyclines

180. drugs that cause

Tendon and

cartilage damage

Fluoroquinolones

181. drugs that cause

Cinchonism

Quinidine, quinine

Can present with tinnitus,

hearing/vision loss, psychosis, and

cognitive impairment

182. drugs that cause

Parkinson-like

syndrome

Antipsychotics, Reserpine,

Metoclopramide

183. drugs that cause

Pseudotumor

cerebri

Growth hormones, tetracyclines,

vitamin A

184. drugs that cause

Seizures

Isoniazid (vitamin B6 deficiency),

Bupropion, Imipenem/cilastatin,

Tramadol, Enfluran

185. drugs that cause

Tardive dyskinesia

Antipsychotics, metoclopramide

186. drugs that cause

Visual disturbance

Topiramate (blurred vision/diplopia,

haloes)

Digoxin (yellow-tinged vision)

Isoniazid (optic neuropathy/color

vision changes), Vigabatrin (bilateral

visual field defects)

PDE-5 inhibitors (blue-tinged vision)

Ethambutol (color vision changes)

187. drugs that cause

Fanconi syndrome

Cisplatin, ifosfamide, expired

tetracyclines, tenofovir

188. drugs that cause

Interstitial nephritis

Penicillins, furosemide, NSAIDs,

proton pump inhibitors, sulfa drugs

189. drugs that cause

Dry cough

ACEi's

190. drugs that cause

Pulmonary fibrosis

Methotrexate, Nitrofurantoin,

Carmustine,

Bleomycin, Busulfan, Amiodarone

191. drugs that cause

Nephrotoxicity/

ototoxicity

Loop diuretics, Aminoglycosides,

cisPlatin, Vancomycin, amphoTERicin

B

Listen And Pee Very TERriBly.

Cisplatin toxicity may respond to

amifostine.

192. Cytochrome

P450 inducers

Modafinil

Chronic alcohol use

St. John's wort

Phenytoin

Phenobarbital

Nevirapine

Rifampin

Griseofulvin

Carbamazepine

Most chronic alcoholics Steal Phen-Phen

and Never Refuse Greasy Carbs

193. Cytochrome

P450 substrates

Anti-epileptics

Theophylline

Warfarin

OCPs

194. Cytochrome

P450 inhibitors

(-)

Sodium valproate

Isoniazid

Cimetidine

Ketoconazole

Fluconazole

Acute alcohol abuse

Chloramphenicol

Erythromycin/clarithromycin

Sulfonamides

Ciprofloxacin

Omeprazole

Metronidazole

Amiodarone

Grapefruit juice

SICKFACES.COM (when I Am drinking

Grapefruit juice)

195. -azole Ergosterol synthesis inhibitor

196. -bendazole Antiparasitic/antihelminthic

197. -cillin Transpeptidase (penicillin-binding

protein)

198. -cycline Protein synthesis inhibitor

199. -ivir Neuraminidase inhibitor

200. -navir Protease inhibitor

201. -ovir DNA pol inhibitor

Acyclovir

202. -thromycin Macrolide antibiotic

203. -azine Typical antipsychotic

Thioridazine

204. -caine Local anesthetic

205. -triptan 5-HT1B/1D agonist

Sumatriptan

206. -chol Cholinergic agonist

Bethanechol, carbachol

207. -curium, -

curonium

Nondepolarizing paralytic

Atracurium, vecuronium

208. -stigmine AChE inhibitor

209. -terol β2-agonist

Albuterol

210. -zosin α1-antagonist

Prazosin

211. -afil PDE-5 inhibitor

Sildenafil

212. -sartan Angiotensin-II receptor blocker

213. -dronate Bisphosphonate

214. -gliptin DPP-4 inhibitors

Sitagliptin

215. -glitazone PPAR-γ activator

Rosiglitazone

216. -limus Calcineurin inhibitor

Everolimus, tacrolimus

217. -prost Prostaglandin analog

Latanoprost

218. -sentan Endothelin receptor antagonist

Bosentan

219. -tidine H2-antagonist

Cimetidine

220. -tropin Pituitary hormone

221. -ximab Chimeric human-mouse monoclonal

Ab

222. -zumab Humanized mouse monoclonal Ab

223. -mumab Human monoclonal Ab

224. -tinib Tyrosine kinase inhibitor

225. -zomib Proteasome inhibitor

226. -ciclib Cyclin-dependent kinase inhibitor

227. -cept TNF-α antagonist

Etanercept

228. -leukin IL-2 agonist/analog

Aldesleukin

229. -kinra Interleukin receptor antagonist

Anakinra

230. Hypertension

with diabetes

mellitus

ACE inhibitors/ARBs are protective against

diabetic nephropathy.

231. remember

ARB is

actually

angiotensin II receptor blockers

232. Hypertension

in asthma

Avoid nonselective β-blockers to prevent

β2-receptor-induced bronchoconstriction.

Avoid ACE inhibitors to prevent confusio

n between drug or asthma-related cough.

233. Hypertension

in pregnancy

Hydralazine, labetalol, methyldopa,

nifedipine.

Pregnant Ladies May Need HTN meds

234. Calcium

channel

blockers

Amlodipine, clevidipine, nicardipine,

nifedipine, nimodipine (dihydropyridines,

act on vascular smooth muscle)

diltiazem, verapamil (non-

dihydropyridines, act on heart).

Block voltage-dependent L-type calcium

channels of cardiac and smooth muscle

Nimodipine: subarachnoid hemorrhage

(prevents cerebral vasospasm).

Non-dihydropyridine adverse effects:

cardiac depression, AV block,

hyperprolactinemia, constipation, gingival

hyperplasia

235. Hydralazine increases cGMPA -> smooth muscle

relaxation.

Vasodilates arterioles > veins -> afterload

reduction.

Safe to use during pregnancy.

Frequently coadministered with a β-blocker

to prevent reflex tachycardia.

adverse: Compensatory tachycardia

(contraindicated in angina/CAD)

236. Hypertensive

emergency

Treat with clevidipine, fenoldopam,

labetalol, nicardipine, or nitroprusside.

237. Nitroprusside Short acting; increases cGMP via direct

release of NO.

Can cause cyanide toxicity (releases

cyanide).

238. Fenoldopam Dopamine D1 receptor agonist—coronary,

peripheral, renal, and splanchnic

vasodilation.

BP, natriuresis. Also used postoperatively as

an antihypertensive.

Can cause hypotension and tachycardia.

239. Nitrates Nitroglycerin, isosorbide dinitrate, isosorbide

mononitrate.

Vasodilate by increasing NO in vascular

smooth muscle -> increase in cGMP and

smooth muscle relaxation

Dilate veins >> arteries. decrease preload

Adverse: Reflex tachycardia (treat with β-

blockers), hypotension, flushing, headache,

"Monday disease" in industrial exposure:

development of tolerance for the

vasodilating action during the work week

and loss of tolerance over the weekend ->

tachycardia, dizziness, headache upon

reexposure.

Contraindicated in right ventricular

infarction.

240. Ranolazine Inhibits the late phase of sodium current

thereby reducing diastolic wall tension and

oxygen consumption.

Does not affect heart rate or contractility.

Angina refractory to other medical therapies.

adverse: Constipation, dizziness, headache,

nausea, QT prolongation.

241. Milrinone Selective PDE-3 inhibitor

In cardiomyocytes: increases cAMP

accumulation -> increased Ca2+ ->

increased inotropy and chronotropy

In vascular smooth muscle:increases

cAMP accumulation -> inhibition of

MLCK activity -> general vasodilation*.

use: Short-term use in acute

decompensated HF

adverse: Arrhythmias, hypotension.

242. HMG-CoA

reductase

inhibitors

(eg, lovastatin,

pravastatin)

Inhibit conversion of HMG- CoA to

mevalonate, a cholesterol precursor

decrease mortality in CAD patients

adverse: Hepatotoxicity (LFTs),

myopathy (esp. when used with

fibrates or niacin)

243. Bile acid resins:

Cholestyramine,

colestipol,

colesevelam

Prevent intestinal reabsorption of bile

acids; liver must use cholesterol to

make more

may decrease absorption of other drugs

and fat-soluble vitamins

244. Ezetimibe

Prevent cholesterol absorption at

small intestine brush border

245. Fibrates:

Gemfibrozil,

bezafibrate,

fenofibrate

greatly reduce TG's

Upregulate LPL -> increase TG

clearance

A

ctivates PPAR-α to induce HDL

synthesis

adverse: Myopathy (risk with statins),

cholesterol gallstones (via inhibition of

cholesterol 7α-hydroxylase)

246. Niacin (vitamin

B3)

Inhibits lipolysis (hormone- sensitive

lipase) in adipose tissue; reduces

hepatic VLDL synthesis

Red, flushed face, which is reduced by

NSAIDs or long-term use

Hyperglycemia Hyperuricemia

247. PCSK9 inhibitors:

Alirocumab,

evolocumab

Inactivation of LDL-receptor

degradation, increasing amount of LDL

removed from bloodstream

Myalgias, delirium, dementia, other

neurocognitive effects

248. Digoxin. Cardiac glycosides

Direct inhibition of Na+/K+ ATPase ->

indirect inhibition of Na+/Ca2+

exchanger.

uses: HF (up contractility); atrial

fibrillation (down conduction at AV

node and depression of SA node).

adverse: Cholinergic- nausea, vomiting,

diarrhea, blurry yellow vision (think van

Gogh), arrhythmias, AV block.

Can lead to hyperkalemia, which

indicates poor prognosis

antidote: Slowly normalize K+, cardiac

pacer, anti-digoxin Fab fragments, Mg2+.

249. digoxin

antidote

Slowly normalize K+, cardiac pacer, anti-

digoxin Fab fragments, Mg2+.

250. Antiarrhythmics

— sodium

channel

blockers (class

IA)

Quinidine, Procainamide, Disopyramide.

Slow or block conduction (especially in

depolarized cells).

decrease slope of phase 0

depolarization. Are state dependent

(selectively depress tissue that is

frequently depolarized [eg, tachycardia]).

increase QT interval, some potassium

channel blocking effects.

use for: Both atrial and ventricular

arrhythmias, especially re-entrant and

ectopic SVT and VT

adverse: Cinchonism (headache, tinnitus

with quinidine),torsades de pointes due

to QT interval.

251. Antiarrhythmics

— sodium

channel

blockers (class

IB)

Lidocaine, MexileTine.

decrease AP duration. Preferentially

affect ischemic or depolarized Purkinje

and ventricular tissue. Phenytoin can also

fall into the IB category.

use: IB is Best post-MI.

252. Antiarrhythmics

— sodium

channel

blockers (class

IC)

Flecainide, Propafenone.

Significantly prolongs ERP in AV node

and accessory bypass tracts. No effect

on ERP in Purkinje and ventricular tissue.

Minimal effect on AP duration.

SVTs, including atrial fibrillation. Only as

a last resort in refractory VT.

Adverse: IC is Contraindicated in

structural and ischemic heart disease.

253. Antiarrhythmics

— β-blockers

(class II)

Decrease SA and AV nodal activity by

decreasing cAMP, down Ca2+ currents.

Suppress abnormal pacemakers by slope

of phase 4

AV node particularly sensitive -

increased PR interval

Metoprolol can cause dyslipidemia.

Propranolol can exacerbate vasospasm in

Prinzmetal angina.

reat β-blocker overdose with saline,

atropine, glucagon

254. Antiarrhythmics

— potassium

channel

blockers (class

III)

Amiodarone, Ibutilide, Dofetilide, Sotalol.

Increased AP duration, increased ERP,

increased QT interval.

Uses: Atrial fibrillation, atrial flutter;

ventricular

tachycardia (amiodarone, sotalol).

Adverse:

Amiodarone—pulmonary fibrosis,

hepatotoxicity, hypothyroidism or

hyperthyroidism (amiodarone is 40%

iodine by weight), acts as hapten (corneal

deposits, blue/ gray skin deposits

resulting in photodermatitis), neurologic

effects, constipation, cardiovascular

effects (bradycardia, heart block, HF)

Amiodarone is lipophilic and has class I,

II, III, and IV effects.

255. Antiarrhythmics—

calcium channel

blockers (class

IV)

Verapamil, diltiazem.

Decreased conduction velocity, up

ERP, up PR interval.

use: Prevention of nodal arrhythmias

(eg, SVT), rate control in atrial

fibrillation.

adverse: Constipation, flushing, edema,

cardiovascular effects (HF, AV block,

sinus node depression).

256. Adenosine increased K+ out of cells ->

hyperpolarizing the cell and

decreasing ICa, decreasing AV node

conduction.

Drug of choice in

diagnosing/terminating certain forms of

SVT.

Very short acting (~ 15 sec).

Effects blunted by theophylline and

caffeine (both are adenosine receptor

antagonists).

Adverse effects include flushing,

hypotension, chest pain, sense of

impending doom, bronchospasm.

257. Mg2+ Effective in torsades de pointes and

digoxin toxicity.

258. Ivabradine

Selective inhibition of funny sodium

channels (If), prolonging slow

depolarization phase (phase 4).

negative chronotropic effect without

inotropy. Reduces cardiac O2 requirement.

for Chronic stable angina in patients who

cannot take β-blockers. Chronic HF with

reduced ejection fraction.

Luminous phenomena/visual brightness,

hypertension, bradycardia

259. Insulin

preparations

Bind insulin receptor (tyrosine kinase activity).

Liver: increase glucose stored as glycogen

Muscle: up glycogen, protein synthesis.

Fat: up TG storage.

Cell membrane: up K+ uptake.

260. Amylin

analogs

(Pramlintide)

down glucagon release and gastric

emptying, early satiety.

261. GLP-1

analogs

Exenatide, liraglutide

down glucagon release, delayed gastric

emptying, up glucose-dependent insulin

release, early satiety.

side: Nausea, vomiting, pancreatitis. Promote

weight loss (often desired).

262. Biguanides Metformin

Inhibit hepatic gluconeogenesis and the

action of glucagon, by inhibiting mGPD

side effects: B12 deficiency.

Promote weight loss (often desired).

263. Sulfonylureas 1st generation: chlorpropamide,

tolbutamide

2nd generation: glimepiride, glipizide,

glyburide

Close K+ channel in pancreatic β cell

membrane -> cell depolarizes -> insulin

release via Ca2+ influx

adverse: Hypoglycemia (risk with renal

failure), weight gain.

264. Meglitinides Nateglinide, repaglinide

Close K+ channel in pancreatic β cell

membrane

(binding site differs from

sulfonylureas).

265. DPP-4 inhibitors

Linagliptin, saxagliptin, sitagliptin

Inhibit DPP-4 enzyme that deactivates

GLP-1

- down glucagon release, gastric

emptying

- up glucose-dependent insulin

release, satiety.

WEIGHT NEUTRAL

266. Glitazones/

thiazolidinediones

Pioglitazone,

rosiglitazone

Binds to PPAR-γ nuclear transcription

regulator -> up insulin sensitivity and

levels of adiponectin -> regulation of

glucose metabolism and fatty acid

storage.

Weight gain, edema, HF

267. Sodium-

glucose co-

transporter 2

(SGLT2)

inhibitors

Canagliflozin, dapagliflozin, empagliflozin

Block reabsorption of glucose in proximal

convoluted tubule.

Glucosuria, UTIs, vaginal yeast infections,

hyperkalemia, dehydration (orthostatic

hypotension), weight loss.

268. α-glucosidase

inhibitors

Acarbose, miglitol

Inhibit intestinal brush-border α-

glucosidases -> delayed carbohydrate

hydrolysis and glucose absorption -> down

postprandial hyperglycemia.

Not recommended if kidney function is

impaired

269. Thioamides Propylthiouracil, methimazole.

Block thyroid peroxidase - inhibiting the

oxidation of iodide and the organification

and coupling of iodine

PTU also blocks 5′-deiodinase -> down

peripheral conversion of T4 to T3

PTU used in first trimester of pregnancy

(due to methimazole teratogenicity);

methimazole used in second and third

trimesters of pregnancy (due to risk of

PTU-induced hepatotoxicity).

Skin rash, agranulocytosis (rare), aplastic

anemia, hepatotoxicity.

Methimazole is a possible teratogen (can

cause aplasia cutis).

270. ADH

antagonists

conivaptan, tolvaptan

SIADH, block action of ADH at V2-

receptor.

271. Desmopressin Central (not nephrogenic) DI, von

Willebrand disease, sleep enuresis,

hemophilia A.

272. GH as a drug GH deficiency, Turner syndrome.

273. Somatostatin

(octreotide)

uses

Acromegaly, carcinoid syndrome,

gastrinoma, glucagonoma, esophageal

varices.

274. Demeclocycline ADH antagonist (member of tetracycline

family). use for SIADH

adverse: Nephrogenic DI,

photosensitivity, abnormalities of bone

and teeth.

275. Fludrocortisone Synthetic analog of aldosterone with

little glucocorticoid effects.

use: Mineralocorticoid replacement in 1°

adrenal insufficiency.

276. Cinacalcet Sensitizes Ca2+-sensing receptor

(CaSR) in parathyroid gland to circulating

Ca2+ -> decrease PTH

use: Refractory hypercalcemia in 1°

hyperparathyroidism, 2°

hyperparathyroidism, or parathyroid

carcinoma.

adverse: Hypocalcemia.

277. Sevelamer nonabsorbable phosphate binder that

prevents phosphate absorption from the

GI tract.

use: Hyperphosphatemia in CKD.

278. Histamine-2

blockers

Cimetidine, ranitidine, famotidine,

nizatidine.

Reversible block of histamine H2-

receptors -> down H+ secretion by

parietal cells.

Cimetidine is a potent inhibitor of

cytochrome P-450 (multiple drug

interactions)

Both cimetidine and ranitidine decrease

renal excretion of creatinine

279. Proton

pump

inhibitors

Omeprazole, lansoprazole, esomeprazole,

pantoprazole, dexlansoprazole.

Irreversibly inhibit H+/K+ ATPase in stomach

parietal cells.

risk of C difficile infection, pneumonia, acute

interstitial nephritis.

reduces serum Mg2+ with long-term

use;serum Mg2+ -> down Ca2+ absorption

(potentially leading to increased fracture risk

in elderly)

280. Antacids All can cause hypokalemia.

Aluminum hydroxide: Constipation and

hypophosphatemia; proximal muscle

weakness, osteodystrophy, seizures

Calcium carbonate: Hypercalcemia (milk-

alkali syndrome), rebound acid up.

Magnesium hydroxide: Diarrhea,

hyporeflexia, hypotension, cardiac arrest

281. Bismuth,

sucralfate

Bind to ulcer base, providing physical

protection and allowing HCO3- secretion to

reestablish pH gradient in the mucous layer.

Require acidic environment; usually not given

with PPIs/H2 blockers

use: ulcer healing, travelers' diarrhea

(bismuth).

282. Misoprostol PGE1 analog.

up production and secretion of gastric mucous

barrier, down acid production.

Prevention of NSAID-induced peptic ulcers

(NSAIDs block PGE1 production).

Also used off-label for induction of labor

(ripens cervix)

Contraindicated in women of childbearing

potential (abortifacient).

283. Octreotide Long-acting somatostatin analog; inhibits

secretion of various splanchnic

vasodilatory hormones.

Acute variceal bleeds, acromegaly,

VIPoma, carcinoid tumors

risk of cholelithiasis due to CCK

inhibition.

284. Sulfasalazine A combination of sulfapyridine

(antibacterial) and 5-aminosalicylic acid

(anti-inflammatory). Activated by colonic

bacteria.

Ulcerative colitis, Crohn disease (colitis

component).

Malaise, nausea, sulfonamide toxicity,

reversible oligospermia

285. Loperamide Agonist at μ-opioid receptors; slows

gut motility. Poor CNS penetration (low

addictive potential).

use for diarrhea

286. Ondansetron 5-HT3 antagonist; down vagal

stimulation.

Powerful central-acting antiemetic.

Control vomiting postoperatively and in

patients undergoing cancer

chemotherapy.

adverse: headache, constipation, QT

interval prolongation, serotonin

syndrome

287. Metoclopramide D2 receptor antagonist.

up resting tone, contractility, LES tone,

motility, promotes gastric emptying

Does not influence colon transport time.

use for Diabetic and postsurgery

gastroparesis, antiemetic, persistent

GERD.

288. Orlistat Inhibits gastric and pancreatic lipase ->

down breakdown and absorption of

dietary fats.

use for weight loss

289. Bulk-

forming

laxatives

Psyllium, methylcellulose

Soluble fibers draw water into gut lumen,

forming a viscous liquid that promotes

peristalsis

Bloating

290. Osmotic

laxatives

Magnesium hydroxide, magnesium citrate,

polyethylene glycol, lactulose

Lactulose also treats hepatic

encephalopathy: gut flora degrade lactulose

into metabolites (lactic acid, acetic acid) that

promote nitrogen excretion as NH4+

291. Stimulant

laxatives

senna

Enteric nerve stimulation -> colonic

contraction

Diarrhea, melanosis coli

292. lexotive

Emollients

Docusate

Promotes incorporation of water and fat into

stool

adverse: Diarrhea

293. Aprepitant Substance P antagonist.

Blocks NK1 (neurokinin-1) receptors in brain.

Antiemetic for chemotherapy-induced nausea

and vomiting.

294. Heparin sed during pregnancy (does not cross

placenta). Follow PTT.

Up antithrombin III -> against thrombin (IIa)

For rapid reversal use protamine sulfate

(positively charged molecule that binds

negatively charged heparin).

Low-molecular-weight heparins

(eg,enoxaparin, dalteparin) act predominantly

on factor Xa.

- Fondaparinux acts only on factor Xa

- Not easily reversible.

295. Heparin-induced

thrombocytopenia

(HIT)

development of IgG antibodies against

heparin- bound platelet factor 4

(PF4).

Antibody-heparin-PF4 complex

activates platelets -> thrombosis and

thrombocytopenia.

296. Direct thrombin

inhibitors

Bivalirudin (related to hirudin, the

anticoagulant used by leeches),

Argatroban, Dabigatran (only oral

agent in class).

Can be used in HIT, when heparin is

BAD for the patient. Does not require

lab monitoring.

can reverse dabigatran with

idarucizumab

297. Warfarin Interferes with γ-carboxylation of

vitamin K- dependent clotting factors

Metabolism affected by

polymorphisms in the gene for vitamin

K epoxide reductase complex

(VKORC1).

Not used in pregnant women

(because warfarin, unlike heparin,

crosses placenta).

Cytochrome P-450 inhibitors increase

warfarin effect

For reversal of warfarin, give vitamin K.

For rapid reversal, give fresh frozen

plasma

(FFP) or PCC.

298. Initial risk of

hypercoagulation

in warfarin

protein C has a shorter half-life than

factors II and X. Existing protein C

depletes before existing factors II and

X deplete, and before warfarin can

reduce factors II and X production->

hypercoagulation.

299. Heparin vs

Warfarin

monitoring

Hep: PTT (intrinsic pathway)

Warfari: PT/INR (extrinsic pathway)

- because of Factor VII

300. Direct factor Xa

inhibitors

ApiXaban, rivaroXaban.

Oral agents do not usually require

coagulation monitoring.

Not easily reversible.

301. Thrombolytics Alteplase (tPA), reteplase (rPA),

streptokinase, tenecteplase (TNK-tPA).

Directly or indirectly aid conversion of

plasminogen to plasmin

increase PT/PTT

Contraindicated in patients with active

bleeding, history of intracranial bleeding,

recent surgery, known bleeding

diatheses, or severe hypertension.

Nonspecific reversal with antifibrinolytics

(eg, aminocaproic acid, tranexamic acid),

platelet transfusions, and factor corrections

(eg, cryoprecipitate, FFP, PCC).

302. ADP receptor

inhibitors

Clopidogrel, prasugrel, ticagrelor

(reversible), ticlopidine.

Inhibit platelet aggregation by irreversibly

blocking ADP (P2Y12) receptor. Prevent

expression of glycoproteins IIb/IIIa on

platelet surface.

TTP may be seen.

303. Cilostazol,

dipyridamol

Phosphodiesterase inhibitors; increase

cAMP in platelets, resulting in inhibition

of platelet aggregation; vasodilators.

Intermittent claudication, coronary

vasodilation, prevention of stroke or TIAs

(combined with aspirin).

Nausea, headache, facial flushing,

hypotension, abdominal pain.

304. Glycoprotein

IIb/IIIa

inhibitors

Abciximab, eptifibatide, tirofiban.

Abciximab is made from monoclonal

antibody Fab fragments

305. Cancer drugs

—cell cycle

306. Cancer drugs

—targets

307. Azathioprine, 6-

mercaptopurine

Purine (thiol) analogs reduce de novo

purine synthesis

Activated by HGPRT.

Use: Preventing organ rejection,

rheumatoid arthritis, IBD, SLE; used to

wean patients off steroids in chronic

disease and to treat steroid-refractory

chronic disease.

Azathioprine and 6-MP are metabolized

by xanthine oxidase; thus both have

increased toxicicy with allopurinol

Adverse: myelosuppresion

S phase specific

308. Cladribine purine analoge

Use: Hairy cell leukemia.

Myelosuppression, nephrotoxicity, and

neurotoxicity.

S phase specific

309. Cytarabine

(arabinofuranosyl

cytidine)

Pyrimidine analog - At higher

concentrations, inhibits DNA

polymerase

Use: Leukemias (AML), lymphomas.

CYTarabine causes panCYTopenia.

S phase specific

310. 5-fluorouracil

Pyrimidine analog bioactivated to 5-FdUMP

covalently complexes with thymidylate

synthase and folic acid -> inhibits

thymidylate synthase -> down dTMP -> down

DNA synthesis

Colon cancer, pancreatic cancer, actinic

keratosis, basal cell carcinoma (topical).

SE: Myelosuppression, palmar- plantar

erythrodysesthesia (hand-foot syndrome).

S phase specific

311. Methotrexate Folic acid analog that competitively inhibits

dihydrofolate reductase -> down dTMP

Use:

- Cancers: leukemias (ALL), lymphomas,

choriocarcinoma, sarcomas.

- Non-neoplastic: *ectopic pregnancy,

medical

abortion (with misoprostol), rheumatoid

arthritis, psoriasis, IBD, vasculitis.*

SE: Myelosuppression, which is reversible

with leucovorin "rescue."

Hepatotoxicity.

Mucositis (eg, mouth ulcers).

Pulmonary fibrosis

S phase specific

312. Antitumor

antibiotics

Bleomycin

Dactinomycin (actinomycin D)

Doxorubicin, daunorubicin

313. Bleomycin Induces free radical formation -> breaks in

DNA strands.

Use: Testicular cancer, Hodgkin lymphoma.

SE: Pulmonary fibrosis, skin

hyperpigmentation. Minimal

myelosuppression.

314. Dactinomycin

(actinomycin

D)

Intercalates into DNA, preventing RNA

synthesis.

Wilms tumor, Ewing sarcoma,

rhabdomyosarcoma. Used for childhood

tumors.

SE: Myelosuppression

315. Doxorubicin,

daunorubicin

Generate free radicals. Intercalate in DNA;

*Interferes with topoisomerase II

enzyme.*

Use: Solid tumors, leukemias, lymphomas.

SE:

- Cardiotoxicity (dilated cardiomyopathy),

- myelosuppression, alopecia.

Dexrazoxane (iron chelating agent), used

to prevent cardiotoxicity

316. Doxorubicin

SE on heart

Dilated CM

use dexrazoxane

317. Busulfan

(alkalizing

agent)

Cross-links DNA.

Used to ablate patient's bone marrow

before bone marrow transplantation.

SE: Severe myelosuppression (in almost

all cases), pulmonary fibrosis,

hyperpigmentation.

318. Alkylating

agents

Busulfan

Cyclophosphamide, ifosfamide

Nitrosoureas

Procarbazine

319. Cyclophosphamide,

ifosfamide

(ALkylating agent)

Cross-link DNA at guanine

Require bioactivation by liver. A

nitrogen mustard.

Solid tumors, leukemia, lymphomas.

Myelosuppression; SIADH;

hemorrhagic cystitis

- prevented with mesna (thiol group

of mesna binds toxic metabolites) or

adequate hydration.

320. Nitrosoureas

(ALkylating agent)

Require bioactivation. Cross-link

DNA.

Cross blood-brain barrier -> CNS.

Brain tumors (including glioblastoma

multiforme)

CNS toxicity (convulsions, dizziness,

ataxia).

321. Procarbazine

(ALkylating agent)

Cell cycle phase-nonspecific

alkylating agent, mechanism not yet

defined.

Hodgkin lymphoma, brain tumors.

Bone marrow suppression, pulmonary

toxicity, leukemia.

322. Microtubule

inhibitors

Paclitaxel, other taxanes

Vincristine, vinblastine

323. Paclitaxel, other

taxanes

(Microtubule

inhibitor)

Hyperstabilize polymerized

microtubules in M phase so that

mitotic spindle cannot break down

(anaphase cannot occur)

Use: Ovarian and breast carcinomas

Myelosuppression, neuropathy,

hypersensitivity.

324. Vincristine,

vinblastine

(Microtubule

inhibitors )

Vinca alkaloids that bind β-tubulin

and *inhibit

its polymerization* into microtubules

prevent mitotic spindle formation

(M-phase arrest)

use: Solid tumors, leukemias, Hodgkin

(vinblastine) and non-Hodgkin

(vincristine) lymphomas.

Vincristine: neurotoxicity (areflexia,

peripheral neuritis), constipation

(including paralytic ileus).

- Crisps the nerves.

Vinblastine: bone marrow suppression.

- Blasts the bone marrow

325. Cisplatin,

carboplatin

Cross-link DNA.

Use: Testicular, bladder, ovary, and

lung carcinomas.

Nephrotoxicity, peripheral neuropathy,

ototoxicity.

Prevent nephrotoxicity with amifostine

(free radical scavenger) and chloride

(saline) diuresis.

326. Etoposide,

teniposide

Inhibit topoisomerase II -> DNA

degradation.

Use: Solid tumors (particularly

testicular and small cell lung cancer),

leukemias, lymphomas

Myelosuppression, alopecia.

327. Irinotecan,

topotecan

Inhibit topoisomerase I and prevent

DNA unwinding and replication.

Use: Colon cancer (irinotecan);

ovarian and small cell lung cancers

(topotecan).

328. Hydroxyurea Inhibits ribonucleotide reductase ->

DNA Synthesis (S-phase specific).

Myeloproliferative disorders (eg, CML,

polycythemia vera), sickle cell (HbF).

Severe myelosuppression.

329. Bevacizumab Monoclonal antibody against VEGF. Inhibits

angiogenesis (BeVacizumab inhibits Blood

Vessel formation).

Solid tumors (colorectal cancer, renal cell

carcinoma), wet age-related macular

degeneration.

Hemorrhage, blood clots, and impaired

wound healing.

330. Erlotinib EGFR tyrosine kinase inhibitor.

Non-small cell lung carcinoma.

Rash.

331. Cetuximab Monoclonal antibody against EGFR

Stage IV colorectal cancer (wild-type

KRAS), head and neck cancer

Rash, elevated LFTs, diarrhea.

332. Imatinib Tyrosine kinase inhibitor of BCR-ABL

(Philadelphia chromosome fusion gene in

CML) and c-kit (common in GI stromal

tumors).

CML, GI stromal tumors (GIST).

Fluid retention

333. Rituximab Monoclonal antibody against CD20, which is

found on most B-cell neoplasms.

Non-Hodgkin lymphoma, CLL, ITP,

rheumatoid arthritis

risk of progressive multifocal

leukoencephalopathy

334. Risk of usin

Rituximab

progressive multifocal

leukoencephalopathy!!!! PML

335. Bortezomib,

carfilzomib

Proteasome inhibitors, induce arrest at G2-

M phase and apoptosis.

Multiple myeloma, mantle cell lymphoma.

Peripheral neuropathy, herpes zoster

reactivation

336. Tamoxifen,

raloxifene

Selective estrogen receptor modulators

(SERMs)—receptor antagonists in breast and

agonists in bone.

Block the binding of estrogen to ER ⊕ cells.

Breast cancer treatment (tamoxifen only) and

prevention. Raloxifene also useful to

prevent osteoporosis.

Tamoxifen: risk of endometrial cancer; "hot

flashes."

Bothr have risk of thromboembolic events

(eg, DVT, PE).

337. Trastuzumab

(Herceptin)

Monoclonal antibody against HER-2 (c-

erbB2), a tyrosine kinase receptor

HER-2 ⊕ breast cancer and gastric cancer

(tras2zumab)..

Cardiotoxicity. "Heartceptin" damages the

heart.

338. Vemurafenib Small molecule inhibitor of BRAF oncogene

⊕ melanoma.

- VEmuRAF-enib is for V600E- mutated

BRAF inhibition.

Metastatic melanoma

339. Rasburicase Recombinant uricase that catalyzes

metabolism of uric acid to allantoin

prevent and treat tumor lysis syndrome

340. Common

chemotoxicities

Cisplatin/Carboplatin -> ototoxicity

Vincristine -> peripheral neuropathy

Bleomycin, Busulfan -> pulmonary fibrosis

Doxorubicin -> cardiotoxicity

Trastuzumab (Herceptin)-> cardiotoxicity

Cisplatin/Carboplatin -> nephrotoxicity

CYclophosphamide -> hemorrhagic

cystitis

341. Arachidonic

acid pathway

342. Acetaminophen Reversibly inhibits cyclooxygenase,

mostly in CNS. Inactivated peripherally.

Antipyretic, analgesic, but not anti-

inflammatory

Used instead of aspirin to avoid Reye

syndrome in children with viral infection.

Overdose produces hepatic necrosis;

acetaminophen metabolite (NAPQI)

depletes glutathione and forms toxic

tissue byproducts in liver.

N-acetylcysteine is antidote—

regenerates glutathione

343. Aspirin NSAID that irreversibly inhibits cyclooxygenase

(both COX-1 and COX-2) by covalent

acetylation -> down TXA (up bleeding time)

and down PGs

Low dose (< 300 mg/day): down platelet

aggregation.

Intermediate dose (300-2400

mg/day)antipyretic and analgesic.

High dose (2400-4000 mg/day): anti-

inflammatory.

Adverse: Gastric ulceration, tinnitus (CN VII),

allergic reactions (especially in patients with

asthma or nasal polyps).

Chronic use can lead to acute renal failure,

interstitial nephritis, GI bleeding.

Risk of Reye syndrome in children treated with

aspirin for viral infection.

Toxic doses cause respiratory alkalosis early,

but transitions to mixed metabolic acidosis-

respiratory alkalosis.

344. Celecoxib

Reversibly and selectively inhibits the

cyclooxygenase (COX) isoform 2 ("Selecoxib")

spares COX-1, which helps maintain gastric

mucosa.

Spares platelet function as TXA2 production

is dependent on COX-1.

risk of thrombosis

use: Rheumatoid arthritis, osteoarthritis.

345. Nonsteroidal

anti-

inflammatory

drugs

Ibuprofen, naproxen, indomethacin,

ketorolac, diclofenac, meloxicam,

piroxicam.

Reversibly inhibit cyclooxygenase (both

COX-1 and COX-2).

Indomethacin is used to close a PDA.

adverse: Interstitial nephritis, gastric

ulcer (prostaglandins protect gastric

mucosa), renal ischemia (prostaglandins

vasodilate afferent arteriole), aplastic

anemia.

346. Leflunomide Reversibly inhibits dihydroorotate

dehydrogenase, preventing pyrimidine

synthesis.

Suppresses T-cell proliferation.

Uses: Rheumatoid arthritis, psoriatic

arthritis.

Diarrhea, hypertension, hepatotoxicity,

teratogenicity.

347. Bisphosphonates Alendronate, ibandronate, risedronate,

zoledronate.

Pyrophosphate analogs; bind

hydroxyapatite in bone, inhibiting

osteoclast activity

Osteoporosis, hypercalcemia, Paget

disease of bone, metastatic bone

disease, osteogenesis imperfecta.

Esophagitis (if taken orally, patients are

advised to take with water and remain

upright for 30 minutes), osteonecrosis

of jaw, atypical femoral stress

fractures.

348. Teriparatide Recombinant PTH analog.

up osteoblastic activity when administered in

pulsatile fashion.

use for osteoporosis. Increase bone growth

compared to antiresorptive therapies

risk of osteosarcoma (avoid use in patients

with Paget disease of the bone or

unexplained elevation of alkaline

phosphatase).

Avoid in patients who have had prior cancers

or radiation therapy.

Transient hypercalcemia

349. Chronic

gout drugs

(preventive)

Probenecid - Inhibits reabsorption of uric

acid in proximal convoluted tubule (also

inhibits secretion of penicillin). Can

precipitate uric acid calculi.

allopurinol - XO competitive inhibitor

- increases concentrations of azathioprine

and 6-MP (both normally metabolized by

xanthine oxidase).

Pegloticase -> Recombinant uricase

catalyzing uric acid to allantoin (a more

water-soluble product).

Febuxostat - inhibits XO

350. Colchicine Binds and stabilizes tubulin to inhibit

microtubule polymerization, impairing

neutrophil chemotaxis and degranulation

Acute and prophylactic value. GI,

neuromyopathic side effects.

351. Etanercept TNF-α inhibitor

Fusion protein (decoy receptor for

TNF-α + IgG1 Fc), produced by

recombinant DNA.

use for: Rheumatoid arthritis,

psoriasis, ankylosing spondylitis

Predisposition to infection, including

reactivation of latent TB

352. Infliximab,

adalimumab,

certolizumab,

golimumab

Anti-TNF-α monoclonal antibody.

Use: Inflammatory bowel disease,

rheumatoid arthritis, ankylosing

spondylitis, psoriasis

Predisposition to infection, including

reactivation of latent TB