Penicillin G (IV), Penicillin V (oral)

 

Mech:  Binds PBP’s, blocks transpeptidase X-linking of cell wall, activates autolytic enzymes

 

Clinical Use:  Bactericidal for Gram+ cocci, rods, and spirochetes. NOT penicillinase resistant.

 

Toxicity:  Hypersensitivity reactions, hemolytic anemia

 

 

 

Methicillin, Nafcillin, Dicloxacillin

 

Mech:  Same as penicillin.  Narrow spectrum; Penicillinase RESISTANT because of bulkier R group.

 

Clinical Use:  Staph. Aureus

 

Toxicity:  Hypersensitivity reactions; Methicillin: Interstitial nephritis

 

 

 

 

Ampicillin, Amoxicillin

 

Mech:  Same as penicillin. Wider spectrum; penicillinase sensitive. Combine with clavulanic acid (penicillinase inhibitor) to enhance spectrum. AmOxicillin has greater Oral bioavailability than ampicillin.

 

Clinical Use:  Extended-spectrum penicillin: certain gram+ bacteria and GNR’s (Haemophilus influenza, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, enterococci – HELPS kill Enterococci)

 

Toxicity:  Hypersensitivity; Ampicillin: rash, pseudomembranous colitis

Carbenicillin, Peperacillin, Ticarcillin

 

Mech:  Same as penicillin. Extended spectrum.

 

Clinical Use:  Pseudomonas species and GNRs; susceptible to penicillinase; use with clavulanic acid

 

Toxicity:  Hypersensitivity

 

 

 

 

Cephalosporins

Mech: b-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinase. Bactericidal.

Clinical Use: 1st Gen: Gram+ cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae (PEcK). 2nd Gen: Gram+ cocci, H. influenzae, Enterobacter aerogenes, Neisseria species, Proteus, E. coli, Klebsiella, Serratia marcescens (HEN PEcKS). 3rd Gen: Serious gram- infections resistant to other b-lactams; meningitis (most penetrate the BBB). Eg. Ceftazidime for Pseudomonas; ceftriaxone for gonorrhea. 4th Gen: increased activity against Pseudomonas and gram+ orgs.

Toxicity: Hypersensitivity, increases nephrotoxicity of aminoglycosides, disulfuram-like rxn w/ ethanol (in ceph. w/ methylthiotetrazole group)

 

Aztreonam

 

Mech: Monobactam RESISTANT to b-lactamases. Inhibits cell wall synthesis (binds to PBP3)

 

Clinical Use: GNRs: Klebsiella, Pseudomonas, and Serratia species. No activity against gram+ or anaerobes. For penicillin-allergic patients and those with renal insufficiency who cant take aminoglycosides

 

Toxicity: Usually nontoxic; occasional GI upset

 

 

Imipenem/Cilastatin

 

Mech: Wide-spectrum, b-lactamase RESISTANT carbapenem. Always given with cilastatin (inhib. of renal dihydropeptidase I) to decrease inactivation in renal tubules. With imipenem “the kill is lastin with cilastatin

 

Clinical Use: Gram+ cocci, GNRs, and anaerobes. Drug of choice for Enterobacter.

Toxicity: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels. 

 

Vancomycin

 

Mech: Inhibits cell wall mucopeptide formation. Bactericidal. Resistance occurs with amino acid change of D-ala D-ala to D-ala D-lac.

Clinical Use: Serious gram+ MDR bugs, incl. Staph aureus and C. difficile (pseudomembranous colitis).

 

Toxicity: Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing – “red man syndrome” (mostly prevented by pre-tx w/ antihistamine and slow infusion). Well tolerated in general: does NOT have many problems.

Protein Synthesis Inhibitors

 

30S Subunit:  A = Aminoglycosides (streptomycin, gentomycin, tobramycin, amikacin); T = Tetracyclines

 

50S Subunit:  C = Chloramphenicol, E = Erythromycin, L = Lincomycin, L = cLindamycin

 

Pneumonic: “Buy AT 30, CELL at 50

 

 

 

Aminoglycosides: Gentamycin, neomycin, amikacin, tobramycin, streptomycin

 

Mech: Bactericidal; inhibit formation of initiation complex and cause misreading of mRNA. Require O2 for uptake; therefore ineffective against anaerobes.

Clinical Use: Severe GNR infection. Synergistic w/ b-lactam abx. Neomycin for bowel surgery.

Toxicity: Nephrotoxicity (esp. w/ cephalosporins), Ototoxicity (esp. w/ loop diuretics). Teratogenic.

AmiNOglycosides

 

Tetracyclines: tetracycline, doxycycline, demeclocycline, minocycline

 

Mech: Bacteriostatic, binds to 30S and prevents attachment of aminoacyl-tRNA, limited CNS penetration. Doxycycline is fecally eliminated so ok in renal failure. Do not take w/ mild/antacids because divalent cations inhibit its gut absorption.

Clinical Use: Vibrio cholerae, Acne, Chlamydia, Ureaplasma, Urealyticum, Mycoplasma pneumoniae, Borrelia burgdorferi (lyme dz), Rickettsia, tularemia. VACUUM your BedRoom.

Toxicity: GI distress, discolors teeth and inhibits bone growth in kids, Fanconi’s syndrome, photosensitivity.

 

Macrolides: Erythromycin, azithromycin, clarithromycin

 

Mech: Inhibits protein synth by blocking translocation; binds the 23S rRNA of the 50S subunit. Bacteriostatic.

 

Clinical Use: URI’s, pneumonias, STD’s: gram+ cocci (strep in pts allergic to penicillin), Mycoplasma, Legionella, Chlamydia, Neisseria.

 

Toxicity: GI discomfort (most common cause of noncompliance), acute cholestatic hepatitis, eosinophilia, skin rash

 

 

 

Chloramphenicol

 

Mech: Inhibits 50S peptidyl transferase. Bacteriostatic.

 

Clinical Use: Meningitis (H. influenzae, Neisseria meningitides, Strep pneumoniae). Conservative use owning to toxicities.

 

Toxicity: Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in preemies because they lack liver UDP-glucuronyl transferase).

 

Clindamycin

 

Mech: Blocks peptide bond formation at 50S subunit. Bacteriostatic.

 

Clinical Use: Anaerobic infections (B. fagilis, C. perfringens). Treats anaerobes ABOVE the diaphragm.

 

Toxicity: Pseudomembranous colitis (C. difficile), fever, diarrhea.

 

 

 

 

Sulfonamides: Sulfamethoxazole (SMX), sulfisoxazole, triple sulfas, sulfadiazine

Mech: PABA antimetabolites inhibit dihydropteroate synthase (nucleotide synth). Bacteriostatic.

Clinical Use: Gram+, Gram-, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.

Toxicity: Hypersensitivity, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), kernicterus in infants, displace other drugs from albumin (eg. Warfarin), Stevens-Johnson Syndrome.

 

 

Trimethoprim

 

Mech: Inhibits bacterial dihydrofolate recuctase (nucleotide synth). Bacteriostatic.

Clinical Use: Used in combination with sulfonamides (TMP-SMX), causing sequential block of folate synthesis. Combination used for recurrent UTI, Shigella, Salmonella, PCP.

Toxicity: Megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folinic acid).

Trimethoprim = TMP: Treats Marrow Poorly

 

 

Fluoroquinolones: Ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin, mortifloxacin, gatifloxacin, enoxacin (fluoroquinolones), nalidixic acid (quinolone)

Mech: Inhibit DNA gyrase (topoisomerase II). Bactericidal.

Clinical Use: GNRs of urinary and GI origin (incl. Pseudomonas), Neisseria, some gram+ organisms. Anthrax.

Toxicity: GI upset, superinfections, skin rash, HA, dizziness. Contraindicated in pregnant women and children because may damage cartilage. Tendonitis and tendon rupture in adults.

 

 

 

Metronidazole

 

Mech: Forms toxic metabolites in the bacterial cell. Bactericidal.

 

Clinical: Antiprotazoal. Giardia, Entamoeba, Trichomonas, Garnerella vaginalis, anaerobes (Bacteroides, Clostridium). Used with bismuth and amoxicillin or tetracycline for “triple tx” against H. pylori.

GET on the Metro! 

Anaerobic infection BELOW the diaphragm.

 

Toxicity: Disulfuram-like reaction with alcohol, HA.

 

Polymyxins:  Polymyxin B, Polymyxin E

 

Mech: Bind to cell membrane of bacteria and disrupt their osmotic properties. Polymyxins are cationic, basic proteins that act like detergents.

 

Clinical: Resistant Gram- infections

 

Toxicity: Neurotoxicity, ATN

 

 

 

Isoniazid (INH)

 

Mech: Decreases synthesis of mycolic acids.

 

Clinical: TB. The only agent used as solo prophylaxis against TB.

 

Toxicity: Hemolysis if G6PD deficient, neurotoxicity, hepatotoxicity, SLE-like syndrome.  Pyridoxine (vit. B6) can prevent neurotoxicity.

INH Injures Neurons and Hepatocytes.

Different INH half-lives in fast vs. slow acetylators

 

 

Rifampin

 

Mech: Inhibits DNA-dependent RNA polymerase.

Clinical: TB, delays resistance to dapsone when used for leprosy. Always used in combination with drugs except in tx of meningococcal carrier state, and chemoprophylaxis in contacts of children w/ H. influenzae type B.

 

Toxicity: Minor hepatotoxicity and drug interactions (increased P450)

 

4 R’s: RNA polym. Inhibitor, Revs up microsomal P450, Red/Orange body fluids, Rapid resistance if used alone.

Anti-TB Drugs

 

Rifampin, Ethambutol, Streptomycin, Pyrazinamide, Isoniazid

 

Cycloserine (second line)

 

All are hepatotoxic.  INH is used alone for TB prophylaxis.

 

 

 

 

 

Amphotericin B

 

Mech: Binds ergosterol (unique to fungi), forms membrane pores that disrupt homeostasis. Amphotericin “tears” holes in the membrane.

 

Clinical: Used for wide spectrum of systemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not cross BBB.

 

Toxicity: Fever/chills, (shake and bake), hypotension, nephrotoxicity, arrhythmias (amphoterrible)

Nystatin

 

Mech: Binds to ergosterol, disrupting fungal membranes.

 

Clinical: “Swish and swallow” for oral candidiasis (thrush).

 

 

 

 

 

 

 

Fluconazole, Ketoconazole, Clotrimazole, Miconazole, Itraconazole

 

Mech: Inhibit fungal steroid (ergosterol) synthesis.

 

Clinical: Systemic mycoses. Fluconazole for cryptocccal meningitis in AIDS patients and candidal infections of all types. Ketoconazole for Blastomyces, Coccidioides, Histoplasma, C. albicans; hypercortisolism.

 

Toxicity: Hormone synth inhibition (gynecomastia), liver dysfxn (inhibits P450), fever, chills.

 

 

Griseofulvin

 

Mech: Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing tissues (eg. Nails).

 

Clinical: Oral tx of superficial infections; inhibits growth of dermatophytes (tinea, ringworm).

 

Toxicity: Teratogenic, carcinogenic, confusion, HA, increased coumadin metabolism.

 

 

Amantadine

 

Mech: Blocks viral penetration/uncoating; may buffer pH of endosome. Also causes release of dopamine from intact nerve terminals.

 

Clinical: Prophylaxis for influenza A; Parkinson’s disease.

 

Toxicity: Ataxia, dizziness, slurred speech.

 

Amantidine blocks influenza A and rubellA and causes problems with the cerebellA

Rimantidine is a derivative with fewer CNS side effects.

Zanamivir

 

Mech: Inhibits influenza neuraminidase

 

Clinical: Influenza A and B

 

 

 

 

 

 

 

Ribavirin

 

Mech: Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase.

 

Clinical: RSV

 

Toxicity: Hemolytic Anemia

 

 

 

 

Acyclovir

 

Mech: Preferentially inhibits viral DNA polymerase when phosphorylated by viral thymidine kinase.

 

Clinical: HSV, VZV, EBV. Mucocutaneous and genital herpes lesions. Prophylaxis in immunocompromised patients.

 

Toxicity: Delirium, tremor, nephrotoxicity

 

 

 

Gancyclovir - DHPG (dihydroxy-2-propoxymethyl guanine)

 

Mech:  Phosphorylation by viral kinase, preferentially inhibits CMV DNA polymerase.

 

Clinical: CMV, especially in immunocompromised patients.

 

Toxicity: Pancytopenia, renal toxicity. More toxic to host enzymes than acyclovir.

 

 

 

Foscarnet

 

Mech: Viral DNA polymerase inhibitor that binds to the pyrophosphate binding site of the enzyme. Does not require activation by viral kinase.

Foscarnet = pyroFosphate analog.

 

Clinical: CMV retinitis in immunocompromised pt when gancyclovir fails.

 

Toxicity: Nephrotoxicity

 

 

HIV Therapy

Protease Inhibitors: Saquinavir, Ritinavir, Indinavir, Nelfinavir, Amprenavir

 

Mech: Inhibits assembly of new viruses by blocking protease enzyme

 

Toxicity: GI intolerance (nausea, diarrhea), hyperglycemia, lipid abnormalities, thrombocytopenia (indinavir)

 

 

Part of triple therapy: 2 RT inhibitors + 1 protease inhibitor

Initiated when CD4 counts drop below 500 or high viral load

HIV Therapy

Reverse Transcriptase Inhibitors: Nucleosides:  Zidovudine (AZT), didanosine (ddI), zalcitabine (ddC, stavudine (d4T), lamivudine (3TC), abacavir; Non-Nucleosides:  Nevirapine, delavirdine, efanvirenz

 

Mech: Preferentially inhibit RT of HIV; prevent incorporation of viral genome into host DNA.

Toxicity: Bone marrow suppression (neutropenia, anemia), peripheral neuropathy, lactic acidosis (nucleosides), rash (non-nucleosides), megaloblastic anemia (AZT)

Clinical: Triple therapy, AZT in pregnancy to reduce vertical transmission.

Interferons

 

Mech: Glycoproteins from human leukocytes that block various stages of viral RNA and DNA synthesis.

 

Clinical: Chronic hepatitis B and C, Kaposi’s Sarcoma.

 

Toxicity: Neutropenia

 

 

 

 

Ivermectin

 

Onchocerciasis (rIVER blindness treated with IVERmectin)

 

 

 

 

 

 

 

 

 

Mebendazole/thiabendazole

 

Nematode/roundworm (eg. pinworm, whipworm) infections.

 

 

 

 

 

 

 

 

 

Pyrantel pamoate

 

Giant roundworm (ascaris), hookworm (Necator/Ancylostoma), pinworm (Enterobius).

 

 

 

 

 

 

 

 

Praziquantel

 

Trematode/fluke (eg. schistosomes, Paragonimus, Clonorchis) and cysticercosis.

 

 

 

 

 

 

 

 

Niclosamide

 

Cestode/tapeworm (eg. D. latum, Taenia species) infections except cysticercosis.

 

 

 

 

 

 

 

 

Pentavalent antimony

 

Leishmaniasis

 

 

 

 

 

 

 

 

 

Chloroquine, quinine, mefloquine

 

Malaria

 

 

 

 

 

 

 

 

 

Primaquine

 

Latent hypnozoite (liver) forms of malaria (P. vivax, P. ovale)

 

 

 

 

 

 

 

 

 

Metronidazole

 

Giardiasis, amoebic dysentery (E. histolytica), bacterial vaginsitis (Garnerella), Trichomonas

 

 

 

 

 

 

 

 

Pentamidine

 

Pneumocystis carinii pneumonia prophylaxis

 

 

 

 

 

 

 

 

 

Nifurtimox

 

Chagas’ disease, American trypanosomiasis (Trypanosoma cruzi)

 

 

 

 

 

 

 

 

 

Suramin

 

African trypanosomiasis (sleeping sickness)

 

 

 

 

 

 

 

 

 

Bethanechol

 

Mech: direct cholinergic agonist

 

Clinical: Postoperative and neurogenic ileus and urinary retention. Activates bowel and bladder smooth muscle.

 

 

 

 

 

 

Carbachol, Pilocarpine

 

Mech: direct cholinergic agonist

 

Clinical: Glaucoma. Activates ciliary muscle of eye (open angle), pupillary sphincter (narrow angle), opening of trabecular meshwork and increased outflow of aqueous humor

 

Toxicity: Miosis, cyclospasm

 

 

 

Neostigmine

 

Mech: Anticholinesterases (indirect cholinergic agonist). Increases endogenous ACh.

 

Clinical: Postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of NMJ blockade (postOP)

 

 

 

 

 

Pyridostigmine

 

Mech: Anticholinesterase (indirect cholinergic agonist). Increases endogenous ACh; inreases strength.

 

Clinical: Myasthenia gravis

 

 

 

 

 

 

Edrophonium (Tensilon)

 

Mech: Anticholinesterase (indirect cholinergic agonist). Increases endogenous ACh.

 

Clinical: Diagnosis of myasthenia gravis (extremely short acting)

 

 

 

 

 

 

Physostigmine

 

Mech: Anticholinesterase (indirect cholinergic agonist). Increases endogenous ACh.

 

Clinical: Glaucoma – causes ciliary muscle contraction, opening of trabecular meshwork and increased outflow of aqueous humor (crosses BBB to CNS); and atropine overdose

 

Toxicity: Miosis, cyclospasm

 

 

Echothiophate

 

Mech: Anticholinesterase (indirect cholinergic agonist). Increases endogenous ACh.

 

Clinical: Glaucoma - causes ciliary muscle contraction, opening of trabecular meshwork and increased outflow of aqueous humor

 

Toxicity: Miosis, cyclospasm

 

 

 

 

What are the symptoms of cholinesterase poisoning?

 

DUMBBELSS

 

Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation , Sweating, Salivation, and abdominal cramping

 

 

 

 

Atropine

 

Mech: Muscarinic antagonist.

 

Clinical: Pupil dilation, reduce acid secretion in acid-peptic disease, reduce urgency in mild cystitis, decrease GI motility, reduce airway secretions, organophosphate poisoning, dangerous arrhythmias.Blocks Salivation, Lacrimation, Urination, Defacation

Toxicity: Increased body temp, rapid pulse, dry mouth, dry flushed skin, disorientation, mydriasis with cycloplegia, and constipation.

Blind as a bat, Red as a beet, Mad as a hatter, Hot as a hare, Dry as a bone

Hexamethonium

 

Mech: Ganglionic nicotinic ACh receptor antagonist (blocks only at ganglion, so no NMJ blockade)

 

 

 

 

 

 

 

 

Pralidoxime

 

Mech: Cholinesterase regenerator

 

Clinical: regenerates active cholinesterase, chemical antagonist, used to treat organophosphate exposure.

 

 

 

 

 

 

Scopolamine

 

Mech: Muscarinic cholinergic antagonist

 

Clinical: Prevention of nausea and vomiting a/w motion sickness

 

Toxicity: dry mouth, drowsiness, blurred vision, disorientation

 

 

 

 

 

Benzotropine

 

Mech: Muscarinic antagonist

 

Clinical: Parkinson’s disease

 

 

 

 

 

 

 

Homatropine, tropicamide

 

Mech: Muscarinic antagonist

 

Clinical: Produce mydriasis and cycloplegia

 

 

 

 

 

 

 

Ipratropium

 

Mech: Muscarinic antagonist

 

Clinical: Asthma, COPD

 

 

 

 

 

 

 

Succinylcholine

 

Mech: NMJ ACh receptor depolarizing blocker. Phase I (prolonged depolarization) – no antidote. Block potentiated by cholinesterase inhibit. Phase II (repolarized but blocked) – antidote: cholinesterase inhibitors (neostigmine).

 

Clinical: muscle paralysis in surgery or mechanical ventilation

 

 

 

 

Tubocurarine, atracurium, mivacurium, pancuronium, vercuronium, rapacuronium

 

Mech: NMJ ACh receptor non-depolarizing blocker. To reverse blockade, give cholinesterase inhibitor.

 

Clinical: Muscle paralysis for surgery or mechanical ventilation

 

 

 

 

 

Dantrolene

 

Mech: Prevents the release of Ca++ from the sarcoplasmic reticulum of skeletal muscle.

 

Clinical: Treatment of malignant hyperthermia, which is caused by the concomitant use of halothane and succinylcholine. Also used to treat neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).

 

 

 

 

Epinephrine

 

Mech: Catecholamine sympathomimetic.  Direct agonist at a1,a2, b1, b2 adrenergic receptors.

 

Clinical: Anaphylaxis, glaucoma (open angle – increased outflow of aqueous humor), asthma, hypotension.

 

Toxicity: Mydirasis, stinging; do not use in closed-angle glaucoma

 

 

 

Norepinephrine

 

Mech: Catecholamine sympathomimetic. Direct agonist at a1,a2, b1 adrenergic receptors.

 

Clinical: Hypotension (but decreases renal perfusion)

 

 

 

 

 

 

Isoproterenol

 

Mech: Catecholamine sympathomimetic. Direct agonist at b1=b2  adrenergic receptors

 

Clinical: AV block (rare)

 

 

 

 

 

 

Dopamine

 

Mech: Catecholamine sympathomimetic. Direct agonist at D1=D2>b>a adrenergic receptors.

 

Clinical: Shock (increases renal perfusion), heart failure.

 

 

 

 

 

 

Dobutamine

 

Mech: Catecholamine sympathomimetic. Direct agonist at b1>b2 adrenergic receptors.

 

Clinical: Shock, Heart failure

 

 

 

 

 

 

Amphetamine

 

Mech: Indirect sympathomimetic. Stimulates release of stored catecholamines.

 

Clinical: Narcolepsy, obesity, attention deficit disorder

 

 

 

 

 

 

Ephedrine

 

Mech: Indirect sympathomimetic. Stimulates release of stored catecholamines.

 

Clinical: Nasal decongestion, urinary incontinence, hypotension

 

 

 

 

 

 

Phenylephrine

 

Mech: Sympathomimetic.  a1>a2  adrenergic receptor agonist.

 

Clinical: Pupil dilator, vasoconstriction, nasal decongestion

 

 

 

 

 

 

 

Albuterol, terbutaline

 

Mech: Sympathomimetic. b2>b1 adrenergic receptor agonist.

 

Clinical: Asthma

 

 

 

 

 

 

 

Cocaine

 

Mech: Indirect general sympathomimetic; catecholamine uptake inhibitor

 

Clinical: Vasoconstriction and anesthesia

 

 

 

 

 

 

Clonidine

 

Mech: Centrally acting a2 agonist.  Decreases central adrenergic outflow.

 

Clinical: Hypertension, especially with renal disease (no decrease in blood flow to the kidney)

 

 

 

 

 

Phenoxybenzamine

 

Mech: Nonselective, irreversible alpha adrenergic blocker

 

Clinical: Pheochromocytoma

 

Toxicity:  Orthostatic hypotension, reflex tachycardia

 

 

 

 

 

Phenolamine

 

Mech: Nonselective, reversible alpha adrenergic blocker

 

Clinical: Pheochromocytoma

 

 

 

 

 

 

 

Prazosin, terazosin, doxazosin

 

Mech:  a1 selective blocker.

 

Clinical: Hypertension, urinary retention in BPH

 

Toxicity: First-dose orthostatic hypotension, dizziness, headache

 

 

 

 

 

Yohimbine

 

Mech: a2 selective blocker.

 

Clinical: Impotence (effectiveness controversial)

 

 

 

 

 

 

 

b-Blockers: Propranolol, metoprolol, atenolol, nadolol, timolol, pindolol, esmolol, labetalol

Mech: Nonselective (b1=b2 ): propranolol, timolol, pindolol, nadolol, labetolol (also blocks alpha-1receptors)

b1 selective (b1>b2): metoprolol, atenolol, esmolol (short acting)

Clinical: Hypertension (decrease CO and renin secretion), Angina Pectoris (decrease HR, contractility, O2 consumption), MI (beta-blockers decrease mortality), SVT: propranolol/esmolol (decrease AV conduction velocity), CHF (slow progression of chronic failure), Glaucoma: timolol (decrease secretion of aqueous humor)

Toxicity: Impotence, exacerbation of asthma, CV effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep prob), caution in DM

Brimonidine

 

Mech: Alpha antagonist

 

Clinical: Glaucoma – decreased aqueous humor synthesis

 

Toxicity: No pupillary or vision changes

 

 

 

 

 

Acetazolamide, dorzolamide, brinzolamide

 

Mech: Carbonic anhydrase inhibitor.

 

Clinical: Diuretic. Glaucoma – decrease aqueous humor secretion due to decreased HCO3-

 

Toxicity: No pupillary or vision changes.

 

 

 

 

Latanoprost

 

Mech: prostaglandin

 

Clinical: Increased flow of aqueous humor

 

Toxicity: Darkens color of urine (browning)

 

 

 

 

 

Barbiturates: Phenobarbital, pentobarbital, thiopental, secobarbital

 

Mech: Facilitate GABAa action by increasing duration of Cl- channel opening, thus decreasing neuron firing.

 

Clinical: Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)

 

Toxicity: Dependence, additive CNS depression with EtOH, resp or CV depression (can lead to death), drug interactions owing to induction of liver microsomal enzymes (cyt. P450)

 

Benzodiazepines: Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide

 

Mech: Facilitate GABAa action by increasing frequency of Cl- channel opening. Most have long half lives and active metabolites.

Clinical: Anxiety, spasticity, status epilepticus (diazepam), detoxification (esp. after alcohol withdrawl  DT’s)

Short Acting = Triazolam, Oxazepam, Midazolam (TOM)

Toxicity: Dependence, additive CNS depression w/ EtOH. Less resp depression and coma than barbi’s,

Treat overdose with flumazenil (competitive antagonist at GABA receptor)

Classical Antipsychotics (neuroleptics): Thioridazine, haloperidol, fluphenazine, chlorpromazine

Mech: Most block dopamine D2 receptors (excess dopamine a/w schizophrenia)

Clinical: Schizophrenia, psychosis

Toxicity: Extrapyramidal system: sedation, endocrine, muscarinic, alpha, and histamine receptor blocking effects.

Neuroleptic Malignant Syndrome: rigidity, autonomic instability, hyperpyrexia (tx w/ dantrolene and dopamine agonists)

Tardive Dyskinesia: stereotypic oral-facial movements probably due to dopamine receptor sensitization; results of long-term antipsychotic use

EPS: 4h acute dystonia-4d akinesia-4wk akathisia-4mo TD

Atypical Antipsychotics: Clozapine, olanzapine, risperidone

 

Mech: Block 5HT2 and dopamine receptors

 

Clinical: Tx of schizophrenia; +/- symptoms. Olanzapine is also used for OCD, anxiety disorder, and depression.

 

Toxicity: Fewer EPS and anticholinergic side effects than other antipsychotics. Clozapine may cause agranulocytosis (wkly WBC cts)

 

 

 

Lithium

 

Mech: not established. May inhibit phosphoinositol cascade.

 

Clinical: Mood stabilizer for bipolar affective disorder, blocks relapse and acute manic events.

 

Toxicity: Tremor, hypothyroidism, polyuria (ADH antagonist causing nephrogenic DI), teratogenesis. Narrow therapeutic window requiring close monitoring of serum levels.

 

 

Tricyclic Antidepressants: Imipramine, amitriptyline, desipramine, nortriptyline, clomipramine, doxepin

 

Mech: Block reuptake of NE and serotonin

Clinical: Endogenous depression, bedwetting (imipramine), OCD (clomipramine).

 

Side effects: Sedation, a-blocking, atropine-like effects. Tertiary TCA’s (amitriptyline) have more anticholinergic effects than secondary (nortriptyline). Desipramine is least sedating.

Toxicity: Tri-C’s: Convulsions, Coma, Cardiotoxicity; resp depression, hyperpyrexia; confusion and hallucinations in elderly

SSRI’s: Fluoxetine, sertraline, paroxetine, citalopram

 

Mech: Serotonin-specific reuptake inhibitors.

 

Clinical: Endogenous depression. It may take 2-3 wks for SSRI’s to have an effect.

 

Toxicity: Fewer than TCA’s. CNS stimulation: anxiety, insomnia, tremor, anorexia, nausea, and vomiting; Serotonin Syndrome w/ MAOIs: hyperthermia, muscle rigidity, CV collapse.

 

 

Trazodone

 

Heterocyclics: 2nd and 3rd generation antidepressants with varied and mixed mechanisms of action. Used in major depressive disorders.

 

Mech: Primarily inhibits serotonin reuptake.

 

Toxicity: Sedation, nausea, priapism, postural hypotension

 

 

 

 

Buproprion

 

Heterocyclics: 2nd and 3rd generation antidepressants with varied and mixed mechanisms of action. Used in major depressive disorders.

Also used for smoking cessation.

 

Mech: not known.

 

Toxicity: Stimulant effects (tachycardia, agitation), dry mouth, aggravation of psychosis

 

 

Venlafaxine

 

Heterocyclics: 2nd and 3rd generation antidepressants with varied and mixed mechanisms of action. Used in major depressive disorders. Also used in GAD.

 

Mech: Inhibits serotonin and dopamine reuptake.

 

Toxicity: Stimulant effects (anxiety, agitation, headache, insomnia)

 

 

 

Mirtazapine

 

Heterocyclics: 2nd and 3rd generation antidepressants with varied and mixed mechanisms of action. Used in major depressive disorders.

 

Mech: a2-antagonist (increases release of NE and serotonin) and potent 5HT2 receptor antagonist.

 

Toxicity: Sedation, increased serum cholesterol, increased appetite.

 

 

 

MAO Inhibitors: Phenelzine, tranylcypromine

 

Mech: Nonselective MAO inhibition

 

Clinical: Atypical depressions (w/ psychotic or phobic features), anxiety, hypochondriasis.

 

Toxicity: Hypertensive crisis w/ tyramine ingestion (cheese or wine) and meperidine; CNS stimulation. Contraindication with SSRIs or beta-agonists.

 

 

Selegiline (deprenyl)

 

Mech: Selectively inhibits MAO-B, thereby increasing the availability of dopamine.

 

Clinical: adjunctive agent to L-dopa in treatment of Parkinson’s dz.

 

Toxicity: May enhance adverse effects of L-dopa.

 

 

 

 

L-Dopa (levodopa)/carbidopa

 

Mech: Increases level of dopamine in brain. Parkinsonism thought to be due to loss of dopaminergic neurons and excess cholinergic fxn. Unlike dopamine, L-dopa can cross the BBB and is converted by dopa decarboxylase in the CNS to dopamine.

Clinical: Parkinsonism

 

Toxicity: Nausea. Arrhythmias from peripheral conversion to dopamine. Carbidopa, a peripheral decarboxylase inhibitor, is given with L-dopa to increase bioavailability in brain and limit peripheral side effects. Dyskinesias also occur.

Parkinson’s disease drugs

 

Dopamine agonists: L-dopa/carbidopa, bromocriptine (ergot alk and partial dopamine agonist), amantidine (enhances dopamine release)

 

MAO inhibitors: Selegiline (selective MAO-B inhibitor)

 

Antimuscarinic: Benztropine (improves tremor and rigidity, but has little effect on bradykinesia)

 

 

 

Opioid Analgesics: Morphine, fentanyl, codeine, heroin, methadone, meperidine, dextromethorphan

 

Mech: Act as agonists at opioid receptors (mu=morphine, kappa=dynorphin, delta=enkephalin) to modulate synaptic transmission

Clinical: Pain, cough suppression (dextromethorphan), diarrhea (loperamide and diphenoxylate), acute pulmonary edema, maintenance programs for addicts (methadone)

Toxicity: Addiction, respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression w/ other drugs. Tolerance does not develop to miosis and constipation. Tx toxicity w/ naloxone or naltrexone (opioid receptor antagonists)

Sumatriptan

 

Mech: 5HT1D agonist. Half life < 2hrs

 

Clinical: Acute migraine, cluster headaches

 

Toxicity: Chest discomfort, mild tingling (contraindicated in pts w/ CAD or Prinzmetal’s angina)

 

 

 

 

Ondansetron

 

Mech: 5HT3 antagonist. Powerful central-acting anti-emetic.

 

Clinical: Control vomiting post-OP and in patients undergoing cancer chemotherapy

 

Toxicity: HA, diarrhea

 

 

 

 

Carbemazepine

 

Mech: Blocks voltage sensitive Na+ channels.  TCA with antiepileptic effects

 

Clinical: Epilepsy (Simple, complex, GTC, trigeminal neuralgia), Mania.

Contraindicated in absence seizures, MAOI’s, glaucoma

 

Toxicity: Diplopia, ataxia, induction of P450, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity (always check LFT’s)

 

Phenytoin

 

Mech: Use-dependent blockade of Na+ channels. Also a class IB antiarrhythmic

 

Clinical: GTC, simple, complex seizures, status epilepticus

 

Toxicity: Nystagmus, ataxia, diplopia, lethargy, gingival hyperplasia (chronic use in children), peripheral neuropathy, hirsutism, megaloblastic anemia (decreased Vit. B12), malignant hyperthermia, teratogenic (fetal hydantoin syndrome)

 

Ethosuximide

 

Mech: Ca++ channel blocker

 

Clinical: Absence seizures

 

Toxicities: GI, lethargy, HA, urticaria, Steven’s Johnson Syndrome

 

 

 

 

 

Phenobarbital

 

Mech: Facilitate GABAa action by increasing duration of Cl- channel opening.

 

Clinical: Epilepsy (GTC), safer in pregnant women and Crigler-Najjar II

 

Toxicity: Sedation, induction of P450, tolerance, dependence

 

 

 

Valproic Acid

 

Mech: Blocks Ca++ channels, weak block of Na+ channels. May potentiate GABA

 

Clinical: Epilepsy (absence, myoclonic, GTC), acute mania

 

Toxicity: GI, rare, but fatal hepatotoxicity, neural tube defects in fetus (teratogen)

 

 

 

Lamotrignine

 

Mech: Blocks voltage sensitive Na+ channels, inhibits excitatory neurotransmission

 

Clinical: Epilepsy (simple, partial, GTC)

 

Toxicity: Life threatening rash, Steven’s Johnson syndrome

 

 

 

 

Gabapentin

 

Mech: Unknown, GABA analog but doesn’t affect GABA-R

 

Clinical: Adjunct in refractory epilepsy (simple, partial, GTC), neurologic pain and neuropathy

 

Toxicity: renal excretion, sedation, movement disorders

 

 

 

 

Topiramate

 

Mech: blocks voltage sensitive Na+ channels, inhibits excitatory neurotransmission

 

Clinical: Adjunct in simple and complex seizure management

 

Toxicity: Sedation, mental dulling, kidney stones, weight loss

 

 

 

 

Lorazepam/Diazepam

 

Mech: Enhance GABAergic inhibitory neurotransmission

 

Clinical: Epilepsy (GTC, status epilepticus), anxiety, panic disorders, conscious sedation

 

Toxicity: sedation, tolerance, dependence

 

 

 

 

 

Inhaled anesthetics: halothane(soluble-slow), enflurane (soluble-slow), isoflurane(soluble-slow), sevoflurane(insoluble-fast), methoxyflurane, nitrous oxide(insoluble-fast)

 

Mech: the lower the solubility in blood, the quicker the anesthetic induction and the quicker the recovery

 

Effects: Myocardial depression, resp depression, nausea/emesis, increased cerebral flow

Toxicity: Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), malignant hyperthermia

Thiopental

 

Mech: Barbiturate, high lipid solubility, rapid entry into brain.

 

Clinical: IV anesthesia.  Induction of anesthesia and short surgical procedures. Effects terminated by redistribution from brain.

 

Toxicity: Decreased cerebral blood flow

 

 

 

 

Midazolam

 

Mech: Benzodiazepine.

 

Clinical: IV anesthetic. Most common used drug for endoscopy; used adjunctively with gaseous anesthetics and narcotics.

 

Toxicity: May cause severe post-operative resp depression and amnesia

 

 

 

 

Ketamine

 

Mech: Arylcyclohexylamine. PCP analog.

 

Clinical: Dissociative IV anesthetic, good for hypovolemic patients. 

 

Toxicity: Cardiovascular stimulant, dissorientation, hallucination, and bad dreams. Increases cerebral blood flow.

 

 

 

 

Local Anesthetics: Esters: procaine, cocaine, tetracaine; amides: lidocaine, bupivicaine

Mech: Block Na+ channels by binding to specific receptors on inner portion of channel. Tertiary amine local anesthetics penetrate membrane in uncharged form, then bind in charged form. 1. In infected (acidic) tissue, anesthetics are charged and cannot penetrate membrane effectively. So more anesthetic is needed. 2. Order of nerve blockade: small diameter fibers>large diameter. Myelinated>unmyelinated. Size predominates over myelination, so small unmyelinated>small myelinated autonomic>large myelinated autonomic. Order of loss: pain>temp>touch>pressure. 3. Given w/ vasoconstrictors (epi) to enhance local action

Clinical: minor surgery, spinal anesthesia

Toxicity: CNS excitation, severe CV (bupivicaine), HTN/arrhythmias (coc)

Hydrochlorothiazide

 

Mech: Bind Cl site and block Na-Cl cotransporter in the distal tubule

 

Clinical: Diuretic, hypertension, edema

 

Toxicity: hypokalemia, slight hyperlipidemia, hyperuricemia, lassitude, hypercalcemia, hyperglycemia

 

 

 

 

Furosemide

 

Mech: Sulfonamide loop diuretic. Inhibits Na-K-2Cl cotransporter in the thick ascending limb of the loop of henle. Abolishes the hypertonicity of the medulla, preventing concentration of urine. Increases Ca++ excretion.

 

Clinical: Edematous states (CHF, cirrhosis, nephrotic syndrome, pulm. edema), HTN, hypercalcemia.

 

Toxicity: Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), interstitial Nephritis, Gout  OH DANG

Hydralazine

 

Mech: Increased cGMP causes smooth muscle relaxation. Vasodilates arterioles > veins; afterload reduction

 

Clinical; Severe HTN, CHF

 

Toxicity: Compensatory tachycardia, fluid retention, lupus-like syndrome, angina, salt retention, nausea, HA

 

 

 

Calcium Channel Blockers: Nifedipine, verapamil, diltiazem

 

Mech: Block voltage-dependent L-type Ca++ channels of cardiac and smooth muscle so reduce muscle contractility.  AV nodal cells primarily. Decrease cond. velocity, increase ERP, PR.

Vascular smooth muscle: nifedipine>diltiazem>verapamil

Heart: verapamil>diltiazem>nifedipine

Clinical: Class IV antiarrhythmic, nodal arrhythmias (SVT), HTN, angina

Toxicity: Cardiac depression (CHF, AV block, sinus node depression), peripheral edema, flushing, dizziness, constipation, torsades de pointes.

 

Guanethidine

 

Mech: blocks catecholamine release and causes depletion

 

Clinical: antihypertensive

 

Toxicity: Orthostatic and exercise hypotension, sexual dysfunction, diarrhea

 

 

 

 

Reserpine

 

Mech: Blocks catecholamine uptake into storage granules leading to depletion

 

Clinical: Hypertension,

 

Toxicity: sedation, depression, nasal stuffiness, diarrhea

 

 

 

 

Methyldopa

 

Mech: a2-adrenergic agonist, centrally acting decreasing adrenergic outflow from CNS

 

Clinical: Hypertension, esp renal insufficiency since it doesn’t block renal blood flow

 

Toxicity: sedation, positive Coomb’s test

 

 

 

Nitroprusside

 

Mech: causes vasodilation via release of Nitrous oxide

 

Clinical: Malignant hypertension

 

Toxicity: Cyanide poisoning (can be metabolized to cyanide)

 

 

 

 

 

ACE Inhibitors: Captopril, enalapril, lisinopril

 

Mech: Inhibit ACE, reducing levels of ATII and preventing inactivation of bradykinin, a potent vasodilator. Renin release increased due to loss of feedback inhib.

 

Clinical: Hypertension, CHF, diabetic renal disease

 

Toxicity: Cough, Angioedema, Proteinuria, Taste changes, hypOtension, Pregnancy problems (fetal renal damage), Rash, Increased renin, Lower ATII, hyperkalemia. CAPTOPRIL

 

Losartan

 

Mech: ATII receptor antagonist.

 

Clinical: Hypertension

 

Toxicity: Fetal renal toxicity, hyperkalemia, does not cause cough

 

 

 

 

 

Acetazolamide, dorzolamide, brinzolamide

 

Mech: Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and reduction in total body HCO3- stores. Acts at proximal convoluted tubule.

Clinical: Diuretic. Glaucoma – decrease aqueous humor secretion due to decreased HCO3-. Urinary alkalinization, metabolic alkalosis, altitude sickness.

 

Toxicity: No pupillary or vision changes. Hyperchloremic metabolic acidosis (normal anion gap), neuropathy, ammonia toxicity, sulfa allergy.

Ethacrynic Acid

 

Mech: Phenoxyacetic acid derivative (not a sulfonamide). Same action as furosemide.

 

Clinical: Diuresis in patients allergic to sulfa drugs

 

Toxicity: similar to furosemide, except no hyperuricemia, no sulfa allergy

 

 

 

Hydrochlorothiazide

 

Mech: Thiazide diuretic. Inhibits NaCl cotransport in early distal tubule, reducing diluting capacity of the nephron. Decreases Ca++ excretion.

 

Clinical: Hypertension, CHF, calcium stones, nephrogenic DI

 

Toxicity: hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, slight hyperLipidemia, hyperUricemia, lassitude, hyperCalcemia

hyperGLUC

Spirononlactone

 

Mech: K+ sparing diuretic:  competitive aldosterone receptor antagonist in cortical collecting tubule.

 

Clinical: Hyperaldosteronism, K+ depletion, CHF

 

Toxicity: hyperkalemia, endocrine effects (gynecomastia, antiandrogen)

 

 

 

Triamterene, Amiloride

 

Mech: K+ sparing diuretics: Block sodium channels in the CCT.

 

Clinical: Hyperaldosteronism, K+ depletion, CHF

 

Toxicity: Hyperkalemia, no endocrine effects

 

 

 

 

 

Mannitol

 

Mech: Osmotic diuretic, increases tubular fluid osmolarity producing increased urine flow

 

Clinical: Acute renal failure, drug overdose, decrease intracranial/intraocular pressure

 

Toxicity: pulmonary edema, dehydration. Contraindicated in anuria, CHF

 

 

Electrolyte changes with Diuretics:

 

Urine NaCl: increase (all diuretics)

Urine K+: increase (all diuretics except spironolactone, triamterene, amiloride)

Blood pH:  Acidosis (carbonic anhydrase inhib, K+ sparing) Alkalosis (loop diuretics, thiazides)

Urine Ca++:  increased (loop diuretics, spironolactone), decreased (thiazides, amiloride)

 

:

 

What is the effect of Nitrates on the heart?

 

Affect Preload

Decrease EDV, BP, Ejection time, MVO2

Increase Contractility (reflex), HR (reflex)

 

 

 

 

 

 

 

What is the effect of Beta Blockers on the heart?

 

Affect afterload

Decrease BP, Contractility, HR, MVO2

Increase EDV, Ejection time

 

 

 

 

 

 

 

What is the effect of Nitrates plus Beta Blockers on the heart?

 

No effect or decrease EDV

Little/no effect on Contractility and Ejection time

Decrease BP, HR, MVO2

 

 

 

 

 

 

 

Nitroglycerin, isosorbide dinitrate

 

Mech: Vasodilate by releasing nitric oxide in smooth muscle, causing increase in cGMP and smooth muscle relaxation. Dilate veins >> arteries

 

Clinical: Angina, pulmonary edema. Also used as an aphrodisiac and erection enhancer.

Toxicity: Tachycardia (reflex), hypotension, HA, “Monday disease” in industrial exposure, development of tolerance for vasodilating action during work week and loss of tolerance over weekend, resulting in tachy, dizziness and HA.

Digoxin (Cardiac Glycoside)

Mech: Inhibit Na-K-ATPase of cell membrane causing increase in intracellular Na. Na-Ca antiport does not function as well causing increased Ca inside; leads to positive inotropy. May cause increased PR, decreased QT, scooping of ST segment, T wave inversion on EKG.

Clinical: 75% bioavailability, 20-40% protein bound, T1/2 40 hrs, urinary excretion.  CHF, atrial fibrillation.

Toxicity: Nausea, vomiting, diarrhea, blurry yellow vision (Van Gogh), Arrhythmias. Toxicities increased in renal failure, hypokalemia (potentiates drug effects), and quinidine (decreases clearance, displaces digoxin from tissue binding sites). Antidote: Normalize K+ slowly, lidocaine, cardiac pacer, anti-dig Fab (digibind)

Quinidine, Amiodarone, Procainamide, Disopyramide

Na Channel blockers - Class Ia Antiarrhythmics 

 

Mech: Increased AP duration, increased ERP, increased QT. Decrease slope of phase 4 depolarization and increase threshold for firing in abnormal pacemaker cells. Are state dependent (fast tachy).

 

Clinical: Affect both atrial and ventricular arrhythmias.

 

Toxicity: Quinidine (cinchonism: HA, tinnitus; thrombocytopenia; torsades de pointes due to increased QT interval); Procainamide (reversible SLE-like syndrome)

 

 

 

Lidocaine, mexiletine, tocainide

Na Channel Blockers - Class Ib Antiarrhythmics 

Mech: Decreased AP duration. Affect ischemic or depolarized Purkinje and ventricular tissue. Decrease slope of phase 4 depolarization and increase threshold for firing in abnormal pacemaker cells. Are state dependent (fast tachy).

Clinical: Used in ventricular arrhythmias (esp. post-MI) and in digitalis-induced arrhythmias.

Toxicity: Local anesthetic. CNS stimulation/depression, CV depression

Flecainide, encainide, propafenone

Na Channel Blockers – Class Ic Antiarrhythmics

 

Mech: No effect on AP duration. Decrease slope of phase 4 depolarization and increase threshold for firing in abnormal pacemaker cells. Are state dependent (fast tachy).

Clinical: Useful in V-tachs that progress to VF and in intractable SVT. Are used as a last resort in refractory tachyarrhythmias because of toxicities.

Toxicity: proarrhythmic

 

 

Class II Antiarrhythmics: Beta-blockers: Propranolol, esmolol, metoprolol, atenolol, timolol

 

Mech: Decrease cAMP, Ca currents. Suppress abnormal pacemakers by decreasing slope of phase 4. AV node particularly sensitive: increased PR. Esmolol is very short acting.

 

Toxicity: Impotence, exacerbation of asthma, CV effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alterations). May mask signs of hypoglycemia.

 

 

Class III Antiarrhythmics: K+ Channel blockers: Sotalol, ibutilide, bretylium, amiodarone

 

Mech: Increase AP, ERP, QT.

Clinical: Used when other antiarrhythmics fail.

 

Toxicity: Sotalol – torsades de pointes, excessive beta-block; Ibutilide – torsades; Bretylium – new arrhythmias, hypotension; Amiodarone – Pulmonary fibrosis, corneal deposits, Hepatotoxicity, skin deposits resulting in photodermatitis, neurologic effects, constipation, CV effects (bradycardia, heart block, CHF), hyper/hypothyroidism.

Check PFTs, LFTs, TFTs with amiodarone.

Class IV Antiarrhythmics: Ca++ Channel blockers: Verapamil, diltiazem

 

Mech: Primarily effects AV nodal cells. Decrease conduction velocity, increase ERP, PR.

 

Clinical: Used in preventing nodal arrhythmias (SVT).

 

Toxicity:  Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression); torsades de pointes (bepridil)

 

 

Adenosine

 

Drug of choice for diagnosing/abolishing AV nodal arrhythmias.

 

 

 

 

 

 

 

 

 

Potassium

 

Depresses ectopic pacemakers, especially in digoxin toxicity.

 

 

 

 

 

 

 

 

 

Magnessium

 

Effective in torsades de pointes and digoxin toxicity

 

 

 

 

 

 

 

 

 

Cholestyramine, colestipol

 

Mech: Bile acid resins block reabsorption of bile acids. Decrease LDL, no effect on HDL, slight increase in triglycerides.

 

Clinical: Hypercholesterolemia

 

Toxicity: Patients hate it. Tastes bad and causes GI discomfort.

 

 

 

 

Lovastatin, pravastatin, simvastatin, atorvastatin

 

Mech: HMG-CoA Reductase inhibitors.  Significantly decrease LDL. Small increase in HDL, small decrease in triglycerides.

 

Clinical: Hypercholesterolemia

 

Toxicity: Myositis (muscle pain/weakness), reversible increase in LFT’s, expensive

 

 

 

Niacin

 

Mech: block cholesterol transport into VLDL particles. Moderate decrease in LDL, Moderate increase in HDL, small decrease in TG.

 

Clinical: Hypercholesterolemia

 

Toxicity: Red, flushed face, which is decreased by aspirin or long-term use.

 

 

 

Gemfibrozil, clofibrate

 

Mech: Lipoprotein lipase stimulators: stimulates conversion of VLDL to IDL. Small decrease in LDL, small increase in HDL, Large decrease in TG’s.

 

Clinical: Hypercholesterolemia

 

Toxicity: Myositis, increased LFT’s

 

 

 

Methotrexate

 

Mech: S-phase specific antimetabolite. Folic acid analog that inhibits dihydrofolate reductase, resulting in decreased dTMP and thus decreased DNA and protein synthesis.

 

Clinical: Leukemias, lymphomas, choriocarcinoma, sarcoma. Abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis.

 

Toxicity: Myelosuppression, which is reversible with leucovorin (folinic acid) rescue. Macrovesicular fatty change in liver.

 

5-Fluorouracil (5-FU)

 

Mech: S-phase specific antimetabolite. Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase, resulting in decreased dTMP and same effects as methotrexate.

 

Clinical: Colon ca. and other solid tumors, basal cell carcinoma (topical). Synergy with methotrexate.

 

Toxicity: Myelosuppression which is not reversible with leucovorin; photosensitivity

6-Mercaptopurine (6-MP)

 

Mech: Blocks purine synthesis

 

Clinical: Leukemias, lymphomas (not CLL or Hodgkins)

 

Toxicity: Bone marrow, GI, liver. Metabolized to xanthine oxidase, thus increases toxicity with allopurinol

 

 

 

 

Busulfan

 

Mech: Alkylates DNA

 

Clinical: CML

 

Toxicity: Pulmonary fibrosis, hyperpigmentation.

 

 

 

 

 

Cyclophosphamide

 

Mech: Alkylating agent; covalently x-links (interstrand) DNA at guanine N-7. Requires bioactivation by liver.

 

Clinical: NHL, breast and ovarian ca. Also an immunosuppressant.

 

Toxicity: Myelosuppression, hemorrhagic cystitis

 

 

 

 

Nitrosureas: carmustine, lomustine, semustine, streptozocin

 

Mech: Alkylates DNA. Requires bioactivation. Crosses BBB to CNS.

 

Clinical: Brain tumors (including glioblastoma multiforme)

 

Toxicity: CNS toxicity (dizziness, ataxia)

 

 

 

 

 

Cisplatin

 

Mech: Acts like an alkylating agent. X-links via hydrolysis of Cl- groups and reaction with platinum.

 

Clinical: Testicular, bladder, ovary, and lung ca.

 

Toxicity: Nephrotoxicity and acoustic nerve damage

 

 

 

 

Doxorubicin (adriamycin)

 

Mech: Noncovalently intercalates in DNA, creating breaks to decrease replication and transcription and generate free radicals. Anthracycline antibiotic.

 

Clinical: Part of AVBD combination regimen for Hodgkins and for myelomas, sarcomas, and solid tumors (breast, ovary, lung).

 

Toxicity: Cardiotoxicity; also myelosuppression and marked alopecia. Toxic extravasation.

 

Bleomycin

 

Mech: Intercalates DNA strands and induces free radical formation, causing strand breaks.

 

Clinical: Testicular ca, lymphomas.

 

Toxicity: Pulmonary fibrosis, skin changes, minimal myelosuppression

 

 

 

 

Etoposide

 

Mech: G2-phase specific inhibits topoisomerase II so that double strand breaks remain in DNA following replication, with subsequent DNA degradation.

 

Clinical: Oat cell carcinoma of the lung and prostate, testicular ca.

 

Toxicity: Myelosuppression, GI irritation, alopecia

 

 

 

Prednisone

 

Mech: May trigger apoptosis. May even work on non-dividing cells. Phospholipase A2 and COX-2 Inhibitor.

 

Clinical: Most commonly used glucocorticoid in cancer chemotherapy. Used in CLL, Hodgkins lymphomas (part of MOPP, CHOP). Also an immunosuppressant used in autoimmune disease. Asthma.

 

Toxicity: Cushing-like symptoms; immunosuppression, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis.

 

Tamoxifen/raloxifene

 

Mech: Estrogen receptor mixed agonist/antagonists that block the binding of estrogen to ER+ cells.

 

Clinical: Breast ca.

 

Toxicity: Tamoxifen may increase the risk of endometrial ca. via partial agonist effects; hot flashes

 

 

 

Vincristine/Vinblastine

 

Mech: M-phase specific alkaloids that bind to tubulin and block polymerization of microtubules so that mitotic spindle can’t form.

 

Clinical: Part of MOPP/CHOP regimens for Hodkins/NHL lymphomas, Wilms tumor, choriocarcinoma

 

Toxicity: Vincristine – neurotoxicity (areflexia, peripheral neuritis), paralytic ileus. Vinblastine – blasts bone marrow (myelosuppression)

 

 

Paclitaxel

 

Mech: M-phase specific agent obtained from yew tree that binds to tubulin and hyperstabilizes polymerized microtubules so that mitotic spindle can’t break down (anaphase cannot occur)

 

Clinical: Ovarian and breast ca.

 

Toxicity: Myelosuppression, hypersensitivity

 

 

 

Lead Poisoning

 

Lead lines on gingivae and on epiphyses of long bones on x-ray.

Encephalopathy and Erythrocyte basophilic stippling

Abdominal Colic and sideroblastic Anemia

Drops: wrist and foot drop. Dimercaprol and EDTA are first line tx

 

LEAD – high risk in houses with chipped paint

 

 

 

 

Drugs that cause SLE-like syndrome:

 

Hydralazine

Procainamide

INH

Phenytoin

 

 

 

 

 

 

Drugs that cause Stevens-Johnson Syndrome

 

Ethosuximide

Sulfonamides

Lamotrignine

 

 

 

 

 

 

 

Drugs that induce P450:

 

Barbiturates, phenytoin, carbamazepine, rifampin, griseofulvin, quinidine

 

 

 

 

 

 

 

 

Drugs that Inhibit P450:

 

Cimetidine, ketoconazole, grapefruit, erythromycin, INH, sulfonamides

 

 

 

 

 

 

 

 

 

Sildenafil

 

Mech: Inhibits cGMP phosphodiesterase, causing increased cGMP, smooth muscle relaxation in the corpus cavernosum, increased blood flow, and penile erection

 

Clinical: Tx of erectile dysfunction

 

Toxicity: HA, flushing, dyspepsia, blue-green color vision, risk of life-threatening hypotension in patients taking nitrates.

 

 

Clomiphene

 

Mech: Partial agonist at estrogen receptors in the pituitary gland. Prevents normal feedback inhibition and increases release of LH and FSH from pituitary, which stimulates ovulation.

 

Clinical: Tx of infertility

 

Toxicity: Hot flashes, ovarian enlargement, multiple spontaneous pregnancies, visual disturbances.

 

 

Mifepristone (RU486)

 

Mech: Competitive inhibitor of progestins at progesterone receptors.

 

Clinical: Abortificant

 

Toxicity: Heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain

 

 

 

 

H2-Blockers: Cimetidine, ranitidine, famotidine, nizatidine

 

Mech: Reversible block of histamine H2 receptors.

 

Clinical: Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome.

 

Toxicity: Cimetidine is a potent inhibitor of P450; it also has an antiandrogenic effect and decreases renal excretion of creatinine. Other H2 blockers are relatively free of these effects.

 

 

Omeprazole, lansoprazole

 

Mech: Irreversible inhibits H+/K+ ATPase in stomach parietal cells.

 

Clinical: Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome.

 

 

 

 

 

 

Sucralfate

 

Mech: Aluminum sucrose sulfate polymerizes in the acid environment of the stomach and selectively binds necrotic peptic ulcer tissue. Acts as a barrier to acid, pepsin, and bile. Sucralfate cannot work in the presence of antacids or H2 blocers (requires acidic pH to polymerize)

 

Clinical: Peptic ulcer disease.

 

 

 

 

Misoprostol

 

Mech: A PGE1 analog. Increases production and secretion of gastric mucous barrier.

 

Clinical: Prevention of NSAID-induced peptic ulcers, maintains a patent PDA.

 

Toxicity: Diarrhea. Contraindicated in women of childbearing age (abortificant)

 

 

Signs/Symptoms of Antacid overuse:

Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying. Overuse can cause:

1. Aluminum hydroxide: constipation and hypophosphatemia

2. Magnesium hydroxide: diarrhea

3. Calcium carbonate: hypercalcemia, rebound acid increase

All can cause hypokalemia

 

 

 

 

Heparin

 

Mech: Catalyzes the activation of antithromin III. Short half-life. Check aPTT.

Clinical: Immediate anticoagulation for PE, stroke, angina, MI, DVT. Used during pregnancy (does not cross placenta). Follow PTT.

Toxicity: Bleeding, thrombocytopenia, drug-drug interactions. Use protamine sulfate for rapid reversal of heparinization (positively charged molecule that acts by binding negatively charged heparin)

Note: Newer low molec. wt heparins (enoxaparin) have better bioavailability and 2-4 times longer half life. Admin. SQ and w/o PTT.

 

Warfarin (Coumadin)

 

Mech: Interferes with normal synthesis and gamma carboxylation of vit-K dependent clotting factors II, VII, IX, X, Protein S and C via vit. K antagonism. Long half-life, slow onset.

 

Clinical: Chronic anticoagulation. Not used in pregnant women (does cross placenta). Follow PT.

WEPT:  Warfarin affects Extrinsic pathway and prolongs PT

 

Toxicity: Bleeding, teratogenic, drug-drug interactions

 

Thrombolytics: Streptokinase, urokinase, tPA (alteplase), APSAC (antistreplase)

 

Mech: Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. It is claimed that tPA specifically converts fibrin-bound plasminogen to plasmin

 

Clinical: Early MI

 

Toxicity: Bleeding, hypersensitivity

 

Aminocaproic acid inhibits Plasminogen activation to Plasmin

Clopidogrel, Ticlopidine

 

Mech: Inhibits platelet aggregation by irreversibly inhibiting the ADP pathway involved in the binding of fibrinogen.

 

Clinical: Actue coronary syndrome; coronary stenting. Decreases the incidence of recurrence of thrombotic stroke. Secondary stroke prevention.

 

Toxicity: Neutropenia (ticlopidine); reserved for those who cannot tolerate aspirin.

 

Zileuton

 

Mech: Selective and specific inhibitor of 5-lipoxygenase preventing formation of both LTB4 and the cysteinyl leukotrienes.

 

Clinical: Asthma

 

Toxicity: Liver, Churg-Strauss syndrome (eosinophilic vasculitis), inhibit P450.

 

 

 

Zafirlukast

 

Mech: Selective, reversible inhibitors of the cysteinyl leukotriene-1 receptor

 

Clinical: Asthma

 

Toxicity: Liver, Churg-Strauss syndrome (eosinophilic vasculitis), inhibit P450.

 

 

 

Aspirin

 

Mech: Acetylates and irreversibly inhibits cyclooxygenase (1 & 2) to prevent coversion of arachidonic acid to prostaglandins

 

Clinical: Antipyretic, analgesic, anti-inflammatory, anti-platelet

 

Toxicity: Gastric ulceration, bleeding, hyperventilation, Reye’s syndrome, tinnitus (CN VIII), renal toxicity

 

 

 

NSAIDS: Ibuprofen, naproxen, indomethacin

 

Mech: Reversibly inhibit cyclooxygenase (1 & 2).  Block prostaglandin synthesis.

 

Clinical: Antipyretic, analgesic, anti-inflammatory. Indomethacin used to close a PDA.

 

Toxicity: Renal damage, aplastic anemia, GI distress

 

 

 

COX-2 Inhibitors: Celecoxib, rofecoxib

 

Mech: Selectively inhibit cyclooxygenase isoform 2, which is found in inflammatory cells and mediates inflammation and pain; spares COX-1, which helps maintain the gastric mucosa. Thus, should not have the corrosive effects of other NSAIDS on the GI lining.

 

Clinical: Rheumatoid and osteoarthritis

 

Toxicity: Similar to other NSAIDS; may have less toxicity to the GI mucosa (lower incidence of ulcers and bleeding)

 

Acetaminophen

 

Mech: Reversibly inhibits COX-1 and 2, mostly in CNS. Inactivated peripherally.

 

Clinical: Antipyretic, analgesic, but lacking anti-inflammatory properties.

 

Toxicity: Overdose produces hepatic necrosis; acetominophen metabolite depletes glutathione and forms toxic tissue adducts in liver. Give Mucomyst (N-acetylcysteine) for overdose – replenishes glutathione.

Glucocorticoids: Hydrocortisone, prednisone, triamcinolone, dexamethasone, beclomethasone

 

Mech: Decrease the production of leukotrienes and prostaglandins by inhibiting phospholipase A2 and expression of COX-2.

 

Clinical: Addison’s disease, inflammation, immune suppression, cancer therapy, asthma (drug of choice in status asthmaticus along with albuterol)

Toxicity: Iatrogenic Cushing’s syndrome: buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruising, osteoporosis, adrenocortical atrophy, peptic ulcers

Albuterol

 

Mech: b2 agonist. Relaxes bronchial smooth muscle.

 

Clinical: Asthma – use during acute exacerbation

 

 

 

 

 

 

 

Salmeterol

 

Mech: b2 agonist. Long-acting agent for prophylaxis.

 

Clinical: Asthma.  Controller

 

Toxicity: tremor and arrhythmia

 

 

 

 

 

Theophylline

 

Mech: Methylxanthine. Bronchodilation mechanism unclear – may cause bronchodilation by inhibiting phosphodiesterase, enzyme involved in degrading cAMP (controversial)

 

Clinical: Asthma

 

Toxicities: Seizures, arrhythmias, drug-drug interactions

 

 

 

Cromolyn

 

Mech: Prevents release of mediators from mast cells.

 

Clinical: Prophylaxis of asthma only. Not effective in an acute attack.

 

Toxicity: rare

 

 

 

 

 

Colchicine

 

Mech: Depolymerizes microtubules, impairing leukocyte chemotaxis and degranulation.

 

Clinical: Acute gout

 

Toxicity: GI, esp. orally. Indomethacin is less toxic and more commonly used.

 

 

 

Probenecid

 

Mech: Inhibits reabsorption of uric acid (also inhibits secretion of penicillin)

 

Clinical: Chronic gout.

 

 

 

 

 

 

Allopurinol

 

Mech: Xanthine oxidase inhibitor, decreases conversion of xanthine to uric acid

 

Clinical: Chronic gout

 

Toxicity: increased with 6-mercaptopurine

 

 

 

 

Insulin

 

Mech: Binds insulin receptor, which has tyrosine kinase activity. In liver, increases storage of glucose as glycogen. In muscle, stimulates glycogen and protein synthesis, and K+ uptake. In adipose tissue, facilitates triglyceride storage.

 

Clinical: Diabetes mellitus.  Life-threatening hyperkalemia, stress-induced hyperglycemia.

 

Toxicity: hypoglycemia, hypersensitivity (rare)

 

Sulfonylureas: Tolbutamide, chlorpropamide, glyburide, glipizide

 

Mech: Oral hypoglycemics used to stimulate release of endogenous insulin in NIDDM. Close K+ channels in b-cell membrane – cell depolarizes – insulin release triggered owing to an increase in Ca++ influx

 

Clinical: NIDDM. Inactive in IDDM because requires islet fxn

 

Toxicity: hypoglycemia (more common with 2nd generation: glyburide, glipizide) and disulfuram-like effects (not seen with 2nd gen)

 

Metformin

 

Mech: Unknown. Possibly inhibits gluconeogenesis and increases glycolysis; decreases serum glucose levels.

 

Clinical: Used as oral hypoglycemic. Can be used in both IDDM/NIDDM

 

Toxicity: most grave effect is lactic acidosis

 

 

 

Glitazones: Pioglitazone, rosiglitazone

 

Mech: Increase target cell response to insulin.

 

Clinical: Used as monotherapy for NIDDM or in combination with above agents.

 

Toxicity:  Weight gain, hepatotoxic (troglitazone)

 

 

 

 

a-glucosidase inhibitors: Acarbose, miglitol

 

Mech: Inhibits intestinal brush border enzymes; delayed hydrolysis of sugars and absorption of glucose leads to decreased post-prandial hyperglycemia.

 

Clinical: Used as monotherapy in NIDDM or in combination with above agents

 

Toxicity: GI disturbances

 

 

Leuprolide

 

Mech: GnRH analog with agonist properties when used in pulsatile fashion and antagonist properties when used continuously (but causes transient initial burst of LH/FSH)

 

Clinical: Infertility (pulsatile), prostate cancer (continuous, use with flutamide), uterine fibroids

 

Toxicity: Antiandrogen, nausea, vomiting

 

 

Propylthiouracil

 

Mech: Inhibits organification and coupling of thyroid hormone synthesis. Also decreases peripheral conversion of T4 to T3.

 

Clinical: Hyperthyroidism

 

Toxicity: Skin rash, agranulocytosis, aplastic anemia

 

 

 

 

Finasteride

 

Mech: 5a-reductase inhibitor (decreases conversion of testosterone to dihydrotestosterone)

 

Clinical: BPH

 

 

 

 

 

 

Flutamide

 

Mech: Non-steroidal competitive inhibitor of androgens at the testosterone receptor.

 

Clinical: Prostate cancer

 

 

 

 

 

 

Ketoconazole, spironolactone

 

Mech: Inhibit steroid synthesis

 

Clinical: Used in treatment of polycystic ovarian syndrome to prevent hirsutism

 

 

 

 

 

 

Cyclosporine

 

Mech: Binds to cyclophilins (peptide proline cis-trans isomerase), blocking differentiation and activation of T cells mainly by inhibiting the production of IL-2 and its receptor.

 

Clinical: Suppresses organ rejection after transplantation; selected autoimmune disorders.

 

Toxicity: Predisposes patients to viral infections and lymphoma; nephrotoxic (preventable with mannitol diuresis)

 

Azathioprine

 

Mech: Antimetabolite derivative of 6-mercaptopurine that interferes with the metabolism and synthesis of nucleic acid.

 

Clinical: Kidney transplantation, autoimmune disorders (including glomerulonephritis and hemolytic anemia)

 

Toxicity: Toxic to proliferating lymphocytes after antigenic stimulus.

 

 

 

Tacrolimus (FK506)

 

Mech: Similar to cyclosporine; binds to FK binding protein, inhibiting secretion of IL-2 and other cytokines

 

Clinical: Potent immunosuppressive used in organ transplant

 

Toxicity: Significant: nephrotoxicity, peripheral neuropathy, hypertension, pleural effusion, hyperglycemia