“Common” Pearls:

Clinical Pharmacology

Chad Douglas, MD, PharmD

Medical Director-OUHSC Student/Employee Health Clinic

Clinical Assistant Professor Department of Family and Preventative Medicine

Objectives

1. Outline the most common empiric therapies for common

bacterial, viral and fungal infections

2. Discuss commonly overdosed mediations and their antidotes

3. Review common adverse reactions and side effects of

pharmacologic therapies

4. Answer general board preparation questions regarding clinical

pharmacology

1st Cephalexin(Keflex®)*, Cefadroxil (Duricef®) Cefazolin (Ancef®) IV

2nd Cefaclor (Ceclor®)*, Cefprozil (Cefzil®), Cefuroxime axetil (Ceftin®)*

3rd Cefixime (Suprax®)*, Ceftibuten (Cedax®), Cefdinir (Omnicef®)

Ceftriaxone(Rocephin®) IM

Cephalosporin Generations (po)

(<10% cross reactivity with PCN allergy and allergy to 1st generation

cephalosporin-cephalexin (Keflex®). <5% cross reactivity with 3rd generation

agents and higher)

Cephalosporin Generations

1st generation gram + (skin infections, Group A Strep Pharyngitis)

-Cephalexin(Keflex®)*, Cefadroxil (Duricef®) Cefazolin (Ancef®) IV

2nd generation gain some gram (–) (H. Influenza, M. catarrhalis)

Some S. pneumo (URI, OM, mild sinusitis, mild bronchitis)

- Cefaclor (Ceclor®)*, Cefprozil (Cefzil®), Cefuroxime axetil (Ceftin®)*

3rd generation gain more gram (-), gain better S. pneumo

coverage (URI, OM, Sinusitis, Bronchitis, CAP (not atypical)

-Cefixime (Suprax®), Cefdinir (Omnicef®), Ceftriaxone (Rocephin®) IM

Cephalosporin Generations Cont.

4rd generation- Cefepime (Maxipime®) (IV) broad spectrum but not

for anaerobes

5rd generation- Ceftaroline fosamil (Teflaro®) (IM, IV) – covers

MRSA, Only cephalosporin that covers MRSA. FDA Indications- CAP,

Skin Infections

Anaerobic coverage- 2nd gen- Cefoxitin and Cefotetan (IM/IV), Pseudomonas –

3rd gen Ceftazidime(IM/IV) 4th gen- Cefepime (IM/IV)

Bacterial Infection Treatment

MRSA

Trimethoprim/Sulfamethoxazole- TMP/SMX (Bactrim

DS, Septra DS®)

Doxycycline (Vibramycin®)

Clindamycin (Cleocin®) po

Linezolid (Zyvox®) mupirocin (Bactroban®)

Ceftriaxone (Rocephin®) IM -Will NOT cover MRSA!

(Beta lactams (dicloxacillin) work better for MSSA)

Streptococcal Skin Infections

Cephalexin (Keflex®)

Doxycycline (Vibramycin®)

Clindamycin (Cleocin®)

(Not TMP/SMX (Bactrim®)

Maxillary Sinusitis

Azithromycin (Zithromax®)

Augmentin, 2nd or 3rd gen ceph, Fluoroquinolone (not

Ciprofloxacin)

Streptococcal pharyngitis PCN VK, Amoxicillin, 2nd or 3rd gen ceph, clindamycin

(not azithromycin*) PCN G IM x 1 dose

Bacterial Infection Treatment

Otitis Media Amoxil®/Augmentin®, Azithromycin, 2nd or 3rd

gen cephalosporin, Ceftriaxone IM- peds

Otitis Externa (‘Swimmer’s Ear’)

Drops- Neomycin, Polymyxin B/HC,

Ciproflox/Dexamethasone (Ciprodex ®),

Ofloxacin (Floxin) Otic®

Pneumonia- Community acquired, strep pneumo

(Acute Bronchitis)

Levofloxacin (Levaquin®), Moxifloxacin

(Avelox®) (Not Cipro),

3rd gen or higher Cephalosporin, Doxycycline,

Azithromycin-peds

Pneumonia (atypical) Azithromycin, Doxycycline, Respiratory

Fluoroquinolones (Not Cipro),

Pseudomonas Ciprofloxacin (Cipro®)

Pertussis Azithromycin

Bacterial Infection Treatment

UTI (uncomplicated)

Nitrofurantoin* (CrCl >60), TMP/SMX*, Ciprofloxacin*,

Levofloxacin, (NOT Moxifloxacin -Avelox®),

Cephalosporin *Get Culture*

Acute Prostatitis

Ciprofloxacin (Cipro®)

Doxycycline + Ceftriaxone (Rocephin®) IM (any concerns

for STD’s)

TMP/SMX (Bactrim®)

Extended po course 21-30 days for all po abx

Rickettsial infections (RMSF, Ehrlichiosis,

Lyme*)

Doxycycline* ( >8 y/o) or Chloramphenicol ?

Giardiasis

Metronidazole (Flagyl®)

Clostridium Difficile (C. diff) Metronidazole, po Vancomycin

H. Pylori

- Amoxicillin + Clarithromycin(or Levaquin) +/-

Metronidazole+ PPI (Prevpac®)

- Bismulth + TCN+ Metronidazole+PPI (Pylera®)

Bacterial Infection Treatment

Bacterial Vaginosis Metronidazole (Flagyl®) or vaginal gel (¼)

Gonorrhea Ceftriaxone (Rocephin®)* IM, cefixime

(Suprax®), Doxycycline

Chlamydia Azithromycin*, Doxycycline

Trichomonas Metronidazole (Flagyl®)

Syphilis PCN G IM, Doxycycline in pen allergic

Pelvic Inflammatory Disease

Ceftriaxone (Rocephin®)IM, + Metronidazole +

Doxycycline at least 14 day treatment

Diverticulitis

Ciprofloxacin (Levoflox or Moxiflox) +

Metronidazole

Anaerobic infections above the diaphragm Clindamycin (gram + anaerobes)

Anaerobic infections below the diaphragm Metronidazole (gram – anaerobes)

Common Viruses and Antiviral Agents

Virus Treatment

Cytomegalovirus

Cidofovir (Vistide®)

Ganciclovir (Cytovene®) *

Foscarnet (Foscavir®)*

Fomivirsen (Vitravene®)

Hepatitis B virus

Adefovir dipivoxil

Interferon alfa-2b (Intron A)*

Lamivudine (Epivir HBV) *

Hepatitis C virus

Interferon alfa-2b/ribavirin*

Pegylated interferon

Sofosbuvir (Sovaldi®)

Simeprevir (Olysio®)

Virus Treatment

Herpes simplex virus (HSV I, HSV II)

Acyclovir (Zovirax®) * po, topical

Famciclovir (Famvir®)

Valacyclovir (Valtrex®) *

Influenza A virus Amantadine (Symmetrel)

Rimantadine (Flumadine)

Influenza A and B virus Oseltamivir (Tamiflu®)*

Zanamivir (Relenza®)

Respiratory syncytial virus (RSV)

Ribavirin

Varicella-zoster virus (Shingles)

Acyclovir (Zovirax®)

Valacyclovir (Valtrex®)

Human Papillomavirus (HPV)

Imiquimod (Aldara®)

Common Fungal infections and Antifungal

Agents

Tinea corporis/cruris/pedis- clotrimazole (Lotrimin®), terbinafine

(Lamisil®) po/topical. Onychomycosis – Get PAS stain, terbinafine po

or efinaconazole (Jublia®)

Tinea capitis- Griseofulvin po 4-6 weeks, Topical treatment not

effective for capitis

Tinea (pityriasis) versicolor (Malassezia furfur)- Ketoconazole topical

or po*, candidiasis-nystatin topical, azoles (fluconazole), Intravaginal

(Miconazole)

Nystatin does not cover Tinea (‘ring worm’), only candida, PO ‘Azoles’

cover both. Fungi (Dermatophytes) that cause human ring worm do

not come from animals

Not every annular lesion is ring worm!

Medication Overdoses/Poison Exposures and Antidotes

Medication Antidotes

Acetaminophen N-Acetylcysteine (NAC)

Benzodiazepines Flumazenil* (Don’t Use!- causes seizures)

Digoxin Digoxin immune fab

Local Epinephrine Vasospasm Phentolamine

Heparin Protamine

Iron Deferoxamine

Methotrexate Leucovorin

Morphine (opiates) Naloxone (Narcan®)

Nitrogen mustard Sodium thiosulfate

Organophosphates Pralidoxime/2-PAM

Warfarin Phytonadione/vitamin K, FFP*

Crotalid Snakes (Rattlesnake, Water Moccasin

‘Cottonmouth’, Copperhead) Crotalidae polyvalent immune FAB (CroFab®)

Drugs That Can Cause Hepatic Failure/Hepatic toxicity

Acetaminophen*

Alcohol

Allopurinol

Carbamazepine*

Erythromycin (estolate salt)*

Flucytosine

Gancyclovir

Isoniazid

Ketoconazole*

Methotrexate

Niacin*

Oral contraceptives

Parenteral nutrition

Rifampin

Sulfonylureas

Valproate*

Drugs That Can Affect Renal Function/Nephrotoxity

Aminoglycosides*

Amphotericin B *

Cisplatin*

Contrast media * (CT iodinated contrast)

Cyclosporine

Foscarnet

Gold salts *

NSAIDs*

Pentamidine

Fluoroquinolones

Common Drugs ‘Safe’ in Pregnancy* Common Use

Beta Lactam abx (PCN’s, Cephalosporins) URI, OM, Sinusitis, Bronchitis, cellulitis (strep),

Methicillin Sensitive Staph Aureus (1/2)

1st generation antihistamines

Diphenhydramine (Benadryl®), Chlorpheniramine

(Chlor-Trimeton®)

Doxylamine* (some Uni-Som®, otc sleep aids)

Meclizine (Antivert®, OTC Dramamine II ®)

Promethazine (Phenergan®)**

2nd generation antihistamines (non sedating) Loratadine (Claritin®), Fexofenadine (Allegra®), Cetirizine (Zyrtec®) Pure antihistamine vs anticholinergic effects, allergies vs viral infections

Azithromycin URI, OM, Sinusitis, Pertussis, Chlamydia

Metronidazole (intravaginal for 1st trimester) po

ok 2nd and 3rd BV, Trichomonas, Diverticulitis

TMP/SMX (Bactrim DS®)* avoid use in 3rd

trimester Increases risk of kernicterus (brain damage from inc bilirubin- jaundice) MRSA, UTI’s

Nitrofurantoin (Macrobid®)* ok until 38 weeks

gestation UTI’s

Drugs That Can Cause Folic Acid Deficiency

Barbiturates

Methotrexate*

Oral contraceptives

Phenytoin

Primidone

Pyrimethamine*

Sulfasalazine

Trimethoprim (Hyperkalemia in high doses)

Drugs That Have Been Associated with

Immunologic (SLE – Like) Reaction

Ethosuximide (For absence seizures)

Hydralazine* (Rebound tachycardia if not on beta blocker, diltiazem or verapamil)

Isoniazid*

Methyldopa (Gold standard for HTN in pregnancy on boards)

Nitrofurantoin (rarely pulm fibrosis)

Penicillamine

Phenothiazines

Phenytoin

Procainamide

Quinidine

Sulfonamides

Tetracyclines

Drugs with notorious/common rxn Reaction

ACE Inhibitors- Lisinopril, enalapril,

ramipril, captopril Dry cough, angioedema*

Digoxin GI upset, halo w/ toxicity (around points of light)

PDE 5 inhibitors- sildenafil Blue tint to vision

Amlodipine (Norvasc®) Non pitting lower extremity edema

Diltiazem, Verapamil Slow conduction, HR. Verapamil- constipation

Anticholinergics Can’t see, can’t pee, can’t ____, can’t spit

Metoclopramide (Reglan®) Extrapyramidal sx (Can be permanent!)

Bupropion (Wellbutrin®) Seizures, avoid excessive ETOH

Tramadol (Ultram®), Linezolid

(Zyvox®) Serotonin syndrome combined with SSRIs, TCA’s- (theoretically)

Drugs with notorious/common rxn Reaction

Statins Myalgia

Metronidazole Disulfiram rxn c ETOH, metallic taste in mouth

Morphine Itching- Histamine release

Oxymetazoline (Afrin®)

Nasal phenylephrine (Neo-

Synephrine ®)

Rhinitis Medicamentosa (po toxicity in peds)

Phenazopyridine (Pyridium®) Orange/red urine, tears

Prednisone

- Inc WBC (Neutrophil demargination from endovascular lining, delayed migration into tissues, and inc bands released from bone marrow)

-Inc Blood glucose (mainly post prandial)

Medications That Should Not Be

Administered with Antacids/Ca++

Digoxin

Fluoroquinolones

Iron preparations*, sulfate, fumarate, gluconate

Isoniazid

Ketoconazole

Quinidine

Tetracyclines ie Doxycycline*

Drugs That Have Been Associated with

Hyperglycemia

Amiodarone

l-asparaginase

Epinephrine

Estrogens

Glucocorticoids* ie Prednisone

Lithium

Nicotinic acid

Oral contraceptives

Pentamidine

Phenytoin

Thyroid hormones

Drugs That Food Decreases Absorption

Ampicillin

Astemizole

Cefaclor

Didanosine

Digoxin (level 6˚after last dose)

Diltiazem

Etidronate

Furosemide

Indinavir

Isoniazid

Labetalol

Lansoprazole

Levodopa

Levothyroxine*

Lithium (level 12˚after PM dose)

Metoprolol

Penicillamine

Propranolol

Rifampin

Zafirlukast

Grapefruit Juice

Inhibition of CYP3A in small intestines

One whole grapefruit or 7oz juice (60ml Lime juice)

3 days for enzyme to recover

Only oral meds, Not Liver CYP3A

INCREASES drug levels

Amiodarone (50% inc AUC)

Colchicine (> 50% inc AUC)

CCB, Statins(ator, simva, lovastatin)

Oxycodone

3/4

Grapefruit,Orange, & Apple Juices

Inhibition of Organic Anion Transporting Poylpeptides (OATPs)

These transport some drugs into cells to increase absorption

Inhibition for 4 hours with only 1 fruit or 7oz juice

DECREASES drug levels

Levothyroxine (11% dec in absorption)

Ciprofloxacin (20% dec)

Fexofenadine (Allergra®) (40% dec)

Atenolol (40% dec)

Agents That Inhibit CYP-

450 Enzymes

Allopurinol

‘Azole’ antifungals*

Chloramphenicol

Cimetidine*

Disulfiram

Isoniazid

Metronidazole

Monoamine oxidase inhibitors

Oral antidiabetic agents

Warfarin

Agents That Induce CYP-450 Enzymes

Alcohol

Chloral hydrate

Chlordiazepoxide

Cortisone

Imipramine

Nicotine

Phenobarbital*

Phenytoin*

Prednisone

Rifampin*

Testosterone

Types of Drug-Drug, Drug-Food Interactions

Problems with absorption

Ca, Mg (divalent cations) with doxycycline, digoxin

Food inhibiting or increasing absorption

Levothyroxine-empty stomach Griseofulvin- with high fat meal

PPI’s decreasing acidic environment, decreased Ca, Fe, Mg absorption

Sucralfate (Carafate®) binding and barrier to absorption

CYP450 Liver Enzyme System

Azoles, cimetidine- broad inhibition

Phenobarbital, phenytoin, rifampin – broad inducers

Can inc or dec drug levels, keep pro drug from becoming active or increase production of active metabolite (codeine- CYP450 2D6)

CYP450 pharmacogenetic testing

Types of Drug-Drug, Drug-Food Interactions Cont

Protein Binding

Warfarin and SMX/TMP (Bactrim®)

Similar mechanism of action/therapeutic duplication

SSRI’s with TCAs and trazodone

Benzodiazepines with alcohol or any CNS depressing medication

Tramadol with SSRI’s (theoretically)

Amphetamine salts with bupropion and prednisone + pseudoephedrine

Drug Allergies

Drug Allergies – Ask rxn Allergy vs Adverse Drug

Reaction/Common Side Effect

True Allergy – Takes out whole drug (chemical) class

Adverse rxn – Just cannot use that specific drug

Document and categorize rxn and allergy vs adverse rxn in

EMR

PCN allergies

Low cross reactivity with cephalosporins <5%

Up to 70% of pts can loose their PCN allergy after 10 yrs*

Drug Allergies Continued

Sulfa Allergies

Sulfonylarylamines* (includes sulfa abx) 3% have true allergy

Avoid SMX/TMP, Sodium sulfacetamide, silver sulfadiazine

(Silvadene®), Sulfasalazine (Azulfidine®)

Nonsulfonylarylamines

Acetazolamide (Diamox®)*, Celecoxib (Celebrex®)*, Loop diuretics-

furosemide, torsemide, bumetamide, Thiazide diuretics- HCTZ*,

chlorthalidone*, Indapamide*, Sulfonylureas-glimepiride*, glyburide,

glipizide.

*Contraindication in U.S.package insert in one with true sulfonylarylamine

allergy

Metoprolol succinate (Toprol XL®) vs tartrate (Lopressor®) salt forms , q day vs bid

Doxycycline salt forms. Extended vs Immediate Release. DETAILS MATTER

Put indication in ‘sig’ (directions) field to be printed on label by the pharmacy. Also, can put

‘dose increase’ ‘dose decrease’, ‘replaces amlodipine’, etc. Avoids confusion from pharmacy

and pts. Can also put specialist/other prescribing/managing provider in sig field

Double check your MAs/Nurses entering medications in EMR. Have all new pt’s, established

complicated pts with multiple specialists, and transition of care pts bring in all medicine bottles

Most Medication errors occur with transitions of care!

Dr. Douglas’ Soap Box

Drugs To Avoid in Pregnancy

ACE Inhibitors/ARBs

Benzodiazepines

Ergotamine

Fluorouracil

Fluoroquinolones

Hormonal agents

Isotretinoin like agents,

Accutane

Methotrexate

Misoprostol

Paroxetine

Raloxifene

Statins

Tetracyclines - Doxycycline,

Minocycline

Thalidomide

Vitamin A palmitate

Warfarin

Common Drugs That Have Been Associated

with Photosensitivity Reactions

Amiodarone

Amitriptyline

Doxepine

Fluoxetine

Furosemide

Griseofulvin

Isotretinoin*

Ketoprofen

Naproxen

Oral contraceptives

Phenothiazines

(prochlorperazine, Compazine®)

Piroxicam

Sulfonamides*

TCN’s- Minocycline*,Doxycycline

Thiazides

Agents That Can Cause Pancreatitis

ETOH*

Azathioprine

Cimetidine

DPP-4 Inhibitors*

Dideoxyinosine (DDI)

Estrogens

Furosemide

Glucocorticoids

GLP-1 agonists

Mercaptopurine

Metronidazole

Parenteral nutrition

Ranitidine

Sulfonamides

Tetracyclines

Thiazides

Valproate