NAPLEX - Key Drug Guy

Drugs with Leaching Adsorption, Absorption issues with PVC containers

p110

Leach Absorbs To Take In Nutrients

Lorazepam

Amiodarone

Tacrolimus

Taxanes (most excluding paclitaxel + albumin bound Abraxane_

Insulin

Nitroglycerin

Common Drugs with Diluent Solution Requirements

- Saline (no dextrose)

p110

SALINE (no Dextrose)

A DIAbetic Can't Eat Pie

Ampicillin

Daptomycin (Cubicin)

Infliximab (Remicade)

Ampicillin/Sulbactam (Unasyn)

Caspofungin (Cancidas)

Ertapenem (Invanz)

Phenytoin (Dilantin)

Common Drugs with Diluent Solution Requirements

- Dextrose (no saline)

p110 D5W

BOAS will strangle the pharmacist who puts these drugs into anything but dextrose

Bactrim - SMX/TMP

Oxaliplatin

Amphotericin B (all)

Synercid - Quinupristin/Dalfopristin

Vesicants

Vasopressors (dopamine and NE)

Anthracyclines (doxorubicin)

Vinca alkaloids (vincristine, vinblastine)

examples of key drugs that have filter requirements

Key drugs guy p112

GAL PLAT (who's head is flat... ampules)

- Golimumab (Simponi)

- Amiodarone

- Lorazepam*

-Phenytoin*

- Lipids (1.2 micron)

- Amphotericin B lipid formulations (5 micron filter)

- Taxanes except docetaxel

- Isavuconazonium (azole)

*only when administered by continuous infusion, not for IV push

key drugs that do not require refrigeration (most IV drugs do though...) BUT NOT THESE

Key drugs guy p112

Dear Sweet Pharmacist, Freezing Makes Me Edgy!

- Dexmedetomidine (Precedex) *

- Sulfamethoxazole/Trimethoprim ( Bactrim)

- Phenytoin - crystallizes

- Furosemide - crystallizes*

- Metronidazole

- Moxifloxacin (Avelox)

- Enoxaparin (Lovenox)

*diluted precedex and furosemide can be kept cold

key drugs that require light-protection during administration

Key drugs guy p113

Protect Every Necessary Med from Daylight

- Phytonadione (vitamin K; Mephyton)

- Epoprostenol (Flolan) for Pulmonary HTN

- Nitroprusside (nitropress) - for acute HF

- Micafungin (Mycamine)

- Doxycycline

Hazardous Key Drugs

Key drugs guy p237

Antineoplastic Drugs (Chemotherapies)

Non-Antineoplastic Hazardous Drugs on NIOSH LIST

Aboritfacient

+ Misoprostol

Antibiotics

+ Chloramphenicol

+ Telavancin

Anticoagulants

+ Warfarin

Antifungals

+Fluconazole, Voriconazole

Antiretrovirals, HIV

+ Abacavir, Entecavir, Nevirapine, Zidovudine

Antivirals, Cytomegalovirus

+ Cidofovir, Ganciclovir, Valganciclovir

Acne

+ Isotretinoin

Arrhythmias

+ Dronedarone

Autoimune Conditions

+ Acitretin (psoriasis), Leflunomide, Teriflunomide

+ Fingolimod

+ Interferon Beta 1b

BPH

+ Dutasteride, Finasteride

Depression

+ Paroxetine

Diabetes

+ Exenatide

Dyslipidemia

+ Lomitapide

Seizures/Epilepsy

+ Clobazam, Clonazepam

+ Carbamazepine, Oxcarbazepine, Eslicarbazepine, Divalproex, Fosphenytoin, Phenytoin, Topiramate, Vigabatrin, Zonisamide

Gout

+ Colchicine

Heart Failure

+ Ivabradine, Spironolactone

Hepatitis

+ Ribavirin

Hormones

+ Androgens (testosterone)

+ Estrogens (estradiol)

+ Progesterones (medroxyprogesterone)

+ SERMS (Raloxifene)

+ Ulipristal

Hypercalcemia of Malignancy

+ Pamidronate

+ Zoledronic Acid (& Osteoporosis)

Hyperthyroidism

+ Methimazole, Propylthiouracil

Insomnia

+ Temazepam

+ Triazolam

Migraine

+ Dihydroergotamine

Parkinson Disease

+ Apomorphine, Rasagiline

PAH

+ Ambrisentan, Bosentan, Macitentan, Riociguat

Renal Disease

+ Darbepoetin alpha (increase RBC count)

Schizophrenia

+ Ziprasidone

Transplant

+ Azathioprine, Cyclosporine, Mycophenolate, Tacrolimus, Sirolimus

micro/macrovascular complications of diabetes

Studytip gal p627

1. micro = retinopathy, nephropathy, neuropathy, autonomic neuropathy (erectile dysfunction, UTI, bladder control loss, gastroporesis)

2. atherosclerosis (ASCVD), hypertension, heart disease, stroke, CVA/stroke, PAD increases amputation

Other conditions

- Depression

- Acutely very high BG = DKA (mostly in T1DM) and HHS (mostly in T2DM)

Diagnosis of

Prediabetes and Diabetes

Treatment goals

Not pregnant, Pregnant

p628 Study Tip Gal

Pre-diabetes:

FPG 100-125 mg/dL,

2-hr PG 140-199, or

A1C 5.7-6.4

Diabetes :

FPG > 126 mg/dL,

2 hour PG: > 200 mg/dL,

A1C > 6.5

require two abnormal test.

FPG= no food for 8hrs

What key drugs cause Kidney Disease?

Key Drug Guy p300

+ Aminoglycosides (Tobramycin, Amikacin, Neomycin, Gentamycin, Streptomycin - TANGS)

+ Amphotericin B

+ Cisplatin

+ Cyclosporine

+ Loop diuretics (ie: Lasix-furosemide)

+ NSAIDs

+ Polymyxins (Colistin, Polymyxin B, depolarizing Daptomycin)

+ Radiographic contrast dye*

+ Tacrolimus

+ Vancomycin

Select Drugs that Require Decrease Dose or Increase Interval in CKD?

Key Drug Guy p302

Anti-lnfectives

+ Aminoglycosides (increase dosing interval primarily - cause nephrotoxicity so give Extended interval)

+ Beta-lactam antibiotics (most, except antistaphylococcal, these are time dependent so increase dose/interval risk of seizure)

+ Fluconazole

+ Quinolones (except moxifloxacin, not cleared through kidney) - risk of seizure

+ Vancomycin (nephrotoxic)

Cardiovascular Drugs - BLEEDING RISK

+ LMWHs (enoxaparin)

+ Rivaroxaban* (for AFib)

+ Apixaban* (for AFib)

+ Dabigatran* (for AFib)

+ Fondaparinux?

Gastrointestinal Drugs

+ H2RAs (famotidine, ranitidine) - CNS effects, thrombocytopenia

+ Metoclopramide - EPS, Parkinson's like sx

Other

+ Bisphosphonates*

+ Lithium (100% excreted in kidney, can be toxic)

Select Drugs that are C/I n CKD

Key Drug Guy p302

CrCl < 60 mL/min

+ Nitrofurantoin

CrCl < 50 mL/min

+ Tenofovir disoproxil fumarate (TDF) containing products (e.g., Stribild*, Complera, Atripla, Symfi, Symfi Lo)

*Stribild is C/I for a patient already on drug but CrCl falls <50, C/I to START NEW at CrCl of <70

+ Voriconazole IV (due to the vehicle)

CrCl < 30 mL/min

+ Tenofovir alafenamide (TAF) containing products (e.g., Genvoya, Biktarvy, Descovy, Odefsey, Symtuza) --> TDF products better

+ NSAIDs

+ Dabigatran* (DVT/PE)

+ Rivaroxaban* (DVT/PE)

+ Fondaparinux????

GFR <30 mL/min/1.73 m2

+ SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin)

+ Metformin

Other***

Mepiridine

Key drugs that raise potassium levels

Key Drug Guy p306

RAAS

+ ACE inhibitors/ARBS

+ Aldosterone receptor antagonists (aldosterone, eplerenone)

+ Aliskiren (direct renin inhibitor)

+ Canagliflozin (SGLT-2i - )

+ Drospirenone-containing COCs (Yaz)

+ Sulfamethoxazole/ trimethoprim (Bactrim tx pneumocystis pneumonia)

+ Transplant drugs (cyclosporine, everolimus, tacrolimus)

Which key drugs cause liver damage?

Key Drug Guy p 317

+ Acetaminophen (high doses, acute or chronic)

+ Isoniazid

+ Ketoconazole (oral)

+ Methotrexate

+ Nefazodone

+ Nevirapine

+ NRTIs (TDF/Viread, TDA/Vemlidy, Entecavir/Baraclude, Lamivudine/Epivir HPB)

+ Propylthiouracil

+ Tipranavir

+ Valproic acid

Live Vaccines

Key Drug Guy p326

COZY IV RM

Cholera

Oral Typhoid

Zoster (Zostavax)

Yellow Fever

Intranasal Influenza

Varicella

Rotavirus

MMR

Remember these are CI in immunocompromised or pregnant patients

Timing and Spacing of Vaccines

Study Tip Gal p327

General Rules for All Vaccines

+ Vaccines can usually be given on same day (exception - Prevnar 13 and Menacta meningitis separate by 4 weeks)

+ Multiple live vaccines can be given on the same day (if not givn on same day then seperate by 4 weeks)

+ In series > 1 dose, intervals can be extended

Simultaneous administration - usually okay

+ Both live and inactivated (same day for live or seperate by 4 weeks)

Vaccines given in a series

+ Extending interval delays protection

+ Do not decrease the interval

Live vaccines and antibody

+ Antibodies interfere with live vaccine replication

Live vaccines and TB skin test (TST or PPD test)

+ Live vaccine can cause a false negative TST result

+ Give the live vaccine on the same day as skin test OR

+ Wait 4 weeks after live vaccine to perform skin test

Live Vaccines and Antibody

+ MMR and varicella containing vaccines (not zoster) require separation from antibody containing products (blood transfusions, IVIG).

+ Spacing: Vaccine --> 2 weeks --> antibody containing product OR

+ Spaciing: Antibody containing product --> 3 months or longer --> Vaccine

+ Simultaneous vacccine + antibody is recommended in post=exposure of certain diseases (Hep A and B, rabies, and tetanus)

Background on Travel Vaccines

Key Drug Guy p344

Inactivated Vaccines

+ Hepatitis A

+ Hepatitis B

+ Hepatitis A/B

+ Japanese encephalitis

+ Meningococcus

+ Polio

+ Typhoid-IM

Live Vaccines

+ Cholera-PO

+ Typhoid PO

+ Yellow Fever-SC

Cholera and Typhoid are both PO

What are common resistant pathogens?

Study Tip Gal p 355

+ Klebsiella pneumoniae (ESBL, CRE)

+ Escherichia coli, (ESBL, CRE)

+ Acinetobacter baumannii

+ Enterococcus faecalis / Enterococcus faecium (VRE)

+ Staphylococcus aureus (MRSA)

+ Pseudomonas aeruginosa

Remember: Kill Each And Every Strong Pathogen

ESBL = extended-spectrum beta-lactamase

CRE= carbapenem-resistant Enterobacteriaceae

VRE= vancomycin-resistant Enterococcus

ESBL usually needs CARBAPENEM

CRE - needs polymixins

Antibiotic Mechanism of Action

1. Cell Wall Inhibitors

=

+ Beta lactams (penicillins, cephalasporins, carbapenems)

+ Monobactams (Aztreonam)

+ Vancymycin, dalbavancin, televancin, oritavancin

2. Protein Synthesis Inhibitors

+ Aminoglycosides

+ Macrolides

+ Tetracyclines

+ Clindamycin

+ Linezolid, tedizolid

+ Quinupristin/Dalfopristin

3. Folic Acid Synthesis Inhibitors

+ Sulfonamides

+ Trimethoprim (added with sulfamethoxazole to overcome resistance = Bactrim)

+ Dapsone

4. Cell Membrane Inhibitors

+ Polymiyxins

+ Daptomycin

+ telavancin

+ Oritavancin

5. DNA/RNA Inhibitors

+ Quinolones (DNA gyrase, topoiomerase IV)

+ Metronidazole, trinidazole

+ Rifampin

Key Feature of Penicillins

Study Tip Gal p359

Class effects

+ All pnc should be avoided in patients with beta-lactam allergy

+ All PNC increase the risk of seizures if accumulation occurs (eg renal failure)

Outpatient (PO)

1. Penicillin VK

+ A first-line treatment for strep throat and mild nonpurulent skin infections (no abscess)

+ Strep throat, mild skin infections

2. Amoxicillin

+ Treats otitis media, infective endocarditis ppx, h. pylori

+ First line treatment for acute otitis media (80-90 mg/kg/day)

+ Drug of choice for infective endocarditis prophylaxis before dental procedure (2 g PO x1, 30-60 min before procedure)

+ Used in H.pylori treatment + PPI

3. Amoxicillin/Clavulanate (Augmentin)

+ First line treatment for acute otitis media (90 mg/kg/day) and for sinus infections (if an antibiotic is indicated)

+ Use the lowest dose of clavulanate to decrease diarrhea

4. Dicloxacillin and Oxacillin

+ Cover MSSA only (no MRSA)

+ No renal dose adjustment needed

Inpatient (Parenteral)

1. Penicillin G Benzathine (Bicillin L-A)

+ Drug of choice for syphilis (2.3 milliion units IM x1)

+ Not for IV use, can cause death - lipid emmulsion

2. Nafcilllin

+ See dicloxacillin and oxacillin above

No renal adjustment and covers MSSA only

3. Piperacillin/Tazobactam (Zosyn)

+ Only PCN active against Pseudomonas

+ Extended infusions (4 hours) can be used to maximize T > MIC

Penicillin Safety and side effects

p358

Penicillin V Potassium - PO

Penicllinin G Benzathine (Bacillinn L=A) - IM

Amoxicillin = Po, chewable, suspension

Augmentin (amox/clav) = Po, chewable, suspension

Ampicillin: injection (dilute in NS only)

Ampcillin/sulbactam (Unasyn): Injection (dilute in NS only)

Zosyn - Injection, prolonged or extened infusion over 4 hours

Nafcillin, Oxacillin - Injection

Dicloxacillin - PO

Boxed warning

+ Penicllin G benzathine - not for IV use

Contraindications

+ Severe renal impairment CrCl < 30 mL/min; do not use extended release oral forms of amoxicilllin and augmentin or 875 mg strength of Augmentin

SE:

+ Seizures (with accumulation - ie renal), GI upset, diarrhea, rash (SJS/TEN)

Notes

+ Aminopenicillins: IV ampicillin and Unasyn must be diluted in NS only

+ Antistaphylococcal Penicillins = preferred for MSSA soft tissue, bone/joint, endocarditis, and BSI

+ No renal adjustment

+ Nafcillin is a veiscant = If extravasation occurs use cold packs and hyaluronidase injections

DDI

+ Probenecid can increase levels of beta-lactams

Which abx only work with NS

Ampicillin (w/wo sulbactam Unasyn), ertapenem

Study Tip Cephalasporins

And Safety

p360

Study Tip Gal p361

Contraindications

+ Ceftriaxone: Neonates - cause biliary sludging, kernicterus (brain damage from bilirubin levels); concurrent use w/ Calcium containing IV products in neonates < 28 days old

Warnings

+ Cross sensitivity (10%) with PCN allergy - do not use in patients who have type 1 PCN allergy (agnioedema, anaphylaxis)

+ Cefotetan (Cefotan) contains a side chain --> increase risk of bleeding and cause disulfiram-like reaction

SE

+ Seizures (with accumulation), GI upset, diarrhea, rash (SAME AS PCN)

Notes

+ Ceftriaxone - no renal adjustment

+ Cefixime available as chewable tablet (3rd gen)

+ Ceftazidime/avibactam: covers some carbapenem resistant enterobaceriacae (CRE)

DDI

+ Cefpodoxime, Cefuroxime + drugs that decrease stomach acids should be separated from short-acting antacids. Avoid H2RAs and PPIs

Outpatient (PO)

1. 1st Generation: Cephalexin (Keflex)

+ Strep throat, MSSA skin infections

+ Keflex PO 250-500 mg Q6-12H

2. 2nd Generation, Cefuroxime

+ Acute otitis media, CAP, sinus infections (if abx indicated)

3. 3rd generation: Cefdinir

+ CAP, sinus infections (if abx indicated)

Inpatient (Parenteral)

1. 1st Generation: Cefazolin

+ Surgical prophylaxis

2. 2nd generation: Cefotetan, Cefoxitin

+ Surgical prophylaxis (GI procedures - colorectal)

+ Anaerobic coverage - b.fragilis

+ Cefototetan: disulfiram like reaction with alcohol = bleeding

3. 3rd Generation: Ceftriaxone and Cefotaxime

+ CAP, meningitis, SBP, pyelonephritis

+ Ceftriaxone: No renal adjustment, do not use in neonates 0-28 days old (biliary sludge)

4. Ceftazidime (3rd generation), Cefepime (4th Gen)

+ Pseudomonas

5. 5th Generation: Ceftaroline (Teflaro)

+ only beta lactam active against MRSA

6. Ceftolozane/Tazobactam and Ceftazidime/Avibactam (3rd gen)

+ used for MDR Gram negative organisms (Including pseudomonas)

dose: keflex

Cephalexin (Keflex)

PO 250-500 mg Q6-12 H

MSSA skin infections, strep throat

p360

Carbapenems

Safety

Study Tip Gal p363

Reserved for MDR Gram negative infection

+ They are active against most Gram + and gram neagative (including ESBL-producing bacteria) and anaerobic pathogens

+ No coverage of atypical pathogens, MRSA, VRE, Cdif, and stenotrophomonas

Drugs

Doripenem

Imipenem

Meropenem (Merrem)

Ertapenem (Invanz)

CI

+ Anaphylactic rx to beta lactam antibiotics

Warning

+ Do not use in patients with PCN allergy

+ CNS AEs - seizures

SE

+ Diarrhea, rash, seizures with high doses (like PCN)

Notes

+ Imipenem is combined with cilastatin to prevent drug degredation

+ Ertapenem has no coverage of Pseudomona, Acinobacter, or Enterococcus (PEA)

Class Effects

+ ESBL-producing organisms (extended beta lac)

+ All except Ertapemen cover Pseudomonas

+ Do not use with penicillin allergy

+ Seizure risk (higher doses, renal failure, or use of imipenem)

+ All are IV only, MUST USE normal saline NS for Ertapenem

DO NOT COVER

+ Atypicals, VRE, MRSA, Cdif

+ ErtAPenem does not cover PEA (Pseudomonas, Acinobacter, or Enterococcus)

Common uses

+ Polymicrobial infections (moderate-severe diabetic food infection)

+ Empiric therapy when resistant organisms suspected, MDR

+ Resistant Pseudomonas or Acinobacter infection (except ertapenem)

ABX antibiotic Spectrum of Activity Summary

p 363

Beta lactam that cover pseudomonas

+ Cefepime

+ Ceftazidime

+ Aztreonam

+ Carbapenems (imipenem, doripenem, meropenem only Not ertapenem)

+ Ceftazidime/Avibactam and Ceftolozane/Tazobactam

Coverage of Aminoglycoside

What are the two dosing strategies of aminoglycosides?

Monitoring

Study tip gal p364

Coverage

+ Gram negatives, including pseudomonas

+ Synergy for Gram-positives (staphyloccci/Enterococci)

Dosing Strategy

1. Traditional - use lower doses more frequently (q8h if renal function normal)

= Trying to get peaks and troughs

2. Extended interval dosing uses higher doses (to attain higher peaks) less frequently (Q24 hr)

= Draw a random level and use nomogram

= Less accumulation = less nephrotoxicity and decrease cost

Monitoring

+ Renal function, serum levels

Study Tip Gal

Pros

+ Kills gram negatives, synergistic with beta=lactams for gram positive infections, low resistance and cost

Cons

+ Highly toxic - renal toxicity and ototoxicity (require monitoring)

Smart Idea

+ Concentration dependent killing (Cmax:MIC) --> give larger doses less frequently -- gives kidneys time to recover between doses

High peak, low trough

Coverage of Aminoglycoside

What are the two dosing strategies of aminoglycosides?

Monitoring

Study tip gal p364

Drugs - All are basically IV and IM

Gentamicin

Tobramycin

Amikacin

Dosing

+ If underweight ( 60 mL/min = q8h (all)

Trough: 30 min before 4th dose (<2 mcg/mL)

Peak: 30 minutes after end of 30 min drug infusion of 4th dose (5-10 mcg/mL)

Tobramycin/Gentamicin

Extended interval dosing: 4-7 mg/kg/dose

Draw random level

Aminoglycosides

Monitor: drug levels, renal function, hearing

Boxed warning - nephrotoxicity, ototoxicity

Caution in elderly, impaired renal function, taking other nephrotoxic drugs (amphotericin B, cisplatin, polymyxins, cyclosporin, loop diuretics, NSAIDs, Radiocontrast dye, vancomycin, tacrolimus

Trough of Gentamicin and tobramycin

< 2 mcg/mL

That is what causes the toxicity so want to know this!!!

If higher than want to hold the dose and give dose less frequently

So traditional dosing is q8h if CrCl > 60

Aminoglycosides

Safety

Drugs that increase LDL AND TG

+ Diuretics (loop, thiazides)

+ Steroids

+ Efavarienz (HIV tx)

+ Immunosuppresants (cyclosporine, tacrolimus)

+ Atypical antipsycotics (ie: Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole)

+ Protease inhibitors (-navir)

Increase LDL Only

+ Fish oils (except Vascepa)

Increase TG Only

+ Propofol

+ IV Lipid emulsions

+ Clevidipine (DHP CCB)

+ Bile Acid Sequestrants (Colesevelam - Welchol, Cholestyramine)

Conditions

+ Obesity

+ Poor Diet

+ Hypothyroidism

+ Alcoholism

+ Smoking

+ Diabetes

+ Renal/liver disease

+ Nephrotic syndrome

Quinolones Safety

Study Tip Gal p 367

Ciprofloxacin (Cipro)

+ dexamethasone (Ciprodex)

Levofloxacin (Levaquin)

Moxifloxacin (Avelox)

Ofloxacin (Ocuflox)

Concentration dependent kill

Gemifloxacin, Levofloxacin, and Moxifloxacin are respiratory quinolones - enhanced coverage of S pneumoniae and atypical coverage

+ (My Good Lungs) = Moxifloxacin (Avelox), Gemifloxacin, Levofloxacin (Levaquin)

+ Ciprofloxacin (Cipro) + Levofloxacin = enhanced gram negative & Pseudomonas coverage

+ Moxifloxacin = enhanced gram positive, anaerobic coverage. Moxi is the ONLY FQ CANNOT be used in UTI

+ Delafloxacin - MRSA activity, other

Boxed warnings

+ Tendon rupture (Achilles)

+ Peripheral neuropathy (long lasting)

+ CNS effects (including seizures)

+ Use last-line (only if no alternatives)

Warnings (MANY!)

+ QT prolongation

+ Hypo and hyperglycemia

+ Psychiatric disturbances (agitation, disorientation, delirirum, etc)

+ Photosensitivity

+ Avoid use in children and pregnancy/breastfeeding - musculoskeletal toxicity

Interaction

+ Chelation with divalent cations

Boxed warning

+ Tendon inflammation and/or rupture

+ Peripheral neuropathy

+ CNS - seizures

+ Caution in patients with CNS disorders or drugs that cause seizures

+ Caution in elderly

Notes

+ Cipro PO suspension - shake before use. DO NOT put through NG or other feeding tube (oil-based)

+ Moxifloxacin cannot reach urine - don't use in UTIs

DDI

+ Lanthanum and sevelamer (Renvela) dereases PO quinolone concentration

+ Caution in CVD because lower K and Mg and other QT prolonging drugs

+ Antacids and other polyvalent cations (Mg, aluminum, Ca, Fe, Zn) - can chelate and inhibit quinolone absorption

Macrolides

Study Tip gal p368

50S ribosomal subunit - RNA inhibitor

Coverage: atypicals, community-acquired respiratory tract infections, STIs - chlamydia, gonorrhea

Agents

+ Azithromycin (Zithromax, Z-Pak)

Z-pak: 500 mg on day 1 then 250 mg on days 2-5

Tri-pak: 500 mg daily for 4 days

+ Clarithromycin (Biaxin)

+ Erythromycin (E.E.S., Ery-Tab, Erythrocin)

Coverage

+ Atypical pathogens (Legionella, Chlamydia, Mycoplasma, Mycobacterium avium)

+ H. influenzae (respiratory)

+ S pneumonia (resp track)

Common Uses

+ CAP, Strep throat

+ Azithromycin: COPD exacerbation, chlamydia, gonorrhea, MAC prophylaxis

+ Clarithromycin: H. pylori (GERD)

+ Erythromycin: increases gastric motility

Safety Issues

+ QT prolongation

+ Drug interactions: clarithromycin/erythromycin CI with simvastatin/lovastatin = Strong 3A4 Inhibitors

+ Azithromycin is minor substrate = less clinically significant drug interactions

+ Hepatotoicty

+ CAD + Clarithromycin = mortality higher in 2+ weeks of treatment

SE:

+ GI Upset

Tetracycline

Study Tip Gal 369

30S ribosomal subunit protein synthesis inhibition

Cover atypicals*

Agents in Class

+ Doxycycline (Vibramycin)

+ Minocycline (Minocin, Solodyn)

+ Tetracycline

Coverage

+ S. aureus (including CA-MRSA)

+ H influ + S. pneumo

+ Richettsiae (Lyme disease, rocky mountain)

+ H. pylor

+ VRE

Doxycyciline

+ No dose adjustment in renal impairment

Common uses

+ Ca-MRSA skin infections, acne

+ Doxycycline: tick-borne infections, CAP, COPD exacerbations, sinusitis, VRE UTI, chlamydia, gonorrhea

+ Tetracycline: H. pylori treatment

Warning

+ Children < 8 years old, pregnancy, breastfeeding

+ Photosensitivity

+ Minocycline = DILE

Notes

+ IV:PO ratio is 1:1 (doxy and minocycline)

+ Doxycycline sit upright for at least 30 minutes after taking to avoid esophageal irritation

DDI

+ Antacids - polyvalent cations (Mg, Al, ), sucralfate, bismuth subsalicylate, bile acid resins can chelate and inhibit tetracycline absorption

Sulfonamides Safety

Study Tip Gal 370

Inhibition of bolic acid pathway

Covers Shingella, Salmonella, Stenotrophomonas, opportunistic pathogs (Penumocytis PCP pneumonia, Toxoplasmosis)

Sulfamethoxazole/trimethoprim (Bactrim)

+ dose based on TMP = 5:1 SMX:TMP ration, SS = 80 mg TMP, DS = 160 mg TMP

+ Uncomplicated UTI = 1 DS PO BID x3 days

Do not use if sulfa allergy, pregnant or breastfeeding

Warnings

+ Skin reactions (including SJS/TEN)

+ TTP

+ G6PD deficiency

Side effects

+ Photosensitivity, Increase K, hemolytic anemia (positive Coombs test), crystalluria, rash risk, take with water 8oz

Interactions

+ CYP2C9 - increase INR with warfarin

+ Levels of bactrim can be lowered by CYP2C9 inducers

Vancomycin

Study Tip Gal 370

Vancomycin (Vancocin)

Inhibits bacterial cell wall synthesis binding to D-Ala-D-Ala

Good for MRSA, Cdif (PO route)

First line tx treatment for MRSA infections

Consider alternative drugs when MRSA MIC > 2mcg/mL

Dosing

IV Systemic infections: 15-20 mg/kg Q8-12H

--> TBW

CrCl 20-49 = Q24h

Cdif PO only

PO: 125-500 mg QID x 10 days

Warnings

+ Ototoxicity, nephrotoxicity

+ PO only for C.dif, not for systemic infections

+ Infusion rxn = red man syndrome in rapid infusion

Monitoring

+ Renal Function SCr, AUC/MIC ratio or trough

+ Serious MRSA infections - target AUC/MIC ratio of 400-600 or goal trough of 15-20 mcg.mL

Monitor SCr and avoid other nephrotoxic and ototoxic drugs

DDI

+ Increased nephrotoxicity with other nephrotoxic drugs (aminoglycosides, amphotericin B, cisplatin, cyclsporin, Vancomycin, tacrolimus, Radiocontrast dye, polymixins , nsaids, loop diuretics)

+ Ototoxic drugs - Aminoglycosides, cisplatin, loop diuretics, Asa (tinnitus)

Lipoglycopeptides

Study Tip Gal p371

Telavancin, oritavancin, dalbavancin

Work on the D-alanyl-D-alanine

Coverage: Similar to IV vanco

Approved for skin infections (SSTI)

- Televanced approved for HAP/VAP

Can ALL CAUSE RED MAN SYNDROME

Oritavancin and dalbavancin are single-dose regimens (stay in system for long time)

Boxed warning

+ Televancin: Fetal risk; nephrotoxicity, increased mortality compared to vanco in pneumonia in patients with CrCl < 50 mL/min

Contraindications

+ Televancin concurrent use of IV UFH, falst aPTT/PR/INR

+ Oritavancin: Use of IV UFH for 5 days after --> can falsely increase PT/INR for up to 12 hours and aPTT for up to 5 days

SE:

+ Infusion reaction (red man syndrome)

Notes

+ Dalbavancin, Oritavancin = singledose regimen for both, have long half life

Daptomycin

Study Tip Gal p372

Daptomycin (Cubicin, Cubicin RF)

Concentration-dependent killing --> MRSA, VRE

Tx SSTIs, blood stream infections, endocarditis

DO NOT USE TO TREAT PNEUMONIA (inactivated by lung)

D for no dextrose in Dapto

Warnings

+ Myopathy and rhabdomyolysis (ie think statins or renal impairment)

+ Can falsely Increase PT/INR

SE

+ Increase CPK

Monitoring

+ CPK levels weekly

Notes

+ Cubicin: compatible with NS or LR

CUbicin RF: Compatibly with NS (no dextrose)

Oxazolidinones

50S subunit inhibitor of protein synthesis

Drug: Linezolid (Zyvox), Tedizolid

Coverage: Similar to vanco - plus VRE

Linezolid approved for SSTI, VRE infections, pneumonia, BSI

Tedizolid only SSTI

No dose adjustment in renal impairment (unlike vanco)

IV:PO ratio is 1:1

CI

+ Do not use with or within 2 weeks of MAO inhibitors

Warnings:

+ Duration related myelosuppression (thrombocytopenia)

+ Optic neuropathy

+ Serotonin syndrome

+ Hypoglycemia

SE

+ Decrease plts

Notes

+ Do not shake

Interactions

+ Linezolid and tedizolid are reversible monoamine oxidase inhibitors

+ Caution with serotenergic drugs (SSRIs, SNRIs, TCAs, meperidine, buspirone)

+ Avoid tyramine containing foods and serotonergic drugs (aged, pickled, smoked)

Quinupristin/Dalfopristin (Synercid)

p373

Coverage: Gram positive organisms --> MRSA, VRE (e faecium)

Indications: SSTIs

Poorly tolerated: arthralgyias/myalgias, infusion reactions, hyperbilirubinemia, phlebitis (Administer via CENTRAL LINE - PICC)

Compatible with D5W only

Clindamycin (Cleocin)

Binds to 50S subunit

COVERS ANAEROBES and Gram Positive Bacteria (INCLUDING CA-MRSA)

Formulations: Injection, topical

Topical (Cleocin-T, Clindagel)

No dose adjustment in renal impairment

Boxed warning

Cdif

SE

+ N/V/D

Notes

+ An induction test (D-test) should be performed on S. aureus that is susceptible to clindamycin but not erythromyci ( a flattened zone indicated inducibile clindamycin resistance - positive = DO NOT USE Clinda)

USE: Purulent and non-purulent skin infections, beta-lactam alternative for dental abscesses

Metronidazole (Flagyl), Tinidazole

Coverage: anaerobic and protozoal infections

Use: bacterial vaginosis, trichomoniasis, intra-abdominal infections

Multiple formulations (topical, vaginal)

IV:PO = 1:1

CI

+ Pregnancy

+ Alcohol (disulfiram reaction)

SE

+ metallic taste

+ Increases INR with Warfarin

Secnidzole - single dose PO f

+ SE vulvovaginal candidiasis

Tinidazole same as flagyl

DDI

+ Flagyl should not be used with alcohol (during or for 3 days after dc = dt disulfiram like reaction (abdominal cramping, N/V, headaches and flushing

+ Flagyl and tinidazole can increase INR

ABX urinary agents

Study Tip Gal p377

Fosfomycin

+ E. coli (including ESBL-producing organisms), E. faecalis (including VRE)

+ Single dose regimen for uncomplicated UTI (cystitis only)

Nitrofurantoin (Macrobid, Macrodantin)

+ Common dosing regimen = Macrobid 100 mg BID x5 days, Macrodantin is QID

+ Warnings

- Avoid in G6PD deficiency

- Can cause hemolytic anemia (positive coombs test)

+ CI: Renal impairment CrCl < 60 mL/min

Warning: hemolytic anemia (caution in G6PD deficient patients)

+ SE: GI upset (take with food), brown urine discoloration (harmless)

Which meds can interfere with coagulation laboratory assays?

lipoglycopeptides (oritavancin, Televancin)

Flagyl

Daptomycin

all effect INR or aPTT

The Following Drugs Outdue --> INR/aPTT

*Bactrim significantly interacts with warfarin and truly increases INR but DOES NOT falsely elevate

Lipoglycopeptides and UFH are CI within 120 hours/5 days of oritavancin false elevation of aPTT

Daptymycin and televancin falsely increase PT/INR

Drugs that increase warfarin INR

+ MAT =

M = Metronidazole, macrolides,

A = Amiodarone, azoles

T = TMP/SMX (FQs, amoxicillin, tetracycline, tigercycline)

Storage requirements: Liquid oral abx

IV antibiotics

Most oral liquid abx in beta lactam category will require refrigeration

Ex: Penicillin VK, Ampicillin, Amoxicillin/Clav (Augmentin)

Exception: Cefdinir (Omnicef - 3rd gen ceph)

Non=beta lactams monly not frigerated (FQs, azoles, nystatin, linezolidl clindamycin, doxycycline, azithromycin, clarithromyciN)

IV ABX

DO not Refrigerate

+ Flagyl (metronidazole)

+ Moxifloxacin (Avelox)

+ Bactrim Sulfameth/trim

Drug Laboratory Interactions

G6PD deficiency - leads to hemolysis, bleeding

+ Chloroquine

+ Dapsone

+ Nitrofurantoin

+ Primaquine

+ Probenecid

+ Sulfamethoxazole, Bactrim

Coombs test, positive = dc drug -> hemolysis occurred, hemolytic anemia

+ Beta-lactamase inhibitors (clavulanate, tazobactam - augmentin, zosyn)

+ Cephlasporins

+ Isoniazid

+ Nitrofurantoin

+ Pencillins

+ Quinine

+ Rifampin

+ Sulfamethoxazole, Batrim

Drug Induced Lupus (DILE) - d/c drug, damages joints

+ Isoniazid

+ Minocycline

+ Terbinafine

False-positive urine glucose test

+ Penicillins

+ Cephlasporins

+ Imipenem

+ Isoniazid

ID 2

Bronchitis Treatment

Acute Bacterial Exacerbation of chronic Bronchitis (ABECB)

want to cover Bordetella pertussis (whooping cough)

Abx not recommended unless pneumonia is present - exception is Bordetella pertusis -->

Tx: macrolide (azithromycin, clarithromycin) or Bactrim

Chronic Bronchitis ABEcb - COPD

+ Supportive tratment (O2, short acting inhaled bronchodilators, IV or PO steroids)

Use Abx for 5-7 days if

+ Increased dyspnea, increased sputum volume, increased sputum purulence

+ Or if mechanically ventilated

+ ABX: Augmentin, or azithromycin, or doxycycline

ID 2 CAP treatment

Outpatient

Empiric treatment depends on 2 categories

Look at comorbidities: chronic heart, lung, liver or renal disease; DM, alcoholism, malignancy, asplenia

1. Category 1: no comorbidities (choose 1)

+ Amoxicillin high dose (1 g TID)

+ Doxycyclin

+ Macrolide (Azithromycin or clarithro)

2. Category 2: Has comorbidities

+ Beta lactam* + Macrolide or Doxycycline

+ Respiritory quinolone monotherapy (MGL)

* Beta lactam (Augmentin, cephalosporin - cefininir, cefuoxime, cefpodoxime)

---- See if patient needs MRSA or pseudomonas coverage (isolation respiratory, hospitalization in past 90 days)

+ Pseudomonas risk = Zosyn, cefepime, or meropenem + Levofloxacin or aminoglycoside and azithromycin

+ MRSA risk = Vanco, linezolid

ID 2

CAP Inpatient Treatment

1. Non-severe (similar to outpatient w/ comorbidities)

+ Beta lactam + Macrolide or doxycycline

+ OR Respiratory quinolone monotherapy (MGL)

2. Severe (typically ICU care required):

+ Beta-lactam + Respiratory quinolone (DO NOT USE MONOTHERAPY Quinolone)

+ OR Beta-lactam + Macrolide

*Beta-lactam preferred: ceftriaxone, cefotaxime, Augmentine

Risk factors for Pseudomonas or MRSA

+ MRSA: - Add vanco or linezolid

+ Psuedomons: Add Zosyn, cefepime, ceftazidime, imipenem, meropenem, aztreonam

ID 2

HAP and VAP

HAP has onset > 48 hours after hospital admission

VAP > 48 hours after start of mechanical ventilation

Pathogens: nosocomial pathogens - MRSA and MDR gram neg rod risk (P. aeruginosa, Acinetobacter, Enterobacter = Pseudomonas, CAPES)

Empiric Treatment

1 drug if low risk for MRSA or MDR pathogen

+ Cefepime or Zosyn or meropenem

Choose 2 drugs - one for MRSA one for Pseudomonas if risk for MRSA but low risk for MDR pathogen

+ Cefepime + Vanoc

+ Meropenem + Linezolid

Choose 3 abx one for MRSA 2 for pseudomonas if risk for both MRSA and MDR pathogen (IV abx w/in 90 days)

+ Zosyn + Ciprofloxacin_ vanco

+ Cefepime + Gentamicin + LInezolid

Risk for MRSA or MRDR pathogens

+ Positive MRSA nasal swab

+ High prevalence of resitant pathogen noted in hospital unitl

+ ABX IV use within past 90 days

ABX for PSueodomonas (do not use 2 beta lactams together0

+ Zosyn

+ Cefepime, ceftazidime, or ceftolozane/tazobactam

+ Levofloxacin or ciprofloxacin

+ Imipenem/cilastatin or meropenem

+ Tobramycin, gentamycin or amikacin (use with another agent!)

+ Colistimethate or polymixin B (use with another agent)

MRSA abx

+ Vanco or linezolid

TB

RIPE intensive phase = 2 months

Continuoation phase x4 months = INH + Rif

Infective Endocarditis

Gentamicin used for synergy

+ Peak 3-4 mcg/mL

+ Trough <1 mcg/mL

Treatment

Streptococci = Penicillin or ceftriaoxne +/- gentamicin (beta allergy uses vanco mono)

MSSA staph = Nafcilin of cefazolin

+ With prostetic valve add gentamicin and rifampin

MRSA = vancomycin + gen/Rif if valve

Use dapto if patient has allergy

Enterococci = penicillin or ampicillin + gent

Allergy = vanco + gent

VRE = daptomycin or linezolid

Dental ppx

KNOW

Amoxicillin 2 g 30-60 min before procedure

If can take PO but allergic to PNC

+ Clindamycin 600 mg

+ Azithromycin or clarithromycin 500 mg

ID 2

Intra-abdominal Infections

SBP

1st: DOC ceftriaxone

2nd: bactrim or ciprofloxacin

ID 2

Outpatient of SSTIs (MSSA, MRSA) and Streptococci SSTI

Want oral for these MSSA SSTI

Impetigo

Folliculitis furuncles carbuncles

ID 2

SSTI MSSA MRSA and streptococci

Non-purulent infection: cellulitis

Purulent infection: abscess

ID 2

Severe Purulent SSTIs

Necrotizing Fasciitis

IV abx here

Diabetic food infection

moderate/severe diabetic foot infections

= combo-

vanco + ceftazidime/cefepime/zosyn/aztreonam/carbapenem

+ Vanco alternatives: daptomycin or linezolid

Adding anaerobe coverage if ceftazidime, cefepime, or aztreonam is selective

No MRSA or Pseudo risk: mono therapy: zosyn/unasyn, carbapenem (except doripenem), moxifloxacin

DOT: 7-14 days-severe, limb threatening infection 4-6 weeks

ID 2

UTI - Definition, classification, diagnosis , symptoms

ID 2

UTI Treatment

Pregnant

+ Bacteruirea

Treat even if asymptomatic (3-7 days)

DOC 1st line = Amoxicillin + Clavulanate or PO cephlasporin

Beta lactam allergy = Nitrofurantoin and Bactrim (avoid in 1st trimester if possible)

Avoid quinolones

ID 2

Cdif

Toxic mega colon

Use metronidazole IV + Vanco NG

ID 2

STI Symptoms

Gonorrhea

Chlamydia

Syphilis

HPV

Trichomoniasis

Bacterial vaginosis

ID 2

STI Treatment

Gonorrhea - ceftriaxone + Azithro of doxy (NO MONOTHERAPY)

Chlamydia - Azithro of amoxicillin

Syphilis

HPV

NEED FLAGYL

Trichomoniasis - PO or Intravaginal (fishy)

Bacterial vaginosis - PO regardless if pregnant

ID 3

Key Issues with Azole Antifungals

Study Tip Gal p406

All IV/PO 1:1

All increase LFTs and QT (except QT cresemba isavuconazonium does not rolong)

Fluconazole (Diflucan) is PO/IV and 1:1

Can use vaginal candiasis 150mg PO x1

Candida albicans (can use fluconazole rather than iconocandids

Ketoconazole - hepatotoxicity = transplant

Itraconazole = can cause HF, don't use in patients with ventricular dysfunction of HF, can increase plasma concentration and lead to QT prolongation and Vtach

Voricoazole (Vfend, Vfend IV)

+ Take VFend on empty stomach

V = vision, vision disturbances, don't try at night, visual changes

+ Avoid direct sunlight - photosensitivity

Monitor SCr b/c CrCl < 50 leads to increase SBECD and so PO is preferred (CNS toxicity hallucinations)

Posaconazole (Noxafil)

+ QT prolongation

+ Take with food for PO

+ Like Voriconazole SBECD can accumulate look at SCr

Isavuconazonium (Cresemba)

= requires a filter

No QT prolongation --> instead has shortening

Ketoconazole and igtraconazole absorption is pH dependent

Azoles can increase wafarin so monitor INR (and apixaban and rivaroxaban)

ID 3

Empiric Treatment for select fungal pathogens

Study Tip Gal p406

Statin Treatment Intensity Based on Patient Risk

Study Tip Gal p443

Statin Pneumonic

Potency

Pharmacists Rock At Saving Lives and Preventing Fat/Flu

Pitavastatin 2 mg

Rosuvastatin 5 mg

Atorvastatin 10 mg

Simvastatin 20 mg

Lovastatin 40 mg

Pravastatin 40 mg

Fluvastatin 80 mg

Potency

+ Pitivastatin = most Potent on a mg basis

+ Rosuvastatin = most potent agent to lower LDL

Toxicities

Think MOA: HMG

+ H = hepatotoxicity

+ M = Myalgia (muscle soreness), Myositis (muscle inflammation), myopathy (muscle weakness + cpk elevation) rhabdoMyolysis (muscule sx with high CPK = can cause renal failure)

+ G = Glucose changes

Dosing needed to be in evening?

+ Simvastatin (Zocor), Lovastatin (Altoprev - evening meal), Fluvastatin (Lescol)

+ Saving Lives from FLU

Key drugs that can increase BP

Key Drug Guy p454

1. Amphetamines and ADHD drugs

2. Cocaine

3. Decongestants (i.e. pseudoephedrine, phenylephrine)

4. Erythropoiesis-stimulating agents (ESA - epopoeitin)

5. Immunosuppressants (i.e. cyclosporine)

6. NSAIDs

7. Systemic steroids

List the key IV HTN meds

Key Drug Guy p467

+ Chlorothiazide (thiazide)

+ Clevidipine, Nicardipine (CCB)

+ Diltiazem Cardizem / Verapamil Calan (non DHP CCB)

+ Enalaprilat - Vasotec (ACEi)

+ Esmolol, Labetalol, Metoprolol tartrate Lopressor, propranolol Inderal (BB) --

MELT the BP in an emergency= Metoprolol, Esmolol, Labetalol, Tart

+ Nitroglycerin, Nitroprusside (post-MI)

Drugs for ACS

Key Drug Guy p475

MONA-GAP-BA

MONA: Immediate

- Morphine

- Oxygen

- Nitrates

- Aspirin

GAP: Give next

- GPIIb/IIIa antagonists (PCI + stent)

- Anticoagulants

- P2Y12 inhibitors

BA: W/in 24 hrs and outpatient

- Beta blockers

- ACEi

- (statin after high intensity unless 75+ might do mod)

NSTEMI/UA: MONO-GAP-BA + PCI

STEMI: MONA-GAP-BA + PCI (preferred) or fibrinolytic

1. Give MONA immediately (PRN)

2. Next give GAP (drug choice relates to plan if PCI vs CABG vs med management)

3. BA: Give within 24 hrs PRN; Continue outpatient

What select drugs cause or worsen HF?

Key Drug Guy p484

Drug Information NATION

DI NATION

Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors)-Alogliptin, sitagliptin, saxagliptin

Immunosuppressants

TNF inhibitors (etanercept, adalimumab, rituximab) and interferons

Nondihydropyridine CCBs- Diltiazem and verapamil (specifically in systolic HF - b/c they have non-inotropic effect)

Antiarrhythmics- Avoid Class I agents (e.g., procainamide, quinidine, flecainide) in HF

Amiodarone and dofetilide have less risk of worsening HF

Thiazolidinediones- increase risk of edema

Itraconazole

Oncology agents Anthracyclines (doxorubicin, daunorubicin)

NSAIDs- All (including celecoxib) compete with loop diuretics

fluid retention/edema, by increasing blood pressure or via negative inotropic effect

What is the oral equivalent dosing for the loop diuretics?

Oral equivalent dosing:

bumetanide(bumex) 1 mg =

torsemide(demadex) 20 mg =

furosemide(lasix) 40 mg =

ethacrynic acid (edecrin) 50 mg

Furosemide IV:PO ratio 1:2

All others are 1:1

Remember T = twenty

F = Fourty

E is 5th leter = 50

B just is 1

Target Doses of HF meds

ACEi

ARBs

ARA

BB

Digoxin

Ivabradine

1. ACEi (REQLC)

+ Rapamil (Altace) = 10 mg QD

+ Enalapril (Vasotec) 10-20 mg BID

+ Quinpril (Accupril) (A 20 mg BID

+ Lisinopril (Prinivil, Zestril)- 20-40 mg QD

+ Catopril (Capoten)- TID

2. ARBs

+ Losartan (Cozaar)

- Target dose: 50-150 mg QD

+. Valsartan (Diovan)

- Target dose: 160 mg BID

Goes from 50-150 qd, then 160 BID

3. ARA

+ Spironolactone (Aldactone)

- Target dose: 25 mg QD or BID

4. Digoxin

- 0.125-0.25 mg PO QD

Target levels of 0.5-0.9 ng/mL

5. Beta Blockers

Beta-1 Selective Beta Blockers

+ Bisprolol

+ Metoprolol succinate ER (Toprolol XL)

- Target dose 200 mg

Non-selective Beta Blocker and Alpha=1 Blocker

+ Carvedilol (Coreg)

Target

< 85 kg = 25 mg BID

> 85 kg = 50 mg BID

6. Ivabradine

Target: resting heart rate between 50-60 BPM

Which key drugs prolong the QTc?

Key Drug Guy p500

Antiarrhythmics

+ Class I (especially Class la) and Class III (amiodarone)

Antibiotics

Quinolones and macrolides

Azole antifungals

All except isavuconazonium

Antidepressants

Tricyclics (e.g., amitriptyline, clomipramine, doxepin)

SSRIs (e.g., citalopram/Celexa 40 mg, escitalopram/Lexipro 20 mg - have max doses to avoid QT prolong); sertraline (Zoloft) is preferred in cardiac patients

SNRIs, mirtazapine and trazodone

Antiemetic agents

5-HT3 receptor antagonists (zofran/ondansetron), droperidol (one of the worst QT prolongers antidopaminergic drug) and phenothiazines

Antipsychotics (most) - haloperidol, thio, and ziprasidone are top antipsychotics

+ Chlorpromazine, clozapine, haloperidol IV, olanzapine (Zyprexa), paliperidone, quetiapine, risperidone, thioridazine, ziprasidone (Geodon)

Other drugs

Donepezil, fingolimod (for Multiple Sclerosis), methadone (anti-arrhythmic at high doses), tacrolimus

Vaughan Williams Classification of antiarrhythmic drugs

Study Tip Gal p501

CLASS I - Sodium Channel Blockers

la: Disopyramide, Quinidine, Procainamide

lb: Lidocaine, Mexiletine

Ic: Flecainide, Propafenone

1a is especiallly dangerous for qt (proarrhythmics)

CLASS II

Beta-blockers (indirectly block calcium channels)

CLASS III Potassium Channel Blockers

- Dronedarone, Dofetilide, Sotalol (also BB), Ibutilide, Amiodarone

Amiodarone

CLASS IV: Calcium Channel Blockers - Rate Control

- Verapamil, Diltiazem

Class 4 mostly rate control, slow HR

Remember:

Double Quarter Pounder, Lettuce Mayo, Fries Please! Because Dieting During Stress Is Always Very Difficult

AFib Rate vs Rhythm Control and Stroke Prophylaxis

Study Tip Gal p501

Rate Control

+ Patient remains in AFib and takes medication to control ventricular rate (HR)

--> BB or non-DHP CCBs (sometimes digoxin)

Rhythm Control

+ Goal is to restore and maintain NSR

--> Class 1a, 1c, or III antiarrhythmatic or electrical cardioversion

+ If Afib is permanent, avoid rhythm control antiarrhythmic drugs (risk > benefit)

Stroke Prophylaxis

+ Clots can form when a patient is in AFib, which can embolize (causing stroke) when patient returns to NSR

+ For many patients, it is safer to remain in Afib with rate control than to try and restore NSR. A rate control strategy may require anticoagulation for stroke prevention dependent on the CHADS-VASc score

--> NOACs (eg apixaban, rivaroxaban) are preferred over warfarin for non-valvular Afib

--> Warfarin is indicated for mechanical heart valves

+ When a rhythm control strategy is chosen, restoration and maintenance of NSR is not guaranteed. Long term anticoagulation decisions depend on the patient's clot risk

Amiodarone interactions

When starting amiodarone, decrease digoxin by 50% and decrease warfarin by 30-50%

+ Simvastatin:

Do not exceed 20 mg/day of simvastatin

+ Lovastatin: 40 mg/day of lovastatin

+ Sofosbuvir can enhance bradycardic effect of amiodarone - don't use together

Amiodarone can increase the level of many other drugs; it is an inhibitor of CYP450 2C9 (moderate), 2D6 (moderate), 3A4 (weak) and P-gp.

■ Amiodarone is a substrate of CYP3A4,2C8 and P-gp. Strong/ moderate inhibitors of these enzymes will increase amiodarone and strong/moderate inducers will decrease amiodarone.

■ When starting amiodarone, decrease digoxin by 50% and decrease warfarin by 30 - 50%. Do not exceed 20 mg/day of simvastatin or 40 mg/day of lovastatin; statin levels will increase. Consider use of alternative statin.

■ Additive effect with other drugs that decrease HR, including non-DHP CCB, digoxin, beta-blockers, clonidine and dexmedetomidine (Precedex).

■ Sofosbuvir (hep C drug) can enhance the bradycardic effect of amiodarone; do not use together.

Warfarin tablet colors

study tip gal p529

Pink = 1 mg

Lavender = 2mg

Green = 2.5 mg

Brown/Tan = 3mg

Blue = 4 mg

Peach = 5mg

Teal = 6mg

Yellow = 7.5 mg

White = 10 mg

Please Let Greg Brown Bring Peaches To Your Wedding

Warfarin Drug Interactions

Hemolytic Anemia Acquired (drug-induced)

Drugs

Key Drug Guy p542

+ Penicillins, Cephlasporins

+ Isoniazid, rifampin

+ Levodopa

+ Methyldopa

+ Cisplatin and other platinum based drugs

+ Quinidine, quinine, ribavirin

+ Sulfonamides (Bactrim)

+ Dapsone

+ Nitrofurantoin

+ Primaquine

+ Rasbucase

+ Probenecid

+ Methylene blue

Identify with coombs test

Elemental Iron amount

Ferrous sulfate

Dried ferrous sulfate

Ferrous fumurate

Ferrous sulfate = 20% (65 mg)

Dried Ferrous sulfate = 30% (50 mg)

Ferrous fumurate = 33%

Drug Treatment - Key vaccines in Sickle Cell Anemia

Routine Childhood series

+ Haemophilus influenzae type B (Hib)

+ Pneumococcal conjugate (PCV13, Prevnar)

Additional Vaccines for Functional Asplenia

+ Meningococcal conjugate series + routine booster

+ Meningococcal serogroup B (Bexsero, Trumenba) --> At age > 10

+ Pneumococcal polysaccharide (PPSV23, Pneumovax23) --> at age > 2 years, booster 5 years later and at age > 65

+ Pneumococcal conjugate (PCV13, Prevnar) x1 in any patient > 6 years of age, if never received as part of routine childhood series

What key drugs cause hyperglycemia?

Key Drug Guy p644

- Beta-blockers (causes hypoglycemia too)

-Cough syrups (OTC and Rx)

-Diuretics (thiazides/loops)

-Immunosuppressants (cyclosporine, tacrolimus)

-Niacin

-Protease inhibitors (-navir)

-Quinolones (causes hypoglycemia too)

-Second gen atypical (clozapine, olanzapine, quetiapine)

-Statins

-Systemic Sterioids

DILE drugs

Hydralazine - HTN (vasodilator)

Procainamide - Class 1a antiarrhythmic Na channel blocker

Methyldopa?

Amiodarone (not as often, class 3 k blocker)

Quinidine (afib class 1a)

Procainamide (afib 1a)

Minocycline - Tetracycline

Methimazole - used as T4 inhibi for hyperthyroidism (less liver tox than PTU)

PTU - hyperthyroid drug

Isoniazid (INH)

Metoprolol tartrate IV conversion

Metoprolol tatrate IV is not equivalent to PO (IV:PO ratio is 1:2.5)

Carvedilol Conversion

Carvedilol (coreg) is 1 BID:3.2 qd CR tab

Steroid equivalency (hydrocortisone, prednisone, methylprednisolone, dexamethasone)

Lithium calculations

Levothyroxine tablet colors

Full replacement dose = 1.6 mcg/kg/day IBW

IV:PO = 0.75:1

CAD patients (MI, UA) take 12.5-25 mcg/day

Orangutans will violet on your rose before they become lilac, pink giants

Orange = 25 mcg

White 50 mcg

Violet = 75 mcg

Olive = 88 mcg

Yellow = 100 mcg

Rose = 112 mcg

Brown = 125 mcg

Turquoise = 137 mcg

Blue = 150 mcg

Lilac = 175 mcg

Pink = 200 mcg

Green = 300 mcg

HF doses to know

1. ACEi (REQLC)

+ Rapamil (Altace) = 10 mg QD

+ Enalapril (Vasotec) 10-20 mg BID

+ Quinpril (Accupril) (A 20 mg BID

+ Lisinopril (Prinivil, Zestril)- 20-40 mg QD

+ Catopril (Capoten)- TID

2. ARBs

+ Losartan (Cozaar)

- Target dose: 50-150 mg QD

+. Valsartan (Diovan)

- Target dose: 160 mg BID

Goes from 50-150 qd, then 160 BID

3. ARA

+ Spironolactone (Aldactone)

- Target dose: 25 mg QD or BID

4. Digoxin

- 0.125-0.25 mg PO QD

Target levels of 0.5-0.9 ng/mL

5. Beta Blockers

Beta-1 Selective Beta Blockers

+ Bisprolol

+ Metoprolol succinate ER (Toprolol XL)

- Target dose 200 mg

Non-selective Beta Blocker and Alpha=1 Blocker

+ Carvedilol (Coreg)

Target

< 85 kg = 25 mg BID

> 85 kg = 50 mg BID

6. Ivabradine

Target: resting heart rate between 50-60 BPM

ACS Benefits of BB (given w/i 24 hours and continue outpatient)

Beta Blockers

+ Oral, low dose BB (Beta-1 selective blockers without ISA preferred) should be started within the first 24 hours

Beta-1 Selective Agents (AMEBBA)

+ Atenolol (Tenormin)

+ Metoprolol (tartrate - Lopressor IV, succinate Toprolol XL)

+ Esmolol IV (Brevibloc)

+ Bisoprolol

+ Betaxolol

+ Acebutolol (has ISA) NO!

If have HFrEF use bisoprolol, metoprolol succinate, or carvedilol)

Might need to use IV BB - metoprolol Tart, Esmolol, Labetolol

ACEi = start in 24 hr

+ PO ACEi should be started within first 24 hours and continued indefinitely in all patients with LVEF <40%

+ Don't use IV ACE in first 24 hrs d/t risk of Hypotension (Enalaprilat - vasotac)

+ Can use ARB if ACEi intolerant

+ ALL PATIENTS SHOULD BE ON AN ACEi = ASCVD

Ascites treatment ratio

Ratio of 40 mg furosemide to 100 mg spironolactone to maintain potassium balance

40 lasix : 100 spiro

G6PD deficiency drugs

Nitrofurantoin

Bactrim

Opioid conversion

Bipolar Disorder

Drug treatment

Bipolar Disorder

Lithium

Drug treatment

5 mL Lithium citrate syrup = 8 mEq of lithium ion

8 mEq of lithium ion = 300 mg lithium carbonate tabs/caps

Pharmacogenomics

Definitions

Study of inherited variations of genees to deterimine a patients response to a drug

Dominant vs recessive

+ Dominant needs 1 copy

+ Recessive needs 2 copies

Nucleotide = basic structural unit of DNA named based on nitrogenous bases (AGTC)

+ Gene = stretch nucleotides that codes for a single protein

+ DNA = genetic material that is the main componenet of chromosome (double helix)

+ Chromosome = made up of many genes that cary the genetic info

+ SNP (single nucleotide polymorphism = change in single nucleotide in a genetic sequence

Required/Strongly Recommended Genomic Testing

Pharmacogenomics

Key Drug Guy p

HLAB Genes

Abacavair (Ziagen) and combo products (Triumeq) --> HLAB*5701 = increase hypersensitivity risk

Azathioprine --> TPMT; decreases activity = increases myelosupression

Carbamazepine (Tegretol) --> HLAB*1502 = increase hypersensitivity risk

Allopurinol is HLA-B

Cetuximab (Erbitux) and panitumumab (Vectibix) --> KRAS neg, if neg = avoid poor response

Trastuzumab (Herceptin), ado-trastuzumab emtanside (Kadcyla), Iapatinib (Tykerb) and pertuzumab (Perjeta) --> want HER2 pos; if neg = avoid not effective

Warfarin - VKORC1

Metabolized by 2C9, S is more potent than R

Pharmacogenomics

Study Tip Gal

Does a positive or negative require action

POSITIVE:

1) HLA-B testing = hypersensitivity increased risk = avoid drug (Abacavair, Triumeq), Carbamazepine (Tegretol)

2) KRAS mutation positive = poor response to drug = avoid (Cetuximab, panitimumab)

NEGATIVE

1) HER2 negative = avoid HER2 inhibitors HERceptin/Trastuzumab

Pharmacogenomics

Consider genetic Testing

Ex: clopidogrel (Plavix) - test for CYP2C19 (used for ACS, PAD, stroke)

1 allele is normal

Poor metabolizers 2C192 and/or 2C193 alleles) will not convert drug to active form = higher CV event rates

Consider alternative therapy

Pharmacogenomics

CPIC Guidelines for CYP2D6 Genotypes and Codeine

Ultra rapid = avoid due to toxicity risk (increased morphine formation = higher tox= respiratory depression or death)

Extensive metabolizer = use label recommended age or weight specific dose (normal morphine formation)

Intermediate metabolizer = reduced morphine formation - use label recommended, if no response use alternative

Poor metabolizer = greatly reduced morphine = avoid use b/c lacks efficacy