Pediatrics Review

Common Antidotes

Common Antidotes

Drug	Antidotes
Acetaminophen	acetylcysteine
Alcohol	thiamine
Anticholinesterase (insecticides)	atropine, pralidoxime
Anticholinergics	physostigmine
Benzodiazepine	flumazenil
Beta blockers	calcium chloride, epinephrine, glucagon
Calcium blockers	calcium chloride, glucagon
Carbon monoxide	hyperbaric, oxygen
Cyclophosphamide	mesna
Cyanide	amyl nitrate, sodium nitrate, sodium thiosulfate
Digoxin	digoxin immune fab
Dopamine	phenotolamine
Extrapyrimidal symptoms	diphenhydramine
Ethylene glycol	fomepizole, ethanol
Heroin	naloxone, nalmefene
Heparin	protamine sulfate
Iron	deferoxamine
Lead	dimercapol, edetate calcium, disodium
Methemoglobinemia	methylene blue
Methotrexate	leucovorin
Neuromuscular blockade	anticholinesterase
Potassium	albuterol inhaler, insulin/glucose, NaHCO3, kayexalate
Serotonin syndrome	cyproheptadine
Sulfonylurea hypoglycemic	octreotide
Theophylline	pyridoxine
Warfarin	phytonadione, vitamin K

Weight Loss and Gain Medications

Weight Loss Medications

Use with reduced-calorie diet and increased physical activity

Contrave (naltrexone/bupropion)

·         Naltrexone is an opiod antagonist

·         BMI

o   30 kg/m² or greater (obese) or

o   27 kg/m² or greater (overweight) + comorbidity

§  Hypertension

§  Type 2 diabetes mellitus

§  Dyslipidemia

·         4-week dose titration schedule

·         ADR – suicidality, neuropsychiatric reactions

·         Administration

o   NOT cut, chew, or crush Contrave tablets

o   NOT take Contrave with high-fat meals à seizures

Belviq (lorcaserin)

·         Serotonin 2C receptor agonist

·         ADR - serotonin syndrome, neuroleptic malignant syndrome

·         Administration

o   with or without food

Qsymia (phentermine/topiramate)

·         Phentermine - sympathomimetic amine anorectic

·         Topiramate - antiepileptic medication

·         ADR - concentration, memory, and speech difficulties

·         Administration

o   With or without food

o   Avoid in evening à insomnia

o   Avoid alcohol à dizziness and sleepiness

o   NOT stop suddenly à seizures

Alli (orlistat)

·         Inhibits gastrointestinal lipases

·         Administration

o   3 times a day with each main meal containing fat

o   Take multivitamin with A,D,E,K

·         ADR – GI effects, gas

Evaluate response after 12 weeks

If 5% weight loss not seen à stop drug

Weight Loss Bariatric Surgery

• BMI > 35 + comorbidity (hypertension, dyslipidemia, type 2 diabtes)
• BMI > 40

Weight Gain Medications

• Anticonvulsants (carbamazepine, gabapentin, pregabalin, valproic acid, lithium)
• Antidepressants (phenelzine, mirtazapine, paroxetine, amitriptyline, nortriptyline)
• Antihistamines (H1 blockers - cetirizine)
• Antihypertensives (atenolol, propanolol)
• Vasodilators (minoxidil)
• Antipsychotics (chlorpromazine, clozapine, iloperidone, olanzapine, quetiapine, risperidone)
• Corticosteroids 
• Hormonals (medroxyprogesterone, megestrol)
• Hypoglycemic (insulin, sulfonylureas, meglitinides, thiazolidinediones)

Source:

http://www.pharmacytimes.com/contributor/anyssa-garza/2015/03/weight-loss-medications-on-the-market

Addyi (filbanserin) Drug Information

·         Background

o   HSDD 7.7 to 14% of premenopausal women in the US or 5.5 to 8.6 million individuals

o   developed by Sprout pharmaceuticals

o   approved by FDA on June 4, 2015

·         Indication

o   hypoactive sexual desire disorder (HSDD)

·         Adverse effects

o   fainting, nausea, dizziness, sleepiness, low blood pressure

·         Mechanism

o   mechanism is unknown

o   mixed agonist/antagonist effect on postsynaptic serotonergic receptors

o   5HT1A agonist and 5HT2A antagonist

·         Concerns

o   avoid with alcohol due to concerns about central nervous system depression, hypotension, syncope

o   avoid in pregnant women

o   avoid with strong or moderate CYP3A4 inhibitors

o   prior to HSDD, it was considered for antidepressant indication and though all antidepressants have a black box warning for suicides, there is no sign of increase risk with filbanserin

·         Pharmacokinetics

o   peak levels reached in 45 to 60 minutes of administration

o   peak levels are delayed by 1 to 3 hours with meal

o   terminal elimination half-life is 12 hours

o   taking with high fat high calorie meal increases exposure 50%

o   administration with CYP3A4 inhibitors (ketoconazole, fluconazole) increases filbanserin 4.5 and 7 times, respectively

o   hormonal contraceptives are weak inhibitors of CYP3A4, but increase filbanserin 40%

Source:
Pharmacy Times. What to Know About “Female Viagra” Backed by FDA Panel.  http://www.pharmacytimes.com/news/what-to-know-about-female-viagra-backed-by-fda-panel#sthash.UW4UXYXR.dpuf

Drug Information Question

Question: Patient asked whether her Metformin interacted with an over-the-counter medication she was taking. 

Answer: Based on researching the information in Micromedex, it was found that there was no interaction of concern. To further understand possible over-the-counter medications interactions with Metformin, I read the journal article Drug Interactions of Medications Commonly Used in Diabetes and learned that the major OTC interaction of metformin is cimetidine.  Cimetidine causes a 60% increase in peak metformin plasma levels. The incidence of metformin-induced lactic acidosis may reach 0.084 cases per 1000 patient-years, with 50% of the cases being fatal.  Other adverse effects associated with metformin are upset stomach, B12 deficiency, and headache.

Source:

Metformin.  Drug Interactions.  Micromedex Solutions.  Truven Health Analytics, Inc. Greenwood Village, CO.  Available at: http://www.micromedexsolutions.com.  Accessed May 22, 2015.

Triplitt, C. "Drug Interactions of Medications Commonly Used in Diabetes." Diabetes Spectrum (2006):19(4); 202-11.

Drug Information Question

Question – Patient receives a prescription for Lamisil (terbinafine) 250mg for 10days and is inquiring when he may be allowed to drink alcohol again as he plans to attend a wedding on day 11.

Answer – Lamasil has a half-life of 22 to 26 hours with the half-life of 200 to 400 hours from skin and adipose tissue. Half-life is the amount of time needed to decrease the amount of drug in the body 50%. It usually takes 5 half-lives for the drug to be eliminated from the body close to 100%. With a half-life of 24 hours it would take approximately 5 days for terbinafine to be eliminated from the body. It would be best to wait 5 days before consuming alcohol after finishing the course of terbinafine. I called Novartis and they recommended not drinking alcohol with this product and they said they could not make a recommendation for after the patient stopped taking the medication.

Source:

Terbinafine hydrochloride.  DrugPoints Summary.  Micromedex 2.0.  Truven Health Analytics, Inc. Greenwood Village, CO.  Available at: http://www.micromedexsolutions.com.  Accessed June 16, 2015.

Key Drug Interactions

Key Drug Interactions

·         Serotonin syndrome

o   Mental status changes, agitation, diaphoresis, tachycardia, death

o   monoamine oxidase inhibitor (MAOI) - phenelzine or tranylcypromine sulfate

o   dextromethorphan, meperidine, and SSRI such as fluoxetine

o   stop fluoxetine 5 weeks before MAOI due to long half-life of metabolite norfluoxetine

o   wait 2 after MAOI ends and SSRI begins 

·         Digoxin and Quinidine

o   Increase in digoxin levels

o   Quinidine displaces digoxin from binding sites and leading to a decreased Vd of digoxin

o   Quinidine decreases renal and nonrenal excretion of digoxin

·         Sildenafil and Isosorbide mononitrate

o   Hypotension due to sildenafil being a PDE5 inhibitor and nitrates increase cGMP

·         Potassium (chloride, bicarbonate, citrate, acetate, gluconite, and iodide) and potassium sparing diuretics (spironolactone, amiloride, triamterene)

o   Leads to hyperkalemia, cardiac failure, and death especially in patients in renal impairment

·         Clonidine and Propanolol

o   Rebound hypertension when suddenly stopping clonidine

o   Clonidine is a central alpha-2 adrenergic agonist that causes a decrease in NE

o   Alpha-1 receptors then become sensitized because of less norepinephrine

o   With suddenly withdrawn a large increase in norepinephrine occurs leading to vasoconstriction by the sensitized alpha1 receptors

o   Body cannot compensate because the beta-2 receptors are blocked

·         Warfarin and NSAID (diflunisal, ketoprofen, piroxicam, sulindac, diclo-fenac, and ketorolac)

o   increase the risk of GI bleeding

o   acetaminophen or nonacetylated salicylates (magnesium salicylate or salsalate) is an alternative

·         Theophylline and Ciprofloxacin

o   Increase in theophylline levels

o   Theophylline is metabolized by CYP1A2

o   Ciprofloxacin, clarithromycin, erythromycin, fluvoxamine, and cimetidine inhibit CYP1A2

o   levofloxacin or ofloxacin is an alternative

·         Pimozide and Ketoconazole

o   Prolong QT interval and ventricular arrhythmias (torsades de pointes)

o   Pimozide is metabolized by CYP3A4

o   Ketoconazole, fluconazole inhibit CYP3A4

o   Terbinafine is safer

·         Methotrexate and Probenecid or Penicillins or Salicylates

o   Increase methotrexate levels

o   Probenecid inhibits renal secretion

o   methotrexate toxicity include diarrhea, vomiting, diaphoresis, renal failure, and death

o   alternatives include acetaminophen not salicylates or NSAIDS (celecoxib okay, rofexcoxib NOT okay)

·         Bromocriptine and Pseudoephedrine

o   peripheral vasoconstriction, ventricular tachycardia, seizures, and possibly death

o   Bromocriptine dopamine agonist for Parkinson’s (first line therapy is bromocriptine or other dopamine agonist such as ropinirole, pramipexole, or pergolide

o   Avoid all sympathomimetics with bromocriptine

Source: http://www.pharmacytimes.com/publications/issue/2002/2002-11/2002-11-7010

Theophylline

Theophylline

·         xanthine derivative

·         treats asthma and stable COPD to relax the bronchial smooth muscle

·         serum theophylline concentration of 10–20mg/L 

·         Symptoms of theophylline toxicity

o   Nausea

o   Vomiting

o   Gastric irritation

o   Diarrhea

o   Palpitations

o   Tachycardia

o   Arrhythmias

o   Headache

o   Central nervous system stimulation

o   Insomnia

o   Convulsions

·         Metabolized in the liver by CYP1A2

o   Cirrhosis, congestive heart failure, and hepatitis reduce theophylline clearance

·         Common drug interactions

o   Benzodiazepines

§  theophylline antagonizes the sedative and anxiolytic effects of benzodiazepines

o   H2-receptor antagonists

§  theophylline concentrations are increased by cimetidine

§  famotidine, nizatidine, and ranitidine do not interact

o   Ciprofloxacin

§  theophylline concentrations are increased

o   Erythromycin

§  theophylline concentrations are increased because theophylline clearance is reduced

o   Levothyroxine

§  theophylline concentrations are increased with hypothyroidism treatment

o   Methotrexate

§  theophylline concentrations are increased because theophylline clearance is reduced

§  might reduce methotrexate-induced neurotoxicity and methotrexate efficacy

o   Phenytoin

§  theophylline concentrations are decreased because increases the clearance of theophylline

·         Age

o   neonates and elderly have reduced theophylline clearance

·         Smokers

o   smokers need higher theophylline doses than non-smokers

o   tobacco smoke induces CYP1A2

o   smoking cessation results in increase in serum theophylline concentrations

o   reduce theophylline dose with smoking cessation

·         Adverse effects

o   risk of QT-interval prolongation with theophylline AND citalopram or fluoxetine together

o   low potassium, magnesium or calcium can cause QT prolongation

Source:

http://www.pharmaceutical-journal.com/learning/learning-article/theophylline-interactions/20065570.article

http://www.rxkinetics.com/manual.html

Important CYP drug interactions

Fungal treatment – Athlete’s foot, Jock itch, Ring worm

Available over the counter creams
Brand	Generic/Strength	uses	age	directions
Lotrim	Clotrimazole 1%	athlete’s foot, jock itch, ring worm	age 2+	athletes foot/ring worm ·         BID between toes for 4 weeks jock itch ·         BID between toes for 2 weeks
Lotrim Ultra	Butenafine HCl 1%	athlete’s foot, jock itch, ring worm	age 12+	athletes foot ·         BID between toes for 1 week ·         QD for 4 weeks jock itch ·         QD for 2 weeks
Tinactin	Tolnaftate 1%	athlete’s foot, jock itch	age 2+	BID for 4 weeks
Lamisil	Terbinafine HCl 1%	athlete’s foot, jock itch, ring worm	age 12+	athletes foot ·         BID between toes for1 week ·         BID foot bottom or side for 2 weeks jock itch/ring worm ·         QD (AM or PM) for 1 week
Micatin	Miconazole nitrate 2%	athlete’s foot, jock itch, ring worm	age 2+	athletes foot/ring worm ·         BID between toes for 4 weeks jock itch ·         BID between toes for 2 weeks
Counseling Points
·         Wash and pat dry affected are daily or twice daily (morning and night) ·         Do not share towels with others or use same towel on other parts of the body ·         Wear protective footwear in areas with other family members or public ·         Launder contaminated towel and clothing in hot water and dry on hot setting ·         Avoid clothing or shoes that cause skin to stay wet such as wool and synthetic fabrics ·         Dry shoes before wearing them again ·         Dust shoes with medicated or nonmedicated foot powder to help dry ·         Change insoles every 3 to 4 months for odor control ·         Stop topical medications if causes irritation, sensitization, or worsening ·         Apply thin layer over affected area ·         Apply to space between toes as well if affected ·         Wear well-fitting ventilated shoes ·         Change socks at least once a day ·         Wash hands with soap and water after applying the cream, avoid getting cream in eye ·         Creams and solutions are easier to get into skin than spray and powder dosage forms ·         Consult doctor if: o    Lasts longer than 4 weeks o    Cause unknown o    Unsuccessful initial treatment or worsening o    Nails or scalp involved o    Face, mucous membranes, or genitalia involved o    Secondary bacterial infection signs such as oozing purulent material o    Excessive continuous exudation o    Widespread, very inflamed, or debilitating o    Diabetes, systemic infection, immune deficiency o    Fever or malaise

Krinsky DL, Berardi RR, Ferreri SP, et al. Handbook of nonprescription drugs: An interactive approach to self-care. 18th ed. Washington, D.C.: American Pharmacists Association; 2015.