lOMoAR cPSD| 37668344
lOMoAR cPSD| 37668344
NAPLEX KEY DRUGS STUDY TIPS
FUNDAMENTALS OF PEDIATRICS
Pharmacy Foundations Part 1
Nervous System
Common Receptors, Substrates and Drugs
Receptor Substrate Agonist Action Drug Agonists Antagonist action Drug Antagonists
Muscarinic ACh ⇧ SLUDD Pilocarpine, bethanechol ⇩ SLUDD Atropine, Oxybutynin
Nicotinic ACh ⇧ HR, BP Nicotine Neuromuscular Neuromuscular blockers
blockade (ex. rocuronium)
Alpha-1 Epi, NE Smooth muscle Phenylephrine, dopamine Smooth muscle �-1 blockers (ex.
vasoconstriction (dose-dependent) vasodilation Doxazosin, Carvedilol,
⇧ BP ⇩ BP phentolamine)
Alpha-2 Epi, NE ⇩ release of Epi, NE Clonidine, brimonidine ⇧ BP, HR Ergot alkaloids,
⇩ BP, HR yohimbine
Beta-1 Epi, NE ⇧ myocardial Dobutamine, ⇩ CO, HR Metoprolol - �1 selective
contractility, CO, HR isoproterenol, dopamine Propranolol, Carvedilol -
(dose-dependent) Non-selective
Beta-2 Epi Bronchodilation Albuterol, terbutaline, Bronchoconstriction Propranolol, Carvedilol -
isoproterenol Non-selective
Dopamine Dopamine Renal, cardiac & Levodopa, pramipexole Renal, cardiac & 1st gen antipsych
CNS effects CNS effects (haloperidol),
Metoclopramide
Serotonin Serotonin Platelet, GI & Triptans Platelet, GI & Ondansetron,
psychiatric effects psychiatric effects 2nd gen antipsych
(quetiapine)
Enzymes
Enzyme Endog. Effects Drug Examples Drug Action
Acetylcholinesterase Breaks down Donepezil, rivastigmine, Blocks acetylcholinesterase → ⇧ ACh
acetylcholine galantamine Tx of Alzheimer’s disease
Angiotensin- Converts angiotensin I ACE-I (Lisinopril, ramipril) Inhibits production of angiotensin II → ⇩
converting enzyme to angiotensin II vasoconstriction & ⇩ aldosterone secretion
(ACE) Tx of HTN, HF, CKD
Catechol-O- Breaks down COMT Inhibitors Blocks COMT to prevent peripheral breakdown
Methyltransferase levodopa (Entacapone) of levodopa → ⇧ DOA of levodopa
(COMT) Tx of Parkinson disease
Cyclooxygenase Converts arachidonic NSAIDs (ASA, ibuprofen) Blocks COX to ⇩ prostaglandins &
(COX) acid to prostaglandins thromboxane A2;
and thromboxane A2 Tx of pain/inflammation; ⇩ platelet
activation/aggregation
, lOMoAR cPSD| 37668344
Monoamine oxidase Breaks down MAO-I (phenelzine, Blocks MAO → ⇧ catecholamine levels
(MAO) catecholamines tranylcypromine, linezolid, Tx of depression
(DA, NE, Epi, 5-HT) isocarboxazid, selegiline,
rasagiline, methylene blue)
Phosphodiesterase Breaks down cGMP, a PDE-5I (sildenafil, tadalafil) Competitively binds to same active site as
(PDE) smooth muscle cGMP on PDE-5 → prevents breakdown of
relaxant cGMP & prolongs smooth muscle relaxation
Tx of erectile dysfunction
Vitamin K epoxide Converts vitamin K to Warfarin Blocks vitamin K epoxide reductase → ⇩
reductase active form required production of clotting factors II, VII, IX, X
for production of select Tx or prevent blood clots
clotting factors
Xanthine oxidase Breaks down Allopurinol Blocks xanthine oxidase → ⇩ uric acid
hypoxanthine & production
xanthine into uric acid Tx of gout attacks
Drug Interactions
Pharmacodynamics: Pharmaco + Dyanmics
● “Pharmaco” refers to a drug // “Dynamic” refers to an activity – type of process or change
● Pharmacodynamics = effect that a drug has on the body
○ Effect can be therapeutic (morphine provides pain relief when it binds to mu receptor)
○ Effect can be toxic (excessive morphine can be fatal)
● PD drug interactions can occur when two or more drugs are given together – effects can be:
○ Additive (such as more sedation)
○ Antagonistic (one drug blocks the effect of another drug)
○ Synergistic, with an amplified effect (more than additive)
Risk with Concurrent use of Benzodiazepines & Opioids
Due to the heightened fatality risk when opioids & benzodiazepines are taken together, the FDA added a
boxed warning to all drugs in both classes
Warning: Risks from Concomitant use with Opioids
● Concomitant use of benzodiazepines & opioids may result in profound sedation, respiratory
depression, coma & death
○ Limit concomitant prescribing of these drugs to patients for whom alternative treatment
options are inadequate
○ Restrict dosages & durations to the minimum require
○ Monitor patients for signs & symptoms of respiratory depression & sedation
Pharmacokinetics: Pharmaco + Kinetics
● “Pharmaco” refers to a drug // “Kinetic” refers to motion
● Pharmacokinetics = affect the body has on the drug as it goes through the ADME processes
○ Absorption: typically occurring in the small intestine with oral drugs
○ Distribution: through the blood & dispersed throughout the tissues
○ Metabolism: including enzymatic reactions
○ Excretion: removal of the drug or end products (metabolites) from the body
● PK drug interactions occur when 1 drug alters the ADME of another drug – harmful or beneficial
, lOMoAR cPSD| 37668344
Prodrugs & active metabolites
Capecitabine → Fluorouracil Fosphenytoin → Phenytoin Example Safety Considerations
Codeine, by itself & in combo products such as Tylenol #3
Tramadol → Active metabolite Primidone → Phenobarbital • Risk of toxicity with ultra-rapid metabolizers (UMs) of CYP2D6
due to more rapid conversion to morphine
Codeine → Morphine Levodopa → Dopamine
- Do not use codeine in UMs of 2D6
Colistimethate → Colistin Valacyclovir → Acyclovir • Risk of poor analgesia with poor metabolizers (PMs) of CYP2D6
- Use alternative analgesic in PMs of 2D6
Cortisone → Cortisol Valganciclovir → Ganciclovir Clopidogrel (Plavix)
• Risk with CYP2C19 inhibitors, which can block conversion to
Prednisone → Prednisolone Famciclovir → Penciclovir
the active form
Isavuconazonium sulfate → Isavuconazole - Do not use with CYP2C19 inhibitors – omeprazole &
esomeprazole (can decrease antiplatelet effects)
Lisdexamfetamine → Dextroamphetamine • Risk with PMs of CYP2C19 (low conversion to active form with
reduced antiplatelet activity)
Clopidogrel → Active metabolite - Use alternative P2Y12 inhibitor in PMs of 2C19
Common CYP Inhibitors
G ❤ PACMAN
Grapefruit Effects on Substrates
• Decreased metabolism
Protease Inhibitors (especially ritonavir) • Increased serum levels & clinical effects
• INhibitors = INcreased effects/levels/ADRs/toxicities
Azole antifungals Effects on Prodrugs
• Decreased conversion to active drug (⇩ serum levels & clinical effects)
Cyclosporine, Cobicistat Recognizing the Problem
• Perform therapeutic drug monitoring
Macrolides (not azithromycin) • Monitor for therapeutic effect
Possible actions: ⇩ dose of substrate (unless prodrug), use alternate
Amiodarone (& dronedarone) drug to avoid combo
Non-DHP CCBs (Verapamil, Diltiazem)
Common CYP Inducers
PS PORCS
Phenytoin Effects on Substrates
• Increased metabolism
Smoking • Decreased serum levels & clinical effects
• InDucers = Decreased effects/levels
Phenobarbital Effects on Prodrugs
• Increased conversion to active drug (⇧ serum levels & clinical effects)
Oxcarbazepine Recognizing the Problem
• Perform therapeutic drug monitoring
Rifampin (& rifabutin, rifapentine) • Monitor for therapeutic effect
Possible actions: ⇧ dose of substrate (unless prodrug), use alternate
Carbamazepine (also auto-inducer)
St. John’s Wort
, lOMoAR cPSD| 37668344
Lab Monitoring
Therapeutic Drug Levels
Drug Therapeutic Range
Carbamazepine 4-12 mcg/mL
Digoxin 0.8-2 ng/mL (AF) 0.5-0.9 ng/mL (HF)
Gentamicin, Tobramycin (traditional dosing) Peak: 5-10 mcg/mL Trough: < 2 mcg/mL
Lithium 0.6-1.2 mEq/L (up to 1.5) – drawn as a trough
Phenytoin/Fosphenytoin 10-20 mcg/mL (if albumin is low, calculate corrected level)
- Free phenytoin - 1-2.5 mcg/mL
Procainamide 4-10 mcg/mL
NAPA (procainamide active metabolite) 15-25 mcg/mL
Combined 10-30 mcg/mL
Theophylline 5-15 mcg/mL
Valproic Acid 50-100 mcg/mL (up to 150 in some patients)
Vancomycin Trough: 15-20 mcg/mL: serious infections Trough: 10-15 mcg/mL for others
Warfarin INR 2-3 (2.5-3.5 for mechanical mitral valves)
Drug References
Locating Guidelines for Common Conditions
Anticoagulation Cardiovascular Disease
Guidelines from the American College of Chest Physicians Guidelines from the American College of
(CHEST guidelines) Cardiology/American Heart Association (ACC/AHA)
• Stroke Prevention in Atrial Fibrillation • Acute Coronary Syndromes • Heart Failure
• Venous Thromboembolism • Atrial Fibrillation • Hypertension
• High cholesterol
Diabetes Oncology
• American Association of Clinical Endocrinologists (AACE) • American Society of Clinical Oncology (ASCO)
• American Diabetes Association (ADA) • National Comprehensive Cancer Network (NCCN)
Pulmonary Conditions Infectious Diseases
• Asthma: Global Initiative for Asthma (GINA) & National • Infectious Diseases Society of America (IDSA)
Heart, Lung & Blood Institute (NHLBI) • HIV/AIDS: US Dept. of Health & Human Services
• COPD: Global Initiative for Chronic Obstructive Lung • Sexually transmitted infections: CDC
DIsease (GOLD)
lOMoAR cPSD| 37668344
NAPLEX KEY DRUGS STUDY TIPS
FUNDAMENTALS OF PEDIATRICS
Pharmacy Foundations Part 1
Nervous System
Common Receptors, Substrates and Drugs
Receptor Substrate Agonist Action Drug Agonists Antagonist action Drug Antagonists
Muscarinic ACh ⇧ SLUDD Pilocarpine, bethanechol ⇩ SLUDD Atropine, Oxybutynin
Nicotinic ACh ⇧ HR, BP Nicotine Neuromuscular Neuromuscular blockers
blockade (ex. rocuronium)
Alpha-1 Epi, NE Smooth muscle Phenylephrine, dopamine Smooth muscle �-1 blockers (ex.
vasoconstriction (dose-dependent) vasodilation Doxazosin, Carvedilol,
⇧ BP ⇩ BP phentolamine)
Alpha-2 Epi, NE ⇩ release of Epi, NE Clonidine, brimonidine ⇧ BP, HR Ergot alkaloids,
⇩ BP, HR yohimbine
Beta-1 Epi, NE ⇧ myocardial Dobutamine, ⇩ CO, HR Metoprolol - �1 selective
contractility, CO, HR isoproterenol, dopamine Propranolol, Carvedilol -
(dose-dependent) Non-selective
Beta-2 Epi Bronchodilation Albuterol, terbutaline, Bronchoconstriction Propranolol, Carvedilol -
isoproterenol Non-selective
Dopamine Dopamine Renal, cardiac & Levodopa, pramipexole Renal, cardiac & 1st gen antipsych
CNS effects CNS effects (haloperidol),
Metoclopramide
Serotonin Serotonin Platelet, GI & Triptans Platelet, GI & Ondansetron,
psychiatric effects psychiatric effects 2nd gen antipsych
(quetiapine)
Enzymes
Enzyme Endog. Effects Drug Examples Drug Action
Acetylcholinesterase Breaks down Donepezil, rivastigmine, Blocks acetylcholinesterase → ⇧ ACh
acetylcholine galantamine Tx of Alzheimer’s disease
Angiotensin- Converts angiotensin I ACE-I (Lisinopril, ramipril) Inhibits production of angiotensin II → ⇩
converting enzyme to angiotensin II vasoconstriction & ⇩ aldosterone secretion
(ACE) Tx of HTN, HF, CKD
Catechol-O- Breaks down COMT Inhibitors Blocks COMT to prevent peripheral breakdown
Methyltransferase levodopa (Entacapone) of levodopa → ⇧ DOA of levodopa
(COMT) Tx of Parkinson disease
Cyclooxygenase Converts arachidonic NSAIDs (ASA, ibuprofen) Blocks COX to ⇩ prostaglandins &
(COX) acid to prostaglandins thromboxane A2;
and thromboxane A2 Tx of pain/inflammation; ⇩ platelet
activation/aggregation
, lOMoAR cPSD| 37668344
Monoamine oxidase Breaks down MAO-I (phenelzine, Blocks MAO → ⇧ catecholamine levels
(MAO) catecholamines tranylcypromine, linezolid, Tx of depression
(DA, NE, Epi, 5-HT) isocarboxazid, selegiline,
rasagiline, methylene blue)
Phosphodiesterase Breaks down cGMP, a PDE-5I (sildenafil, tadalafil) Competitively binds to same active site as
(PDE) smooth muscle cGMP on PDE-5 → prevents breakdown of
relaxant cGMP & prolongs smooth muscle relaxation
Tx of erectile dysfunction
Vitamin K epoxide Converts vitamin K to Warfarin Blocks vitamin K epoxide reductase → ⇩
reductase active form required production of clotting factors II, VII, IX, X
for production of select Tx or prevent blood clots
clotting factors
Xanthine oxidase Breaks down Allopurinol Blocks xanthine oxidase → ⇩ uric acid
hypoxanthine & production
xanthine into uric acid Tx of gout attacks
Drug Interactions
Pharmacodynamics: Pharmaco + Dyanmics
● “Pharmaco” refers to a drug // “Dynamic” refers to an activity – type of process or change
● Pharmacodynamics = effect that a drug has on the body
○ Effect can be therapeutic (morphine provides pain relief when it binds to mu receptor)
○ Effect can be toxic (excessive morphine can be fatal)
● PD drug interactions can occur when two or more drugs are given together – effects can be:
○ Additive (such as more sedation)
○ Antagonistic (one drug blocks the effect of another drug)
○ Synergistic, with an amplified effect (more than additive)
Risk with Concurrent use of Benzodiazepines & Opioids
Due to the heightened fatality risk when opioids & benzodiazepines are taken together, the FDA added a
boxed warning to all drugs in both classes
Warning: Risks from Concomitant use with Opioids
● Concomitant use of benzodiazepines & opioids may result in profound sedation, respiratory
depression, coma & death
○ Limit concomitant prescribing of these drugs to patients for whom alternative treatment
options are inadequate
○ Restrict dosages & durations to the minimum require
○ Monitor patients for signs & symptoms of respiratory depression & sedation
Pharmacokinetics: Pharmaco + Kinetics
● “Pharmaco” refers to a drug // “Kinetic” refers to motion
● Pharmacokinetics = affect the body has on the drug as it goes through the ADME processes
○ Absorption: typically occurring in the small intestine with oral drugs
○ Distribution: through the blood & dispersed throughout the tissues
○ Metabolism: including enzymatic reactions
○ Excretion: removal of the drug or end products (metabolites) from the body
● PK drug interactions occur when 1 drug alters the ADME of another drug – harmful or beneficial
, lOMoAR cPSD| 37668344
Prodrugs & active metabolites
Capecitabine → Fluorouracil Fosphenytoin → Phenytoin Example Safety Considerations
Codeine, by itself & in combo products such as Tylenol #3
Tramadol → Active metabolite Primidone → Phenobarbital • Risk of toxicity with ultra-rapid metabolizers (UMs) of CYP2D6
due to more rapid conversion to morphine
Codeine → Morphine Levodopa → Dopamine
- Do not use codeine in UMs of 2D6
Colistimethate → Colistin Valacyclovir → Acyclovir • Risk of poor analgesia with poor metabolizers (PMs) of CYP2D6
- Use alternative analgesic in PMs of 2D6
Cortisone → Cortisol Valganciclovir → Ganciclovir Clopidogrel (Plavix)
• Risk with CYP2C19 inhibitors, which can block conversion to
Prednisone → Prednisolone Famciclovir → Penciclovir
the active form
Isavuconazonium sulfate → Isavuconazole - Do not use with CYP2C19 inhibitors – omeprazole &
esomeprazole (can decrease antiplatelet effects)
Lisdexamfetamine → Dextroamphetamine • Risk with PMs of CYP2C19 (low conversion to active form with
reduced antiplatelet activity)
Clopidogrel → Active metabolite - Use alternative P2Y12 inhibitor in PMs of 2C19
Common CYP Inhibitors
G ❤ PACMAN
Grapefruit Effects on Substrates
• Decreased metabolism
Protease Inhibitors (especially ritonavir) • Increased serum levels & clinical effects
• INhibitors = INcreased effects/levels/ADRs/toxicities
Azole antifungals Effects on Prodrugs
• Decreased conversion to active drug (⇩ serum levels & clinical effects)
Cyclosporine, Cobicistat Recognizing the Problem
• Perform therapeutic drug monitoring
Macrolides (not azithromycin) • Monitor for therapeutic effect
Possible actions: ⇩ dose of substrate (unless prodrug), use alternate
Amiodarone (& dronedarone) drug to avoid combo
Non-DHP CCBs (Verapamil, Diltiazem)
Common CYP Inducers
PS PORCS
Phenytoin Effects on Substrates
• Increased metabolism
Smoking • Decreased serum levels & clinical effects
• InDucers = Decreased effects/levels
Phenobarbital Effects on Prodrugs
• Increased conversion to active drug (⇧ serum levels & clinical effects)
Oxcarbazepine Recognizing the Problem
• Perform therapeutic drug monitoring
Rifampin (& rifabutin, rifapentine) • Monitor for therapeutic effect
Possible actions: ⇧ dose of substrate (unless prodrug), use alternate
Carbamazepine (also auto-inducer)
St. John’s Wort
, lOMoAR cPSD| 37668344
Lab Monitoring
Therapeutic Drug Levels
Drug Therapeutic Range
Carbamazepine 4-12 mcg/mL
Digoxin 0.8-2 ng/mL (AF) 0.5-0.9 ng/mL (HF)
Gentamicin, Tobramycin (traditional dosing) Peak: 5-10 mcg/mL Trough: < 2 mcg/mL
Lithium 0.6-1.2 mEq/L (up to 1.5) – drawn as a trough
Phenytoin/Fosphenytoin 10-20 mcg/mL (if albumin is low, calculate corrected level)
- Free phenytoin - 1-2.5 mcg/mL
Procainamide 4-10 mcg/mL
NAPA (procainamide active metabolite) 15-25 mcg/mL
Combined 10-30 mcg/mL
Theophylline 5-15 mcg/mL
Valproic Acid 50-100 mcg/mL (up to 150 in some patients)
Vancomycin Trough: 15-20 mcg/mL: serious infections Trough: 10-15 mcg/mL for others
Warfarin INR 2-3 (2.5-3.5 for mechanical mitral valves)
Drug References
Locating Guidelines for Common Conditions
Anticoagulation Cardiovascular Disease
Guidelines from the American College of Chest Physicians Guidelines from the American College of
(CHEST guidelines) Cardiology/American Heart Association (ACC/AHA)
• Stroke Prevention in Atrial Fibrillation • Acute Coronary Syndromes • Heart Failure
• Venous Thromboembolism • Atrial Fibrillation • Hypertension
• High cholesterol
Diabetes Oncology
• American Association of Clinical Endocrinologists (AACE) • American Society of Clinical Oncology (ASCO)
• American Diabetes Association (ADA) • National Comprehensive Cancer Network (NCCN)
Pulmonary Conditions Infectious Diseases
• Asthma: Global Initiative for Asthma (GINA) & National • Infectious Diseases Society of America (IDSA)
Heart, Lung & Blood Institute (NHLBI) • HIV/AIDS: US Dept. of Health & Human Services
• COPD: Global Initiative for Chronic Obstructive Lung • Sexually transmitted infections: CDC
DIsease (GOLD)
