Therapeutic

Class Medication

Mechanism of

Action Metabolism

Route of

Administration

(neonates) Dose and Frequency Reversal

Agent Comments

Synthetic opioid

agonists

Alfentanil Binds with sterospecific receptors

at many sites

within CNS, ↑s

pain threshold,

alters pain reception, inhibits

ascending pain

pathways

Hepatic

Onset of action: <5 min

Duration: <15–20 min

IV

IV Injection:

500 mcg/mL preservative free

(2 mg/5 mL

vial)

10–20 mcg/kg for procedural analgesia Naloxone: Neonatal depression:

0.1 mg/kg/dose.

May repeat q2–3

min as needed

Neonatal opiate

intoxication:

0.1 mg/kg/dose IV

Chemical derivative of fentanyl—1/4 as

potent as fentanyl

Chest wall rigidity common in doses

≥20 mcg/kg. Administer slowly over

3–5 min.

May produce more hypotension than

fentanyl

CYP3A4 polymorphisms may affect

response to fentanyl, alfentanil, and

sufentanil.

Monitor for CYP3A4 drug interactions:

e.g., inhibitors fluconazole, macrolide

antibiotics. Consult reference/clinical

pharmacist for updated information.

Fentanyl Binds with sterospecific receptors

at many sites

within CNS, ↑s

pain threshold,

alters pain reception, inhibits

ascending pain

pathways

Hepatic:

CYP3A4 oxidative N

dealkylation to norfentanyl (>90%) and

inactive metabolites.

↑ lipid solubility:

Onset of action: 3 min

Duration: 30 min

Clearance 70% of adult

values in term neonates, ↑s rapidly at

birth.

Intranasal, IV IV: Pain/sedation:

0.5–4 mcg/kg/dose slow

IV q2–4h

Intranasal:

1.5–2 mcg/kg/dose

Continuous IV:

0.5–2 mcg/kg/h and titrate

Naloxone:

Neuromuscular

blocking agent

(prevents chest

wall rigidity)i

Rapid infusion of IV fentanyl can lead to

chest wall rigidity.i

Infuse slowly over 3–5 min.

Less histamine release than morphine;

more suitable for neonates with

chronic lung disease (CLD)

↓s pulmonary vascular resistance—may

be useful in persistent pulmonary

hypertension (PPHN).

Shows more rapid tolerance and withdrawal versus morphine (3–5 d fentanyl vs. 2 wk morphine).j

Monitor for CYP3A4 drug interactions:

e.g., inhibitors fluconazole, macrolide

antibiotics. Consult reference/clinical

pharmacist for updated information.

Methadone Binds to opiate

receptors in

CNS. These mureceptors inhibit

ascending pain

pathways, which

alter perception

and response to

pain. Causes

generalized CNS

depression.

Desensitizes

δ-opioid receptors, antagonizes

NMDA receptors

involved in pain

sensitization.k

Hepatic:

CYP3A4/CYP2D6

N-demethylated to an

active metabolites

Onset of action: 20 min

IV, 30–60 min Oral

(slow)

Prolonged elimination

half-life (15–55 h)

Half-life: ↑ variability

when used for analgesia in neonates:

(3.8–62 h)k

Oral (liquid,

tablets), IV,

IM, SC

Neonatal abstinence

syndrome:

0.05–0.2 mg/kg/dose

q12–24h

Naloxone

Neonatal depression:

0.1 mg/kg/dose IV/

IM/SC

May repeat q2–3

min as needed

Neonatal opiate

intoxication:

0.1 mg/kg/dose IV

Difficult to titrate doses due to prolonged

half-life.

Oral solutions may contain propylene

glycol or benzyl alcohol “gasping syndrome” in neonates.

Some references consider equipotent

with morphine.

Varies with age, disease state, and previous opioid exposure.

Use caution as incomplete cross-tolerance

has occurred with methadone and

other opioids.

Long-term effects of NMDA-receptor

antagonism in the neonate is unknown.

High oral bioavailability, low cost, minimal SE once optimal dose is achieved.

Many drug interactions with CYP3A4,

CYP2D6 substrates in the NICU (fluconazole, zidovudine, macrolides,

phenobarbital, etc). Consult updated

drug interaction databases.

Table

A.2 Sedative and Analgesic Agents Commonly Used in Pediatrics (Continued) 404