Angela Stein, Pharm.D.PGY-1 Pharmacy Resident

St. Johns Mercy Medical CenterSt. Louis College of Pharmacy

FDA Approved Indications• Essential hypertension

Non-FDA Approved Indications• Attention deficit hyperactivity disorder• Hot sweats• Ischemic foot ulcer; Adjunct• Nicotine dependence• Opioid withdrawal• Tic disorder

Stimulates the presynaptic alpha-2 receptor in the brain and imidazoline receptor • leading to inhibition of norepinephrine

release

Inhibitory effects on NE release in the locus coeruleus

Opioids activate opiate receptors in the locus coeruleus

↓ adenylate cyclase→ ↓ cAMP production

K+ efflux↑, Calcium influx↓

OVERALL RESULT= ↓ NE release

NE release gradually ↑ to normal levels as tolerance develops

Once opioids is withdrawn, loss of inhibitory effect increase in NE release to well above normal levels

Increase NE leads to withdrawal symptoms

Administration of opioids results in ↓ in neuronal activity and ↓ withdrawal symptoms

Initial treatment of a neonate experiencing drug withdrawal should be supportive, since pharmacologic therapy prolongs hospitalization and subject the infant to exposure to drugs that may not be warrented

Supportive care: swaddeling, frequent small feedings of hypercaloric (24 cal.oz) formula o suppl additioanl caloric requirements, observation of sleeping patterns, temperature stability, weight gain or loss, or change in clinical status

Assess infants of drug abusing mothers includes Heatitis B and C and sexually transmitted diseases including HIV

Clonidine Pharmacologic therapy Effectively reduces withdrawal signs in adults 0.5-1 ug/kg in a single dose followed by a maintenance dose

of 3 to 5 ug.kg/day, divided every 4 ti 6 hours Blood levels 0.1-0.3 ng/ml Poor sleep only sign that seems refractory Length of therapy for infants treated with clonidine was

significantly shorter when compared to phenobarbital (13 vs 27 days (P=0.05)

Larger controlled trials and pharmacokintic data is needed before clonidine can be avocated as routine treatment.

Background: Treatment of NAS often prolongs hospitalization Study Design: Prospective, block-randomized, double-blind, placebo-

controlled trial Outcomes:

• Total duration of pharmacotherapy for NAS• Amount of DTO required to treat NAS • Treatment failures• Seizures• weight gain• Blood pressure, heart rate, hemoglobin saturation

Methods: Treatment

• Clonidine 1 ug/kg every 4 hours+ diluted tincture of opium (DTO) 0.4 mg/ml

• DTO alone Inclusion

• 0-14 days old

• Pernatal exposure to opioids

• Moderate to severe NAS Exclusion

• Gestational age <35 weeks

• Intrauterine growth retardation (birth weight below 5th percentile

• Congenital anomalies

• Illness requiring oxygen

• breastfeeding 3 baltimore hospitals 80 patients were eligible and randomized 0.2 ml DTO was started on all infants (0.08 mg ME) Q4H Uncontrolled if 2 consecutive MFS > 9. DTO dose escalation to 0.3, 0.4, 0.5 ml every 4 hours

then 0.5, 0.7, . 0.9 ml every 3 hours untill withdrawal syptoms were controlled (MFS < 9) Once controlled, infants were maintained on that dose for 48 hours DTO was de-escalated by 0.05 ml/dose for each 24 hour period If 2 consecutive MFSs of >12 during de-escalatio., the last controlled dose was re-initiated 2 consecutive MFSs > 9 on the highest dose (0.9 ml Q3H were classified as treatment failures

• Total opioid dose, length of treatment, MFSs, and vital signs were collected

Additioanl AssessmentsTemperature, heart rate, respiratory rate, oxygen saturation, blood pressure, MFSs scores

every 3 to 4 hoursBlood pressure every 4 hours for the first 48 hours and after stopping clonidine or placebo

otherwise every 12 hours

To demonstrate a 25% reduction in primary outcome, a power of 0.8 and a 2-sided alpha value of 0.05 were needed for each study group

Log-rank test reported for time-dependent data Fischer’s exact test is reported for categorical variables T-test between group comparisons corrected for multiple comparisons Mann-Whitney U test used for continuous variables with non-normal

distribution

Scheduled morpine…failed scheduled morpine + clonidine

Background: clonidine is a potential benificial therapy for NAS due to safety profile, ease of administration, and lack of a requirement for tapering

Study Design: retrospectiveOutcomes:

Methods 14 patients were identified 11 patients were treated with fentanyl for sedation and

3 were born unto opioid-dependent mothers All treated with clonidine 0.5-1 mcg/kg orally every 6

hours No patients received opioids Stability of patients and NAS scores were assessed at

24-48 hours NAS scoring system was done every 3 to 4 hours

during pharmacologic intervention and every 48 hours after discontinuation of intervention

Vital signs and oxygen saturation were recorded hourly No exclusion criteria

Results Mean duration of treatment was 6.8

days (range 4-15) Mean abstinence scores were 6.4

pretreatment (range 0-20) and 1.9 posttreatment (range 0-5)

No patient suffered from adverse events from clonidine

Mean GA 30.1 weeks Treatment started in 10 patients in

anticipation of withdrawal and 4 after NAS scores were optained

Clonidine was stopped abruptly in 12 patients and tapered (by 0.25 mcg/kg every 6 hours) in 2 patients without adverse effects

Opiates effect on nervous system Clonidine protective effect of nervous

system

How do we d/c it? Dose Adverse effects to monitor

Gauanfacine Guanabenz lofixidine

Angela Stein, Pharm.D.PGY-1 Pharmacy Resident

St. Johns Mercy Medical CenterSt. Louis College of Pharmacy