Buprenorphine in the Buprenorphine in the treatment of Opioid treatment of Opioid

DependenceDependence

““Addiction doesn’t come heralded by a brass band, it Addiction doesn’t come heralded by a brass band, it sneaks up on you, and sometimes with extraordinary sneaks up on you, and sometimes with extraordinary speed”speed”

C. Everett Koop (former US Surgeon General), 2003

Dr Jacqueline BOUTROUILLEDr Jacqueline BOUTROUILLE

What is the cost to society?

• $20 billion per year total cost of heroin abuse (Harwood et al, 1998)

• The economic cost of drug use and dependence estimated to be $98 billion (Harwood et al, 1998)

• Figures do not take into account social impact of drug addiction– Crime / legal costs – Absenteeism from work / unemployment– Welfare / medical costs

Choosing to use?

• A non-dependent user controls his/her use• A dependent person is controlled by his/her addiction

– People suffering from addiction often seek treatment because they “want their life back”

“Addiction doesn’t come heralded by a band, it sneaks up on you, and sometimes with extraordinary speed”

Koop, 2003

Are opioid-dependent individuals bad or sick?

• Opioid dependence has several features in common with diabetes and hypertension

– Chronic, relapsing nature

– Genetic vulnerability

– Physiologic brain changes

– Responds to chronic disease management strategies, not short-term symptomatic relief

Diagnosing addiction?

• More than 3 of the following during last 12 months:

– Tolerance– Withdrawal syndrome– Use of the drug to avoid/reverse withdrawal symptoms– Compulsion to use drug, especially when trying to stop– Narrowed repertoire of behaviors associated with

drug use– Drug-related behaviors more important than other

previously more important activities/behaviors – Early relapse after withdrawal

World Health Organization

What are the usual signs and symptoms?

• Sweating• Yawning• Anxiety• Increased BP and respiratory rate• Cravings • Lacrimation • Piloerection• Rhinitis• Gastrointestinal symptoms

– Abdominal cramps – Diarrhea

Once addicted, why isn’t it easy to stop?

• Withdrawal from opioids is associated with an extremely unpleasant syndrome:

– Physical pain (muscle aches, cramps)– Nausea and vomiting– Diarrhea– Dysphoria– Depression– Irritability and anxiety– Dysregulation of brain reward systems

• Pharmacologic intervention proven to help relieve symptoms of withdrawal

OPIOID RECEPTORS:OPIOID RECEPTORS:Activity determined by -Activity determined by -

• AffinityAffinity - how tight does the drug bind to the - how tight does the drug bind to the receptorreceptor

• Intrinsic ActivityIntrinsic Activity - how much does the drug - how much does the drug stimulate the receptorstimulate the receptor

• DissociationDissociation - how fast does the drug leave the - how fast does the drug leave the receptor receptor

OPIOID RECEPTOR PHARMACOLOGYOPIOID RECEPTOR PHARMACOLOGY

Agonists, antagonists, and partial Agonists, antagonists, and partial agonistsagonists

Agonists:Agonists: substances that bind to the receptor and substances that bind to the receptor and produces a full biological responseproduces a full biological response

Antagonists:Antagonists: substances that bind to the receptor substances that bind to the receptor and do not produce a biological responseand do not produce a biological response

Partial agonists:Partial agonists: substances that bind to the substances that bind to the receptor and produce a limited response – less than receptor and produce a limited response – less than the full response produced an agonistthe full response produced an agonist

EFFECT

DECREASED MAXIMAL EFFECT

LOG DOSE

PARTIAL AGONIST

AGONIST

Antagonist

ProvisionsProvisions An Amendment to the Controlled Substances An Amendment to the Controlled Substances Act that allows certified physicians to Act that allows certified physicians to prescribe and dispense Schedule III, IV, and prescribe and dispense Schedule III, IV, and V narcotic drugs that have been approved by V narcotic drugs that have been approved by the Food and Drug Administration for use in the Food and Drug Administration for use in addiction treatment (i.e., maintenance or addiction treatment (i.e., maintenance or medical withdrawal (detoxification))medical withdrawal (detoxification))

What is DATA (Drug & Alcohol What is DATA (Drug & Alcohol Treatment Act) 2000?Treatment Act) 2000?

LimitationsLimitations

• The total number of patients for a The total number of patients for a practitioner or group practice to 30practitioner or group practice to 30

• Secretary of HHS may change this number Secretary of HHS may change this number by regulation (group practice number is by regulation (group practice number is currently under review)currently under review)

Enter buprenorphine

• Effective treatment option for opioid dependence (Ling et al 1998)

• Reduces morbidity and mortality (Auriacombe et al 1998)

• Improves quality of life (Giacomuzzi, et al 2003, Anisse, 2001)

BuprenorphineBuprenorphine • AA synthetic opioid synthetic opioid• PPartial agonist at the artial agonist at the receptorreceptor

- - LLow intrinsic activity ow intrinsic activity only partially activating only partially activating opiate receptors opiate receptors

- E- Exhibits xhibits ‘‘ceilingceiling’’ effects on respiratory effects on respiratory depressiondepression

• High affinity for the High affinity for the receptor receptor

- B- Binds inds more more tightly to opiate receptorstightly to opiate receptors than than other opiates or opiate antagonistsother opiates or opiate antagonists

• Slow dissociation from the receptorSlow dissociation from the receptor–milder withdrawalmilder withdrawal

Duration of effectsDuration of effects

• RRapid onset of action: 30 apid onset of action: 30 –– 60 min 60 minutes utes (after S/L administration)(after S/L administration)

• PPeak effects: 1 eak effects: 1 –– 4 hours 4 hours

• DDuration of action is dose relateduration of action is dose related

• low dose : 4 low dose : 4 –– 12 hrs 12 hrs• med dose : med dose : ~~ 24 hrs 24 hrs• high dose : 2 high dose : 2 –– 3 days 3 days

• Elimination Elimination half-life half-life ~24 to 36 hours~24 to 36 hours

Pharmacological & Clinical Pharmacological & Clinical PropertiesProperties

•Similar to other opiates, but less Similar to other opiates, but less sedating and safer in overdosesedating and safer in overdose

•Side effectsSide effects

•Daily or alternate day dosingDaily or alternate day dosing •Long duration of actionLong duration of action

•Reduces opioid useReduces opioid use•‘‘Blocks’ effects of opiatesBlocks’ effects of opiates

•Reduces cravingsReduces cravings•Increases treatment retentionIncreases treatment retention

•Opiate-like effectsOpiate-like effects

•Prevents withdrawalPrevents withdrawal•Can be used for maintenance / Can be used for maintenance /

withdrawalwithdrawal•Substitutes for heroin Substitutes for heroin

Clinical implicationClinical implicationPharmacological Pharmacological propertyproperty

Drug Interactions

PharmacokineticMetabolic interactions (CYP P450 3A4)

InhibitorInducer

Pharmacodynamic interactionsCNS depressantsBenzodiazepines

Interactions with other opioids?

• Opioid antagonists:– Incomplete reversal by naloxone

• Opioid agonists:– Blockade effect, limiting the effects of

additional opioid use– Potential for precipitated withdrawal when

taken too soon after a full agonist

SideSide--effectseffects

• AAll opioids have ll opioids have a a qualitatively similar qualitatively similar profile of profile of sideside--effectseffects

• SSideide--effects generally transient effects generally transient

• Experience of side-effects variableExperience of side-effects variable-A client may experience sideA client may experience side--effect to one effect to one opioid but not to anotheropioid but not to another

• Not all symptoms are necessarily sideNot all symptoms are necessarily side--effects:effects: consider consider other other causescauses