Healthcare

On Cracking Addiction this week

Taking an accurate substance use history is of great importance in the management of addiction. There are a number of strategies that one could use but the most important part of history taking is that of demeanour and empathy. The best results and most accurate information are often obtained when one treats one’s patients with human empathy and in a non-judgemental manner. There is a quote by Walt Whitman ‘be curious and not judgemental’ which I try and use as my guiding principle when I am taking a substance use history.
A good tool for taking a comprehensive substance use history is the DUDIT .
Dr Ferghal Armstrong usually utilises his own mnemonic ‘TARCD’ when taking a substance use history:

Timing
• First use
• Last use
• Frequency of use
• Time within the day
• Periods of abstinence

Amounts (and overdoses)

Routes
• Oral nasal intravenous etc

Risk
• Drug specific risks e.g. seizures with alcohol withdrawal
• Access to Needle syringe programs
• Transmission of BBV

Costs
• Financial
• Relationships
• Loss of activities and hobbies

Dependency Factors
• DSM 5 criteria – CHEW THAT COP

A question that is not frequently asked but is of great importance is a simple one: ‘What do the drugs do for you?’. This question asks not about dependence or withdrawal but rather what reason is the person taking drugs and from personal experience can cause some quite profound revelations or open up some deep emotions or profound hurts that have caused the individual to start using drugs.

In summary it is very important to be empathetic, non-judgemental when conducting a substance use history regardless of the actual technique used to elicit the history-the non-verbal cues the patient perceives will be vital in the accuracy of the history obtained.

In this episode of Lifestyle Matters.

This week Dr Ferghal and I explore one of the most common addictive habits known to mankind – smoking. Back in the 50s-60s, smoking was considered the epitome of fashion and glamour. It was around then too when they started discovering the ill effects of smoking due to the various carcinogenic components, tar and carbon monoxide found in cigarettes. Of course, nicotine itself has deleterious effects on our health as it constricts our blood vessels, but the main offending agents are the other components that make up cigarettes.

We know that 2/3 of long-term smokers will cut their life expectancy by 10 years compared to non-smokers and will die of a smoking related disease.

The following include some but not all the health issues that we are at a higher risk of should we smoke regularly:
• Heart disease
• Stroke
• Peripheral vascular disease –e.g. clots in legs (Deep Vein Thrombosis), poor blood flow to our extremities resulting in poor wound healing, ulceration, poor exercise tolerance
• Eye disease e.g., macular degeneration
• Diabetes i.e., 30-40% higher risk in a smoker
• Lung disease e.g., chronic obstructive pulmonary disease (COPD)
• Cancers e.g., lung cancers, throat, mouth, stomach, liver etc.

Nicotine is a highly addictive substance as it binds to the nicotinic receptors in our brain causing the release of a good feeling hormone called Dopamine. Once nicotine wears off, we understandably crave for more. This is where the various therapies come into play such as:
• Nicotine replacement therapy – gum, patches, inhalers
• Pharmacological therapy – Vareniciline (Champix) and Bupropion ( Zyban)
• Vaping – which has nicotine but not the other more harmful substances

Whichever therapy a patient chooses, the success rate is markedly increased when it is combined with some form of counselling, especially cognitive behaviour therapy. Caffeine is another factor that needs to be taken into consideration when quitting smoking as our body does not metabolise it as quickly as it would when smoking. What this means is that the effects of caffeine our body when quitting smoking can be increased by up to 50%. Hence reducing caffeine consumption would be highly advisable during this period to reduce the risk of agitation and insomnia.

Having a supportive network and not giving up despite a relapse are important factors in increasing success in smoking cessation. Reaching out to your GP would be a great starting point in this journey.

On Cracking Addiction this week

There are a whole range of drugs of concern that one can become dependent upon or become addicted to and this list can seem daunting. The list of drugs that a ‘use disorder’ can be appended to under the DSM 5 criteria is similarly long. Dr Ferghal Armstrong though provides us with a useful mnemonic to remember these drugs ‘COCA SHITS’.

• Cocaine
• Opioids
• Cannabis
• Alcohol
• Stimulants
• Hallucinogens
• Inhalants
• Tobacco
• Sedatives

Similarly an alternative classification system of drugs of dependence making it easier to remember these drugs is as follows:

The Legals
Alcohol tobacco
The prescribed
Opiates benzodiazepines quetiapine pregabalin stimulants
The uppers
Cocaine amphetamine methamphetamine
Downers
Heroin cannabis
Party drugs
MDMA LSD magic mushrooms GHB

Identifying those patients who may be ta risk of prescription drug aberrancy can be difficult and is an area that can leave a doctor feeling quite fraught. A useful set or patterns of behaviours to be aware of can be remembered through Dr Armstrong’s mnemonic ‘USE TALK’

Urgency
Unscheduled medical appointments
Splitting
“You are the only one who can help”
Efficacy
“Nothing else works for me”
Timing
Saturday afternoon and I have run out of my medication – no option for cross checking with other agencies
Allergies
“I am intolerant of all other pharmacological options”
Lost
Lost prescriptions that trigger requests for further replacement prescriptions
Knowledge
High degree of knowledgeability surrounding the drug in question

On Cracking Addiction this week

Most women presenting with opioid dependence are of child-bearing age with chaotic drug use predisposes to amenorrhoea. The initiation of opioid substitution therapy (OST) facilitates stability and reinstatement of regular menstrual cycles and thus OST is a risk factor for unplanned pregnancy. Contraception needs to be discussed with all female patients of child bearing age who present to OST treatment services.

Substance use disorder in pregnancy mandates referral to a specialist services with best practice including involvement in a multidisciplinary drug and alcohol antenatal clinic. This multidisciplinary team should include: midwives, Obstetricians, Paediatricians, social workers and Addiction Medicine specialists.

Counselling needs to be provided regarding the risks and benefits of OST during pregnancy and lactation. There is a significant risk of miscarriage if doses of OST missed/opioid withdrawal occurs. Pregnant patients may be reluctant to engage with antenatal services or OST treatment programs because of chaotic lifestyles, stigma or concerns about child protective services and removal of their child from them post birth. By focussing on the health of the baby this may promote engagement with treatment services.

Suboxone, Subutex and Methadone are all Category C drugs in pregnancy. However inadequately treated opioid use disorder is a significant risk to the viability of the pregnancy. Opioid withdrawal in the first trimester can cause uterine contractions and does increase the risk of miscarriage in the first trimester and opioid withdrawal in the third trimester increases the risk of intrauterine growth restriction as well as risk of premature labour.

Another concern about OST in pregnancy is adequately dosing the pregnant woman. The half life of Methadone is reduced in pregnancy from 22-24 hours in non-pregnant women to 8.1 hours in pregnant women. Methadone metabolism is accelerated due to increased CYP3A4 expression by liver, intestine, and placenta and methadone clearance increases with advancing gestational age. As a result of this higher doses and split dosing of Methadone may be required.

An optimal dose of methadone remains controversial with doses of 80-120mg per day not inappropriate. Twice or thrice daily dosing can result in more sustained plasma levels, fewer withdrawal symptoms, and less illicit drug use and less suppression of foetal movement and breathing.

Thus in summary it is important to adequately treat women who are pregnant with opioid use disorder to prevent harms to both the woman and foetus.

On Cracking Addiction this week

Post birth the patient’s usual oral methadone dose can be continued in the peripartum and post partum period. There is a theoretical concern in the postpartum period of over-sedation as methadone levels may increase as plasma volume and hepatic clearance normalise post the delivery of the child. Women should be closely monitored during this time period to guard against complications.

There are three approaches to manage this potential problem including: stay on the same dose of Methadone with close monitoring, decrease the Methadone dose by 10-20% or reduce the methadone dose by 20 to 40 percent immediately postpartum and closely monitor and follow up the woman to ensure the patient is not in significant withdrawal.

Most women who undergo buprenorphine maintenance therapy will not experience large dose adjustments during their pregnancies and may continue the same doses after delivery

Breast feeding should be promoted with confidence unless active substance use is occurring or otherwise contraindicated. Breastfeeding may reduce the severity of neonatal withdrawal syndrome in the neonate. With Methadone about 1-3% of maternal dosage will be transferred into the breast milk and with buprenorphine the amount of buprenorphine in breast milk is <1 percent of maternal dose. There is a low oral bioavailability with significant absorption unlikely.

Neonatal abstinence syndrome (NAS) is a phenomena when the infant withdraws from drugs that they have been exposed to in utero. NAS is not unique to opioids and can occur with benzodiazepines, nicotine and also SSRI and SNRIs. Methadone causes a withdrawal syndrome in 60–80% of cases with symptoms occurring usually between 48 to 72 hours after birth but also up to five days. In rare circumstances symptoms can be delayed by up to a month. The severity of NAS is not related to the maternal dose of Methadone.

There are lower rate of NAS with buprenorphine compared to methadone which is thought to be secondary to: lower bioavailability, lower transplacental passage and partial agonism. The risk of NAS with buprenorphine is also not dose dependent. However overall the risks of opioid withdrawal during pregnancy are greater to the foetus than those of NAS to the infant so it is important to adequately treat the pregnant woman with opioid use disorder rather than be concerned about the risks of NAS.

On Cracking Addiction this week

Methadone is a synthetic long acting mu receptor agonist suitable for the treatment of opioid use disorder. Methadone has a longer plasma half life than morphine (average 22 hours (15-32 hours) vs 2 hours for morphine) which permits once daily supervised dosing. Methadone is well absorbed after oral administration with a peak effect after four hours and does cross the blood-brain barrier. It is thought that 20 to 50 mg daily of Methadone usually prevents opiate withdrawal phenomena and doses of > 60 mg prevents the euphoria from additional use of unsanctioned opioids.

Regardless of previous opiate or opioid usage the same low starting dose of methadone is prescribed. Starting doses of Methadone are usually between 20-30mg daily with higher risks patients starting at 20mg daily and doses can be up-titrated every 3-5 days based on clinical need. It is important to remember that it takes 5 half lives for Methadone to reach steady state in plasma. Methadone has a half life of approximately one day and thus half of each day’s dose remains in the body and is added to the next day’s new dose. Serum methadone levels will continue to rise (which can reach dangerous levels if doses are excessive) until steady state is achieved. It can take 5 days for Methadone to reach a steady state in plasma and can take 10 days for Methadone to equilibrate between plasma and body tissues.

Causes of Methadone overdose include:
• Single overdose
• Starting dose too high
• Accidental ingestion
• Accumulated toxicity
• Rapid induction
• Polypharmacy
• Hypnosedative combinations -benzodiazepines etc
• Reduced opioid tolerance
• Low neuroadaptation
• Comorbidity

Safety principles to consider when prescribing Methadone include:
• Risk of overdose highest in the first two weeks of treatment
• Safety principle: Start low and go slow
• No cross tolerance with other opioids
• Same low starting dose irrespective of previous opioid burden
• Never increase dose without a face-to-face review
• Usual practice to review patient weekly and increase the dose weekly
• Can take 6-8 weeks to achieve stability
• Cease other illicit and prescribed opioids / hypno-sedatives

On Cracking Addiction this week

Methadone is a drug with a wide variability in its absorption with oral bio-availability ranges from 35% to 100%. This is a significant amount of variability and explains why the same dose of Methadone can impact different patients differently. Methadone is also highly protein bound and there is a four fold variability in Methadone’s distribution within the body-further explaining the differing effects that can occur when taking Methadone.

Methadone is metabolised within the liver by the cytochrome P450 enzymes but mainly 3A4. There is a 17-fold inter-individual variation of methadone blood concentration for a given dosage and variations in metabolism account for a large part of this variation. Kinetic interactions influenced by the CYP 450 enzyme can affect plasma methadone levels.

• Inducers of CYP450 can
• Accelerate the metabolism of methadone
• lower methadone plasma levels
• Precipitate opioid withdrawal
• Inhibitors of CYP450 can
• Slow the metabolism of methadone
• Increase plasma levels
• Produce opioid toxicity (sedation, overdose)

Methadone is excreted renally with approximately 10% of drug renally eliminated unchanged. Renal excretion of methadone urinary pH dependent with increased Methadone excretion noted at pH less than 6 and decreased Methadone excretion at higher pH levels.

On Cracking Addiction this week

Long acting injectable buprenorphine (LAIB) are long acting buprenorphine depot preparations that are injected subcutaneously and provide patients with a sustained release of buprenorphine for the duration of the depot preparation. Currently, two LAIB products are available for the Australian market. They differ in their formulations, administration and pharmacology. The two products available are Buvidal and Sublocade. Buvidal formulations allow for weekly or monthly dosing frequency. Sublocade formulations allow for monthly dosing only.

Buvidal Weekly strengths: 8 mg, 16 mg, 24 mg, 32 mg
Buvidal Monthly strengths: 64 mg, 96 mg, 128 mg
Sublocade strengths: 300mg, 100mg

Buvidal dose should be determined according to patient’s Suboxone dose and subsequent doses can be titrated post clinical review. Buvidal may be initiated directly if required and usually a 24 mg Buvidal Weekly dose is started and the dose is titrated from this starting point until clinical effect is achieved.

Sublocade dosage is usually commenced post initiating treatment with Suboxone and a dose of Suboxone greater than 8mg daily. The recommended induction is: 300 mg monthly injections x 2 doses (8 weeks) and then 100 mg monthly doses (if the patient is stable on initial 2 x 300 mg doses) or 300 mg monthly doses if require additional buprenorphine effects.

If there are any issues, concerns or uncertainty about dosing it is always worthwhile to contact a more experienced prescriber or seek specialist assistance to ensure the right dosage of medication is being prescribed and given in an appropriate manner.

Weekly or monthly administration of LAIB takes away the need for daily dosing and takeaways, and reduces the frequency of supervised dosing to weekly or monthly intervals. This serves to reduce travel, stigma and out of pocket expenses for patients. Eliminating takeaway doses also reduces the scope for medication diversion. It is a medication with great potential but it is not for every patient and appropriate patient selection and follow up is important to ensure patients do not get destabilised on a new treatment.

On Cracking Addiction this week

This episode of Cracking Addiction is the second of a two-part series on Suboxone.

Buprenorphine acts as a partial agonist on the mu opioid receptor and an antagonist on the kappa opioid receptor.

The effects of buprenorphine on the mu receptor are best described by Dr Ferghal Armstrong’s pneumonic SPEAR:
• Sweating sedation
• Pinpoint pupils
• Physiological dependence
• Emesis
• Euphoria
• Analgesia
• Retention or urine and faeces
• Respiratory depression

Buprenorphine is also an antagonist of the kappa receptor and opposes the effects of the kappa receptor which can cause dysphoria so buprenorphine can assist with some improvement in mood.

Agonists bind to and activate a receptor to cause a biological response. Inverse agonist binds to the same receptor as an agonist but induces a biological response opposite to that induced by the agonist. Neutral antagonists bind to a receptor and causes no biological response in the absence of an agonist or inverse agonist but can block the activity of either. A partial agonist binds to but only partially activates a given receptor.

Buprenorphine is a partial agonist of the mu receptor which results in a plateauing of effect on the dose-response curve upon which a further dose increase results in no further effect. Buprenorphine’s dose plateaus at 32mg.

Buprenorphine is effective as a form of opioid substation therapy as it:
• Has a long half life
• Suppresses cravings and withdrawal
• Freedom from the shackles of dependence

With Suboxone it is important to administer the first dose when the patient is in opioid withdrawal or there is a risk of precipitated withdrawal. Buprenorphine has a high avidity for the mu opioid receptor but is a partial agonist but will still displace full agonists from the mu receptor if they are still bound to the receptor resulting in an acute withdrawal syndrome.

Overall Suboxone is a safe and effective form of opioid substation therapy and is a useful tool to assist patients with opioid use disorder achieve stability and possibly remission of their substance use disorder.