Matthew AdetifaNurse Practitioner (Mental Health & AOD)

Latrobe Regional HospitalTraralgon ,Victoria, Australia

Knowledge of the Country (National) Medicines Policy

The doctrine of Quality use of Medicines

Classes of medications use in psychiatry Antipsychotics

Antidepressants

Mood stabilisers

Anti-cholinergic

Anxiolytics

Antipsychotics (conventional & Atypical )

Side effects

Drug Interactions

World health Organisation(WHO) 1999 - National Medicines Policy recommendation.

To ensure timely access to medicines at a cost both individual and community can afford.

Medicines meet appropriate standards of quality, safety and efficacy.

Maintain a responsible and viable medicines industry

Improve positive health outcomes.

Quality use of medicines:

is a risk management approach to ensure safe and effective use of medicines for better healthcare outcomes.

Judiciously used: only when non medication alternatives have been considered.

Appropriately used: being the most appropriate therapy after considering clinical condition, risks and benefits, dose, length of treatment and cost.

Safely used: under or over use is minimised.

Efficaciously used: Achieve the goals of therapy, treatment delivers actual health outcomes.

Role of Health Professionals (Mental Health Nurses)

Provide psycho-education

Choice of treatments.

Provide most appropriate treatment

Collaboration with consumers and other health professionals

Action-

Treatment of psychotic disorders (Schizophrenia, mania, psychotic depression).

Reduces positive symptoms: Delusions, hallucinations, thought disorder.

Some relief on negative symptoms: Amotivation, Blunted affect, cognitive impairment.

Relapse prevention for psychotic illnesses.

Mode of action: Antagonise dopamine D2 receptors

Dopamine Theory The dopamine hypothesis of psychosis– Overactivity of dopamine neurons in

the mesolimbic pathway of the brain may mediate the positive symptoms of psychosis. Mesolimbic pathway responsible for pleasure, effects of drugs and alcohol and

hallucinations and delusions.

Mesocortical Pathway: Enhance negative and cognitive psychotic symptoms

Nigrostriatal Pathway: EPSE & Tardive Dyskinesia

Tuberoinfundibular pathway: hyper-prolactinemia (Lactation, sexual dysfunction)

Blockade of dopamine receptors increases the activity of Acetylcholine

Over activity of acetylcholine causes EPSE

Blockade of dopamine causes movement disorder in the Nigrostriatal pathway.

Long term blockade causes “upregulation” and leads to Tardive Dyskinesia.

Actions= Blockade of receptors Example

• Dopamine 2

• Muscarinic / Cholinergic • Movement disorder

• Alpha Adrenergic• Causes dizziness, reduced BP

• Histaminergic receptors• Causes Weight gain, drowsiness

• Haloperidol (Haldol)

• Thioridazine ( Melleril)

• Loxapine (Loxitane)

• Fluphenazine (prolixin)

• Trifluoperazine (stelazine)

• Chlorpromazine (Largactil)

• Depots such as Flupenthixol, zuclopenthixol etc

The Ability of a drug to bind to a receptor

Tightly bound drugs lead to increased sensitivity to dopamine blockade and likely to cause EPSE

Low Affinity (loosely Bound)

Example: Quetiapine, Olanzapine, Amisulpride, Clozapine

High Affinity (tightly bound)

Chlopromazine, Haloperidol, Flupenthixol, Fluphenazine

Mode of action

Blockade of Dopamine (D2) and serotonin (5HT2A)

receptors (as opposed to typical antipsychotics that

blocks Dopamine and not serotonin receptors)

Also acts on histamine, alpha adrenergic and

cholinergic receptors

Atypical antipsychotic first binds to the D2 receptor then binds to the serotonin (5HT2A) receptor.

The second action reverses the first –by reverses the blockade of D2.

The blocking of the serotonin receptor causes the dis-inhibition of the dopamine neuron causing dopamine release

Serotonin opposes the release of dopamine in the Nigro-striatal and tuberofundibular pathways.

Typical Vs Atypical Antipsychotic

Same efficacy (except Clozapine)

Consider:

Merits of high vs low affinity drugs ( the higher the affinity the more the EPSE)

Adverse effect profile

Physical health baseline

Patient tolerability, preference and response

Examples in Australia

• Olanzepine

• Risperidone

• Quatiapine

• Amisulpride

• Ziprasidone

• Clozapine

• Risperdal consta injection• Aripiprazole oral & depot• Paliperidone oral & Depot

Sedation

Postural hypotension

Anticholinergic effects Dry mouth

Blurry vision

Constipation

Urinary hesitancy

weight gain– commonest in Olanzapine and clozapine

Metabolic effects-- Increases serum lipids, impaired glucose tolerance

Hyper-prolactinaemia –Leads to galactorrhoea,

amenorrhoea &

low libido

Osteoporosis

QTc prolongation– causing cardiac arrhythmias

Sexual dysfunction

EPSE Acute dystonia

Laryngeal spasm, oculogyric crisis

Akathesia

Parkinsonism (Neurological movement disorder) Tremor, rigidity, hyper-salivation

Tardive Dyskinesia ( Irreversible Involuntary hyperkinetic movement) Involuntary movement of the mouth, lips, tongue, jaws with smacking

Tic-like movements affecting the limbs and trunk

Neuroleptic malignant Syndrome (Rare but potentially fatal) Characterised by

hyperpyrexia, muscle rigidity, increased creatinine Kinase (CK), altered consciousness

May occur at anytime during the antipsychotic treatment– So “Watch out”

Stop antipsychotics immediately if NMS occurs

Cytochrome P450 system

The cytochrome P450 system is an evolutionary system to deal with the breakdown of endogenous and exogenous chemicals in the body.

It performs this function by oxidising, hydrolysing or reducing the chemicals thereby exercising regulatory mechanism to control the activity of the chemicals.

Its significant in psychotropic drug interactions.

The regulatory mechanism involve chemicals which induce or inhibit other cytochromes.

Inducer inhibitors

Anticonvulsants: Carbamazepine, Phenytoin reduces the concentration of oral contraceptives and quetiapine—Inducing CYP3A4.

• Smoking induces olanzapine and clozapine metabolism

SSRI: Fluvoxamine, fluoxetine & Paroxetine inhibit CYP2D6 thereby preventing the metablism of codeine to morphine.

• Fluvoxamine inhibits olanzapine and clozapine metabolism.

Matthew AdetifaNurse Practitioner (Mental Health & AOD)

Latrobe Regional HospitalTraralgon ,Victoria, Australia

https://www.youtube.com/watch?v=-I_Lche2otU

Def.

Epidemiology

Pharmacology

Clinical Manifestations

Course

Screening Assessment

Diagnosis

management

A Chronic, relapsing illness that involves the misuse

of prescribed opioid medications, use of diverted

opioid medications or illicitly obtained opioid.

Refers to natural or synthetic substances that act at one of the three main opioid receptor systems: Mu

Kappa

Delta receptor

Slang terms for opioid use Intranasal use– Snorting or sniffing

IV use– Shooting up

Subcutaneous Use--- Skin-popping

Intramuscular use -- Muscling

Heroin– Derivative of morphine commonly abused by injection

Slang terms for heroin are Dope, horse, smack, china white, junk or tar

Opium– Extract of opium poppy containing morphine and codeine, mostly abused by smoking or eating.

Prescribed Opioid

Opiate: Morphine and codeine

Synthetic opioid: Fentanyl, methadone, Oxycodone and

Semi synthetic: hydrocodone

In the US– 5.1million people (1.9% of persons age 12 or older) were estimated in 2015 to have used heroin in their lives.

3.8Million people aged 12 and older reported past misuse of a prescription pain medication in 2015 (National Survey on drug use and health, 2015).

Heroin use is increasing for persons who begin by first having nonmedical use of opioid analgesics

Prescription opioid is obtained mostly from friend or relative rather than clinician.

Prescription opioid user at highest risk of Overdose obtain it from clinicians, relatives or friend.

Prior history of substance use disorder

Demographic features including age (Peer pressure, adventure

Severe or chronic pain

Co-morbid mental disorders

Mechanism of action

Opioid activates specific transmembrane neurotransmitter Opioid receptors of Mu, Kappa, Delta

Some opioids also activate other CNS neurotransmitters like Dopamine, GABA and glutamate.

Effects of activation will depend on location, type of neural tissue, frequency and duration of use.

CNS = Respiratory depression, Analgesia and euphoria

PNS = stimulation of smooth muscle of the bronchi leading to suppression of cough

And smooth muscle of the intestine leading to opioid-induced constipation

Acute Intoxication Opioid Withdrawal Opioid Overdose

Itching and Scratching Dilation of pupils Hypotension

Slurred Speech Anxiety Bradycardia

Drowsiness Muscle and bone ache Pulmonary Oedema

Pinpoint pupils (meiosis)+ Sleep disturbance Respiratory Depression

Fresh injection sites Sweating, Hot and cold flushes Pinpoint Pupils

Lowered BP Dilation of pupils Loss of Consciousness

Slowed Pulse Nausea & Vomiting

Increased Pulse and BP

Infection– HIV, Hep C, Localised or systemic infections

Opioid-induced Hyperalgesia

Opioid-induced Bowel Syndrome

Increased risk of accidents

Risk of Overdose and High Mortality

Substance use history

Age of first use

Frequency of consumption,

Route (IV , Intranasal (snorting) )

Amount, past history of problematic use

Sign of tolerance

Treatment history

Physical examination ( to detect common complication of OUD)

Laboratory evaluation – UDS, Hepatitis serology, LFT, FBE

Problematic pattern of Opioid use that causes significant impairment manifested by 2 or more of the under-listed within a 12 month period: Taking large amount over a longer period than intended

Persistent desire or unsuccessful effort to control use

Increased Time spent in obtaining, using and recovering from the effect of use.

Craving

Evidence of aberrant behaviours

Use resulting in a failure to fulfil role obligations like work, school or home

Persistent use despite knowledge of having a persistent physical or psychological problem.

Tolerance and withdrawal

Type of Treatment Advantages Disadvantages

Substitution Therapy • Reduce opioid use • Expenses to patient

• Decrease mortality • Stigma

• Improve quality of life• Prevent withdrawal symptoms

in physically ill or unstable patients

• Restriction due to superviseddosing.

Detoxification • Short-term commitment • Poor long term outcome

• Easy access point to treatment • Increased risk of overdose if patient return to using

• Re-emergent of chronic pain conditions

Antagonist Treatment (Naltrexone)

Effective in patient keen to end opioid abuse with using opioid

• Requires detox first: All detox disadv. applies

Type of treatment Advantages Disadvantages

Residential (rehab) • Effective for those with complex social problems

• Mostly medication free•

Entry is ONLY post detox.• Long waiting list• Expensive to provide service• Outcome is mostly dependent

on aftercare available.

Outpatient counselling (No Medication)

• Effective during the early stage of OUD with less severity

• Poor outcome in patients with severe dependence

• Dependent on the quality of counselling services

Methadone Introduced in 1969 Synthetic opioid agonist with long half-life (20-36 Hrs)

Buprenorphine / Buprenorphine-naloxone Introduced in 1980 Mixed agonist/antagonist (partial opioid agonist with high receptor affinity) 8-12 hrs half life at low doses (2mg) & 24-72 hrs at high dose (>16mg)

Natrexone Introduced in 1999 Opioid Antagonist with less effect on opioid with high affinity for opioid

receptors (e.g Buprenorphine )

Thanks You.

Martin, J & Fay, Michael 2001. Cytochrome P450 drug interactions: are they clinically relevant? Australian Prescriber. DOI: 10.18773/austprescr.2001.007

RACGP guidelines on management of pain. Retrieved on 1/5/18 from www.racgp.org.au/your-practice/guidelines/silverbook/common-clinical-conditions/pain-management/#1

Gowing, L, Ali, R, Dunlop, A, Farrell, M & Lintzeris, N, (2014). National Guidelines for Medicated-Assisted Treatment of opioid Dependence. Commonwealth of Australia

Johnson, R. E., Strain, E. C., & Amass, L. (2003). Buprenorphine: how to use it right. Drug and Alcohol Dependence, 70 (Suppl.2). S59-S77.

www.opioiddruginteractions.com