Methadone synoptic 2025

Question 1

What are the functional groups in methadone?

Answer 1

• Ketone
• Tertiary amine
• Aromatic rings
• Chiral centre

Question 2

What does the functional group: Ketone, contribute to in methadone?

Answer 2

• Makes sure drug is in proper orientation at receptor binding site
• Enhances binding affinity/stability by forming weak hydrogen bonds with amino acids in receptor
• Adds slight polarity but aromatic rings and amine group helps maintain a balanced lipophilic profile

Question 3

What does the functional group: Tertiary amine, contribute to in methadone?

Answer 3

• binds with mu-opiod receptor) by mimicking natural opiods e.g. endorphins
• Can be protonated making it positively charged
• This allows it to electrostatically interact with negatively charged asparte residue in receptor
• Contributes to lipophilicity when it is neutral/deprotonated as it becomes non polar
• Amine group undergoes N-methylation which gives longer drug duration -> longer half life -> long lasting effects (so good for long term maintance such as for addition therapy)

Question 4

What does the functional group: Aromatic rings, contribute to in methadone?

Answer 4

• lipophilic property bc they are hydrophobic- helps cross cell membranes e.g. BBB
• penetrates brain efficiently to bind to receptors leading to faster onset of action
• lipophilicity allows methadone to be distributed and stored in tissues like fat -> long half life
• Interacts w lipophillic areas of receptor to stabilise the binding

Question 5

What does the functional group: chiral centre, contribute to in methadone?

Answer 5

• Has 1 chiral carbon
• Standard methadone is administered as a racemic mixture (50:50 of both enantiomers R and S methadone)
• R is the active opioid- responsible for pain releif and addiction treatments
• S has little to no opioid activity but may influence side effect especially cardiac ones
• It takes time and money to develop enantiopure formulations e.g. Levomethadone (R)

Question 6

Physical properties: Solubility, What is it and what does it mean?

Answer 6

• Low in water, high in organic solvents e.g. ethanol
• lipophilic nature allows absorption across cell membranes like in GI tracts and BBB
• Low solubility in water: can be easily absorbed when taken orally (esp at high concs) even if it does not dissolve in blood much

Question 7

Physical properties: lipophilicity/log p , What is it and what does it mean?

Answer 7

• log p= 3.93 (high lipophilicity)
• Helps absorption through GI tract and cross BBB efficiently to reach opioid receptors in the brain.
• Allows accumulation in fat tissue leading to long lasting effects and long half-life (good for opioid addiction treatment)

Question 8

Physical properties: molecular weight, What is it and what does it mean?

Answer 8

• 309.4 g/mol
• Moderate sized molecule compared to smaller opioids e.g. morphine
• Efficient metabolisation in liver and still have enough size to interact effectively with opioid receptors after
• This reduces oral bioavailability to 70-90% which is still higher than most other opioids

Question 9

Physical properties: Mp and Bp, What is it and what does it mean?

Answer 9

• High MP: 230-232 degrees and BP: 500 degrees
• Relatively stable compound under normal environmental conditions
• good for storage and shelf life
• Also solid at room temp so formulated mostly as oral tablets (or liquids) for medical use

Question 10

Physical properties: pKa, What is it and what does it mean?

Answer 10

• pKa: 9.2
• Measure of acid dissociation constant
• Means Methadone is weak base, and its tertiary amine group can accept protons under more acidic conditions making it positively charged/ionised -> water soluble
• higher pH will be deprotonated and is neutral -> lipophilic
• at physiological pH/body’s normal pH (7.4), methadone exists as a mix of protonated and deprotonated forms (more deprotonated forms)

Question 11

Physical properties: density, What is it and what does it mean?

Answer 11

• Density: 1.05 g/cm^3
• Slightly denser than water so will remain in solution when prepared in liquid form
• so can be easily suspended in solutions for oral or injectable administration.

Question 12

Physical properties: refractive index, What is it and what does it mean?

Answer 12

• Around 1.57
• measure of how much light bends when passes through substance
• used for quality control of formulation consistency in the drug

Question 13

Side effects: Constipation

Answer 13

• Methadone can slow down GI tract by acting on mu-opioid receptors in the gut and so results in slower movement of stool through intestines

Question 14

Side effects: Nausea/vomiting

Answer 14

• Opioids inc methadone can stimulate chemoreceptor trigger zones in the brain that controls sensation of nausea
• Methadone’s binding to receptors in CNS can trigger this response

Question 15

Side effects: Drowsiness

Answer 15

• Methadone is a CNS depressant
• By binding to mu-opioid receptors in brain it produces analgesia (pain relief) and sedative effects- these effects can cause drowsiness.

Question 16

Side effects: Respiratory depression

Answer 16

• Methadone binds to mu-opioid receptors in brainstem which is responsible for regulating breathing
• This can lead to shallow or slow breathing- can lead to hypoxia (low o2 levels)

Question 17

Side effects: Dizziness/temp vision loss

Answer 17

• Methadone cns depressant effects can cause drop in BP
• bc opioids can affects the autonomic nervous system which regulates bp and hr

Question 18

Side effects: How to manage?

Answer 18

• Dose adjustments
• careful monitoring
• use of additional meds e.g. laxatives for constipation

Question 19

Contraindications: What is the difference between relative and absolute?

Answer 19

Relative- if benefits outweigh risk
Absolute- should never do

Question 19

Contraindication: Severe liver disease (for methadone maintenance treatment):

Answer 19

• could cause/worsen brain conditions due to dysfunction to liver - happens when liver isn’t filtering toxins as it should
• Toxins build up in blood and affects brain causing confusion, disorientation and other changes
• Treatable but can be life threatening especially for those already at risk.]

Question 20

Contraindication: Intolerance

Answer 20

• Can do more harm than good due to adverse reactions

Question 21

Contraindication: Respiratory depression (hypoventilation- when breathing too slow or shallow), asthma, and CNS related conditions (e.g. trauma, increased intercranial pressure (rise of pressure in skull due to fluid buildup or brain swelling), dementia, and delirium:

Answer 21

• Caution advised bc methadone can cause CNS depression (decrease brain activity) and compromise respiratory system even more

Question 22

Contraindication: drug interactions

Answer 22

• Some can increase methadone’s ability which means higher overdose/dependance risk e.g benzodiazepines
• some decrease this ability e.g. phenobarbituals which means methadone isn’t working as it should as e.g. pain reliever

Question 23

What are the indications for methadone treatment?

Answer 23

• Pain reliver/anagesic for long term pain
• For treatment/therapy of opioid addiction/dependancy

Question 24

Routes of administration: oral

Answer 24

- (most common) - Convenient and easily absorbed through GI tract - high oral bioavailability (70-90%) - long duration of action so often used in maintenance therapy for opioid addiction and chronic pain releif - Long half-life allows for less frequent dosing -> convenient for patients

Question 25

Routes of administration: IV

Answer 25

- Hospital use such as for acute pain management, or detoxification of opioid dependent patients who need rapid relief from withdrawal symptoms - Has faster onset and more intense effects- not used for long term treatment due to overdose and addiction risks

Question 26

Routes of administration: SC and IM

Answer 26

- For specific cases e.g palliative care - steady but less rapid onset of effects

Question 27

Routes of administration: Rectal

Answer 27

- When oral isn’t possible such as patients who cannot swallow of have GI issues that impair absorption - As it bypasses some metabolism in the liver, it can have higher bioavailability than oral

Question 28

How should you counsel patient on methadone?

Answer 28

- Refer to bnf for specifics - Background checks e.g. health record - Side effects - Label 2: Warning: This medicine may make you sleepy. If this happens, do not drive or use tools or machines. Do not drink alcohol