CH Flashcards
Why be wary of CYP2D6 variations when it comes to codeine, Tramadol, Oxycodone, and Dihydrocodeine?
Genetic variation in the CYP2D6 liver enzymes can either result in morphine toxicity in the case of ultra rapid metabolisers (in which case reduce consciousness, somnolence, constipation, respiratory depression, pinpoint pupils and nausea and vomiting should be monitored for).
At the other end, poor metabolisers will have reduced therapeutic effect. However it’s worth mentioning that Dihydrocodeine parent compound has analgesic effect too and Tramadol parent compound is theorised to affect pain via increased inhibition in the spinal cord by acting as a neurotransmitter reuptake inhibitor)
What are the symptoms of opioid overdose for patients on tramadol, codeine, morphine?
Circulatory / Respiratory depression Coma Pinpoint pupils Reduced consciousness Somnolence Nausea and vomiting
How does mu opioid binding affect respiratory rate?
It causes CO2 sensing chemoreceptors to lose their sensitivity resulting in a slower rate of respiration.
Why might Remifentanil be of benefit over Fentanyl and Alfentanyl?
Remi has a unique method of metabolism, in that it is more lipid soluble than morphine and yet is metabolised by non-specific enterases extra-hepatically in blood / tissues, resulting in a faster clearance and consequently if of more use in cases where faster recovery is required.
Why should you avoid Opioids in respiratory depression?
Due to reduced CO2 sensitivity it will further depression the breathing rate.
What are the contra indications of opioids?
Risk of paralytic ileus
Acute respiratory depression
Head injury / raise intercranial pressure ( can reduce the pupillary response needed for neurological assessment).
When would you reduce the dose of opioids?
Adrenalcorticoid insufficiency Debilitated Elderly Hypothyroidism Hepatic impairment (as it may cause a coma).
Why can increasing the dose of Buprenorphine result in reduced pain relief?
Buprenorphine is a partial agonist - Low doses results in interaction with MOP receptor to give pain relief however as doses increases it binds to both NOP and KOP receptors causes anti-analgesic effects.
How does Tramadol act other than via MOP binding? How does this affect drug-drug interactions?
Modulates reuptake of serotonin and noradrenaline.
Increasing serotonin levels can increase the risk of serotonin syndrome when given with SSRI’s, SNRI’s, MAOIs, TCAs, Lithium, Methadone, Triptans, Pethidine, Pentazocine, Amphetamines. Serotonin syndromes presents with neuromuscular hyperactivity,, autonomic dysfunction, altered mental state. So be wary of patients who are potentially on these medications for; anxiety, depression, migraines, addiction, bipolar disorder, parkinsons, chronic pain or ADHD
Can increase the risk of seizures in those prone or with history of epilepsy.
A patient on Tramadol comes back with creatinine clearance of 28ml/min, what is your recommendation?
Does this differ in hepatic impairment?
Increase dosing interval to 12 hours as renal elimination may be impaired.
With hepatic impairment the dosing interval can be increased to 12 hours OR halve dose. C/I in severe.
Our previous patient on Tramadol lab results show creatinine clearance of 9ml / min, how do we proceed?
It is not recommended to be used in this patient.
What are the very common and common side effects of Tramadol?
Very common; Nausea
Common; Vomiting,
Why might you prefer Tapentadol as a strong painkiller?
Due to MOP and noradrenaline reuptake modulation it can result less opioid side effects such as constipation, nausea and vomiting.
Why do patients on methotrexate (for non malignant indications, e.g. Crohns, RA) take folic acid?
Methotrexate inhibits dihydrofolate reductase the enzyme responsible for reducing dihydrofolate to tetrahydrate folate (co factor in thymidylate synthesis - purines) this can result in various side effects (ab pain, diarrhoea, GI bleeding, malaise, nausea, visual disturbances are a few of many) due to affecting DNA synthesis.
Folic acid reduces the incidence of these.
Why would you refer a patient on Methotrexate experiencing:
Sore throat, mouth ulcers, bruising
N+V, ab discomfort, dark urine
Breath shortness, dyspnoea, cough, fever
Respiratory effects including shortness of breath could be signs of pulmonary toxicity, referral needed if above and if pneumonitis suspected - discontinue
Liver issues such as cirrhosis
Could be signs of infection due to reduced immune response
Why can Trimethroprin and proguanil/ pyrimethamine increase risk of side effects when taken with methotrexate?
Act via a similar mechanism - dihydrofolate reductase inhibition.
Why is it important to continually confirm a patients methotrexate dose, frequency, tablet strength and enquiry about health issues?
Due to risk of various toxicities, blood disorders presenting as sore throat, mouth ulcers, bruising. Liver toxicity presenting as NV, abdominal discomfort, dark urine. Respiratory toxicity presenting as SoB, dyspnoea, cough and fever.
GI toxicity first presenting as stomatitis
It is contraindicated in infection so signs of this require referral.
Why monitor FBC on methotrexate?
To check for clinically significant bone marrow suppression, in which the risk increases with age / renal impairment and if on Trimethropin
Why would a patient on methotrexate prescribed the following require possible intervention?
NSAIDs
PPIs
Retinoids
Trimethropin
Quinolones
Sulfamethoxazole/Sulfadiazine/Sulfadoxine
Others…
NSAIDs, retinoids Trimethropin, Penicillins, Quinolones all increase risk of toxicity so would be avoided (except NSAIDs in which dose monitoring and reduction appropriate)
PPIs reduce clearance so use with caution or avoid.
Sulfa’s increase exposure so use caution or avoid.
Caution in hepatotoxic, nephrotoxic, myelosuppressive or drugs that increase risk of thromboembolism.
Why are opioids contraindicated in acute respiratory depression and cautioned in asthma?
The mew receptors mediate respiratory depression so when activated reduce sensitivity to plasma CO2 and inhibit respiratory rhythm generation. It should be avoided in acute asthma attack and COPD.
Opioids also cause histamine release leading to itching, bradycardia, hypotension and importantly BRONCHOCONSTRICTION.
Why might you need 5HT3 antagonists, antihistamines, droperidrol or Prochlorperazine, especially initially, in opioid use?
Nausea and vomiting due to opioid action on chemoreceptor trigger zone in medulla.
Why are opiates contraindicated in biliary disease?
Opioids cause biliary sphincter contraction and gall bladder contraction
increase risk of gallstones (increased amylase and lipase) in biliary colic so avoid
Why does morphine need dose reduction in liver and renal impairment?
In liver metabolised primarily by glucoronide conjugation and impaired function may cause a coma.
In renal the 3/6 metabolites are excreted.
Why would you be vigilant administrating Naloxone to buprenorphine, methadone and pentazocine?
Both Buprenorphine and Pentazocine are partial agonists so may not have full effect.
Both Buprenorphine and Methadone are long acting and repeated dosing of Naloxone May be required.
Why would you stop Phenelzine before surgery?
As a MAOI (other monoamine oxidase inhibitors include Isocarboxazid, Tranylcypromine, and Moclobemide, the latter a reversible type A antagonist) it has many interactions (could potentiate hypotension or hypertension) and so should be stopped 2 weeks before surgery, albeit and ideally in a tapered withdrawal of 4 weeks (can cause movement disorders, insomnia, agitation and even potentially hallucinations)
Why would you stop Yasmin before surgery?
Yasmin is a COC combining ethinylestradiol and drosperidone, other Monophasic COCs include Gedarel, Cilest, Rigevidon, Loestrin, which all vary in their progesterone element. Some biphasic include Logynon, which vary amounts per week.
Ideally COCs should be stopped 4 weeks before all major surgery/ leg surgery/ surgery resulting in prolonged immobilisation due to increases of venous thrombosis. A progesterone only contraceptive, such as Levonogestrel (Cerazette, Cerelle, Zelleta) should be started after a complete cycle (no break) in this case. COC can be restarted 2 weeks after the first menses after mobilisation.
How would you deal with a patient unable to stop COC before major surgery, ie. in emergency trauma?
Recommend a low molecular weight heparin (Enoxaparin, Dalteparin, Tinzaparin) and graduated compression hosiery in order to reduce risk of thrombosis.
Why would you stop Lithium 24 hours before major surgery? Is it different for minor?
Lithium should be stopped 24 hours before surgery due to fluid and electrolyte changes.
In minor surgery, can continue with lithium if fluid and electrolytes are monitored (contraindicated in dehydration and low salt as can change lithium plasma concentration leading to overdose - GI issues, tremor, CNS and cardiac issues).
Why give premedication to patients before surgery?
Use of benzodiazepines (Temazepam, Diazepam. Midazolam) will reduce anxiety/ sleep issues, augment anaesthesia, reduce extraneous movements from drugs like Propofol and Etomidate and potentially give amnesia.
This can be given as dose night before and smaller one just before or just the first dose on day of surgery.
The alpha adrenergic agonist Clonidine is also used when standard treatment does not give enough sedation.
In what situations would the short recovery of Midazolam increase?
May have slower recovery if used repeatedly, if used in the elderly or in patients with low cardiac output.
Increased dose and a large drug combination before surgery could cause profound sedation too.
Why might you use oral Temazepam over IV Diazepam?
Temazepam is fast acting even when oral so less invasive and diazepam can be painful upon injection due to low water solubility (therefore preferable to use emulsion).
Why might you avoid use of Ketamine in anaesthesia?
Psychotic effects can present, albeit transiently, giving rise to hallucinations, nightmares (though benzos can reduce this). Ketamine can also give a slow recovery and extraneous muscle movements.
How would you prevent NO associated hypoxia?
Mixture to have at least 30% oxygen and run the oxygen for several minutes after stopping NO.
Do not give longer than 24 hours and do not use more than once every 4 days without close supervision and haematological monitoring.
Why might you avoid intramuscular injections of Diclofenac and Ketopofen post op?
Patients with cardiac impairments, heart disease/ failure, elderly or with Crohns / UC (may exacerbate)
Why give IV infusion of Remifentanil over repeated IV Alfentanil dosing during surgery as opioid enhancement of anaesthesia?
Remifentanil has a short half life (metabolised by blood and tissue esterases not in the liver) allowing the infusion to be terminated and giving no respiratory depression affects making it far more preferable in cases where ventilation is needed, whereas Alfentanil can give rise to post op respiratory depression.
Please note; all fentanils can lead to muscle rigidity requiring antimuscarinic management.
Why might you switch to Atracuronium from the other non depolarising neuromuscular blockers?
All the others require caution, monitoring a dose changes in renal (impairment = increased duration) and liver impairment
