Ruth Flashcards
What are the advantages of taking both paracetamol and ibuprofen?
- Similar duration of action half-life:
- Paracetamol 1-3hrs
- ibuprofen 2-4hrs - Taking at alternate timed does of paracetamol and ibuprofen. If does are alternated gets good analgesic coverage.
- Act on different parts of the pain pathway (different mechanisms)
- Paracetamol: no anti-inflammatory effects, does not inhibit prostaglandins in the periphery, acts by central mechanisms that are not fully understood
- Ibuprofen: Inhibits prostiaglandins in the periphery and inhibits prostaglandins from sensitisation in the nocireceptors - Decrease risk of ADR’s
– different risk profiles
- alternating
- Different metabolic pathways - Synergistic effects (1+1=more than 2 bigger effect that just one drug alone combined effect, additive (1+1=2)
Explain how ibuprofen acts in the pain pathway
Ibuprofen is a NSAID that is a non specific
inhibitor of the COX enzyme.
When cells are damaged, they and other nearby cells start producing a chemical called Arachidonic Acid. The COX enzymes (Cox-1 and Cox-2) convert this Arachidonic Acid into a chemical called Prostaglandin H2. Prostaglandins release from COX2 are inflammatory mediators. These Chemicals cause effect such as increase in body temp, inflammation and lower the pain threshold. Decreased pain threshold means the area becomes sore even to touch.
Cox-1 and Cox-2 have specific receptors for Arachidonic Acid to bind to. Ibuprofen works by temporarily blocking the receptor that the Arachidonic Acid binds to and therefore stopping the production of prostaglandins, which in turn stops the decrease of the pain threshold.
Why is ibuprofen a useful drug for the management of rheumatoid arthritis?
Rheumatoid arthritis is an autoimmune disease. Typical the immune system is in place for fighting of disease or viruses that are foreign to the body and want to cause it harm, but in an autoimmune disease the body turns on itself and attacks the persons own body. In the cause of rheumatoid arthritis, the immune system attacks tissues and other materials that make up our joints. R.A typically beings in the hand and feet causing inflammation and pain. The attack on the tissue causes damage to the cells.
Ibuprofen dose not inhibit the disease process
Ruth experiences a lot of indigestion. This has been attributed to the ibuprofen. She is prescribed omeprazole 20 mg / day. Explain how the pharmacodynamics of ibuprofen can cause symptoms of indigestion
In the stomach, COX1 acts to
1) Increases mucus production
2) Reduces acid secretion - Maintains blood flow
3) Increases bi-carbonate secretion - Maintained ph levels.
This helps protect the stomach lining.
When Ibuprofen is administrated the COX1 enzyme is inhibited. this results in:
- Decrease HCO3 Bicarbonate and Mucosa.
- Increase in stomach acid.
This therefore leads to damage to stomach wall, which results in indigestion.
Symptoms: Acid reflux, pain, bloating, epigastric discomfort.
- Explain why omeprazole is more effective at preventing the symptoms of indigestion than an antacid such as Gaviscon or Mylanta
Ibuprofen indigestion via COX 1 inhibition - loss of mucus and bicarbonate.
Omeprazole- inhibits the hydrogen and potassium pump in the parietal cells, this inhibits the acid secretion. It is irreversible, has a fast onset of action, take for more than 4 days you will get continuous coverage, its onset of action is about 1 hour duration up to 3 days
Antacids Gaviscon and Mylanta- change the ph in the stomach, act directly to neutralise the stomach (acid that’s already been secreted) they are alkaline buffers
So omeprazole is better because it stops the acid secretion in the first place
Antacids- rapid onset, duration is 2-3 hours maximum, therefore omeprazole is a better drug because it has a longer duration of action
Explain what happens when the recommended dose of paracetamol is exceeded
Maximum does of paracetamol is 4g for an adult.
Paracetamol normal metabolism:
- 90% through the liver, via phase 2 glucoronidation or sulphation,
- 10% is via phase one CYP enzymes converting it to the highly reactive N-acetyl-p benzoquinoneimine (NAPQI) enzyme
In cases of paracetamol overdose, the phase 2 (sulfate and glucuronide) pathways become saturated so matabolim moves the phase 1. Gluctone is rapidly used up, leads to excess of NAPQI binds to macro molecules in the liver (e.g proteins and enzymes ) this cause hepatic toxicity.
If enough hepatic cells die, this can lead to live failure and then death.
Over doses can be treated with Acetylcysteine with the first 24hrs.
Acetylcysteine is a precursor molecular to glutathine and binds to NAPQI
Ruth explains that she has blood tests for a blood count and kidney function. She knows that this has something to do with her medication regime. Why is it important for Ruth to have these tests?
Ruth has a past medical history of thrombocytopenia and renal impairment
Thrombocytopenia - Low platelet count.
Low platelet count- increase risk of bleeding
At risk of GI alteration- GI bleeds
COX1 inhibition from ibuprofen
Renal function- inhibition of COX 1 takes away the prostaglandins which are used in the renal function to cause pathways to open and close, prostaglandins cause filtration pressure in renal system.
Renal Failure - impaired glomerular filtration rate.
Ibuprofen
Ibuprofen, paracetamol and aspirin are all classed as non steroidal anti-inflammatory drugs. Explain why Ruth can still take diclofenac and paracetamol but not aspirin.
Aspirin and Ibuprofen have the same ADRs and work on the same place in the pain pathway - so no benefit in taking both. ib prevents aspirin from binding
synergistically increase risk of bleeding due to asp prevention of platelet aggregation.
Explain why that is, using the concepts of minimum effective concentration, half-life and steady state. Paracetamol
(Every 4 hours the amount of the drug is halved)
In order for paracetamol to work it has to be above is minimum effective concentration, in order for ruth to get analgesic effect must be above minimum effective concentration, to get sustained analgesia she has to maintain it about the minimum effective concentration
For paracetamol to do this must be taken every 4-6 hours- needs this because its half life is 3-5 hours, it taken at its half life’s it will maintain its therapeutic state
Ruth is never going to achieve steady state because she is only taking the drug twice daily, she is not going to get continuous cover from drug, because every time she leaves it , to achieve steady state needs to take drug within its half life.
Describe how tramadol works as an analgesic
Synthetic opioids, works on mui receptors, inhibits reuptake or nor adrenaline and serotonin (descending inhibitory pathway), therefore tramadol acts to inhibit nociception, transmission dorsal horn, inhibit transmission central pathways
Outline the advice that Ruth should receive when starting on tramadol
1) Do not exceed prescribed dose,
2) Can cause drowsiness + postural hypertension, caution with driving, or operating heavy machinery, can cause increased risk of fall, dizziness, do not drink alcohol
3) Do not take any over the counter prescribed herbal remedies with out advice – because of its reuptake inhibition with SSRI’s SNRI’s she is at risk of serotonin syndrome, cyp enzymes because of phase 1 metabolism
4) watch for bowel motions check for constipation as it is a opoid, therefore should increase fluid intake
Explain why tramadol is started at a low dose in older adults
Less lean body mass, and higher body fat, tramadol distributes mostly to lean body mass, you have a lower VD (volume distribution) therefore plasma concentration is higher
Clearance decreased by 40% -metabolism and excretion- as you are older less liver function, impaired renal function (excretion of unchanged drug is increased from 15-30 precent because less is getting metabolised in the liver)
Half life is increased
Older adult sensitive to drug effects (pharmacodynamics) including the ADR’s she is processing it less efficiently
What is the classification of morphine under the Misuse of Drugs Act 1975?
CLASS B drug – Pose high risk of causing harm, to individual or society by there misuse
- Explain the meaning of this classification. Misuse of Drugs Act 1975?
- Regulates Controlled Drugs in NZ
- Controlled drugs are substances (licit and illicit) that have potential to cause harm to individuals and society if improperly used
- Drugs are classified as per their potential
a. Class A have a very high potential for harm e.g. heroin
b. Class B have a high potential for harm e.g. morphine
c. Class C have a moderate potential for harm and some addictive potential e.g. products containing pseudoephedrines
