Commonly prescribed analgesic Flashcards
What are commonly prescribed analgesics Called
Non steroidal anti inflammatory drugs (NSAIDS)
What do we need to consider before prescribing NSAIDS
- Drug interactions
2. Patient factors
What is the major ode of action of NSAIDS
Inhibition of the cyclo-oxygenase enzymes 1 and 2 to reduced prostaglandin synthesis
Talk through the synthesis of prostaglandins
1. Phospholipid (Phosphlipase) 2. Arachidonic acid (Cyclic oxygenase COX1, COX2) 3. Cyclic endopeloxides PGG2 (Cyclo oxygenase) 4. prostaglandin 5. PGE2, PGD2, PGF2,
What do prostaglandins produce
- Analgesic actions
- Antipyretic action
3Inflammatory actions
Name the 2 Cyclic oxygenase enzymes
COX1
COX2
Describe COX 1
- It is constitutionally active
- Expressed in many tissues eg kidneys, blood vessels, stomachs
- Unwanted/ adverse affects of NSAID are predominately down to COX 1
Describe COX 2
Is an inducible enzyme inducted by inflammatory cells
The unwanted effects of NSAIDS are due to which COX enzyme
COX1
What do several prostaglandin make
Nociceptors that response to mediators such as 5-HT, bradykinin
How are NSAIDS effective painkillers
They stop prostaglandin synthesis
Talk through the antipyretic effect of NSAIDS
- Bacteria leads to infection in a healthy body
- Bacterial toxin released
- Macrophages activated
- NSAIDS block COX2 metabolised PG synthesis
- This returns the body back to normal rather than pyrexia occurring
What is pyrexia
Body temperature greater than 38
What are the anti inflammatory effects of NSAIDS
COX-2 inhibition of prostaglandins synthesis leads to:
- Less vasodilaiton
- Less tissue oedema
- Less sensitisation of nociceptors
What does less vasodilation lead to
Reduced flushing and reduced redness of skin
What do we mean by less tissue oedema
Reduced swelling
What do we mean by less sensitisation of nociceptors
Analgesia
Name the most common NSAID agents
- Salicylates e.g. aspirin
- Paracetamol
- Proprionic acid derivatives EG ibuprofen, naproxen
- Selective COX-2 inhibitors
- Enoic acids
What is aspirin made of
acetylsalicylic acid
Give examples of Proprionic acid derivatives
Ibuprofen
Naproxen
What is the half life of ibuprofen
2 hours
What is the half life of naproxen
14 hours
why might we prefer Proprionic acid derivatives over aspirin
As Proprionic acid derivatives are better tolerated in regards to gastrointestinal effects
Give examples of selective COX-2 inhibitors
etoricoxib,
celecoxib,
parecoxib
When are selective COX-2 inhibitors used
most commonly prescribed in Rheumatology
Give example of Enoic acids NSAIDS
piroxicam,
meloxicam,
ketorolac,
diclofenac
Aspirin and ibuprofen selectively inhibit which form of COX
Weakly COX-1 Selective
How does aspirin work
It binds irreversibly to COX-1 hence the effects outlasts presence of the drug
Diclofenac selectively inhibit which form of COX
Weakly COX-2 selective
Celecoxib selectively inhibit which form of COX
Moderately COX-2 selective
Etoricoxib selectively inhibit which form of COX
Very COX-2 Selective
How does paracetamol work
It is a reversible non competitive COX inhibitor
What is paracetamol effective against
Pain relief and anti pyretic actions
What are gastrointestinal effects of NSAIDS
- Dyspepsia
- Nausea
- Gastritis
- Intestinal damage
- Bleeding
- Oral ulcerations
what are the bleeding risks of NSAIDS
- Anti platelets activity exacerbates gastrointestinal bleeding
- Increased risk of thrombotic effects eg MI or stroke
What other side effects may NSAIDS have
- May have irritant effect on skin or mucosa
- Skin rashes
- Bronchospasm
- Nephritis and papillary necrosis
What does aspirin overdose have an impact on
Acid base balance
What can changes in acid base balance lead to
respiratory alkalosis or respiratory and metabolic acidosis
What can overdose of aspirin cause
- Hyperpyrexia
- Nausea and vomiting
- Vertigo, tinnitus and haring impatient
What is Hyperpyrexia
Body temperature of 40 plus
What is reyes syndrome
A syndrome present in children given aspirin for viral infections to lower their high temper
What is the mortality rate for reyes syndrome
20-40%
How do we avoid reyes syndrome
Never prescribe aspirin for those under the age of 16
Above what dose can paracetamol start causing problems
A dose of 10-15g
What is the maximum dose of paracetamol for a Healthy adult
1g per day in 4 divided doses
What are the major side effects of paracetamol overdose
Severe liver damage
How does liver damage manifest as a consequence of paracetamol over dose
Hepatitis which can be severe enough to end in acute liver failure and death
What is the toxic metabolite produced as a consequence of paracetamol overdose
N-acetyl-p-benzoquinone
Why is N-acetyl-p-benzoquinone toxic
There is limited capacity for the body to remove this
How is N-acetyl-p-benzoquinone toxic usually metabolised
In conjugation with GLUTATHIONE
What are paracetamol overdose patients given
given IV N-acetylcysteine or PO methionine to increase glutathione production to mop up the excess toxic metabolite
