NSAIDs and Paracetamol Flashcards
What nerve and its divisions cause dental pain?
Maxillary and mandibular divisions of the trigeminal nerve
What 2 types of fibres are found in the dental pulp?
- High threshold (fast) mechanoceptors connected to Aδ axons
- Polymodal nociceptors (slow) which are bare nerve endings of C fibres
What type of pain is felt if high threshold mechanoceptors are stimulated?
Sharp pain
What type of pain is felt if polymodal nociceptors are stimulated?
Dull ache
What is the name given to 2 drugs working together?
Synergy
Why can synergistic drugs help control dental pain?
Drugs work at different levels to control pain
Describe the peripheral mediators of pain
- Trauma or infection stimulates activity of phospholipase A₂
- Increases arachidonic acid formation from cell membrane phospholipids
- Phospholipids acted on by cyclooxygenases and lipoxygenases to create prostaglandins and leukotrienes
Give 5 methods of relieving pain
- Remove stimulus
- Interrupt nociceptive input
- Stimulate nociceptive inhibitory mechanisms
- Modulate central pain awareness
- Treat secondary factors contributing to pain
Name 2 ways which nociceptive input can be interrupted
- NSAIDs
2. Local anaesthetic
Name a method of controlling central pain awareness
Opiates
Name 5 drugs which can control pain (in ascending order of effectiveness)
- Paracetamol
- Codeine
- Dihydrocodeine
- Tramadol
- Morphine
Why is paracetamol not considered an NSAID?
It does not have anti-inflammatory properties
Give 2 ways paracetamol can be described
- Simple analgesic
2. Antipyretic
Why is paracetamol considered an antipyretic?
Inhibits hypothalamic heat-regulation centre
What is the likely mechanism of how paracetamol works as a simple analgesic?
Inhibits prostaglandin synthesis in the brain so inhibits pain via CNS inhibition of COX-3
What inactivates paracetamol?
Conjugation with glucuronide
What occurs if paracetamol is consumed in overdose?
Supply of glucuronide is depleted leading to liver and renal toxicity
Name 2 metabolites in which paracetamol is removed from the body
- Sulphate metabolite
2. Glucuronide metabolite
What occurs if paracetamol is not conjugated?
- It is oxidised by cytochrome P450
- It conjugates with glutathione to form non-toxic mercapturic acid
- If glutathione is absent, hepatic and renal damage can occur
Describe aspirin as a drug
Irreversible non-selective inhibitor of cyclooxygenase (COX)
For what COX does aspirin have greater affinity?
COX-1
What are the 3 therapeutic doses of aspirin?
- Low (<300mg/d)
- Medium (300-2400mg/d)
- High (>2400mg/d)
What is the function of each therapeutic dose of aspirin?
- Low - Anti-platelet
- Medium - Analgesic and antipyretic
- High - Anti-inflammatory
Name 4 potential toxic side effects of aspirin
- Dyspepsia (gastric upset)
- Gastric ulceration and bleeding
- Analgesic nephropathy
- Increase bronchoconstriction in asthmatic patients
Name 5 potential effects of aspirin if taken in overdose
- Tinnitus
- Hyperventilation
- Respiratory alkalosis
- Hyperthermia
- Coma
What can occur in children is aspirin is taken in overdose?
Reye’s syndrome
What is the major difference between aspirin and NSAIDs?
NSAIDs are reversible inhibitors of COX1 and COX2
Name 4 main NSAIDs used in the UK
- Ibuprofen
- Naproxen
- Indometacin
- Diclofenac
What 3 processes are prostaglandins produced by COX-1 involved in?
- Protection of gastric mucosa
- Platelet aggregation
- Renal blood flow autoregulation
Why is it desirable to have NSAIDs with greater affinity to COX-2?
COX-2 is induced at sites of inflammation so if NSAID has greater affinity to these enzymes, it is more likely to reduce inflammation with less physiological side effects i.e. reduction of processes carried out by prostaglandins
What are the 5 main uses of NSAIDs?
- Analgesia
- Anti-inflammatory
- Antipyretic
- Prolongation of labour
- Patency of ductus arteriosus
How do NSAIDs work as antipyretics?
Block PG action on hypothalamus
Name 5 areas of the body which can be adversely affected by NSAIDs
- GIT
- Kidney
- Cutaneous
- Liver
- Blood
How can the GIT be affected adversely by NSAIDs?
Inhibition of mucosal prostaglandins can promote erosions and ulceration
What 2 ways can the kidney be affected adversely by NSAIDs?
- Renal blood flow can decrease
2. Analgesic Nephritis
Name 3 adverse affects of NSAIDs on cutaneous areas of the body
- Urticaria
- Rhinitis
- Asthma
Name 6 possible drug interactions with NSAIDs
- ACE inhibitors and ARBs can cause loss of renal function
- Quinolone antibiotics can lead to convulsions
- Anticoagulants can lead to bleeding
- Antihypertensive drugs can reduce effect of NSAIDs
- Antidepressant drugs can lead to GI bleeding
- Lithium can cause high levels of toxicity as NSAIDs stop lithium elimination
Name 6 situations where NSAIDs are contraindicated
- Patient with peptic ulcer disease
- Patient with history of GI bleeding
- Patient receiving anticoagulants
- Patient with renal impairment, heart failure or hypertension
- Used with caution in pregnancy
- Previous history of allergic reactions e.g. asthma
Name 2 COS-2 selective inhibitors
- Rofecoxib
2. Celecoxib
