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Medsci305 > Lecture 17: NSAIDs and local anaesthetics > Flashcards

Lecture 17: NSAIDs and local anaesthetics Flashcards

1
Q

What is an inflammatory response?

A
  • the dynamic response of tissue to injury

- it is a protective response which serves to bring defense and healing mechanisms to the site of injury

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2
Q

What is the normal function of the inflammatory response?

A
  • one which switches on and off.

- in diseased states this switch is broken so we require drugs to control this reaction in order to treat the symptoms

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3
Q

What are the causes of inflammation?

A
  • microbial infections (bacterial, viral, fungal)
  • physical agents (burns, trauma-like cuts, radiation)
  • chemicals (drugs, toxins or caustic substances like battery acid.)
  • immunological reactions (rheumatoid arthritis)
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4
Q

What are the 4 signs of inflammation?

A
  1. redness due to vasodilation
  2. swelling due to influx of plasma proteins, phagocytes, and other inflammatory cells into the site.
  3. heat due to local vasodilation and fever aimed to destroy pathogen
  4. pain due to local release of cytokines and increased tissue pressure
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5
Q

How can inflammation be controlled?

A

we can inhibit PG synthesis through the use of:

NSAIDs which target and block cyclooxygenase, (enzyme)

or glucocorticoids which prevents the conversion of phospholipid to arachadonic acid

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6
Q

What is the PG production pathway?

A
  • phospholipids are converted into arachadonic acids.
  • arachadonic acid is then converted into cyclic endoperoxidises by COX
  • these will then form prostaglandins
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7
Q

What are the different functions of the prostaglandins?

A

PGA2- bronchoconstriction
PGD2- vasodilation
PGE2- increases gastric mucous and decreases gastric secretions. also involved in thermoregulation
PGI2- dilator and inhibits platelets
TXA2- activates platelets to increase pain

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8
Q

Why is COXII the ideal enzyme to target for NSAID drugs?

A

-Cox I is constructive and found in a lot of cells and involved in the formation of PGs with homeostatic roles while COXII is induced in inflammatory cells by specific stimuli and prostaglandins.
COX II has a major role in mediating inflammation, therefore it is the better anti-inflammatory target

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9
Q

What are NSAIDs?

A
  • group of drugs of different chemical classes
  • main functions are anti-inflammatory, analgesic and antipyretic
  • normally they will target COX enzymes and bind irreversibly to the active site (aspirin is reversible)
  • unwanted side effects stem from inhibition of COX I activity
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10
Q

What are the COXI specific drugs?

A
  • aspirin
  • indomethacin
  • Sulindac
  • piroxicam
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11
Q

Which NSAIDs bind less to COXI?

A
  • ibuprofen
  • paracetamol
  • naproxen
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12
Q

Which NSAIDs bind equally to both COX enzymes?

A
  • diclofenac

- keterolac

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13
Q

Which NSAIDs are COXII selective?

A

celecoxib
rofecoxib
valdecoxib

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14
Q

What are the desired effects of NSAIDs?

A
  • analgesia: reduction of PG production
  • antipyretic: Reduged PGE2 production in hypothalamus
  • very strong anti-inflammatory effects
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15
Q

What are the undesired effects of NSAIDs?

A
  • often stem from widespread, long term use
  • dyspepsia, gastric ulceration, bleeding
  • sometimes can cause skin reactions (rare)
  • renal effects as PGs mediate afferent arteriole vasodilation
  • inhibits platelets (mainly aspirin)
  • exacerbation of asthma
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16
Q

What are the symptoms of aspirin toxicity?

A
  • headache
  • dizziness
  • hearing impairment
  • dimmed vision
  • confusion and drowsiness
  • sweating and hyperventilation
  • nausea and vomiting
  • disturbances in acid base balance
  • fever
  • dehydration
  • CV or respiratory collapse
  • coma, convulsions
  • death
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17
Q

What is indomethacin?

A
  • commonly causes adverse reactions like GI bleeds, ulceration, CNS reactions.
  • can also cause depression, seizures, headaches and dizziness
  • ibuprofen and naproxen are better and widely used for arthritis and will have fewer side effects
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18
Q

What is the cardiac risk of COX inhibitors and the example?

A

Vioxx was released into the market but had to be withdrawn as it was COXII selective and found there was a 4fold increased risk of heart attacks.

  • due to inhibition of endothelium PGI2
  • TXA2 production was not inhibited causing problems
  • diclofenac is similar in the risk of CV events
  • naproxen is the safest for the heart
19
Q

What are the common drug interactions with NSAIDs ?

A

oral anticoagulatns + NSAIDs
lithium + NSAIDs
anti-hypertensive agents + NSAIDs

20
Q

What is the drug interaction between oral anticoagulatns + NSAIDs?

A
  • most cause increased risk of internal bleeding (e.g. warfarin)
  • both drugs reduce platelet activity
  • monitor using prothrombin time and for faecal occult test and urine test
  • avoid concurrent use of aspirin
21
Q

What is the interaction between lithium and all NSAIDs?

A
  • lithium concentrations will be affected, increases risk of lithium toxicity
  • need to monitor Li concentrations carefully
  • these interactions are less likely to occur with aspirin than they are with naproxen or ibuprofen
22
Q

What is the interaction between anti-hypertensives and NSAIDs?

A
  • hyperkalaemia can occur with potassium sparing diuretics and ACE inhibitors
  • antihypertensive effect is antagonised with NSAIDs
  • need to monitor BP and cardiac function as well as K+ concentrations
  • low dose aspirin (7.5mg/day) may not interact with ACE inhibitors
23
Q

Why does diclofenac and warfarin cause serious internal bleeding?

A
  • diclofenac plays a role in reducing platelet aggregation leading to poor clotting
  • warfarin also induces poor clotting through reduction in vitamin K and hydroquinone in tissues.
  • This also inhibits the Vitamin K dependent clotting factors (2, 7, 9, 10)
  • stop the drug and change to safer drugs
24
Q

What are anaesthetics?

A
  • agents who reversibly block the conduction of APs in the nerve fibres when administered locally
  • mostly esters/amides
  • most modern agents are amides
25
Q

What are examples of anaesthetics which are esters?

A
  • procaine
  • benzocaine
  • tetracaine
26
Q

What are examples of anaesthetics which are amides?

A
  • prilocaine
  • lignocaine
  • bupivacaine
  • ropivacaine
27
Q

What is proprionic acid?

A

better tolerated but differ in pharmacokinetics.

ibuprofen, naproxen are widely used for inflammatory joint disease with few side effects

28
Q

What do all of the anaesthetics have in common?

A

they are all weak bases and release H+ to become a free base in the body. This allows them to cross membranes and into cells

  • the amount of free base present at physiological pH depends on the pKa of the drug (henderson hasselbach)
  • the more free base present, the faster the onset of action
29
Q

What is the general trend with pKa and % base?

A

as pKa decreases, the % of free base increases as pKa is close to the physiological pH.

30
Q

Which anaesthetic has the fastest onset of action according to pKa?

A

mepivacaine

31
Q

What is the mechanism of action of anaesthetics?

A
  • dissociates to become a free base
  • inside the cell, it binds with a H+ to form a full molecule again
  • This can bind with the sodium channel which blocks the function of the channel
  • prevents Na ions from influxing into the cell.
  • reduces depolarisation, reduces action potential transmission of nerves
32
Q

How are anaesthetics used?

A

-used widely by dentists for small surgery:

  • topical administration to skin
  • topical admin to mucous membranes
  • local infiltration
33
Q

How are anaesthetics administered to the skin?

A
  • can apply directly to numb before putting needles in

- these anaesthetics have a special formula which make it easier to penetrate the skin

34
Q

How are anaesthetics administered to topical mucous membranes?

A
  • added benefit of cocaine is to cause vasoconstriction

- e.g. Lignocaine spray and viscous preparations are used before endoscopy

35
Q

How are anaesthetics administered by local infiltration?

A

-they can be diffused into soft tissues and used for minor surgeries like mole removal and post operative pain relief

36
Q

What are the different options for treating pain?

A

the site of function of local anaesthetics blocks the nerve condutions, targeting to different sites will achieve slightly different effects.

  1. peripheral nerve block
  2. central nerve block
37
Q

What is peripheral nerve block?

A
  • lignocaine is infiltrated around specific nerve to remove teeth
  • can also be used in a mixed nerve or smaller sensory fibres.
  • for a small surgical operation you can block peripheral nerve to achieve the general anaesthetic e.g. managing post operative pain relief
38
Q

What is central nerve block?

A
  • use of local anaesthetic to achieve spinal anaesthetic
  • administration is very important
  • allows us to do major surgery like hip replacement or caesaren section
39
Q

What is an epidural?

A
  • where anaesthetic is inserted using a catheter
  • usually for women in labour
  • the tube is left in there to achieve the best anaesthetic effect where you don’t have pain, but can still control the muscles to push the baby out
  • need to control the dose very carefully as it could be needed for 2 hours
  • drug is released by computer controlled device
40
Q

What is the advantage of an epidural?

A
  • allows women to retain energy which occurs when in pain
  • can still feel muscles to control and push baby out
  • helps oxygen supply to baby as procedure is under control
  • excellent for post operative pain control too
41
Q

What are the limitations of an epidural?

A
  • there are still some side effects and potential risks

- however pros seem to outweigh the cons

42
Q

What is lignocaine?

A
  • low pKA (fast onset) amide derived anaesthetic
  • has lower protein binding, so short duration of action
  • ideal to be used in a short procedure where a rapid onset is required (dental surgery)
43
Q

What is bupivacaine?

A
  • high pKa (slow onset) amide derived anaesthetic
  • has high protein binding - longer duration of action
  • ideally used when prolonged action is needed e.g. post operative pain relief using nerve blocks or tissue infiltration, spinal or epidural anaesthesia

Medsci305 (17 decks)

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