Antipyretics Flashcards
1
Q
what are antipyretic analgesics?
A
- Analgesic drugs that also reduce fever by reducing the body temperature
- Aspirin, ibuprofen (Non-steroidal anti-inflammatory drugs)
- Analgesic
- Antipyretic
- Anti-inflammatory
- Paracetamol
- Analgesic
- Antipyretic
2
Q
how is the body temp normally controlled?
A
- Normal body temperature is circadian
- 36.4°C in morning to 36.9 °C in the late afternoon
- Thermoregulation is produced by a network of neural connections:
- Hypothalamus, limbic system, brainstem, reticular formation, spinal cord and sympathetic ganglia
- The hypothalamus “sets” the mean body temperature
- Temperature-sensitive neurons integrate afferent messages from core body and periphery to modulate behaviour to maintain this “set” mean body temp
3
Q
what happens if the core temp of the body gets too low?
A
body needs to increase heat conservation
- vasoconstriction of blood vessels causing them to contract and move away from skin whilst maintaining blood flow to heart and core organs
- piloerections causes hairs to raise and trap air and insulate the boyd
- body would also shiver to increase heat production
4
Q
what happens if the core body temp is too high?
A
the body needs to increase heat loss
- vasodilation
- sweating, this cause water to be evaporated off the skin and remove heat with this
- body has to try and decrease heat production
5
Q
what is pyresis?
A
- Thermostat raised
- Heat production and loss is in balance
- Feel cold
6
Q
what is hyperthermia?
A
- Thermostat not altered
- Heat production > heat loss
- Feel hot
7
Q
what is the pathogensis of a fever?
A
- Occurs due to release of cytokines released in response to tissue injury and infection
- microbial surface components
- Gram-negative endotoxin (outer membrane lipopolysaccharide)
- “Critical” endogenous mediators are:
- Interleukin 1b (IL-1b), tumour necrosis factor (TNF) & Interleukin 6 (IL-6)
- They work directly on the hypothalamus to effect a fever (pyretic) response
8
Q
what is the pathogenesis of pyresis?
A
- IL-1b, TNF and IL6 causes increase in prostaglandin synthesis
- PGE2 raises “thermostat” in the thermoregulatory centre in the hypothalamus
- Through binding to E-prostanoid receptors (EP3 and EP4 receptors)
- Core temperature is sensed as too low
- Feel cold
- Increased heat gain / conservation
9
Q
what is the common mechansims of action?
A
- inflammatory stimulus
- release phosphilipase A2
- this produces AAcid
- this goes to produce lipoxygenase and cyclooxygenease –> this is the on that is important
10
Q
what are the different types of Cox enzymes?
A
- COX-1
- Constitutive
- Present in many tissues
- Functions to maintain physiological levels of prostaglandins
- COX-2
- Induced during inflammation
- COX-3
- Constitutive
- Splice variant of COX-1
- Present in the spinal cord and brain
11
Q
which cells produce Cox 2?
A
- Macrophages, endothelial cells, synoviocytes, chondrocytes all have the capacity to rapidly produce COX-2 enzyme when required
- In the CNS (hypothalamus), microvascular endothelial cells are the most important in producing COX-2 during the fever response
12
Q
how does a cox inhibitions enzyme work?
A
this blocks AA from producie cyclooxygenases
13
Q
which drugs inhibit cox enzyme?
A
- Aspirin, ibuprofen…
- COX-1 & COX-2
- Selective COX-2 inhibitors
- COX-2 only
- Paracetamol
- COX-3? & COX-2 (weak
14
Q
how does aspirin bind?
A
irreversible
15
Q
how does ibuprofen bind?
A
reversible and competitive
16
Q
how does paracetamol bind?
A
reversible and non-competitve
17
Q
what is anti-pyretic action/
A
- Aspirin, NSAIDs and paracetamol inhibit COX enzymes
- COX-2
- COX-3
- Prostaglandin production decreased
- Thermostat brought back to normal
- Sweat and vasodilate to lose heat
- Core temperature restored
18
Q
what is the analgesic effect of paracetamol?
A
- PGE2 receptor (EP3/EP4) present on most of the serotonergic, noradrenergic, and adrenergic cell groups suggests that PGE2 modulates many physiologic processes
- PGE2 may modulate nociceptive and autonomic processes by affecting the descending serotonergic pathway
- AM404 is similar in structure to anandamide
- Acts as a cannabinoid (CB1) receptor agonist
- Produces analgesic effect at the level of the spinal cord and brain
- Also activates TRPV1 channels
- Analgesic effect through desensitisation of the channels after initial activation
• Paracetamol is also a free radical scavenger
19
Q
what happens with the use in combination with opioids?
A
- Different mechanisms of analgesia
- Additive or synergistic
- Lower doses can be used
- Reduces incidence of side effects
20
Q
when would you use paraetamol?
A
- Safe for use in children
- Very effective antipyretic
- Central effect – better for headache?
21
Q
when would you use aspirin?
A
- Effective antipyretic (not used with children)
* Effective for inflammatory pain
22
Q
when would you use NSAIDs?
A
- Best for inflammatory pain
- Mainly peripheral effect
- Effective antipyretic
23
Q
what is the physiological role of Coxx 1/
A
- gastrointestinal protection
- platelet aggregation
- blood flow regulation
24
Q
what is the phsyiological role of cox 2?
A
- renal function
- CNS fucntion
- tissue repair and healing
- reproduction
- uterine contraction
- blood vessel dilation
- pancreas
25
what is the pathophysiological role of cox1?
- inflammation
- chronic pain
- increae blood pressure
26
what is the pathophysiological role of coxx2?
inflammation
fever
blood vessel permeability
chornic pain
27
what is the drug safety of aspirin and NSAIDs?
- toxic at high doses
- death and suicide absuse
- can cause ulceration
- can cause bleeding
- bronchoconstriction
28
what is the drug safety issues of paracetamol?
- toxic at high dose
- abuse may lead to death or suicide
- safer alternative at therapuetic dose
- risk of liver damage with higher doses
29
what is the side effect of aspirin and NSAIDS on GI?
direct
| - acidici drug and therefore increase the HCl output because of PGE1 loss
30
how does apisrin and NSAIDS cause bronchoconstriction?
diversion of AA to produce leukotrines
31
how does NSAIDs and aspirin cause bleeding?
* Decrease in thromboxane A2 induces change in platelet behaviour
* Decrease in PGI2 (prostacyclin) too
32
what do high doses of NSAIDs and aspirin cause?
* CNS stimulation
* Hyperventilation
* Decreased pCO2
* Respiratory alkalosis
* Disturbance of cellular metabolism
* Increased lactic acid & ketoacid production
* Leads to metabolic acidosis
* Imbalance in acid / base balance
33
how do you treat the over dose of Aspirin?
depends on time of taking -might need to drain stomach
- monitor plasma electrolytes
- HCO3 to make the urine alkaline and increase the ionisation of the aspirin so it can be removed quikce
34
how do you treat the overdose of paracetamol?
- minor metabolite of paracetamol is toxic to the liver and kidney
- becomes a major metabolite in oversoe, leading to cell damage
- may need to drain the stomach to remove toxins
- may need to give methionine and N-acetylcysteine to prevent further cellular damage
