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
