Anti-Inflammatory Drugs Flashcards
What mediators could cause vasodilation, increased permeability and migration of white blood cells during inflammation?
Histamine, prostaglandins, leukotrienes, platelet activating factor (PAF), kinins, products of complement system activation, cytokines, chemokine, interleukins, adhesion molecules, etc.
What mediators do cause vasodilation, increased permeability and migration of white blood cells?
Varies with the situation. The mediators involved will be a function of the nature, dose and route of the injurious stimuli (or antigen). REDUNDANCY!!
What causes redness and heat?
vasodilation
What causes swelling?
Increased vascular permeability
What is histamine and where is it found?
Endogenous amine found in nearly every mammalian tissue with highest concentrations found in the lung, skin and stomach. It is also found in many venoms, bacteria and plants.
What are the two pools of histamine?
- Mast cell histamine
2. Non-mast cell histamine
What is important about histamine store in mast cells and basophils?
- Slow turnover
- Found preformed in granules
- Histamine is bound by ionic bonds to a heparin-protein complex within the granules
What is important about non-mast cell histamine?
- Uncertainty regarding the function of this pool
- Rapid turnover
- Found in cells in CNS, including nerve endings
- Cells in epidermis (rapidly growing) and tissues undergoing rapid growth or repair i.e. bone marrow, wounds, etc.
- Enterochromaffin-like cells in the fundus of the stomach that release histamine to activate acid producing parietal cells (GI course)
What can histamine do if it’s given orally?
Large doses can be administered without causing effects. As it’s absorbed - it’s inactivated by enzymes in the intestinal wall or liver. Also intestinal bacteria convert it to N-acetylhistamine.
What is the “triple response” that happens when histamine is administered intracutaneously?
- Itching and pain is caused by stimulation of nerve endings
- Wheal and flare (urticaria or hives) also occurs
1. Localized redness
2. Flare
3. Localized edema or wheal formation
Histamine: Localized redness
- Appears within seconds and maximizes in about a minute
- Arteriolar dilation
Histamine: Flare
- Diffuse redness around and beyond the original redness
- Develops more slowly
- Though to be due to nerves dilating neighboring arterioles
Histamine: Localized edema or wheal formation
- Occurs in 1 to 2 min in the same area as the original localized redness
- Increased capillary permeability with leakage of the post capillary venules
What symptoms are caused by intranasal histamine?
- Intense itching
- Sneezing (reflex)
- Hypersecretion (reflex)
- Nasal blockage - vasodilation & edema, along with increased secretions
What can intravenous administration of histamine cause?
- bp decreases due to vasodilation, increased capillary permeability and fluid loss. Sometimes there’s a secondary increased in blood pressure due to histamine-induced release of catecholamines from the adrenal medulla.
- Tachycardia - increased heart rate. Probably a reflex response elicited by the decrease in bp. Histamine has direct positive inotropic (increased force of contraction) and chronotropic (increased heart rate) effects but they are overshadowed by reflex effects.
- Bronchoconstriction - primarily in asthmatics with hyperactive airways
- Flushing of the face - cutaneous vasodilation
- Headache - cerebrovascular dilation
- Wheal and flare - urticaria or hives
- Stimulates mucus secretion
- Stimulation of gastric acid secretion
