Term
| principle mediators of inflam & allergy |
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Definition
1. histamine
2. eicosanoids
3. PAF
4. Bradykinin
5. N2O
6. neuropeptides
7. cytokines
8. plasma proteins |
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Term
| physical and pathophysical roles of histamine = |
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Definition
1. tissue repair
2. control of local BF (vasodilation)
3. contributes to allergic & anaphylactic reactions
4. neurotransmission in CNS
5. gastric acid secretion
6. drug induced release of histamine
7. direct effects on CVS = incr HR, incr contractility, vasodilation |
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Term
| where is histamine found? |
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Definition
in nearly every cell, espec lung, skin and GIT
found largely in mast cells |
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Term
| histamine is bound in large cytoplasmic granules with heparin and protein in what ratio? |
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Definition
| heparin:histamine:protein 1:3:6 |
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Term
|
Definition
| inhibits blood coagulation |
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Term
| histamine release from mast cells occurs... |
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Definition
| ...during inflam or allergic reactions |
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Term
| histamine release is caused by... |
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Definition
...incr in IC Ca2+ due to
-Ags interacting with IgE
-C' components C3a and C5a bind to R on mast cell surface)
-neuropeptides eg substance P
-certain drugs eg morphine can initiate an allergic response |
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Term
| histamine release is inhibited by... |
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Definition
| ...incr cAMP eg beta adrenoceptor agonists or adr |
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Term
| what sp is v sensitive to histamin? |
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Definition
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Term
|
Definition
| endothelium, brain and smooth mm |
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Term
|
Definition
| surface of mast cells (negative feedback mech -decr release of histamine |
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Term
|
Definition
| presynaptic Rs on neurons |
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Term
|
Definition
| incr IP3 and DAG = contraction of smoooth mm in ileum, bronchi, bronchioles and uterus (EXCEPT in bvs where activation of H1Rs here =vasodilation) and incr vascular perm |
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Term
|
Definition
| incr cAMP = activate gastric secretion, incr HR and incr contractility of heart = incr CO |
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Term
|
Definition
| decr cAMP = inhibit neurotransmitter release |
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Term
| What type of Rs are Histamine Rs? |
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Definition
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Term
| H1 R antagonists used to tx... |
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Definition
...allergies (hay fever and urticaria)
nausea
vom |
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Term
| H1 R antagonists can be admin... |
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Definition
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Term
| H1 R antagonists are metabolised by... |
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Definition
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Term
| H1 R antagonists duration of action = |
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Definition
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Term
| 1st generation of H1 antagonists = |
|
Definition
mepyramine
promethazine
diphenhydramine |
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Term
| 2nd generation H1 antagonists = |
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Definition
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|
Term
| H1 antagonist used in prevention or tx of feline asthma with bronchodilators and steroids = |
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Definition
| cyproheptadine (usually a last resort) |
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Term
| Diphenhydramine used to tx... |
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Definition
...skin disorders
and causes sedation in Dogs and horses |
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Term
| chlorphenamine used to tx... |
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Definition
| ...skin disorders (stops scratching) and causes mild sedation |
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Term
| hisatmine antagonists used for... |
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Definition
...allergic skin & resp disorders
sedation
motion sickness
coughs |
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Term
| all antihistamines most useful... |
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Definition
| ...b4 an allergen challenge, better prophylactically |
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Term
| H2 R anatgonists used to tx |
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Definition
| gastric ulcers (decr gastric acid secretion) |
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Term
|
Definition
cimetidine
ranitidine
famotidine |
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Term
|
Definition
systemic life-threatening reaction (fatal in few mins)
Occurs in previously sensitised animal |
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Term
| chemical meiators of inflam causidng anaphylaxis induce... |
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Definition
...smooth mm contraction
vasodilation throughout body = decr BP
incr vascular perm = exudation and oedema
(eg histamine) |
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Term
| within a min of anpahylaxis = |
|
Definition
nausea
abdo pain
palpitation (rapid strong irregular heart beat)
urticaria
dyspnoea
decr BP = inadequate circ |
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Term
| within 2-7mins of anaphylaxis = |
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Definition
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Term
| immediate Tx of anaphylaxis = |
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Definition
| Adr -activate R on mast cell = incr cAMP = inhibit degranulation -activate alpha1R = vasoconstriction -activate beta2R in airway = bronchodilation -activate beta1in heart = incr HR and contractility to incr BP and IV infusion -to maintain intravascular vol & supply additional drugs |
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Term
| other drugs to tx anaphylaxis = |
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Definition
H1R antagonist - give IV
Glucocorticosteroids -hydrocortisone IV -supress urticaria, bronchospasm, laryngeal oedema and /or hypotension |
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Term
| Major effects of Bradykinin = |
|
Definition
vasodilation
incr bv perm
potent pain producing agent :(
spasmogenic (of intestine, bronchi and uterus)
stim of epi ion transport & fluid secretion in airways & GIT |
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Term
| Bradykinin1 R present in... |
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Definition
| ...normal vascular smooth mm |
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Term
| Bradykinin1 Rs are upregulated by... |
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Definition
| ...inflam, cytokines, endotoxins and GFs |
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Term
|
Definition
| ...predominate R, normall activated and found in most normal tissues |
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Term
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Definition
| mediates most of bradykinins effects in the absence of inflam |
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Term
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Definition
| inducible form of NO synthase thats involved in inflam reactions |
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Term
|
Definition
| ...virtually all inflam cells in response to cytokine stim |
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Term
|
Definition
-potenet vasodilator
-incr bv perm
-incr production of pro-inflam PGs - positive feedback =PG upregulates other mediators of inflam
-when released from endothelial cells, NO inhibits platelet aggregation and the adhesion of neutrophils and platelets |
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Term
| neuropeptides are released from... |
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Definition
| ...sensory neurones = 'neurogenic inflam' |
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Term
| neuropeptides are released from.. |
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Definition
| ...sensory neurones = 'neurogenic inflam' |
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Term
| main neuropeptides involved in inflam = |
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Definition
substance P
neurokinin A
calcitonin gene-related peptide |
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Term
| substance P and neurokinins A affect = |
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Definition
| activate mast cell degran = release hisatmine & other mediators of inflam and cause smooth mm contraction and mucus secretion |
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Term
| calcitonin gene-related peptide causes.. |
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Definition
|
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Term
|
Definition
| phospholipid derived mediators of inflam all derived from arachidonic acid |
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Term
|
Definition
| platelet activating factor |
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Term
|
Definition
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Term
|
Definition
vasodilation
inhibition of platelet aggregation |
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Term
|
Definition
myometrial contraction
bronchoconstriction |
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Term
|
Definition
vasodilation
inhibition of platelet aggregation
hyperalgesia |
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Term
|
Definition
vasoconstriction
thrombotic |
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Term
|
Definition
cell adherence
chemotaxis
activate Polymorphonuclear cells and monocytes
activate prolif
activate cytokine production from macro & lymphocytes |
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Term
| leukotriene C4, D4 and E4 = |
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Definition
| cysteinyl leukotrienes (have a cystein in their structure) |
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Term
| cysteinyl leukotriene v. imp in ... |
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Definition
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Term
| cysteinyl leukotrienes mediate: |
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Definition
contraction of bronchial smooth mm
vasodilation of most bvs
vasoconstriction of coronary bvs |
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Term
| lkotrienes all bind to what type of Rs? |
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Definition
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Term
|
Definition
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Term
| Leukotriene anatagonists effects = |
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Definition
block effects of cysteinyl leuykotrienes in airways
prophylactic use in preventing feline asthma |
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Term
| PAF generated and released from... |
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Definition
| ...most inflammatory cells (mast cells, neutro, macro) |
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Term
| PAF effects= (dose=dependent) |
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Definition
local vasodilation
incr bv perm
hyperalgesia
chemotaxis
activate leukocytes
activate and aggregate platelets
spasmogenic for smooth mm |
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Term
|
Definition
| ...bronchial hypersensitivity and asthma |
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Term
|
Definition
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Term
| most imp cytokines in inflam = |
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Definition
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Term
| what inhibits synthesis of some cytokines? |
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Definition
|
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Term
| glucocorticoids and gold compounds decr formation and action of... |
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Definition
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Term
|
Definition
antiviral actions
pyrexic (induce fever)
antitumour effects |
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Term
|
Definition
|
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Term
|
Definition
17mg tablet to take prophylactically if had heart attack to decr risk of stroke or another heart attack
Low dose aspririn inhibits platelet aggregation |
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Term
| aspirin is a weak acid, this means... |
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Definition
| ...theres gd absorption of aspirin from the stomach |
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Term
| aspirin is hydrolysed to what in plasma? |
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Definition
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Term
| at low doeses most aspririn is... |
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Definition
| ...bound to plasma proteins |
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Term
| how much aspirin is excreted unchange? |
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Definition
|
|
Term
| how much aspirin is oxidised? |
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Definition
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Term
| some aspirin is conjugated to......or......and then excreted |
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Definition
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|
Term
| dose of aspirin for anti-inflam effect = |
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Definition
| BIG - careful of side effects eg gastric ulcers and bleeding |
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Term
| side effects of aspirin = |
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Definition
inhibit cox1 = loss of mucosal protection by PGs
inhibit platelet aggregation
both = GI bleeding :( |
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Term
|
Definition
| salicylate/aspirin overdose! |
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Term
|
Definition
tinnitis (ringing/buzzing in ears)
dizziness
hearing loss
nausea
skin rashes
Reyes Syndrome |
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Term
|
Definition
follows viral infection
liver/CNS disturbances
20-40% fatal
children under 16 can develop this so give children paracetamol instead of aspirin |
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Term
| large doses of aspirin alters... |
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Definition
| ...acid/base balance = uncouples oxidative phosphorylation =resp and metabolic acidosis |
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Term
| aspirins interaction with warfarin = |
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Definition
| incr effects of warfarin (as aspirin displaces warfarin from plasma proteins) - dont use together as will lead to bleeding in patient :( |
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Term
|
Definition
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|
Term
| carprofen is used in hwat sp? |
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Definition
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Term
|
Definition
| analgesic and antipyretic |
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Term
|
Definition
| some selectivity for cox2 over cox1 |
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Term
| phenylbutazone is used in what sp? |
|
Definition
horses and dogs
but can get toxicity in dogs! :( |
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Term
| advantage of phenylbutazone= |
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Definition
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|
Term
| slectivity of phenylbutazone? |
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Definition
| less selective for cox2 than carprofen |
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Term
| use of phenylbutazone in horses = |
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Definition
| commonly used to relieve pain and anti-inflam |
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Term
| phenylbutazone used in dogs for... |
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Definition
| ...chronic osteoarthritis |
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Term
|
Definition
antipyrexic
analgesic
weak anti-inflam (not used for anti-inflam effects) |
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Term
|
Definition
|
|
Term
| pk effect of paracetamol = |
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Definition
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Term
| paracetamol inactivated in liver by... |
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Definition
...conjugation with glucuronide or sulphate
Cats have limited glucuronide, so paracetamol is contraindicated in cats |
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Term
| half life of paracetamol = |
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Definition
|
|
Term
| toxic dose half life, (if not metabolised by liver)= |
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Definition
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Term
|
Definition
| dont really understood, think might inhibit cox3 in dogs brain... |
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Term
| side effects of paracetamol= |
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Definition
| serious potentially fatal liver toxicity |
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Term
|
Definition
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Term
| toxic dose of paracetamol = |
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Definition
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Term
|
Definition
| cats dont have a lot of glucuronide therfore lievr starts to metabolize paracetamol an alternative way by mixed function oxidases = N-acetyl-p-benzoquinone imine (an oxidant = toxic metabolite - kills cells) |
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Term
|
Definition
antpyretic
gd analgesic - used for moderate pain releif |
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Term
| ibuprofen effects on dogs = |
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Definition
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Term
| tx of poisoning with aspirin, ibruprofen or paracetamol = |
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Definition
-AC if poisoining happened recently
-acetyl cysteine precursor of glucuronide (but this is limited) |
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Term
| cox2 inhibitors inhibit... |
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Definition
| ...PGI production in epi cells = incr risk of thrombosis and vasoconstriction = incr risk of heart attacks and strokes with cox 2 inhibitors :( |
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Term
| co2 selective drugs should nly be used for patients with... |
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Definition
| ...gastroduodenal ulcers and bleeding and ppl in chronic pain |
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Term
| cox2 inhibitors are contraindicated in... |
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Definition
| ...patients with ischaemic heart dz or cerbrovascular dz |
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Term
| biggest use of NSAIDs in SA field = |
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Definition
| canine and feline osteoarthritis |
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Term
| uses of NSAIDs in vetmed = |
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Definition
1. anti-inflam, analgesic and antipyretic agents
2. peri-and post op in C&D and horses
3. canine and feleine osteoarthritis
4. bovine: resp dz, acute toxic conditions, anti-inflam and analgesia
5. Equine: colic, musculoskeletal disorders, analgesia |
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Term
| usues of NSAIDs in cattle = |
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Definition
resp dz
actute toxic conditions
anti-inflam
pain relief |
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Term
| uses of NSAIDs on horses = |
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Definition
colic (endotoxaemia)
musculoskeletal disorders
pain
pre- and post op analgesia |
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|
Term
carprofen half life in..
a) dogs
b) cats
c) cow |
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Definition
|
|
Term
| factors to consider when using NSAIDs.. |
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Definition
1. intersp variation eg half life
2. metabolism (renal and hepatic function/health?)
3. hypovolaemia/hypotension = incr risk of renal adverse effects
4. concurrent drug usage - already using NSAID - dont want to overdose, steroids can exacerbate side effects, propofol - competes for plasma proteins with propofol, ACE inhibitors, diuretics also effects renal BF. |
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