Pharmacology of anti-inflammatories and immune suppression Flashcards
Cardinal signs of inflammation
Rubor Tumor Calor Dolore Functio laesa
causes of acute inflammation
Infections (viral, bacterial, parasitic)
Trauma and foreign bodies
Chemical, physical, endogenous agents -> cell death
Acute immune reactions (Allergy
causes of chronic inflammation
Persisting infections
Chronic exogenous or endogenous toxicity
Chronic immune reactions
(Autoimmunity & transplant rejection)
examples of the immune driven inflammation
Allergies Contact dermatitis Celiac disease Autoimmune disease Organ rejection Clearing bacterial and viral infections Graft vs Host disease
name 5 NSAIDS
Aspirin, Indomethacin, Paracetamol, Ibuprofen, Diclofenac
when are NSAIDS taken
Prescribed for pain & chronic inflammation
OTC for minor aches and pains.
what symptoms do NSAIDS treat
anti-inflammatory
analgesic
antipyretic
what are the significant adverse effects of NSAIDS on the GI tract
abdominal discomfort, dyspepsia
Stomach / duodenal ulceration
Myocardial infarction
which is the only NSAID to irreversibly inactivate both isoforms of the COX enzymes (COX-1 and COX-2)
Aspirin
which NSAID Acetylates the catalytic serine residue in position 529.
Aspirin
at which levels does aspirin affect COX2 expression
at both transcriptional and posttranscriptional levels
in what way does COX-2 acetylation modifies the enzyme
enzyme in such a way that it performs an incomplete reaction ultimately resulting in the generation of lipoxins
what else does Aspirin do?
Inhibits IκB kinase and prevents NF-κB activation
Acetylates many proteins and RNA
what are the two COX inhibitors
Aspirin and Ibuprofen
how does ibuprofen block the antiplatelet effect?
by blocks the activity of aspirin
Side effect of asprin
Nausa Stomach pain Heart burn Vomitting
more serious side effects of Aspirin
swelling of eyes, face,lips,tongue,throat
wheezing, difficulty breathing, horseness, fast breathing
fast heart beat
cold clammy skin
hives rash
bright red blood in stools, black or tarry stolols
ringing in the ears, loss of hearing
bloody vomit, vomit resembling coffee grounds
what are coxibs
family of drugs more targeted to COX-2
Selective anti-inflammatory
example of a coxibs
Celecoxib
where is cox 2 found
in cancer cells/Vascular endothelium/kidney
why were coxibs made?
to minimise gastric problems
what concurrent use of celecoxib increase the risk of
Hyponatraemia low sodium
Nephrotoxicity
Hyperkalaemia high potassium
bleeding
what are NO-NSAIDs (nitric oxide-donating NSAID)
New class of NSAIDs having a gastro-protective effect and increased anti-inflammatory activity.
SAIDS:glucocorticoids examples
hydrocortisone, prednisolone and dexamethasone
what are SAIDS based on
Based on adrenal steroids
what are SAIDS synthesized from
synthesized from cholesterol
when are SAIDS released
released as needed under the influence of ACTH
when are SAIDS used
Used clinically in many inflammatory disease
when are SAIDS used Topically
low toxicity
when are SAIDS used Acutely
acceptable toxicity
when are SAIDS used Chronically
severe side effects and toxicity.
when do you normally experience side effects of glucocorticods
Occurring mainly with prolonged systemic use as anti-inflammatory or immunosuppressive
side effects of glucocorticoids
Suppression of response to infection
Suppression of endogenous glucocorticoid synthesis.
Metabolic actions (effecting carbohydrate and proteins metabolism)
Iatrogenic Cushing’s Syndrome
Osteoporosis
Lewis triple response of histamine
Reddening -> Vasodilatation -small arterioles and pre-capillary vessels
Wheal -> Increased permeability of post- capillary venules
Flare -> antidromic stimulation of local nerve resulting in the release of vasodilators
what receptors does Histamine affect?
H1, H2, H3 and H4 GPCRs
what cells release histamine
mast cells
when are histamines released
by exocytosis during inflammatory and allergic reactions
what do histamines cause
Stimulation of gastric secretion Contraction of smooth muscle (other than that of blood vessels) Cardiac stimulation Vasodilation Increased vascular permeability
Sedating Antihistamines H1, H2
Chlorphenamine
promethazine
Non Sedating Antihistamines H1, H2
Cetrizine
fexofenadine
what do antihistamines do
Reduce the increased vascular permeability caused by histamine
when are antihistamines used
Allergic rhinitis (hay fever), urticaria, insect bites, drug sensitivitiesTopical preparations (e.g. for eye, nose)As a adjunct to adrenaline in emergency treatment of anaphylaxis
other effects of antihistamines
5-hydroxytryptamine (5-HT) receptors, α!-adrenoreceptors and ACH muscarinic receptors
Immunosuppression
Tissue rejection
Psoriasis
Rheumatoid arthritis
Corticosteroids +
Immunosuppressive drugs
Cyclosporine A
Tacrolimus (F506)
Rapamycin
Two therapies for rheumatoid arthritis, psoriasis, asthma, Crohn’s, MS
Monoclonal Antibody therary
Disease Modifying Anti-Rheumatic Drugs (DMARDs):
whar are monoclonal antibodies
Humanized or human monoclonal antibodies. Inhibit cytokines, receptors, adhesion molecules
da foq
TNF: Cimzia, Humira, Remicade, Simponi IL6: Actemra IL12 and IL23: Stelara IL1α: Illaris IgE: Xolair α4 and α4β7: Tysabri, Entyvio CD11a: Raptiva CD20: Rituxan, Mabthera Other biologics: Anakinra, recombinant human IL-1RA; Enbrel, Human TNFR2–Fc fusion protein
