Autacoids Flashcards
H3 histamines use:
Presynaptic receptors
In heart: decrease histamine release
In sympathetic nerve: decrease NE
H4 receptors are in ……(3)
Hematopoetic cells
Eosinophil
Neutrophils
Cd4 T cells
Name an H3 related drug . MOA and use
Tiprolisant
MOA: inverse H3
Use: narcolepsy
Problem when using astemizole and terfenadine
When used with enzyme inhibitors can cause Torsades de pointes
Prodrug for fexofenadine is …..importance
Terfenadine
Does not cause torsades de pointes
5HT is formed from …….
Structures rich in 5HT (6)
Tryptophan
1. GIT enterochromaffin cells
2. Platelets
3. Lungs
4. Bone marrow
5. Pineal gland
6. CNS
MOA of 5HT1
MOA of 5HT4
MOA of 5HT2
Cerebral vasoconstriction
Hippocampal excitation
Smooth muscle contraction and plt aggregation.
LSD is a …..agonist
MOA of prucalopride. Use for…..
5HT2
5HT4, use for constipation
Drug to rx Irritable bowel syndrome with constipation
Tegaserod - 5HT4 Agonist
…….receptor of bradykinin activates phospholipase C
Eg of 2 bradykinin B2 receptor antagonists
B2
Icatibant: for acute hereditary angioedema
Aprotinin: CABG to minimise bleeding
MOA of zileuton and zafirleukast
Zileuton: 5 lipooxygenase inhibitor
Zafirleukast: LT1 receptor antagonist
PG that is a chemoattractant to neutrophils
PG that is increased in hypothalamus during fever
PGD2
PGE2
Leukotrienes that increase neutrophil chemo taxis and that which inhibit chemotaxis ?
Increase: LTA4,LTB4
Inhibit: lipoxin
Weak COX2 inhibitor is ……
NSAID that do not inhibit PG synthesis is …..(2)
Nimesulide
Atypical NSAIDS: Nefopam
Diacerein
Low dose aspirin is beneficial in …… diseases (2)
Colon cancer
Alzheimer’s disease
Features of aspirin toxicity
- Respiratory alkalosis :
Tinnitus,headache,vertigo,hyperventilation - Respiratory acidosis
- Metabolic acidosis
Special feature of aspirin as per dose
<2g/d:
increase Uric acid by decreasing Uric acid excretion in urine.
High doses: >2g/d: Uricosuric
First line of drugs for acute gout
- NSAIDS: indomethacin
- Steroids: oral,iv, intra articular: if one or two joints only.
- Colchicine
DOC for acute flare if resistance or C/I to first line drugs
IL1 receptor antagonist
Canakinumab
Anakinra
Rilunacept
DOC for chronic gout is ……
Allopurinol
Inhibit xanthine oxidase.
This leads to decrease in blood uric acid, the body tries to increase blood Uric acid by secreting from tissues.
This opposing factors can ppt urate crystals.
Thus allopurinol not given for acute gout.
Drug to prevent flare up during initial allopurinol rx
Colchicine > NSAID
Drug for severe chronic tophaceous gout resistant to other drugs
Pegloticase iv
Pegylated uricase
Uric acid ————-> allantoin
Uricase
Oil of wintergreeen is ……
Methylsalicylate- used in iodex
Use of sulfasalazine
Converted to 5- ASA by bacteria in colon
Rx of ulcerative colitis
NSAIDS that are not given iv (2)
Diclofenac
Acelofenac
They are 99% protein bound
Long acting NSAIDS (2)
Piroxicam
Tenoxicam
……..NSAID has been banned
Rofecoxib secondary to cardio toxicity
Major metabolic pathway of PCM
Minor pathway
Glucoronide, sulfate conjugation
Cytochrome P450 to form NAPQI which is broken down by glutathione as mercapturic acid that undergoes renal excretion
Toxic doses of PCM
4-5g/day
Can’t be taken up by glutathione and NAPQI accumulates leading to centrilobular necrosis in liver.
MOA of colchicine
Antispindle, antimitotic drug
Disrupts microtubules
Inhibit neutrophil migration into joints
( MSU crystals attract WBC leading to I.F and pain- colchicine inhibits that).
Uricosuric drugs used in chronic gout (4)
Probenecid
Sulfinpyrazone
Benzbromarone
Lesinurad
S/E of colchicine (3)
- GI epithelium : N/V/D/Abdominal pain
When diarrhoea develops, STOP the drug as colchicine can cause intestinal hemorrhage. - BMS
- Myopathy -rhabdomyolysis
Colchicine should never be given with …..(3)
Colchicine has low therapeutic drug, thus it should never be given with …..
- Erythromycin,clarithromycin,azithromycin
Both are metaboliized by CYP3A4 oxidation
- P-glycoprotein inhibitors: verapamil, cycloserin
- Statins : if given together can cause serious myopathy.
Non gout uses of colchicine (6)
- Pseudogout
- Familial Mediterranean Fever
- Recurrent pericarditis
- Amyloidosis
- Scleroderma
- Cirrhosis
Non gout uses of allopurinol (2)
Lymphoma
Leukaemia
To prevent Tumor lysis syndrome
Drugs where dose reduction should be done when giving allopurinol or febuxostat
Allopurinol (XO inhibitor)(purine analogue)
Febuxostat(XO inhibitor)(non purine)
6MP ( purine analogue) used in cancer
Azathioprine (purine) used in immunosuppressants
Azathioprine ——> 6MP
Prodrug
Azathiprine and 6MP are metabolised by XO, thus when given with febuxostat can cause toxicity.
Drugs causing hyperuricemia (3)
- Thiazides, furosemide
- Pyrazinamide, Ethambutol
- Aspirin <2g/d
Drug with antiHTN and uricosuric action
Losartan
1st line drugs in Rheumatoid arthritis
DMARDS
Methotrexate
Leflunomide
Sulfasalazine
HCQ
When are corticosteroids used in RA?
As a bridge therapy until DMARDS take effect -slow action -6-10 weeks
Drug which increases adenosine extra cellularly
Methotrexate
Dose for methotrexate
High dose : 0.5g/m2 iv
Osteosarcoma
CNS lymphoma
Burkitts lymphoma
Low - moderate dose:
7.5-25 mg/week
RA
Psoriatic arthritis
MOA and S/E of DMARDS
- Methotrexate:
DHFR inhibitor
Increase adenosine release
S/E : Hepatotoxicity, BM suppression
- Leflunomide:
Dihydro orate dehydrogenase
Pyrimidine synthesis inhibitor
Decrease lymphocytes proliferation
S/E: weight loss, teratogenic, hepatotoxic
- Sulfasalazine:
5ASA + sulfapyradine
S/E: BMS, oligospermia
Hemolysis in G6PD deficiency
- HCQ:
Antimalaria
S/e: bull’s eye retinopathy
Leflunomide should be avoided in …(3)
Pregnant
Lactating mothers
Children
AntiTNF alpha drugs should not be used with ….(3)
- Active TB
- HBV
- Severe CHF
2 tests to screen for Tb
- PPD, Mantoux test
Does not tell whether the patient has Tb, only that pt is exposed to Tb
If positive : do sputum for tb - IFN gamma release assay
WBC of patient + MTBAg —> if exposed= IFN gamma will be elevated
Uses of antiTNF drugs (4)
- Rheumatoid arthritis
- Psoriatic arthritis
- Ankylosing spondylitis
- Inflammatory bowel disease : UC, Crohn’s disease.
New drug for SLE
Belimumab - antibody against B lymphocytes stimulation
MOA of Etanercept
Recombinant DNA fusion protein - decoy receptor for TNF alpha
Non TNF alpha drugs used for rheumatoid arthritis
ATT for RA
1. Anakinra : IL-1 blocker
2. Tocilizumab: IL-6 blocker
3. Tofacitanib : oral drug : JAK 1/3 blocker
4. Rituximab: CD20 blocker
5. Abatacept: T cell costimulation blocker:
Binding to CD80 & 86 , blocking interaction with CD 28.
Ruxotinib is used for …..
Myelofibrosis : JAK 1/2 blocker
Drug regimen for RA
- Methotrexate alone
- If not effective: add DMARD ( sulfazalazine, HCQ, leflunomide)
- Add TNF alpha inhibitor
