Drugs for Gout Flashcards
Recap:
Gouty arthritis is a ____ disorder due to ____. This occurs when serum ____ ____ levels is more than ____mg/dL.
- Most common inflammatory joint disorder in >____ y.o
- ____ ___ ___ deposition in joint/cartilage
- Men: Women = __ : __
Gouty arthritis is a METABOLIC disorder due to HYPERURICAEMIA. This occurs when serum URIC ACID levels is more than 6.8 mg/dL. **
- Most common inflammatory joint disorder in >40** y.o
- MONOSODIUM URATE CRYSTAL deposition in joint/cartilage
- Men: Women = 5 : 1
Recap:
State some risk facotrs for gouty arthritis (5)
- ageing
- high protein diet
- htn
- diabetes
- hyperlipidemia
State 3 drugs that can cause drug-induced hyperuricaemia
- thiazide/loop diuretics
- low-dose aspirin
- ciclosporin
Define tophaceous growths
Tophaceous growths = tissue growth around extracellular crystal deposits in soft tissue near joints
State the 2 goals of drug treatment in treating gouty arthritis
- relieve acute gouty attack
- prevent recurrent gouty episodes
List anti-inflammatory drugs used to control acute gouty attacks
- Nonselective NSAIDs (e.g., naproxen, indometacin)
- COX‐2 selective NSAIDs (e.g., celecoxib)
- glucocorticoids (corticosteroids) (prednisolone)
- colchicine
State the NSAIDs used in acute gouty attack
non-selective nsaids: naproxen, indomethacin
cox-2 selective: celecoxib
Recap:
State the MOA of NSAIDs used in treatment of acute gout attack
Inhibition of COX1 and COX2 to prevent conversion of arachidonic acid to prostanoids.
PGI2 - vasodilation, inhibit platelet aggregation, anti-coagulant
PGE2 - pain, vascular permeability
TXA2 - vasoconstriction, promote platelet aggregation, coagulant
Recap:
State the common adverse effects of NSAIDs in treatment of acute gouty arthritis
- GI - dyspepsia (PGE2)
- Renal - renal failure (PGE2, PGI2)
- Asthma
cox-2 selective
1. nephrotoxicity
2. impaired wound healing
3. thrombosis
State the contraindications for NSAIDs
- severe heart failure
- severe renal impairment
- active GI bleeding or ulcer
- bleeding disorders
- use of systemic corticosteroids or antiplastelet agents/anticoagulants
- multiple risk factors for NSAID toxicity
- third trimester for pregnancy
State the corticosteroid used to control acute gouty attacks
prednisolone
State the MOA of prednisolone in treatment of acute gouty attacks
- decreased expression of pro-inflammatory genes (cytokines - tnfa and il-2 and ifna, chemokines - rantes, inflammatory enzymes - cox-2 and 5-lox and 15-lox, adhesion molecules - ICAM-1 and VCAM-1, receptors - IL2R and TCR)
- increased expression of anti-inflammatory genes (annexin A1, IL1R antagonist, ILIR2, B2 adrenoceptor, NF-Kb Inhibitor)
State the duration of action of prednisolone.
12-36 hours
State the MOA of colchicine
Reduced leukocyte migration into joints by
1. Binds tubulin
2. Preventing tubulin polymerization into microtubules
3. Inhibits leukocyte migration and phagocytosis
4. Inhibits leukotriene B4 (LTB4) and prostaglandin (PG) production
5. Relieves pain and inflammation of acute gouty attack within 24-36 hours
What is the dose-limiting adverse effect of colchicine?
Diarrhoea and GIT disturbance.
At higher doses, binding tubulin and preventing microtubule polymerization prevents cell proliferation. As cells of the GIT walls are rapidly proliferating, diarrhoea and GIT disturbance is usually the first adverse effect seen. The colchicine dose must be titrated to control the acute gouty attack without causing intolerable diarrhoea.
List adverse effects of colchicine
- diarrhoea
- n/v
- abdominal pain
- muscle weakness
- unusual bleeding
- pale lips
- change in urine amount
List TWO classes of drug used to reduce uric acid levels
(1) Uric acid synthesis inhibitors
(xanthine oxidase inhibitors)
(A) Purine analogue e.g., allopurinol
(B) non-purine e.g., febuxostat
(2) Uricosuric agents (solute carrier family 2 & 22 inhibitor) e.g, probenecid
State the uric acid synthesis inhibitors used to prevent gouty episode (urate-lowering therapy)
- purine analog - allopurinol
- non-purine - febuxostat
State the MOA of the uric acid synthesis inhibitors
Inhibits xanthine oxidase to decrease uric acid production to <6.0mg/dL
Statethe clinical uses of uric acid synthesis inhibitors
- debilitating gout attacks
- chronic erosive arthritis
- urate nephrolithiasis
State the adverse effects of uric acid synthesis inhibitors
- skin rash
- n/v
- diarrhoea
- stomach pain
- fever
- sore throat
- dark urine
- jaundice
List THREE risk factors for allopurinol causing severe cutaneous adverse reaction
- Renal impairment
- HLA‐B*58:01 genotype
- Thiazide therapy
State the uricosuric agent used for urate-lowering therapy
probenecid
State the MOA of probenecid
- inhibits proximal tubule anion transport
- inhibits uric acid reabsorption
- increaed uric acid excretion
State the adverse effects of probenecid
- allergic reaction (hypersensitivity)
- rash
- n/v
- dysuria
- lower back pain
What measures can be taken to reduce the risk of kidney stones when probenicid is prescribed
Precautions:
● Take plenty of fluid to minimize renal stone formation
● Keep urine pH >6.0 by administration of alkaline (e.g., potassium citrate)
Which drugs should not be started during an acute gouty attack?
- Uric acid synthesis inhibitors
● Reduction of plasma urate levels can increase mobilisation ftom joints and hence recognition and attack by immjne cells - Uricosuric agents
● Use during acute attack when increased urate is mobilised to plasma and excreted pushes more urate out into urine and increases risk of kidney stones
What can be done to reduce the risk of precipitating acute gouty attack when starting uric acid synthesis inhibitors or uricosuric agents?
Combine with low dose NSAID or colchicine
Name the 4 compartments and 3 things of immune cell reponses
Compartments:
Innate immunity:
(1) Complement
(2) Phagocytes
Adaptive immunity:
(3) B cells
(4) T cells
3 things immune cells do when activated:
(1) Proliferate
(2) Cytokine production
(3) Trafficking and adhesion
