Module: Pharmacotherapy III Module Coordinator: Dr. Arwa M. Amin Mostafa Academic Level: Postgraduate, Master of Pharmacy in Clinical Pharmacy School: Dubai Pharmacy College Year of first presented in Class: 2018 This presentation is for Educational purpose. It has no commercial value associated with it.

1. Gout and Hyperuricemia
ARWA M. AMIN MOSTAFA
PHD, M.PHARM CLINICAL PHARM, DIP MANGT, B.PHARM.

2. Outlines
What is Gout and Hyperuricemia?
What is the Pathophysiology of Hyperuricemia and
Gout?
What are the stages of Gout?
What are the risk factors of Gout?
How to diagnose Gout?
What are the Non-Pharmacological treatment of
Gout?
What are the Pharmacological treatment of Gout?

3. Gout and Hyperuricemia
 Gout is heterogenous metabolic disorder which involves:
 Hyperuricemia: elevated serum uric acid.
 > 7 mg/dL for Men
 > 6 mg/dL for Women
 Recurrence of acute arthritis attacks (Gouty arthritis) with
monosodium urate (MSU) crystals in the synovial fluid leukocytes.
 Deposition of monosodium urate (MSU) crystals (Needle-like-
crystals) in tissues and around joints (Tophi).
 Interstitial Renal disease.
 Uric acid Nephrolithiasis.

4. Gout and Hyperuricemia
Needle-Like
Crystals

5. Gout and Hyperuricemia
 Gout has been referred to as “ King of Diseases ” and the “
Disease of Kings .”.
• Historically Precepted that it
only affects Rich Men.
• Has been associated with
affluent societies and
lifestyles of overindulgence,
and intemperance.

6. Pathophysiology of Hyperuricemia
Endogenous
Nucleotides
Dietary High
Purines
Purines
Uric Acid
Intestinal
Elimination
Renal
Excretion
Xanthine
30%
70%
Hypoxanthine
Xanthine Oxidase

7. Pathophysiology of Hyperuricemia
Production
of Uric acid
Excretion
of Uric acid
Hyperuricemia

8. Pathophysiology of Gout
Deposition of
MSU in
synovial fluids
↑↑ Uric acid
Hyperuricemia
MSU crystals
MSU: Monosodium urate
Na
Uric acid level
exceeds saturation
level
Leukocytes Phagocytosis
of MSU crystals
Inflammatory Reaction
(Joint pain, Erythema & swelling)

9. Figure source: Top 4 Strategies to Beat Gout Naturally, https://drjockers.com/top-4-strategies-to-beat-gout-naturally/

10. Uric Acid Nephrolithiasis
 Uric Acid Nephrolithiasis occurs in 10% to 25% of patients
with gout.
 Predisposing factors:
 Include excessive urinary excretion of uric acid
 Acidic urine
 Highly concentrated urine (Dehydration).
 Acute Uric Acid Nephropathy: Acute Renal failure occurs
because of blockage of urine flow from massive
precipitation of uric acid crystals in collecting ducts and
ureters.
 Chronic Urate Nephropathy is caused by long-term
deposition of urate crystals in the renal parenchyma.

11. Video of Hyperuricemia and Gout
https://www.youtube.com/watch?v=4edrfpzg9wQ
Pathophysiology of Gout

12. Stages of Gout
 There are various stages of gout including:
Asymptomatic Hyperuricemia
Acute Gout attack
Chronic Gout
Chronic Tophaceous gout
Gouty Nephropathy.

13. Case Discussion
Mr. KT is a 58-year-old man who has
been admitted to the surgical ward for
a total knee replacement. He lives with
his wife and two sons. He smokes 15
cigarettes a day and usually drinks
about 35 units of alcohol a week. He is
slightly overweight with a BMI of 27
kg/m2.

14. Case Discussion.. Cont.
Apart from hypertension, he has no other
co-morbidities or relevant past medical
history. His operation was a success and
he is recovering well. However, during his
stay he develops Excruciating Pain in the
big toe of his right foot and his toe is very
swollen. He is subsequently diagnosed
with gout.
His serum uric level was 9 mg/dL.

15.  His current medication includes:
Amlodipine 5 mg daily
Bendroflumethiazide 2.5 mg daily
Paracetamol 1 g four times a day
Codeine phosphate 30 mg 4 times a day when required.
Enoxaparin 40 mg s.c. daily.
Case Discussion

16. Case Discussion
 List the risk factors for developing gout
 Discuss which risk factors Mr. KT potentially may have for
developing gout.

17. Risk Factors of Gout
 Genetic Factors
 Elevated Serum Uric acid level.
 Overweight and Obesity
 Metabolic Syndrome
 Insulin resistance
 Hypertension
 Hyperlipidaemia
 Aging
 Sex:
 Gout affects Men three times more often than women.
 The risk of women developing gout increases with menopause
occurrence

18. Risk Factors of Gout
 Renal Failure
 Un-usual Physical Exercise activity
 Dietary excess of purines rich food
 Seafood and Organ Meat
 Alcohol Consumption
 High-sugar soft drinks (High fructose corn syrup)
 Elevated serum urate level
 Surgery
 Drugs
 Thiazide diuretics, Cyclosporine, low dose Aspirin (minimum effect)

19. Let's Go back to Mr. KT Case Discussion
Discuss which risk factors Mr. KT potentially may have for developing
gout.

20. Let's Go back to Mr. KT Case Discussion
 He has Elevated serum Uric acid.
 He is overweight and he is probably suffering
from Metabolic syndrome (suffering from
hypertension and overweight).
 He drinks 35 units of Alcohol a week which is
more than the recommended weekly amount.
 He has recently undergone a surgical procedure.
 He is taking Bendroflumethiazide (thiazide
diuretic) which can increase serum level of uric
acid.
Discuss which risk factors Mr. KT potentially may have for developing
gout.

21. Gout Symptoms and Clinical Presentation
Describe the symptoms and clinical
Presentations of Acute gout Attack.
How to diagnose Gout?
What are gout signs and symptoms that Mr. KT
have?

22. Clinical Presentations of Acute Gout Attack
 Rapid onset of Excruciating Pain in a joint (Monoarticular)
Most often the great Toe (Podagra).
Then, the insteps, ankles, heels, knees, wrists, fingers, and
elbows.
Attacks commonly begin at night, with the patient
awakening with the sensation that big toe is on fire..

23. Gout Attack
Locations

24. Clinical Presentations of Acute Gout Attack
 Affected joints are erythematous, warm, inflamed and
swollen.
 Fever and leukocytosis are common.
 Untreated attacks last from 3 to 14 days before spontaneous
recovery.

25. Gout Diagnosis
Presumptive diagnosis
 Presence of characteristic signs and symptoms,
as well as the response to treatment.
 Serum Uric supports diagnosis but Not definitive.
Definitive Diagnosis
 Aspiration of synovial fluid from the affected
joint:
Identification of intracellular crystals of MSU in
synovial fluid leukocytes using polarized light
microscope.

26. Let's Go back to Mr. KT Case Discussion
What are gout signs and symptoms that Mr. KT have?
• Excruciating Pain in the big toe of his right foot
• His toe is very swollen.
• His serum uric level was 9 mg/dL.

27. Treatment Goals of Gout
Goals of Treatment
Terminate the acute attack
Prevent recurrent attacks
Prevent complications associated with chronic
deposition of urate crystals in tissues.
What are Gout treatment Goals?

28. Treatment of Acute Gout Attack
Mr. KT requires treatment for his acute attack of gout.
• Please discuss the options available for treating an acute
gout attack.
• Which option would you recommend for Mr. KT?

29. Nonpharmacological Treatment of Acute Gout Attack
• Local ice application is the most effective adjuvant
treatment.
• Rest

30. Pharmacological Treatment of Acute Gout
Management of Acute Gout
Source: Osteoarthritis, Pharmacotherapy: A Pathophysiologic Approach, 10e, Citation:
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. Pharmacotherapy: A
Pathophysiologic Approach, 10e; 2017

31. Pharmacological Treatment of Acute Gout
Comments:
• NSAIDs should be used with caution in patients with a history of
cardiac impairment, which includes hypertension.
• Colchicine dose related adverse effects
• GI disturbance
• Neutropenia
• Neuromyopathy (Interaction with Statin → ↑↑ Myopathy)
• Adverse effects more common in Hepatic or Renal
insufficiency
• Colchicine should not be used concurrently with strong CYP3A4
inhibitors (eg. Clarithromycin) →
• It may lead to increased plasma colchicine levels and toxicity.

32. Pharmacological Treatment of Acute Gout
• Acute pain of an initial gout attack should
begin to ease within 8 hours of treatment
initiation.
• Complete resolution of pain, erythema, and
inflammation usually occurs within 48 to 72
hours.

33. Let's Go back to Mr. KT Case Discussion
Which option would you recommend for Mr. KT?
• Colchicine would be the agent of choice for Mr. KT due to
his concurrent medical history of Hypertension.
• Use only within 36 hours of attack onset because the likelihood
of success decreases if treatment is delayed.
• Dose
• 1.2 mg Initial dose
• After initial dose, 0.6 mg once or twice daily

34. Back to Mr. KT Case Discussion
When you are clinically checking Mr. KT’s medication chart,
you notice that he is on the following medication:
• Amlodipine 5 mg daily
• Bendroflumethiazide 2.5 mg daily
• Paracetamol 1 g four times a day.
Which of these medications can aggravate gout and why?
Bendroflumethiazide.
Thiazide Diuretics increase the blood level of Uric acid due to
their renal action.

35. What advice would you give to the doctor looking after Mr. KT?
• To discuss with the doctor and the patient whether
Bendroflumethiazide could be stopped.
• To check Mr. KT’s blood pressure and see if an alternative
antihypertensive could be given instead.
Back to Mr. KT Case Discussion
What possible alternative antihypertensive could be given
instead?

36. Antihypertensive Drugs and Uric acid level
Possible alternative to treat HTN in Mr. KT is …….
Treating Hypertension in Gout Patients
↑↑ Uric acid level
• Diuretics
• B-Blockers
• ACEI
• Non-Losartan ARBs
↓↓ Uric acid level
• Losartan
• CCBs
ACEI: Angiotensin Converting Enzyme Inhibitor, ARB: Angiotensin II-Receptor Blocker, CCB: Calcium Chanel Blocker

37. Now, we discussed how to manage Acute Gout Attack
What about Managing Hyperuricemia?
Production
of Uric acid
Excretion
of Uric acid
Hyperuricemia

38. Now, we discussed how to manage Acute Gout Attack
What about Managing Hyperuricemia?
Production
of Uric acid
Excretion
of Uric acid
Hyperuricemia

39. Nonpharmacological Treatment of Hyperuricemia
During your rounds, Mr. KT asks you if you could tell him what
he could do to avoid another attack of gout. What lifestyle
advice would you give him?

40. Nonpharmacological Treatment of Hyperuricemia
• Promote weight loss and exercise.
• Restrict Alcohol consumption.
• Dietary recommendations:
• Limiting consumption of high-fructose corn syrup and
purine-rich foods (organ meats and some seafood).
• Evaluate the medication list for potentially unnecessary
drugs that may elevate uric acid levels.
• Low-dose aspirin for cardiovascular prevention should be
continued in patients with gout because aspirin has minimum
effect on elevating serum uric acid.

41. Pharmacological Treatment of Hyperuricemia
Management of Hyperuricemia in Gout
Source: Osteoarthritis, Pharmacotherapy: A Pathophysiologic Approach, 10e, Citation: DiPiro JT,
Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. Pharmacotherapy: A Pathophysiologic
Approach, 10e; 2017

42. Pharmacological Treatment of Hyperuricemia
Comments:
• Allopurinol Hypersensitivity Syndrome characterized by fever,
eosinophilia, dermatitis, vasculitis, and renal and hepatic
dysfunction
• Allopurinol should be discontinued at the first appearance
of skin rash or allergic reaction.
• Febuxostat is well tolerated (↓↓ side effects), with adverse
events of nausea, arthralgias, and minor hepatic
transaminase elevations.
• Does not require dose adjustment in mild to moderate
hepatic or renal dysfunction

43. Pharmacological Treatment of Hyperuricemia
Comments:
• Patients with a history of urolithiasis should not receive
uricosurics (Probencide).
• Major side effects of probenecid include GI irritation, rash
and hypersensitivity, precipitation of acute gouty arthritis,
and Stone Formation.
• Contraindicated in impaired renal Function
• Pigloticase was withdrawn from Europe in 2016 due to serious
life-threatening side effects (Hemolysis,
Methemoglobinemia)

44. Let's Go back to Mr. KT Case Discussion
Mr. KT’s acute attack of gout resolves and he is discharged
home. His GP is aware of his problem with gout and after he
experiences a second attack of gout, his GP decides that it
would be prudent to start him on some long-term prophylaxis
against future attacks.
a. Why wasn’t Mr. KT prescribed prophylactic treatment after
his first attack?
b. What options are available and which one is the drug of
choice?

45. • Long-term Hypouricemic agents should be considered if a
patient experiences ≥ 2 gouty attacks/year.
• Long-term Hypouricemic agents that decrease serum uric
levels should not be used during an acute gout attack, why?
• Because these drugs cause mobilization of uric acid stores
in response to a decreasing serum level. This can then
prolong the attack or precipitate another attack of gouty
arthritis.
Let's Go back to Mr. KT Case Discussion
Why wasn’t Mr. KT prescribed prophylactic treatment after his
first attack?

46. • First line is Xanthine-Oxidase-Inhibitors: Allopurinol or Febuoxostat
• Allopurinol starting dose not more than 100 mg daily and then
gradually titrating every 2 to 5 weeks up to a maximum dose of
800 mg/day until the serum urate target is achieved.
• Colchicine may be given at a dose of 0.6 mg twice or three
times daily when allopurinol are initially commenced in order to
prevent an attack of gout.
• NSAIDs may also be used but this would not be an appropriate
option for Mr. KT. Why?
Let's Go back to Mr. KT Case Discussion
What Drug options are available and which one is the drug of
choice?

47. Evaluation of Gout treatment Therapeutic Outcome
• Serum Uric acid level in patients suspected of having an acute
gout attack should be checked. However, acute gout can occur
with normal serum uric acid concentrations.
• Monitor Symptomatic Relief of joint pain in patients with Acute
gout.
• Monitor potential adverse effects and drug interactions related to
drug therapy.
• For patients receiving urate-lowering therapy, obtain baseline
assessment of Renal Function, Hepatic enzymes, Complete Blood
Count, and Electrolytes.
• Recheck every 6 to 12 months for patients on long-term
treatment.

48. Evaluation of Gout treatment Therapeutic Outcome
• During titration of urate-lowering therapy, monitor serum uric acid
every 2 to 5 weeks; after the urate target is achieved, monitor uric
acid every 6 months.
• Because of the high rates of comorbidities associated with gout
(DM, CKD, HTN, obesity, MI, HF, Stroke), elevated serum uric acid
levels or gout should prompt evaluation for CVD and
appropriate risk reduction measures should be applied.
• Modify medications which cause ↑ in uric acid level
• ↓ Obesity, ↓ Alcohol consumption