Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharm302A > Gout > Flashcards

Gout Flashcards

0
Q

What is the pathophysiology of gout?

A

The two main sources of purines are from the diet and cell turnover.
This is degraded to uric acid.
Humans lack the uricase enzyme which converts uric acid to allatoin (more soluble) so we have higher uric acid levels.
There is a delicate balance of uric acid in the body.
A sustained elevation will produce gout but hyperuricaemia does not always produce gout.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

What is the prevalence of gout?

A

10% maori, 2.9% European
Predominantly male
Higher incidence in obese, alcohol drinkers, and people with high intake meat me fish diets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the two main types of disease states in gout?

A

Over producers of uric acid (90% of patients)

Underexcretors of uric acid (10% of patients)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is gout?

A

The excess of uric acid accumulation due to overproduction of underexcretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What causes an over production of uric acid?

A

Abnormalities in two main enzymes:
Increased Phosphoribosyl pyrophosphate synthetase activity leads to increased posphoribosyl pyrophosphate which is the key determinant of purine synthesis

Deficiency of hypoxanthine-guanine Phosphoribosyltramsferase results in more purines present in the bloodstream and an increased metabolism of guanine and hypoxanthine to uric acid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the role of hypoxanthine-guanine Phosphoribosyltransferase normally?

A

Conversion of guanine to gunalyic acid

Conversion of hypoxanthine to inosinic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What causes underexcretion of uric acid?

A

Uric acid is mostly excreted renally (only 1/3 is excreted by gut bacteria)
Declined urinary excretion of uric acid below the rate of production leads to hyperuricaemia and increased miscible pool of sodium urate.
There is a close link between proximal tubular sodium reabsorption and uric acid reabsorption.
Dehydration is a common cause
Can also be caused by diuretics, nicotinic acid, low dose salicylate a, ethanol, pyrazinamide, levodopa, ethambutol, cyclosporine and cytotoxic drugs which decrees the renal clearance of uric cis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How are over producers of uric acid defined?

A

Individuals with gout who excrete >600mg on a Purine free diet for 3-5 days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How are underexcretors defined?

A

Individuals with gout who excrete <600mg of uric acid per 24 hours on a purine free diet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does inflammation arise in gout?

A

Deposition of urate crystals in synovial fluid causes an inflammatory reaction involving chemical mediators which cause

Vasodilation
Increased vascular permeability
Complement activation
Chemotactic activity for polymorphonuclear leukocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the result of phagocytosis of urate crystals by leukocytes?

A

Rapid lysis of cells and a discharge of proteolytic enzymes into the cytoplasm.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is inflammation in gout associated with?

A

Intense joint pain
Erythema
Warmth
Swelling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the main processes of the inflammatory response?

A

Inflammatory response occurs due to precipitation of uric acid crystals in joint

Release of cytokines and Chemokines: neutrophils and leukocytes migrate to the site of inflammation

Aggressive phagocytosis of uric acid crystals results in neutrophil death and enzyme/mediator release

Causing an acute gouty attack

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is uric acid nephrolothiasis?

A

Occurs in 10-25% of patients with gout
When urine is acidic, uric acid exists in the unionised form
When there is saturation of uric acid, spontaneous precipitation of stones can occur

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the predisposing factors to uric acid nephrolothiasis ?

A

Excessive urinary excretion of uric acid
Acidic uirne
Highly concentrated urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the foods that contain purines?

A

Beer and other alcoholic beverages
Anchovies, sardines in oil (fatty acids found in certain fish like sap,on may possess some anti inflam effects)
Yeast
Organ meat (liver, kidneys, gravies)
Meat extracts
Mushrooms, spinach, asparagus, cauliflower

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the precipitating factors of gout?

A

Hypertension (thiazide diuretics decrease renal CL of uric acid)
Obesity (strong corr. With hyperuricaemia and gout)
High alcohol intake
Dietary factors
Hyperinsulineamia (occurs in 76-95% of gout sufferers)
Also associated with hyperlipidaemia, type II diabetes, coronary artery disease.
Higher risk of gout in maori and Pacifica, (1/8 men, 1/20 women)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the 6 principle contributing factors leading to increased gout?

A 
Incidence of hypertension
Obesity
Incidence of diabetes
Renal failure
Cardiac failure
Changing dietary trends and alcoholism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are tophi?

A

Deposits of uric acid salts appearing around the affected joint due to frequent recurrent attacks of gout, or high levels of uric levels for a long period of time.

These appear as chalky coloured nodules and may also appear in other areas of the body e,g, ears.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the role of surgery in the treatment of gout?

A

It may be required to restore joint function as recurrent severe attacks of gout and development of tophi can cause permanent damage to the joints.
May involve a joint replacement surgery.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How can gout impair kidney function?

A

Damage to the delicate filters within the kidneys and development of kidney stones.
This is a escort of high uric acid levels for a long period of time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the main riggers of gout?

A

Trauma
Alcohol
Dehydration
acidic pH (causes uric acid crystallisation)
Anything that compete is with uric acid transport systems like aspirin
Dietary excess
Irritation of uricosuric or allopurinol therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the symptoms of gout?

A

Fever and intense pain
Erythema
Warm, inflammation and swelling of involved joints
Observation of mono sodium urate crystals in synovial fluid or tophus
Max inflammation developed within a day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How do acute attacks of gouty arthritis begin?

A

At night, characterised by a rapid onset of excruciating pain, swelling and inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How long do gout attacks last?

A

If untreated, may last from 3-14 days before spontaneous recovery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the pattern of gout attacks?

A

Typically mono articular.
Most often affecting the great toe
Then ankles, heels, knees, wrists, fingers and elbows.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Can atypical gout occur?

A

Yes, in the elderly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How is gout diagnoses?

A

Elevated serum uric acid levels and elevated WBC
Increased ESR and CrP (markers of inflammation)
Definitive diagnosis by aspiration of synovial fluid from affected joint and identification of intracellular crystals of monosodium urate monohydate in synovial fluid leukocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the differential diagnosis in gout?

A

Septic arthritis,

You would need to confirm this by checking for infection and if there is improvement if infection is treated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the symptoms of chronic gout?

A

Elevated serum urate
Recurrent attacks of acute gouty arthritis + monosodium urate crystals in synovial fluid leukocytes
Deposits of monosodium urate crystals in tissues and around joints (tophi)
Interstitial renal disease
Uric acid nephrolithiasis (crystallisation in renal tubules)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is used to treat acute gout?

A

NSAIDs
Colchicine
Corticosteroids

31
Q

How are NSAIDs used in acute gout?

A

As a first line short term treatment to reduce pain and inflammation.
Given in high doses for a short course

32
Q

What are the NSAIDs commonly used in acute gout?

A

Indomethacin

Diclofenac

33
Q

What is indomethacin ?

A

A non selective inhibitor of cox I and II enzymes that participate in prostaglandin synthesis from archi sonic acids

34
Q

What is diclofenac?

A

NSAID which achieves analgesic action by cox inhibition

35
Q

Why is aspirin not used in acute gout?

A

It inhibits the kidneys ability to eliminate uric acid and may exacerbate these conditions

36
Q

What are the adverse reactions with NSAID use?

A

GI: gastritis, bleeding, perforation
Kidneys: reduced CrCl,
Cardiovascular: sodium and fluid retention, increased BP
CNS: impaired cognitive function, headache, dizziness

37
Q

When should NSAIDs be used with caution?

A

In patients with peptic ulcer disease, congestive heart failure and renal insufficiency

38
Q

How does colchicine work?

A

It affects the mitosis of WBC by inhibiting spindle fibre separation, thus stopping the proliferation and inflammation of inflammatory cells

39
Q

When should colchicine be used in acute gout?

A

Should be reserved for patients with contraindications to NSAID use or whom have ineffective relief with NSAIDs

40
Q

How is colchicine given in acute gout attacks?

A

Give until relief, nausea, vomiting, diarrhoea or until maximum dose is reached. (Need to wait 3 days between courses)
Selling and pain usually resolves in 24-48 hours

41
Q

What should be avoided if a patient is on colchicine?

A

Macrolide antibiotics such as clarithromycin due to reduced biliary excretion which can lead to increased plasma colchicine levels and agranulocytosis (lower WBC), also avoid if patient is on prophylactic colchicine especially if CrCl <80ml/min

Avoid grapefruit juice as this increases blood levels of colchicine, putting patient at risk of toxicity

42
Q

Why is IV colchicine avoided?

A

Can cause serious side effects like bone marrow suppression

43
Q

Why is colchicine treatment stopped if patient displays vomiting/diarrhoea?

A

Patient needs to avoid being dehydrated

Elderly with reduced renal/hepatic clearance may suffer toxicity

44
Q

What are the adverse effects of oral colchicine?

A

Dose dependent GI effects such as vomiting and diarrhoea

45
Q

Can colchicine be used for prophylactic treatment of gout?

A

Yes, 12 hours after the symptoms have dissipated.

Give 0.5mg twice daily, max 1.2mg

46
Q

When is colchicine for the short term prophylactic treatment of gout given until?

A

Urate levels are <0.36mmol/L and there are no acute attacks for 3-6 months

47
Q

When are corticosteroids used to treat acute attacks of gouty arthritis?

A

Reserved primarily for patients with a Contraindication or who are unresponsive to colchicine or NSAID therapy

48
Q

What is the main corticosteroid used to treat gout?

A

Prednisolone

49
Q

How is prednisolone given?

A

20-40mg orally once daily then decrease by 5-10mg increments every 3 days until discontinuation.

Or 1mg/kg orally as a single dose

50
Q

What is the mechanism of prednisolone?

A

It is lipophilic and readily crosses the membrane to combine irreversibly with the glucocorticoid receptor.
Activated complex then enters the nucleus where it acts as a transcription factor leading to gene activation

51
Q

When should prednisolone be used with caution?

A

In diabetics, as it can increase blood sugar

Patients with history of GI problems, bleeding disorders or CVD

52
Q

What are the adverse effects of prednisolone?

A

Fluid retention of the face,
Acne
Can cause ulcers, constipation and mood swings

53
Q

What is the aim of using Allopurinol?

A

To reduce uric acid levels to below 0.36mmol/L

54
Q

What is the mechanism of allopurinol?

A

Reduces uric acid production by inhibiting xanthine oxidase (which is a Structural isomer of hypoxanthine )

55
Q

Is allopurinol active?

A

No. 60-70% of allopurinol undergoes hepatic conversion to the active metabolite oxipurinol

56
Q

How is allopurinol given?

A

Start on a low dose of 100mg PO OD

Increase by 100mg/day every week according to serum urate level until maximum 800mg/day

57
Q

When is allopurinol co administered with colchicine or NSAID?

A

Usually in the first 3 months of chronic therapy until serum urate levels <0.36mmol/L

58
Q

What are the adverse effects with allopurinol use?

A

Hypersensitivity reactions (dose related): skin rash
GI upset
Severe data rash occurs in 2% of patients

59
Q

What does allopurinol interact with?

A

Cytotoxic agents
Alcohol interferes with effectiveness
Probenecid decreases concentration of allopurinol

60
Q

How much should allopurinol dose be decreased in patients with renal impairment?

A

200mg/day for CrCl 60mL/min or less

100mg/day for CrCl 30mL/min or less

61
Q

Should allopurinol be given for acute attacks?

A

No. But if an attack occurs while patient is on allopurinol, the allopurinol should not be stopped

62
Q

Why must patients be given a low dose of allopurinol and then slowly increase it?

A

A sudden decrease in serum urate levels can precipitate an attack

63
Q

What are the uricosurics used for long term gout?

A

Probenecid
Sulphpyrazone
Benzbromarome
Febuxostat

64
Q

How do probenecid, sulphinpyrazole and benzobromarome work?

A

Increases renal clearance of uric acid by inhibiting tubular resorption of uric acid

Probenecid:
Give 250-1000mg orally BD

Sulphinpyrazole:
Give 100-400mg orally OD

Benzobromarome:
Give 100-200mg orally OD

65
Q

When should probenecid, sulphinpyrazole and benzobromarone be used?

A

In patients who underexcrete uric acid

AVOID in patents with poor renal function (CrCl< 20-30mL/min) or who overproduce uric acid)

66
Q

What are the adverse effects with probenecid, sulphinpyrazole and benzbromarone use?

A

GI irritation
Rash
Hypersensitivity
Precipitation of acute gouty arthritis and stone formation

67
Q

What is Febuxostat?

A

A non purine selective inhibitor of xanthine oxidase.

It is tolerated in renal impairment

68
Q

How does Febuxostat work?

A

By inhibiting xanthine oxidase, it reduces serum uric acid

69
Q

How is Febuxostat given?

A

40-80mg orally OD

70
Q

What are The adverse effects with Febuxostat ?

A

Nausea diarrhoea headache and rash

71
Q

When should long term therapy for gout be initiated?

A

When patient has two or more attacks per year

Monitored serum urate levels every 3-6 months and adjust therapy according to levels in symptomatic patients

72
Q

What are the key things to remember with long term gout therapy?

A

Use uricosurics if a atient is allergic to allopurinol

Consider co adminstration with colchicine until serum urate levels have been lowered

73
Q

What are the non pharmacological treatments of gout?

A 
Reduce dietary intake of saturated fats and meats high in purines (organ meats)
Increase fluid intake 
Decrease salt consumption
Promote joint exercise 
Avoid applying heat to the area
Weight loss through caloric restriction 
Restrict alcohol intake 
Withdraw drugs that induce gout
Joint rest for 1-2 days encouraged
Local application of ice, insoles in shoes may be beneficial
Avoid diuretics
74
Q

Why is alcohol highly correlated with gout symptoms?

A

Alcohol contains guanosine which is converted to uric acid by bacteria

75
Q

What monitoring is involved in gout?

A

Most medications (esp. Allopurinol) have multiple drug interactions, requiring adjustments to medication dosages.
When initiating allopurinol, patients should be closely monitored for hypersensitivity (such as dermatitis and multi system failure)
Long term colchicine use may be assoc. with neuromyopathy Probenecid may increase risk of nephrolothiasis
Acute pain of an initial attack of gouty arthritis should begin to ease within 8 hours of treatment initiation
Complete resolution of pain erythema and inflammation occurs within 48-72 hours
Patients should be monitored for the development of trophi and radiographic changes

Patients taking uric acid lowering agents showed be followed up every 1-3 months initially, then every 6 months (target level is <0.36mmol/L)
FBC, renal function test and LFTs should be obtained every 3-6 months to test for adverse effects of NSAIDs and colchicine, especially if they are used for prolonged periods

76
Q

How is gout different from osteoarthritis?

A

Age of onset usually over 35 years of age in men, and after menopause in females (earlier than osteoarthritis)

Sudden onset of disease (OA is slow)

Big toe joint most common. Other affected joints are ankle, heel, knee, wrist, fingers, elbow etc (OA is one side of body large weight bearing joints, usually limited to ONE set of joints like finger joints next to fingernail)

Duration of morning stiffness is not seen in gout (but lasts less than 1 hour in OA and returns in the evening)

Chills and mild fever along with general malaise can accompany severe pain and inflammation in gout, but not in OA

Tophi may form in gout, whereas in OA symptoms occur in isolation with no systemic symptoms

Pharm302A (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions