Drugs

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• Urate crystals are able to initiate &maintain
intense acute inflammation because:
I. They induce phagocytes & synovial cells to release
inflammatory mediators as:
** Cycloxygenases & lipoxygenase metabolites of
Arachidonic Acid
** Phospholipase A2 Activating Protein
** Lysosomal Proteases
** TNF,IL-1,IL-6 & IL-8

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II. Proteolysis of proteins with the release of soluble
mediators as C5a,Bradykinin & Kallikrein
Some of these mediators have a chemotactic effect
on Neutrophils especially IL-8.
Neutrophils’ ingress into the joint appears to induce
SYNOVITIS.
The intraarticular Neutrophils can be activated either
directly by crystals or by some soluble mediators
enhancing more neutrophil ingress

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• Colchicine is an alkaloid derived from the dried seeds
of Colchicum Autumnale, also known as Autumn
Crocus or Meadon Saffron.
• Inspite of its anti-inflammatory properties, its uses for
types of pain other than gout is limited because it
works differently than other pain relievers or
antiinflammatory drugs

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• COLCHICINE INTERFERES WITH SEVERAL
STEPS OF THE INFLAMMATORY RESPONSE
IN WHICH
NEUTROPHILS
PLAY A MAJOR ROLE
NEUTROPHILS

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• It interferes with the organization of microtubular
systems concerned with cell structure & movement
leading to:
microtubular disaggregation
↓↓↓ neutrophil motility, metabolism & chemotaxis
↓↓ phagocytosis
↓↓ the release of chemotactic factors mainly LTB4
& IL-6
↓↓ cell division

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COLCHICINE
INHIBITS
**NEUTROPHIL MIGRATION AT THE SITE OF
INFLAMMATION
&
**METABOLISM AND PHAGOCYTOSIS OF
NEUTROPHILS
ALREADY PRESENT

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HENCE ITS ROLE IN REDUCING
THE SEVERITY OF THE
INFLAMMATORY
PROCESS

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• It is essentially metabolised in the liver, so its side
effects may be enhanced in presence of liver
diseases or extrahepatic biliary obstruction.
• It is excreted mainly in bile, faeces & in urine but to
a lesser degree
• Only 10% is excreted during the first 24 hours so it
could be detected in serum & urine for up to 10
days after IV administration

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INDICATIONS :
Essentially in acute gouty arthritis
Prophylactic against recurrent attacks
Pseudogout
Familial Mediterranian Fever as it reduces the
incidence of amyloidosis
Behcet’s disease for oral ulcers, genital ulcers or
follicullitis

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Cutaneous necrotizing vasculitis
Amyloidosis
Sarcoid arthropathy
Acute febrile neutrophilic dermatosis (Sweet’s
syndrome) may be used for cutaneous lesions of
Progressive Systemic Sclerosis
Paget’s disease

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ADMINISTRATION :
*** ORALLY:
I.. Acute gouty attack: 0.5-0.6 mg/1-2 hours until
remission is achieved or
signs of toxicity appear (nausea, vomiting or
diarrhea) or
12-16 doses had been given with no improvement.
In the last case
BE SURE OF YOUR DIAGNOSIS
II.. As prophylactic against acute attacks of
gout or in Behcet’s disease :1-3 tablets /day

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*** INTRAVENOUS ROUTE:
Its advantages
..Rapid onset of action
..Decreases the incidence of GIT toxicity
..Postoperatively
It is given as 2mg diluted in 20 c.c.saline given over
20 minutes then repeated every 6 hours until a total
daily dose of 4 mg

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But take care in IV infusion
1. The drug is not given S.C. nor I.M. for fear of local
irritation
2. Good catheter for fear of extravasation
3. The patient should not receive Colchicine by any
route for 7 days after I.V.dose.
4. Check liver and kidney functions as well as blood
picture

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SIDE EFFECTS
1.GIT manifestations: (mainly with oral route)
nausea,vomiting,diarrhoea with or without
cramping abdominal pain
2.Fatal bone marrow depression (mainly with IV route)
especially if the recommended dose is exceeded
or with Kidney or Liver diseases
3. Liver & Kidney toxicity

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4.Neuromyopathy
5.Cardiopulmonary failure
6.Amenorrhoea,Dysmenorrhoea
7.Oligospermia or Azospermia
8.Hair loss
9.Teratogenic

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CONTRAINDICATIONS
(mainly for I.V.therapy)
• ABSOLUTE:
• Combined renal and hepatic diseases.
• Glomerular filtration rate <25c.c./min.
• Extrahepatic biliary obstruction.
• RELATIVE:
• Bone marrow depression.
• Preexisting significant infection.
• Concomitant oral colchicine.

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IMPROPER USE OF COLCHICINE IS VERY
TOXIC AND MAY LEAD TO SERIOUS
COMPLICATIONS EVEN DEATH
•

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• So before starting Colchicine therapy
(mainly with I.V.route):
- Check Liver and Renal functions
- Check Blood picture
- Respect the proper dose
- > 60 years, don’t exceed 0.6mg/day
- Respect contraindications
- Keep precautions in your mind

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• What drug(s) may interact with colchicine?
 Alcohol
 NSAIDs
 Cyanocobalamin, vitamin B12
 Cytochrome P 450 isoenzyme 3A4 (CYP 3A4)
inhibitors
 P-glycoprotein (P-gp) inhibitors as Cyclosporin

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Drugs that inhibit cytochrome P 450 isoenzyme 3A4
(CYP 3A4)
STRONG:ataza/indi/nelfi/saqui/ritonavir,
clari/telithromycin as well as keto/itraconazole, and
nafazodone
MODERATE:ampre/fosamprenavir, as well as
aprepitant, diltiazem, erythromycin, fluconazole,
verapamil, and grapefruit juice Protease inhibitors
P-gp Inhibitors
cyclosporine and ranolazine

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• I/Restriction: Any orders written for i.v. colchicine
require rheumatology approval.
• II/ Safety checks
a//I.V. administration
1. Give no more than a 2-mg single dose over two to five
minutes via an i.v. line.
2. Do not exceed 4 mg in a seven-day period.
3. Give an initial dose of 2 mg, followed by 0.5 mg every 6
hours until 4 mg has been reached in a 24-hour period.
4. Gastrointestinal symptoms should not be used as an
endpoint of therapy (they often are in monitoring oral
therapy).
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b//Elderly patients should receive no more than 2 mg
of i.v. colchicine per attack, with at least three weeks
between courses
c// Verify previous therapy:
1. Check to see if the patient was admitted on oral
colchicine.
2. If the patient is to be switched from oral to i.v.
colchicine, then the total i.v. dose should not exceed
50% of the oral dose and should be adjusted
appropriately for renal and hepatic dysfunction.
3. Give a maximum of 1-2 mg in a seven-day period
(instead of the normal 4-mg total-dose cap).
d//Special populations

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