‫محمود عبدهللا زغبر‬

20170346
Group C

Describe the pathogenesis of drugs that induced gingival

enlargements and how each one of them work (nifedipine,
cyclosporin, phenytoin), also make search about drugs that
can be used instead of them and replaced by the physician?

All of the above of drugs are associated with gingival enlargement (drug-
indued gingival overgrowth), but each of them has its own mechanism of
pathogenesis as the following: -

• Nifedipine:
It is a hypotensive (antihypertensive) drug works on Ca channels (Ca channels
blocker). it decreases Ca uptake which leads to decreased cellular folate uptake by
gingival fibroblasts = No activation of collagenase enzyme = decreased degradation of
CT. (accumulation of CT.) = Increase the accumulation of CT.
o Can be replaced by Isradipidine.

❖ Isradipidine
It belongs to the dihydropyridine (DHP) class of calcium channel blockers.
It binds directly to inactive calcium channels stabilizing their inactive conformation.
It decreases arterial smooth muscle contractility and subsequent vasoconstriction by
inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions
entering the cell through these channels bind to calmodulin. Calcium-bound
calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated
MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a
key step in muscle contraction. Signal amplification is achieved by calcium-induced
calcium release from the sarcoplasmic reticulum through ryanodine receptors.
Inhibition of the initial influx of calcium decreases the contractile activity of arterial
smooth muscle cells and results in vasodilation. The vasodilatory effects of isradipine
result in an overall decrease in blood pressure.
 o Uses:
For the management of mild to moderate essential hypertension.

o Side effects:
- Headache
- Edema
- Tachycardia
- Dizziness
- Skin rash

• Cyclosporin:
It is an immunosuppressant drug used usually in cases of organs transplantation.
It effects directly on fibroblast and keratocytes no. which result in high amount of
collagen so enlargement of gingiva.
o No other choice until now.

• Phenytoin:
It is an anticonvulsant drug, the mechanism of pathogenesis it is the same of
Nifedipine.
o Can be replaced by Valprote.

❖ Valprote
It is an Na channel and Ca channal blocker.

o Uses:
It is used to treat epilepsy and bipolar disorder.
It's occasionally used to prevent migraine headaches.

o Side effects:
- Reversible hair loss
- Teratogenicity
- Tremor
- thrombocytopenia Encephalopathy