60 - Anti-Epileptic drugs

1. Hydantoin derivatives : Phenytoin, methotoin and ethotoin

2. Barbiturates : Phenobarbitone, primidone.

3. Iminostillbenes : Carbamazepine.

4. Succinimides : Ethosuximide, methosuximide

5. GABA transaminase inhibitors : Sodium valproate, Vigabatrin

6. GABA reuptake inhibitors : Tiagabine

7. GABA agonists : Gabapentin.

8. Benzodiazepines : Clonazepam, diazepam and clobazam.

59 - Characteristics of antituberculous drugs

Drug Most Common Side Effects Tests for Side Effects Drug Interactions Isoniazid- Bactericidal to both extracellular and intracellular organisms. Pyridoxine, 10 mg orally daily as prophylaxis for neuritis; 50–100 mg orally daily as treatment. Peripheral neuropathy, hepatitis, rash, mild CNS effects. AST and ALT; neurologic examination. Phenytoin (synergistic); disulfiram. Rifampin- Bactericidal to all populations of organisms. Colors urine and other body secretions orange. Discoloring of contact lenses. Hepatitis, fever, rash, flu-like illness, gastrointestinal upset, bleeding problems, renal failure. CBC, platelets, AST and ALT. Rifampin inhibits the effect of oral contraceptives, quinidine, corticosteroids, warfarin, methadone, digoxin, oral hypoglycemics; aminosalicylic acid may interfere with absorption of rifampin. Significant interactions with protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Pyrazinamide- Bactericidal to intracellular organisms. Hyperuricemia, hepatotoxicity, rash, gastrointestinal upset, joint aches. Uric acid, AST, ALT. Rare. Ethambutol- Bacteriostatic to both intracellular and extracellular organisms. Mainly used to inhibit development of resistant mutants. Use with caution in renal disease or when ophthalmologic testing is not feasible Optic neuritis (reversible with discontinuance of drug; rare at 15 mg/kg); rash. Red-green color discrimination and visual acuity (difficult to test in children under 3 years of age). Rare. Streptomycin- Bactericidal to extracellular organisms. Use with caution in older patients or those with renal disease. Eighth nerve damage, nephrotoxicity. Vestibular function (audiograms); BUN and creatinine. Neuromuscular blocking agents may be potentiated and cause prolonged paralysis.

AST, aspartate aminotransferase; ALT, alanine aminotransferase; CBC, complete blood count; BUN, blood urea nitrogen.

58 - Dexrazoxane

Dexrazoxane hydrochloride (Zinecard [Pfizer for USA & Canada]; Cardioxane [Novartis for EU & ROW]) is a cardioprotective agent.

It is used to protect the heart against the cardiotoxic side effects of anthracyclines, such as doxorubicin.

FDA has also approved a dexrazoxane hydrochloride drug, brand name Totect or Savene (developed by TopoTarget), for use as a treatment of extravasation resulting from IV anthracycline chemotherapy. Extravasation is an adverse event in which chemotherapies containing anthracylines leak out of the blood vessel and necrotize the surrounding tissue.

As a derivative of EDTA, dexrazoxane chelates iron, but the precise mechanism by which it protects the heart is not known.

57 - Anti-arrhythmic agents classification

Classes	Known as	Examples
Ia	fast-channel blockers	Quinidine Procainamide Disopyramide
Ib		Lidocaine Phenytoin Mexiletine
Ic		Flecainide Propafenone Moricizine
II	Beta-blockers	Propranolol Esmolol Timolol Metoprolol Atenolol
III		Amiodarone Sotalol Ibutilide Dofetilide E-4031
IV	slow-channel blockers	Verapamil Diltiazem
V		Adenosine Digoxin

56 - The Ceiling effect

*When the dosage of a drug is increased, its effect increases proportionally; but after a certain dosage, any amount of increase in the dosage of the drug shows no additional effect. This upper limit of the dosage, above which no additional effect is seen, is called the ceiling dose and this effect is called the CEILING EFFECT.

*Examples of drugs showing ceiling effect are :

- Loop diuretics (high ceiling diuretics)

- Ceiling effects for analgesia and respiratory depression are observed above 50 to 100 mg pentazocine. Pentazocine has opioid agonistic actions and weak opioid antagonistic activity. It is a type of opioid analgesic.

-  Nalbuphine exhibits a ceiling effect such that increases in dosage beyond 30 mg produce no further respiratory depression. However, a ceiling effect for analgesia also is reached at this point.

Nalbuphine is related structurally to naloxone and oxymorphone. It is an agonist–antagonist opioid with a spectrum of effects that qualitatively resembles that of pentazocine; however, nalbuphine is a more potent antagonist at MU receptors and is less likely to produce dysphoric side effects than is pentazocine.

- Buprenorphine is a semisynthetic, highly lipophilic opioid derived from thebaine. It is 25 to 50 times more potent than morphine. This drug is also believed to show the ceiling effect. Patients receiving methadone or buprenorphine will not experience the ups and downs experienced while on heroin. Drug craving diminishes and may disappear.  Buprenorphine, as a partial agonist, has a ceiling effect at about 16 mg of the sublingual tablet equaling no more than 60 mg methadone. If the patient has a higher level of physical dependence, methadone, a full agonist, must be used.

- The patient's ability to tolerate and absorb medicinal iron is a key factor in determining the rate of response to therapy. The small intestine regulates absorption, and with increasing doses of oral iron, limits the entry of iron into the bloodstream. This provides a natural ceiling on how much iron can be supplied by oral therapy.