Pharmacology Of Valproic Acid

Indication	For treatment and management of seizure disorders, mania, and prophylactic treatment of migraine headache.
Pharmacodynamics	Valproic Acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat migraine headaches and schizophrenia. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome. Valproic Acid is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain. Valproic Acid dissociates to the valproate ion in the gastrointestinal tract. Valproic acid has also been shown to be an inhibitor of an enzyme called histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection.
Mechanism of action	Valproic Acid binds to and inhibits GABA transaminase. The drug's anticonvulsant activity may be related to increased brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Valproic Acid may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. It is also a histone deacetylase inhibitor.
Absorption	Rapid absorption from gastrointestinal tract.
Volume of distribution	11 L/1.73 m2 [total valproate] 92 L/1.73 m2 [free valproate]
Protein binding	Concentration-dependent, from 90% at 40 µg/mL to 81.5% at 130 µg/mL.
Metabolism	Valproic Acid is metabolized almost entirely by the liver. In adult patients on monotherapy, 30-50% of an administered dose appears in urine as a glucuronide conjugate. Mitochondrial ß-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose. Usually, less than 15-20% of the dose is eliminated by other oxidative mechanisms. Less than 3% of an administered dose is excreted unchanged in urine.
Route of elimination	Valproate is metabolized almost entirely by the liver. Less than 3% of an administered dose is excreted unchanged in urine. Mitochondrial ß-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose.
Half life	9-16 hours
Clearance	total valproate cl=0.56 L/hr/1.73 m2 free valproate cl=4.6 L/hr/1.73 m2 4.8 +/- 0.17 L/hr/1.73 m2 [males, unbound clearance] 4.7+/- 0.07 L/hr/1.73 m2 [females, unbound clearance]
Toxicity	Oral, mouse: LD50 = 1098 mg/kg; Oral, rat: LD50 = 670 mg/kg. Symptoms of overdose may include coma, extreme drowsiness, and heart problems.

Pharmacology Of Diphenidol

Indication	For use in the prevention and symptomatic treatment of peripheral (labyrinthine) vertigo and associated nausea and vomiting that occur in such conditions as Meniere's disease and surgery of the middle and inner ear. Also for the control of nausea and vomiting associated with postoperative states, malignant neoplasms, labyrinthine disturbances, antineoplastic agent therapy, radiation sickness, and infectious diseases.
Pharmacodynamics	Diphenidol is used for control of nausea and vomiting. It has an antivertigo effect on the vestibular apparatus, inhibiting the chemoreceptor trigger zone to control nausea and vomiting, thus preventing motion sickness.
Mechanism of action	The mechanism by which diphenidol exerts its antiemetic and antivertigo effects is not precisely known. It is thought to diminish vestibular stimulation and depress labyrinthine function and as an antimuscarinic agent. An action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect. Diphenidol has no significant sedative, tranquilizing, or antihistaminic action. It has a weak peripheral anticholinergic effect.
Absorption	Well absorbed from gastrointestinal tract following oral administration.
Volume of distribution	Not Available
Protein binding	Not Available
Metabolism	Not Available
Route of elimination	Not Available
Half life	4 hours
Clearance	Not Available
Toxicity	Symptoms of overdose include drowsiness (severe); shortness of breath or troubled breathing; unusual tiredness or weakness (severe).

Pharmacology Of Dimethylthiambutene

Indication	Dimethylthiambutene is an opioid analgesic previously used in moderate pain relief.
Pharmacodynamics	Not Available
Mechanism of action	Not Available
Absorption	Not Available
Volume of distribution	Not Available
Protein binding	Not Available
Metabolism	Not Available
Route of elimination	Not Available
Half life	Not Available
Clearance	Not Available
Toxicity	Not Available

Pharmacology Of Dimenhydrinate

Indication	Used for treating vertigo, motion sickness, and nausea associated with pregnancy.
Pharmacodynamics	Dimenhydrinate is an antiemetics drug combination that contains diphenhydramine and theophylline. It is not effective in the treatment of nausea associated with cancer chemotherapy. Dimenhydrinate directly inhibits the stimulation of certain nerves in the brain and inner ear to suppress nausea, vomiting, dizziness, and vertigo. Diphenhydramine and dimenhydinate both reduce vestibular neuronal excitation due to angular or linear acceleration motions.
Mechanism of action	The mechanism by which some antihistamines exert their antiemetic, anti–motion sickness, and antivertigo effects is not precisely known but may be related to their central anticholinergic actions. They diminish vestibular stimulation and depress labyrinthine function. An action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect. Dimenhydrinate is a competitive antagonist at the histamine H1 receptor, which is widely distributed in the human brain. Dimenhydrinate's anti-emetic effect is probably due to H1 antagonism in the vestibular system in the brain.
Absorption	Well absorbed after oral administration.
Volume of distribution	Not Available
Protein binding	98 to 99%.
Metabolism	Hepatic (cytochrome P-450 system).
Route of elimination	Not Available
Half life	1 to 4 hours
Clearance	Not Available
Toxicity	Symptoms of overdose include delerium, hallucinations, and excitment. Patients may be violent and confused.

Pharmacology Of Digitoxin

Indication	For the treatment and management of congestive cardiac insufficiency, arrhythmias and heart failure.
Pharmacodynamics	Digitoxin is a cardiac glycoside sometimes used in place of DIGOXIN. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting (From Martindale, The Extra Pharmacopoeia, 30th ed, p665). Unlike digoxin (which is eliminated from the body via the kidneys), it is eliminated via the liver, so could be used in patients with poor or erratic kidney function. However, it is now rarely used in current UK medical practice. While there have been several controlled trials which have shown digoxin to be effective in a proportion of patients treated for heart failure, there is not the same strong evidence base for digitoxin, although it is presumed to be similarly effective.
Mechanism of action	Digitoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digitoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.
Absorption	Not Available
Volume of distribution	Not Available
Protein binding	Not Available
Metabolism	Hepatic.
Route of elimination	Not Available
Half life	Not Available
Clearance	Not Available
Toxicity	Digitoxin exhibits similar toxic effects to the more-commonly used digoxin, namely: anorexia, nausea, vomiting, diarrhoea, confusion, visual disturbances, and cardiac arrhythmias.

Pharmacology Of Dicyclomine

Indication	For the treatment of functional bowel/irritable bowel syndrome including Colicky abdominal pain; diverticulitis
Pharmacodynamics	Dicyclomine is an anticholinergic drug, a medication that reduces the effect of acetylcholine, a chemical released from nerves that stimulates muscles, by blocking the receptors for acetylcholine on smooth muscle (a type of muscle). It also has a direct relaxing effect on smooth muscle. Dicyclomine is used to treat or prevent spasm in the muscles of the gastrointestinal tract in the irritable bowel syndrome. In addition, Dicyclomine inhibits gastrointestinal propulsive motility and decreases gastric acid secretion and controls excessive pharyngeal, tracheal and bronchial secretions.
Mechanism of action	Action is achieved via a dual mechanism: (1) a specific anticholinergic effect (antimuscarinic) at the acetylcholine-receptor sites and (2) a direct effect upon smooth muscle (musculotropic).
Absorption	Not Available
Volume of distribution	3.65 L/kg [20 mg oral dose]
Protein binding	>99%
Metabolism	Not Available
Route of elimination	The principal route of elimination is via the urine (79.5% of the dose). Excretion also occurs in the feces, but to a lesser extent (8.4%).
Half life	Not Available
Clearance	Not Available
Toxicity	Not Available

pharmacology Of Dicumarol

Indication	For decreasing blood clotting. Often used along with heparin for treatment of deep vein thrombosis.
Pharmacodynamics	Dicumarol is an coumarin-like compound found in sweet clover. It is used as an oral anticoagulant and acts by inhibiting the hepatic synthesis of vitamin K-dependent coagulation factors (prothrombin and factors VII, IX, and X). It is also used in biochemical experiments as an inhibitor of reductases.
Mechanism of action	Dicumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
Absorption	Not Available
Volume of distribution	Not Available
Protein binding	Not Available
Metabolism	Not Available
Route of elimination	Not Available
Half life	Not Available
Clearance	Not Available
Toxicity	LD50=233 mg/kg (orally in mice); LD50=250 mg/kg (orally in rats)