Mechanism of Action Spironolactone and Clinical Uses

Mechanism of Action Spironolactone

Spironolactone (Aldactone) is structurally related to aldosterone and acts as a competitive inhibitor to prevent the binding of aldosterone to its specific cellular binding protein. Spironolactone thus blocks the hormone induced stimulation of protein synthesis necessary for Na+ reabsorption and K+ secretion. Spironolactone, in the presence of circulating aldosterone, promotes a modest increase in Na+ excretion associated with a decrease in K+ elimination.The observations that spironolactone is ineffective in adrenalectomized patients and that the actions of spironolactone can be reversed by raising circulating ldosterone blood levels (surmountable antagonism) support the conclusion that spironolactone acts by competitive inhibition of the binding of aldosterone with receptor sites in the target tissue. Spironolactone acts only when mineralocorticoids are present.

Clinical Uses Spironolactone

Spironolactone has been used clinically in the fol lowing conditions:

1. Primary hyperaldosteronism. Used as an aid in preparing patients with adrenal cortical tumors for surgery.

2. Hypokalemia.Used in patients with low serum K+ resulting from diuretic therapy with other agents.Its use should be restricted to patients who are unable to supplement their dietary K intake or adequately restrict their salt intake or who cannot tolerate orally available KCl preparations.

3. Hypertension and congestive heart failure.Although spironolactone may be useful in combination with thiazides, the latter remain the drugs of first choice. Fixed-dose combinations of spironolactone and a particular thiazide (e.g.,Aldactazide) generally offer no therapeutic advantage over either component given separately and tend to restrict the ability of the clinician to determine the optimal dosage of each drug for a particular patient.
,
4. Cirrhosis and nephrotic syndrome. Spironolactone is a mild diuretic and may be useful in treating the edema that occurs in these two clinical conditions,
that is, when excessive K+ loss is to be avoided.

Read More »

Unknown Action, Clinical Pharmacology, Mechanism, Spironolactone, Uses

Citalopram Pharmacodynamics and Mechanism of action

Introduction
A furancarbonitrile that is one of the serotonin uptake inhibitors used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia in preference to tricyclic antidepressants, which aggravate this condition

Pharmacodynamics
Citalopram is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of Citalopram are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. In vitro studies show that Citalopram is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Citalopram has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. The chronic administration of Citalopram was found to downregulate brain norepinephrine receptors, as has been observed with other drugs effective in the treatment of major depressive disorder. Citalopram does not inhibit monoamine oxidase.

Mechanism of action
The antidepressant, antiobsessive-compulsive, and antibulimic actions of Citalopram are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Citalopram blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.

Side Effect of Citalopram
Call your doctor at once if you have any of these serious side effects:
    very stiff (rigid) muscles, high fever, sweating, fast or uneven heartbeats, tremors, overactive reflexes;
    nausea, vomiting, diarrhea, loss of appetite, feeling unsteady, loss of coordination; or
    headache, trouble concentrating, memory problems, weakness, confusion, hallucinations, fainting, seizure, shallow breathing or breathing that stops.

Less serious citalopram side effects may include:

•     Drowsiness;
•     Sleep problems (insomnia);
•     Mild nausea, gas, upset stomach;
•     Weight changes;
•     Urinating more than usual;
•     Decreased sex drive, impotence, or difficulty having an orgasm;
•     Dry or watery mouth, yawning; or
•     Cold symptoms such as stuffy nose, sneezing, sore throat.

Interaction of Citalopram
Citalopram (HBr) is known to interact with other drugs like Alcohol, Cimetidine (HCl), Iproniazid Phosphate, Methotrimeprazine (Maleate), Methylamphetamine, Naratriptan, Paregoric, Phenelzine, Sumatriptan, Trimeprazine (Tartrate).These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.

Half Life of Citalopram
35 hours

Dosge of Citalopram 

 Adults: Depression:
Initial: 20 mg/day, generally with an increase to 40 mg/day; doses of more than 40 mg are not usually necessary. Should a dose increase be necessary, it should occur in 20 mg increments at intervals of no less than 1 week. Maximum dose: 60 mg/day; reduce dosage in elderly or those with hepatic impairment.

Read More »

Unknown Action, Citalopram, Mechanism, Pharmacodynamics

Amikacin Pharmacodynamics and Mechanism of Action

Introductin

Amikacin is a semi-synthetic aminoglycoside antibiotic derived from kanamycin A. Similar to other aminoglycosides, amikacin disrupts bacterial protein synthesis by binding to the 30S ribosome of susceptible organisms. Binding interferes with mRNA binding and tRNA acceptor sites leading to the production of non-functional or toxic peptides. Other mechanisms not fully understood may confer the bactericidal effects of amikacin. Amikacin is also nephrotoxic and ototoxic.

Indication
For short-term treatment of serious infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species. Amikacin may also be used to treat Mycobacterium avium and Mycobacterium tuberculosis infections.

Pharmacodynamics
Amikacin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.


MECHANISM OF ACTION

The aminoglycosides primarily act by binding to the aminoacyl site of 16S ribosomal RNA within the 30S ribosomal subunit, leading to misreading of the genetic code and inhibition of translocation . The initial steps required for peptide synthesis are uninterrupted, such as binding of mRNA and the association of the 50S ribosomal subunit, but elongation fails to occur due to disruption of the mechanisms for ensuring translational accuracy . The ensuing antimicrobial activity is usually bactericidal against susceptible aerobic gram-negative bacilli.

Amikacin Dosing Information

Usual Adult Dose for Bacteremia:

15 to 22.5 mg/kg/day IV or IM in 1 to 3 divided doses, depending on severity of infection (initial maximum of 1.5 g/day, then adjust dose based on desired serum levels)

Usual Adult Dose for Intraabdominal Infection:

15 to 22.5 mg/kg/day IV or IM in 1 to 3 divided doses, depending on severity of infection (initial maximum of 1.5 g/day, then adjust dose based on desired serum levels)

Usual Adult Dose for Joint Infection:
15 to 22.5 mg/kg/day IV or IM in 1 to 3 divided doses, depending on severity of infection (initial maximum of 1.5 g/day, then adjust dose based on desired serum levels)

Usual Adult Dose for Osteomyelitis:

15 to 22.5 mg/kg/day IV or IM in 1 to 3 divided doses, depending on severity of infection (initial maximum of 1.5 g/day, then adjust dose based on desired serum levels)

Usual Adult Dose for Pneumonia:

15 to 22.5 mg/kg/day IV or IM in 1 to 3 divided doses, depending on severity of infection (initial maximum of 1.5 g/day, then adjust dose based on desired serum levels)

Usual Adult Dose for Skin or Soft Tissue Infection:

15 to 22.5 mg/kg/day IV or IM in 1 to 3 divided doses, depending on severity of infection (initial maximum of 1.5 g/day, then adjust dose based on desired serum levels)

Usual Adult Dose for Cystic Fibrosis:

Higher doses may be required for the treatment of Pseudomonas aeruginosa pulmonary infections in cystic fibrosis patients. Dosing should be individualized and based on serum concentrations. Doses of up to 35 mg/kg/day once daily by IV infusion or in divided doses every 6 to 8 hours have been reported.

Usual Adult Dose for Febrile Neutropenia:

Higher doses may be required. Dosing should be individualized and based on serum concentrations. Doses of up to 15 to 30 mg/kg/day IV in 1 to 3 divided doses have been reported in conjunction with a beta-lactam antibiotic (initial maximum of 1.5 g/day, then adjust dose based on desired serum levels).

Usual Adult Dose for Meningitis:

IV or IM: 15 to 22.5 mg/kg/day in 1 to 3 divided doses, depending on severity of infection (initial maximum of 1.5 g/day, then adjust dose based on desired serum levels)
Intrathecal: 0.1 mg per mL of CSF or approximately 2 mg/kg body weight per day has been used to treat gram-negative bacillary meningitis in conjunction with parenteral antibiotics

Usual Adult Dose for Nosocomial Pneumonia:

20 mg/kg /day IV in 1 to 3 divided doses

Initial empiric treatment with broad-spectrum coverage according to the hospital's and/or ICU's antibiogram is recommended if multidrug-resistant organisms are suspected.

Duration: If the causative organism is not Pseudomonas aeruginosa, the duration of treatment should be as short as clinically possible (e.g., as little as 7 days) to reduce the risk of superinfections with resistant organisms.

Usual Adult Dose for Peritonitis:
Peritoneal dialysis-related peritonitis:
CAPD intermittent dosing: 2 mg/kg in 1 exchange/day (based on ideal body weight) intraperitoneally for anuric patients and 2.5 mg/kg/bag for nonanuric patients (investigational)
CAPD continuous dosing: 24 mg/L exchange intraperitoneally for anuric patients and 30 mg/L for nonanuric patients

Maximum dose: 1.5 g/day by all routes

Usual Adult Dose for Tuberculosis -- Active:

15 mg/kg (maximum 1 g) IM or IV every 24 hours

May be given in combination with at least 3 other active drugs for treatment of multi-drug resistant TB, or when the patient is intolerant of first-line agents. AFB smear and culture should be monitored monthly.

Duration: Treatment for TB should generally continue for 18 to 24 months, or for 12 to 18 months after culture results are negative.

Usual Adult Dose for Urinary Tract Infection:

Uncomplicated: 250 mg IV or IM every 12 hours
Amikacin is not recommended for mild to moderate infections.

Usual Pediatric Dose for Febrile Neutropenia:

1 to 18 years: Higher doses may be required. Dosing should be individualized and based on serum concentrations. Doses ranging from 15 to 30 mg/kg/day in 1 to 3 divided doses have been reported in conjunction with a beta-lactam antibiotic.

Usual Pediatric Dose for Cystic Fibrosis:

1 to 18 years: Higher doses and/or more frequent intervals may be required. Dosing should be individualized and based on serum concentrations. Doses of up to 35 mg/kg/day IV in 1 to 3 divided doses have been reported.

Usual Pediatric Dose for Peritonitis:

Peritoneal dialysis-related peritonitis:
17 years or less:
Initial dose: 25 mg/L dialysate intraperitoneally
Maintenance dose: 12 mg/L dialysate

Maximum dose: 1.5 g/day by all routes

Usual Pediatric Dose for Tuberculosis -- Active:

15 to 30 mg/kg (maximum 1 g) IM or IV every 24 hours

May be given in combination with at least 3 other active drugs for treatment of multi-drug resistant TB, or when the patient is intolerant of first-line agents. AFB smear and culture should be monitored monthly.

Duration: Treatment for TB should generally continue for 18 to 24 months, or for 12 to 18 months after culture results are negative.

Read More »

Unknown Amikacin, Mechanism, Pharmacodynamics

Metformin MECHANISM DOSING and Side Effects

Metformin hydrochloride is a type of antidiabetic medicine known as a biguanide. It works in a number of ways to decrease the amount of sugar in the blood of people with type 2 diabetes.

DRUG CLASS AND MECHANISM:
Metformin is an oral medication that lowers blood glucose (sugar) and is used for treating type 2 diabetes. Insulin is a hormone produced by the pancreas that controls glucose levels in blood by reducing the amount of glucose made by the liver and by increasing the removal of glucose from the blood by muscle and fat tissues. As a result, blood glucose levels fall. Diabetes caused by a decrease in production of insulin that causes increased production of glucose by the liver, and reduced uptake (and effects) of insulin on fat and muscle tissues. Metformin acts by increasing the sensitivity of liver, muscle, fat, and other tissues to the uptake and effects of insulin. These actions lower the level of sugar in the blood.

Unlike glucose-lowering drugs of the sulfonylurea class, for example glyburide (Micronase; DiaBeta) or glipizide (Glucotrol), metformin does not increase the concentration of insulin in the blood and, therefore, does not cause excessively low blood glucose levels (hypoglycemia) when used alone. In scientific studies, metformin reduced the complications of diabetes such as heart disease, blindness and kidney disease. Metformin was approved by the FDA in December 1994.

DOSING: For treating type 2 diabetes in adults, metformin (immediate release) usually is begun at a dose of 500 mg twice a day or 850 mg once daily. The dose is gradually increased by 500 mg weekly or 850 mg every two weeks as tolerated and based on the response of the levels of glucose in the blood. The maximum daily dose is 2550 mg given in three divided doses. If extended tablets are used, the starting dose is 500 mg or 1000 mg daily with the evening meal. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg (2500 mg of Fortamet) once daily or in two divided doses. Glumetza tablets are given once daily. Metformin should be taken with meals.

For pediatric patients 10-16 years of age, the starting dose is 500 mg twice a day. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg. Glucophage XR has not been studied in children.

Side Effects of Metformin

•     shakiness
•    dizziness or lightheadedness
•    sweating
•    nervousness or irritability
•    sudden changes in behavior or mood
•    headache
•    numbness or tingling around the mouth
•    weakness
•    pale skin
•    hunger
•    clumsy or jerky movements

Metformin Pregnancy Warnings

Metformin has been assigned to pregnancy category B by the FDA. Animal studies have failed to reveal evidence of fetotoxicity. There are no controlled data in human pregnancy. Insulin remains the mainstay of therapy for gestational diabetes due to the close glucose control it affords. Metformin is only recommended for use during pregnancy when benefit outweighs risk

Metformin Breastfeeding Warnings

There are no data on the excretion of metformin into human milk. Metformin is excreted into the milk of rats and achieves milk concentrations comparable to those found in plasma. The manufacturer recommends that due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Read More »

Unknown dosing, Mechanism, Metformin, Side Effects