Dothiepin Vs Fluoxetine Mechanism of Action and Ph Essay

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Dothiepin Vs Fluoxetine Mechanism of Action and Pharmacodynamics



Comparison Between Mechanism of Action and Pharmacodynamics of Dothiepin and Fluoxetine

Description of medicines

Mechanism of action and pharmacodynamics

Dothiepin

Dothiepin is a tricyclic antidepressant. It acts by promoting the effectiveness of several
amines (dopamine, norepinephrine, and 5-hydroxytryptamine, which is also known as 5HT and
serotonin). It functions by inhibiting their reuptake at the terminals of nerve cells,
thus leading to their prolonged presence at the synaptic cleft and an increased effect on
the neuron.(1) The reuptake pumps for the above amines are responsible for reducing the
concentration of these amines. Dothiepin works by blocking the pumps.


According to the amine hypothesis, a decreased concentration of the amines and the
resulting decrease in amine dependant synaptic transmission is associated with depression,
therefore an increase in the above would help relieve the symptoms of depression. (2)


Dothiepin has other actions as well. It reduces norepinephrine induced CAMP formation in
the brain, as well as inhibiting the uptake of 5HT into platelets. It also has some
anticholinergic and antihistaminic activity.(3)


Dothiepin begins to take effect after approximately 2-3 weeks. Usual daily doses of
Dothiepin range from 75mg to 200mg in the more severe cases. (2)


Fluoxetine

Fluoxetine belongs to a group of antidepressants known as the SSRI’s, or Selective
serotonin reuptake inhibitors. It functions is similar to that of dothiepin above. It also
acts as a reuptake inhibitor, but is highly selective. It only inhibits 5HT reuptake, and
lacks many of the less useful functions of dothiepin, such as the antihistaminic
properties. (1) As above the result in increase in the presence of serotonin at the
synaptic cleft results in a decrease in many symptoms of depression.


Fluoxetine does however have some side effects including nausea, tremors, loss of libido
and in some cases decreased sexual function. (2) It is also possible that it may have an
effect on dopamine function. In some cases it also reduces sleep efficiency. (3)


Daily doses of Fluoxetine range between 10mg and 60mg. However it has been found that
effectiveness does not appear to be strongly related to dose. 20mg is as affective as
40mg, and there is some evidence to suggest that higher doses may be even less effective.
However the lower doses result in fewer and less sever adverse effects.(3)


Adverse effects or adverse drug interactions

Dothiepin

Adverse effects of dothiepin range from potentially life threatening to mildly
discomforting. Fatalities associated with dothiepin include cardiac failure, neonatal
cardio-respiratory failure, myocardial infarction, arrhythmia, cardiac arrest, ventricular
fibrillation, stroke, congenital heart disease, haematemesis, aplastic anemia, leukopenia,
hepatorenal syndrome, cholestatic jaundice, coma, neuroleptic malignant syndrome,
aggravated Parkinson’s disease, intrauterine death, renal failure, respiratory arrest.
These however are very rare. (1) Other severe side effects include hepatitis,
inappropriate ADH secretion, hypomania, and convulsions. Psychotic manifestations, e.g.
paranoid delusions, may be brought about or worsened if already present. These symptoms
are also very uncommon, though less life threatening than those listed above.(3)

The less dangerous side effects are a bit more common, found in many patients,
particularly those on higher doses of the drug. These include dry mouth, tachycardia,
constipation, drowsiness, sweating, nausea, vomiting, diarrhea, tremor, rashes, and
interference with sexual function.(3)


The greatest dangers in overdose stem from convulsions, and the cardiac and respiratory effects listed above. (3)

Adverse drug interactions include MAO inhibitors and SSRI's as concurrent administration
may lead to increased plasma tricyclic levels. CNS depressants, including alcohol will
also have an increased effect when taken in conjunctions with dothiepin. Anesthetics may
increase the risk of arrhythmia. Antihypertensive agent activity may be reduced by
dothiepin. Barbiturates may decrease the serum concentration of dothiepin, while methyl
phenidate may increase it. Smoking may reduce the serum concentration of dothiepin by
increasing its metabolism. (1)


Fluoxetine

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