The reason for the delay in therapeutic effect is not fully understood, but it is believed to be due to many factors, including achieving steady-state levels of MAO inhibition and the resulting adaptations in mean neurotransmitter levels, the possibility of necessary desensitization of autoreceptors which normally inhibit the release of neurotransmitters like serotonin and dopamine, and also the upregulation of enzymes such as serotonin N-acetyltransferase. Typically, a therapeutic response to MAOIs is associated with an inhibition of at least 80-85% of monoamine oxidase activity. Pharmacokinetics
Phenelzine is administered orally in the form of phenelzine sulfate and is rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration is 43 minutes and half-life is 11.6 hours. Unlike most other drugs, phenelzine irreversibly disables MAO, and as a result, it does not necessarily need to be present in the blood at all times for its effects to be sustained. Because of this, upon phenelzine treatment being ceased, its effects typically do not actually wear off until the body replenishes its enzyme stores, a process which can take as long as 2–3 weeks. Phenelzine is metabolized primarily in the liver and its metabolites are excreted in the urine. Oxidation is the primary routine of metabolism, and the major metabolites are phenylacetic acid and parahydroxyphenylacetic acid, recovered as about 73% of the excreted dose of phenelzine in the urine over the course of 96 hours after single doses. Acetylation to N2-acetylphenelzine is a minor pathway.
Dysuria refers to painful or uncomfortable urination.It is one of a constellation of irritative bladder symptoms (also sometimes referred to as lower urinary tract symptoms), which includes nocturia and urinary frequency. Diagnosis
The clinician should also look for physical findings of fever, rash, direct tenderness over the bladder area, and joint pain. Physical findings of increased temperature, increased pulse, low blood pressure in the presence of dysuria can indicate systemic infection. Urological obstruction due to stone or tumor can result in findings of hematuria, decreased urination, and bladder spasms. All these physical findings should be looked for carefully while obtaining history. History regarding recent sexual activity is crucial.Urinalysis is the most useful test to start the work up in a patient of dysuria. Urinalysis positive for nitrite carries a high predictive value of a positive urine culture. Also, urine dipstick showing leukocytes as equal predictive value as the presence of nitrites. When both are present, the predictive value goes even higher. If the patient only has leukocyte esterase or bacteria in the urine, then dysuria may suggest that the patient probably has urethritis. Differential diagnosis
This is typically described to be a burning or stinging sensation. It is most often a result of a urinary tract infection. It may also be due to an STD, bladder stones, bladder tumors, and virtually any condition of the prostate. It can also occur as a side effect of anticholinergic medication used for Parkinsons disease.