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'Simprovised' is the twenty-first episode of the twenty-seventh season of the animated television series The Simpsons, and the 595th episode of the series overall. It aired in the United States on Fox on May 15, 2016, and includes a three-minute live-animated segment in which viewers were able to ask Homer Simpson questions.

Plot[edit]

Homer is going to make an annual speech at the Nuclear Plant. His original plan is to repeat the comedy speech he did every year, but most of his punchlines were already used or they would be offensive, including jokes about Lenny's grandmother who is sick. This makes him so nervous that he passes out on the stage, leading to a trauma of public speaking. Trying to cheer Homer up, Marge takes him to a standup comedy show.

At the show, Homer is amazed by the actors' talent to improvise. He, Lenny, and Carl then choose to join an improvisation class, where Homer learns that he has a talent for improvising scenes. They decide to form their own stand-up comedy troupe at Moe's Tavern, where Homer's act is acclaimed by the public and the critics.

In a secondary plot, Bart and Lisa go to Ralph's birthday party, where Bart realizes that Ralph's new treehouse (built with money that Chief Wiggum took from the evidence locker) is much better than his old current treehouse. Feeling envious, Bart destroys his treehouse. However, when he says that mothers can't build a treehouse, Marge plans to work hard and build him the best treehouse she can.

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Later, at the new treehouse, Marge overhears Bart saying to Milhouse that there isn't any need to thank her, because she is only doing her job. Marge gets irritated at him, and storms off during dinner when Bart offends her, where Homer learns that he is invited to perform at the Springfield Fringe Festival. When Marge complains to him about Bart and learns about the fringe festival, she accidentally makes Homer insecure about his own act.

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The next morning, Bart takes Marge's breakfast into her bedroom and apologizes (with Homer's help), and they reconcile. Later at the festival, Moe advises a still insecure Homer that he should cheat on his improvisation act, letting Moe pick his premises. However, Lisa finds out about their plans and convinces Homer to make his show the proper way. He does so, and his on-the-spot act is well-received by the audience.

In a segment advertised as 'Homer Live', Homer puts his improvisation skills to use by taking questions from viewers during the credits. This segment was performed live twice by Dan Castellaneta, for both east and west coast broadcasts. In the international version, Homer gives a three minute monologue chronicling his intentions to run for presidency, only to talk himself out of it by the end of his speech. Different characters (including Bender from Futurama picketing for another revival of his show) pass by him throughout the segment.

Reception[edit]

'Simprovised' scored a 1.2 rating and was watched by 2.80 million viewers, making it Fox's highest rated show of the night.^[1]

Dennis Perkins of The A.V. Club was positive on 'Simprovised', giving it a B+. He explained 'What’s so entertaining about Homer’s journey in 'Simprovised' is how it grows out of his character. Sure, the episode is pretty streamlined, since those last three minutes were set aside for the big ratings-grab, but lopping off the opening credits entirely helped. There’s even time for a truncated but effective B-story, with Marge getting pissed at Bart for not appreciating her building him a new treehouse. Honestly, underdeveloped, gag-happy storylines are a sad fact of life in modern-day 'Simpsons' but 'Simprovised' proves that—even when compressed—a simple story well told and rooted in the characters can be both funny and affecting.'^[2]

IGN reviewer Jesse Schedeen gave the episode a 6.4/10. He criticized the episode itself, but enjoyed the improvised part, adding 'For the most part, this episode was very textbook, late-era Simpsons fare. There were some humor to be had (mainly in the first act), but mostly a lot of missed opportunities and well-worn Simpson family drama. However, the live segment that closed out the episode was definitely a welcome change from the norm. That segment proved that this show still can take risks from time to time, and furthermore, that those risks can pay off.'^[3]

Den of Geek's Tony Sokol was critical, giving the episode 2.5/5 stars, writing 'The episode moved, but for a comedy show doing a show about comedy, the laughs were slim.'^[4]

References[edit]

1. ^Porter, Rick (May 17, 2016). 'Sunday final ratings: 'Once Upon a Time' finale, everything else hold'. TV by the Numbers. Retrieved May 17, 2016.
2. ^'The gimmick is the least impressive part of a funny Simpsons'. The A.V. Club. May 15, 2016. Retrieved May 16, 2016.
3. ^Schedeen, By Jesse (May 15, 2016). 'The Simpsons: 'Simprovised' Review'. IGN. Retrieved May 16, 2016.
4. ^'The Simpsons: Simprovised Review'. Den of Geek. May 15, 2016. Retrieved May 16, 2016.

External links[edit]

• 'Simprovised' on IMDb
• 'Simprovised' at TV.com

Dosage Form: shampoo

Medically reviewed by Drugs.com. Last updated on Aug 1, 2019.

Ketoconazole Shampoo Description

Ketoconazole Shampoo, 2%

For Topical application only.

Rx only

Ketoconazole Shampoo, 2%, is a red-orange liquid for topical application, containing the broad spectrum synthetic antifungal agent ketoconazole in a concentration of 2% in an aqueous suspension. It also contains: sodium laureth sulfate, disodium laureth sulfosuccinate, cocamide diethanolamide, hydrochloric acid, PEG-120 methyl glucose dioleate, imidurea, sodium chloride, sodium hydroxide, fragrance, FD&C red No. 40, and purified water.

Ketoconazole is cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine and has the following structural formula:

Ketoconazole Shampoo - Clinical Pharmacology

Tinea (pityriasis) versicolor is a non-contagious infection of the skin caused by Pityrosporum orbiculare (Malassezia furfur). This commensal organism is part of the normal skin flora. In susceptible individuals the condition is often recurrent and may give rise to hyperpigmented or hypopigmented patches on the trunk which may extend to the neck, arms and upper thighs. Treatment of the infection may not immediately result in restoration of pigment to the affected sites. Normalization of pigment following successful therapy is variable and may take months, depending on individual skin type and incidental skin exposure. The rate of recurrence of infection is variable.

Ketoconazole was not detected in plasma in 39 patients who shampooed 4-10 times per week for 6 months, or in 33 patients who shampooed 2-3 times per week for 3-26 months (mean: 16 months).

An exaggerated use washing test on the sensitive antecubital skin of 10 subjects twice daily for five consecutive days showed that the irritancy potential of Ketoconazole Shampoo, 2%, was significantly less than that of 2.5% selenium sulfide shampoo.

A human sensitization test, a phototoxicity study, and a photoallergy study conducted in 38 male and 22 female volunteers showed no contact sensitization of the delayed hypersensitivity type, no phototoxicity and no photoallergenic potential due to Ketoconazole Shampoo, 2%.

Mode of Action: Interpretations of in vivoChimpoo simpoo cartoon 32. studies suggest that ketoconazole impairs the synthesis of ergosterol, which is a vital component of fungal cell membranes. It is postulated, but not proven, that the therapeutic effect of ketoconazole in tinea (pityriasis) versicolor is due to the reduction of Pityrosporum orbiculare (Malassezia furfur) and that the therapeutic effect in dandruff is due to the reduction of Pityrosporum ovale. Support for the therapeutic effect in tinea versicolor comes from a three-arm, parallel, double-blind, placebo controlled study in patients who had moderately severe tinea (pityriasis) versicolor. Successful response rates in the primary efficacy population for each of both three-day and single-day regimens of Ketoconazole Shampoo, 2%, were statistically significantly greater (73% and 69%, respectively) than a placebo regimen (5%). There had been mycological confirmation of fungal disease in all cases at baseline. Mycological clearing rates were 84% and 78%, respectively, for the three-day and one-day regimens of the 2% shampoo and 11% in the placebo regimen. While the differences in the rates of successful response between either of the two active treatments and placebo were statistically significant, the difference between the two active regimens was not.

Microbiology: Ketoconazole is a broad spectrum synthetic antifungal agent which inhibits the growth of the following common dermatophytes and yeasts by altering the permeability of the cell membrane: dermatophytes: Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum canis, M. audouini, M. gypseum and Epidermophyton floccosum; yeasts: Candida albicans, C. tropicalis, Pityrosporum ovale (Malassezia ovale) and Pityrosporum orbiculare (M. furfur). Development of resistance by these microorganisms to ketoconazole has not been reported.

Indications and Usage for Ketoconazole Shampoo

Ketoconazole Shampoo, 2%, is indicated for the treatment of tinea (pityriasis) versicolor caused by or presumed to be caused by Pityrosporum orbiculare (also known as Malassezia furfur or M. orbiculare).

Note: Tinea (pityriasis) versicolor may give rise to hyperpigmented or hypopigmented patches on the trunk which may extend to the neck, arms and upper thighs. Treatment of the infection may not immediately result in normalization of pigment to the affected sites. Normalization of pigment following successful therapy is variable and may take months, depending on individual skin type and incidental sun exposure. Although tinea versicolor is not contagious, it may recur because the organism that causes the disease is part of the normal skin flora.

Contraindications

Ketoconazole Shampoo, 2%, is contraindicated in persons who have known hypersensitivity to the active ingredient or excipients of this formulation.

Precautions

Severe hypersensitivity reactions, including anaphylaxis, have been reported during post-marketing use of Ketoconazole Shampoo, 2%. If a reaction suggesting sensitivity or chemical irritation should occur, use of the medication should be discontinued.

Information for Patients

Patients should be advised of the following:

• Ketoconazole Shampoo, 2% may be irritating to mucous membranes of the eyes and contact with this area should be avoided.
• The following have been reported with the use of Ketoconazole Shampoo, 2%: hair discoloration and abnormal hair texture, removal of the curl from permanently waved hair, itching, skin burning sensation and contact dermatitis, hypersensitivity, angioedema, alopecia, rash, urticaria, skin irritation, dry skin, and application site reactions.
• Patients who develop allergic reactions, such as generalized rash, skin reactions, severe swelling, angioedema, or shortness of breath should discontinue Ketoconazole Shampoo, 2% and contact their physician immediately.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies to assess the carcinogenic potential of Ketoconazole Shampoo, 2% have not been conducted. A long-term feeding study of ketoconazole in Swiss Albino mice and in Wistar rats showed no evidence of oncogenic activity. The dominant lethal mutation test in male and female mice revealed that single oral doses of ketoconazole as high as 80 mg/kg were not genotoxic. The Ames Salmonella microsomal activator assay was also negative.

Pregnancy

Teratogenic effects: Pregnancy Category C:

There are no adequate and well-controlled studies in pregnant women. Ketoconazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In humans, ketoconazole is not detected in plasma after chronic shampooing on the scalp.

Ketoconazole has been shown to be teratogenic (syndactylia and oligodactylia) in the rat when given orally in the diet at 80 mg/kg/day (a dose 10 times the maximum recommended human oral dose). However, these effects may be related to maternal toxicity, which was seen at this and higher dose levels.

Nursing Mothers

There are no adequate and well-controlled studies in nursing women. Ketoconazole is not detected in plasma after chronic shampooing on the scalp. Caution should be exercised when Ketoconazole Shampoo, 2%, is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in children have not been established.

Adverse Reactions

Clinical Trials Experience

In 11 double-blind trials in 264 patients using Ketoconazole Shampoo, 2%, for the treatment of dandruff or seborrheic dermatitis, an increase in normal hair loss and irritation occurred in less than 1% of patients. In three open-label safety trials in which 41 patients shampooed 4-10 times weekly for six months, the following adverse experiences each occurred once: abnormal hair texture, scalp pustules, mild dryness of the skin, and itching. As with other shampoos, oiliness and dryness of hair and scalp have been reported. In a double-blind, placebo-controlled trial in which patients with tinea versicolor were treated with either a single application of Ketoconazole Shampoo, 2%, (n=106), a daily application for three consecutive days (n=107), or placebo (n=105), drug-related adverse events occurred in 5 (5%), 7 (7%) and 4 (4%) of patients, respectively. The only events that occurred in more than one patient in any one of the three treatment groups were pruritus, application site reaction, and dry skin; none of these events occurred in more than 3% of the patients in any one of the three groups.

Post-marketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency. The following adverse drug reactions have been identified during post-marketing experience with Ketoconazole Shampoo, 2%: there have been reports of hair discoloration and abnormal hair texture, itching, skin burning sensation, contact dermatitis, hypersensitivity, angioedema, alopecia, rash, urticaria, skin irritation, dry skin, and application site reactions.

Overdosage

Ketoconazole Shampoo, 2%, is intended for external use only. In the event of accidental ingestion, supportive and symptomatic measures should be employed. Induced emesis and gastric lavage should not be performed to avoid aspiration.

Ketoconazole Shampoo Dosage and Administration

Apply the shampoo to the damp skin of the affected area and a wide margin surrounding this area. Lather, leave in place for 5 minutes, and then rinse off with water.

One application of the shampoo should be sufficient.

How is Ketoconazole Shampoo Supplied

Ketoconazole Shampoo, 2%, is a red-orange liquid supplied in a 4-fluid ounce nonbreakable plastic bottle (NDC 71713-097-04).

Storage conditions: Store at 20-25ºC (68-77ºF) [see USP Controlled Room Temperature]. Protect from light.

To report SUSPECTED ADVERSE REACTIONS contact Thirty Madison, Inc. at 1-833-745-3377 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Poor Impoverished Nations

Manufactured by: Tolmar, Inc.
Fort Collins, CO 80526
Distributed by: Thirty Madison, Inc.
New York, NY 10016
04006149 Rev. 0 05/19

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