title: 2022 New York gubernatorial election

text: In June 2020, Lewis County sheriff Mike Carpinelli became the first Republican to enter the race. He was the only announced challenger until Long Island congressman Lee Zeldin announced his own campaign in April 2021; he announced by the end of the month that the Erie and Niagara Counties' Republican Party chairs had endorsed his campaign, giving him the necessary 50% of state committee support to gain the Republican nomination. Trump administration official Andrew Giuliani and 2014 New York gubernatorial nominee Rob Astorino made campaign announcements the following month. Contractor and podcast host Derrick Gibson was also in the race.


title: 2022 New York gubernatorial election

text: In June 2021, Zeldin was named the 'presumed nominee' of the New York's Republican Party by state chairman Nick Langworthy after he earned 85 percent of a straw poll vote of county leaders, and was also called the 'presumptive nominee' of New York's Conservative Party by Conservative state chairman Gerard Kassar. As of February 2022, Zeldin had the endorsement of 59 of New York's 62 county Republican committees.


title: 2022 New York gubernatorial election

text: In February 2022, shortly before the Republican convention, businessman Harry Wilson announced his candidacy for governor of New York. Wilson stated that he intended to invest $12 million of his own money in the race.


title: 2022 New York gubernatorial election

text: At the Republican convention in Nassau County, Zeldin received 85 percent support from the party's voting committee members, with Astorino and Wilson receiving 7 percent of the vote each, and Giuliani receiving less than one percent of the vote.


title: 2022 New York gubernatorial election

text: On June 28, 2022, the primary election was held. Astorino's strongest performance was in his native Westchester County, Giuliani performed well across New York City (although Manhattan was won by Zeldin), and Wilson performed best in his native Fulton County. It was Zeldin who won the Republican nomination, receiving the most votes in 48 of New York's 62 counties, including earning 76% of the vote in his native Suffolk County.


title: 2022 New York gubernatorial election

text: At the 2022 Conservative Party convention, the party endorsed Congressman Lee Zeldin for governor and NYPD deputy inspector Alison Esposito for Lieutenant Governor.


title: 2022 New York gubernatorial election

text: On February 8, 2022, the Working Families Party endorsed New York City Public Advocate Jumaane Williams for the governorship. On February 28, 2022, the party announced that their preferred candidate for Lieutenant Governor was activist Ana María Archila.


title: 2022 New York gubernatorial election

text: Following Hochul and Delgado's respective wins in the Democratic gubernatorial and lieutenant gubernatorial primary, the party filed to put the two Democratic nominees on the Working Families ballot line.


title: 2022 New York gubernatorial election

text: In an unprecedented decision, the New York State Board of Elections rejected all petitions for non-qualified party ballot access in July 2022. Among the parties who submitted rejected petitions:


title: 2022 New York gubernatorial election

text: On February 16, 2022, Larry Sharpe, the Libertarian Party's candidate for Governor of New York in 2018, officially announced his campaign to run for Governor of New York on "Kennedy". He received his party's nomination at the convention in Albany on February 19, 2022. In July 2022, the New York State Board of Elections disqualified Sharpe for not meeting the qualifications for ballot access.


title: 2022 New York gubernatorial election

text: On April 25, 2022, Howie Hawkins, who has run for numerous elected offices including Governor of New York launched his campaign. In July 2022, the New York State Board of Elections disqualified Hawkins for not meeting the qualifications for ballot access.


title: 2022 New York gubernatorial election

text: New York has been a solidly Democratic state, and has not elected a Republican to statewide office since George Pataki's win in 2002. Despite this, polls showed the race narrowing, with the main focus of the election being crime. Zeldin accused Hochul of being weak on crime and education issues, while promising to declare a statewide crime emergency and to repeal cashless bail, while Hochul attacked him for his ties to former President Donald Trump and the pro-life movement.


title: 2022 New York gubernatorial election

text: Ultimately, Hochul defeated Zeldin by a margin of 5.7%, making her the first woman to be elected governor of New York. Despite his loss, Zeldin's performance was the best a Republican had done since George Pataki's victory in 2002, the closest gubernatorial race since 1994, and the most amount of votes a Republican had received for the position in 52 years, since Nelson Rockefeller in 1970. Additionally, Zeldin's coattails significantly narrowed other statewide races, with Democratic Senator Chuck Schumer, who last won by over 40 points in 2016, only winning by just over 12 points in 2022. Republicans also flipped 4 congressional seats in the state, contributing to them winning the House Of Representatives. Due to his overperformance, Zeldin was considered to be a challenger to Ronna McDaniel as chair of the Republican National Committee, however later declined, though he stated that he will remain in politics.


title: Opioid

text: Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use disorder, reversing opioid overdose, and suppressing cough. Extremely potent opioids such as carfentanil are approved only for veterinary use. Opioids are also frequently used non-medically for their euphoric effects or to prevent withdrawal. Opioids can cause death and have been used for executions in the United States.


title: Opioid

text: Side effects of opioids may include itchiness, sedation, nausea, respiratory depression, constipation, and euphoria. Long-term use can cause tolerance, meaning that increased doses are required to achieve the same effect, and physical dependence, meaning that abruptly discontinuing the drug leads to unpleasant withdrawal symptoms. The euphoria attracts recreational use, and frequent, escalating recreational use of opioids typically results in addiction. An overdose or concurrent use with other depressant drugs like benzodiazepines commonly results in death from respiratory depression.


title: Opioid

text: Opioids act by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. These receptors mediate both the psychoactive and the somatic effects of opioids. Opioid drugs include partial agonists, like the anti-diarrhea drug loperamide and antagonists like naloxegol for opioid-induced constipation, which do not cross the blood–brain barrier, but can displace other opioids from binding to those receptors.


title: Opioid

text: Because opioids are addictive and may result in fatal overdose, most are controlled substances. In 2013, between 28 and 38 million people used opioids illicitly (0.6% to 0.8% of the global population between the ages of 15 and 65). In 2011, an estimated 4 million people in the United States used opioids recreationally or were dependent on them. As of 2015, increased rates of recreational use and addiction are attributed to over-prescription of opioid medications and inexpensive illicit heroin. Conversely, fears about overprescribing, exaggerated side effects, and addiction from opioids are similarly blamed for under-treatment of pain.


title: Opioid

text: Opioids include "opiates", an older term that refers to such drugs derived from opium, including morphine itself. Other opioids are semi-synthetic and synthetic drugs such as hydrocodone, oxycodone and fentanyl; antagonist drugs such as naloxone; and endogenous peptides such as the endorphins. The terms "opiate" and "narcotic" are sometimes encountered as synonyms for opioid. "Opiate" is properly limited to the natural alkaloids found in the resin of the opium poppy although some include semi-synthetic derivatives. "Narcotic", derived from words meaning 'numbness' or 'sleep', as an American legal term, refers to cocaine and opioids, and their source materials; it is also loosely applied to any illegal or controlled psychoactive drug. In some jurisdictions all controlled drugs are legally classified as "narcotics". The term can have pejorative connotations and its use is generally discouraged where that is the case.


title: Opioid

text: The weak opioid codeine , in low doses and combined with one or more other drugs, is commonly available without a prescription and can be used to treat mild pain. Other opioids are usually reserved for the relief of moderate to severe pain.


title: Opioid

text: Opioids are effective for the treatment of acute pain (such as pain following surgery). For immediate relief of moderate to severe acute pain, opioids are frequently the treatment of choice due to their rapid onset, efficacy and reduced risk of dependence. However, a new report showed a clear risk of prolonged opioid use when opioid analgesics are initiated for an acute pain management following surgery or trauma. They have also been found to be important in palliative care to help with the severe, chronic, disabling pain that may occur in some terminal conditions such as cancer, and degenerative conditions such as rheumatoid arthritis. In many cases opioids are a successful long-term care strategy for those with chronic cancer pain.


title: Opioid

text: Just over half of all states in the US have enacted laws that restrict the prescribing or dispensing of opioids for acute pain.


title: Opioid

text: Guidelines have suggested that the risk of opioids is likely greater than their benefits when used for most non-cancer chronic conditions including headaches, back pain, and fibromyalgia. Thus they should be used cautiously in chronic non-cancer pain. If used the benefits and harms should be reassessed at least every three months.


title: Opioid

text: In treating chronic pain, opioids are an option to be tried after other less risky pain relievers have been considered, including paracetamol/acetaminophen or NSAIDs like ibuprofen or naproxen. Some types of chronic pain, including the pain caused by fibromyalgia or migraine, are preferentially treated with drugs other than opioids. The efficacy of using opioids to lessen chronic neuropathic pain is uncertain.


title: Opioid

text: Opioids are contraindicated as a first-line treatment for headache because they impair alertness, bring risk of dependence, and increase the risk that episodic headaches will become chronic. Opioids can also cause heightened sensitivity to headache pain. When other treatments fail or are unavailable, opioids may be appropriate for treating headache if the patient can be monitored to prevent the development of chronic headache.


title: Opioid

text: Opioids are being used more frequently in the management of non-malignant chronic pain. This practice has now led to a new and growing problem with addiction and misuse of opioids. Because of various negative effects the use of opioids for long-term management of chronic pain is not indicated unless other less risky pain relievers have been found ineffective. Chronic pain which occurs only periodically, such as that from nerve pain, migraines, and fibromyalgia, frequently is better treated with medications other than opioids. Paracetamol and nonsteroidal anti-inflammatory drugs including ibuprofen and naproxen are considered safer alternatives. They are frequently used combined with opioids, such as paracetamol combined with oxycodone (Percocet) and ibuprofen combined with hydrocodone (Vicoprofen), which boosts the pain relief but is also intended to deter recreational use.


title: Opioid

text: Codeine was once viewed as the "gold standard" in cough suppressants, but this position is now questioned. Some recent placebo-controlled trials have found that it may be no better than a placebo for some causes including acute cough in children. Thus, it is not recommended for children. Additionally, there is no evidence that hydrocodone is useful in children. Similarly, a 2012 Dutch guideline regarding the treatment of acute cough does not recommend its use. (The opioid analogue dextromethorphan, long claimed to be as effective a cough suppressant as codeine, has similarly demonstrated little benefit in several recent studies.)


title: Opioid

text: In cases of diarrhea-predominate irritable bowel syndrome, opioids may be used to suppress diarrhea. Loperamide is a peripherally selective opioid available without a prescription used to suppress diarrhea.


title: Opioid

text: The ability to suppress diarrhea also produces constipation when opioids are used beyond several weeks. Naloxegol, a peripherally-selective opioid antagonist is now available to treat opioid induced constipation.


title: Opioid

text: Opioids may help with shortness of breath particularly in advanced diseases such as cancer and COPD among others. However, findings from two recent systematic reviews of the literature found that opioids were not necessarily more effective in treating shortness of breath in patients who have advanced cancer.


title: Opioid

text: Each year 69,000 people worldwide die of opioid overdose, and 15 million people have an opioid addiction.


title: Opioid

text: In older adults, opioid use is associated with increased adverse effects such as "sedation, nausea, vomiting, constipation, urinary retention, and falls". As a result, older adults taking opioids are at greater risk for injury. Opioids do not cause any specific organ toxicity, unlike many other drugs, such as aspirin and paracetamol. They are not associated with upper gastrointestinal bleeding and kidney toxicity.


title: Opioid

text: Prescription of opioids for acute low back pain and management of osteoarthritis seem to have long-term adverse effects


title: Opioid

text: According to the USCDC, methadone was involved in 31% of opioid related deaths in the US between 1999–2010 and 40% as the sole drug involved, far higher than other opioids. Studies of long term opioids have found that many stop them, and that minor side effects were common. Addiction occurred in about 0.3%. In the United States in 2016 opioid overdose resulted in the death of 1.7 in 10,000 people.


title: Opioid

text: Tolerance is a process characterized by neuroadaptations that result in reduced drug effects. While receptor upregulation may often play an important role other mechanisms are also known. Tolerance is more pronounced for some effects than for others; tolerance occurs slowly to the effects on mood, itching, urinary retention, and respiratory depression, but occurs more quickly to the analgesia and other physical side effects. However, tolerance does not develop to constipation or miosis (the constriction of the pupil of the eye to less than or equal to two millimeters). This idea has been challenged, however, with some authors arguing that tolerance "does" develop to miosis.


title: Opioid

text: Tolerance is a physiologic process where the body adjusts to a medication that is frequently present, usually requiring higher doses of the same medication over time to achieve the same effect. It is a common occurrence in individuals taking high doses of opioids for extended periods, but does not predict any relationship to misuse or addiction.


title: Opioid

text: Physical dependence is the physiological adaptation of the body to the presence of a substance, in this case opioid medication. It is defined by the development of withdrawal symptoms when the substance is discontinued, when the dose is reduced abruptly or, specifically in the case of opioids, when an antagonist ("e.g.", naloxone) or an agonist-antagonist ("e.g.", pentazocine) is administered. Physical dependence is a normal and expected aspect of certain medications and does not necessarily imply that the patient is addicted.


title: Opioid

text: The withdrawal symptoms for opiates may include severe dysphoria, craving for another opiate dose, irritability, sweating, nausea, rhinorrea, tremor, vomiting and myalgia. Slowly reducing the intake of opioids over days and weeks can reduce or eliminate the withdrawal symptoms. The speed and severity of withdrawal depends on the half-life of the opioid; heroin and morphine withdrawal occur more quickly than methadone withdrawal. The acute withdrawal phase is often followed by a protracted phase of depression and insomnia that can last for months. The symptoms of opioid withdrawal can be treated with other medications, such as clonidine. Physical dependence does not predict drug misuse or true addiction, and is closely related to the same mechanism as tolerance. While there is anecdotal claims of benefit with ibogaine, data to support its use in substance dependence is poor.


title: Opioid

text: Critical patients who received regular doses of opioids experience Iatrogenic withdrawal as a frequent syndrome.


title: Opioid

text: Drug addiction is a complex set of behaviors typically associated with misuse of certain drugs, developing over time and with higher drug dosages. Addiction includes psychological compulsion, to the extent that the affected person persists in actions leading to dangerous or unhealthy outcomes. Opioid addiction includes insufflation or injection, rather than taking opioids orally as prescribed for medical reasons.


title: Opioid

text: In European nations such as Austria, Bulgaria, and Slovakia, slow-release oral morphine formulations are used in opiate substitution therapy (OST) for patients who do not well tolerate the side effects of buprenorphine or methadone. buprenorphine can also be used together with naloxone for a longer treatment of addiction. / In other European countries including the UK, this is also legally used for OST although on a varying scale of acceptance.


title: Opioid

text: Slow-release formulations of medications are intended to curb misuse and lower addiction rates while trying to still provide legitimate pain relief and ease of use to pain patients. Questions remain, however, about the efficacy and safety of these types of preparations. Further tamper resistant medications are currently under consideration with trials for market approval by the FDA.


title: Opioid

text: The amount of evidence available only permits making a weak conclusion, but it suggests that a physician properly managing opioid use in patients with no history of substance use disorder can give long-term pain relief with little risk of developing addiction, or other serious side effects.


title: Opioid

text: All of the opioids can cause side effects. Common adverse reactions in patients taking opioids for pain relief include nausea and vomiting, drowsiness, itching, dry mouth, dizziness, and constipation.


title: Opioid

text: Tolerance to nausea occurs within 7–10 days, during which antiemetics ("e.g." low dose haloperidol once at night) are very effective. Due to severe side effects such as tardive dyskinesia, haloperidol is now rarely used. A related drug, prochlorperazine is more often used, although it has similar risks. Stronger antiemetics such as ondansetron or tropisetron are sometimes used when nausea is severe or continuous and disturbing, despite their greater cost. A less expensive alternative is dopamine antagonists such as domperidone and metoclopramide. Domperidone does not cross the blood–brain barrier and produce adverse central antidopaminergic effects, but blocks opioid emetic action in the chemoreceptor trigger zone. (The drug is not available in the U.S.) Some antihistamines with anticholinergic properties ("e.g." orphenadrine or diphenhydramine) may also be effective. The first-generation antihistamine hydroxyzine is very commonly used, with the added advantages of not causing movement disorders, and also possessing analgesic-sparing properties. Δ-tetrahydrocannabinol relieves nausea and vomiting; it also produces analgesia that may allow lower doses of opioids with reduced nausea and vomiting.


title: Opioid

text: Vomiting is due to gastric stasis (large volume vomiting, brief nausea relieved by vomiting, oesophageal reflux, epigastric fullness, early satiation), besides direct action on the chemoreceptor trigger zone of the area postrema, the vomiting centre of the brain. Vomiting can thus be prevented by prokinetic agents ("e.g." domperidone or metoclopramide). If vomiting has already started, these drugs need to be administered by a non-oral route ("e.g." subcutaneous for metoclopramide, rectally for domperidone).


title: Opioid

text: Evidence suggests that opioid-inclusive anaesthesia is associated with postoperative nausea and vomiting.


title: Opioid

text: Patients with chronic pain using opioids had small improvements in pain and physically functioning and increased risk of vomiting.


title: Opioid

text: Tolerance to drowsiness usually develops over 5–7 days, but if troublesome, switching to an alternative opioid often helps. Certain opioids such as fentanyl, morphine and diamorphine (heroin) tend to be particularly sedating, while others such as oxycodone, tilidine and meperidine (pethidine) tend to produce comparatively less sedation, but individual patients responses can vary markedly and some degree of trial and error may be needed to find the most suitable drug for a particular patient. Otherwise, treatment with CNS stimulants is generally effective.


title: Opioid

text: Itching tends not to be a severe problem when opioids are used for pain relief, but antihistamines are useful for counteracting itching when it occurs. Non-sedating antihistamines such as fexofenadine are often preferred as they avoid increasing opioid induced drowsiness. However, some sedating antihistamines such as orphenadrine can produce a synergistic pain relieving effect permitting smaller doses of opioids be used. Consequently, several opioid/antihistamine combination products have been marketed, such as "Meprozine" (meperidine/promethazine) and "Diconal" (dipipanone/cyclizine), and these may also reduce opioid induced nausea.


title: Opioid

text: Opioid-induced constipation (OIC) develops in 90 to 95% of people taking opioids long-term. Since tolerance to this problem does not generally develop, most people on long-term opioids need to take a laxative or enemas.


title: Opioid

text: Treatment of OIC is successional and dependent on severity. The first mode of treatment is non-pharmacological, and includes lifestyle modifications like increasing dietary fiber, fluid intake (around per day), and physical activity. If non-pharmacological measures are ineffective, laxatives, including stool softeners ("e.g.", polyethylene glycol), bulk-forming laxatives ("e.g.", fiber supplements), stimulant laxatives ("e.g.", bisacodyl, senna), and/or enemas, may be used. A common laxative regimen for OIC is the combination of docusate and bisacodyl. Osmotic laxatives, including lactulose, polyethylene glycol, and milk of magnesia (magnesium hydroxide), as well as mineral oil (a lubricant laxative), are also commonly used for OIC.


title: Opioid

text: If laxatives are insufficiently effective (which is often the case), opioid formulations or regimens that include a peripherally-selective opioid antagonist, such as methylnaltrexone bromide, naloxegol, alvimopan, or naloxone (as in oxycodone/naloxone), may be tried. A 2018 Cochrane review found that the evidence was tentative for alvimopan, naloxone, or methylnaltrexone bromide. Naloxone by mouth appears to be the most effective. A daily 0.2 mg dose of naldemedine has been shown to significantly improve symptoms in patients with OIC.


title: Opioid

text: Opioid rotation is one method suggested to minimise the impact of constipation in long-term users. While all opioids cause constipation, there are some differences between drugs, with studies suggesting tramadol, tapentadol, methadone and fentanyl may cause relatively less constipation, while with codeine, morphine, oxycodone or hydromorphone constipation may be comparatively more severe.


title: Opioid

text: Respiratory depression is the most serious adverse reaction associated with opioid use, but it usually is seen with the use of a single, intravenous dose in an opioid-naïve patient. In patients taking opioids regularly for pain relief, tolerance to respiratory depression occurs rapidly, so that it is not a clinical problem. Several drugs have been developed which can partially block respiratory depression, although the only respiratory stimulant currently approved for this purpose is doxapram, which has only limited efficacy in this application. Newer drugs such as BIMU-8 and CX-546 may be much more effective.


title: Opioid

text: The initial 24 hours after opioid administration appear to be the most critical with regard to life-threatening OIRD, but may be preventable with a more cautious approach to opioid use.


title: Opioid

text: Patients with cardiac, respiratory disease and/or obstructive sleep apnoea are at increased risk for OIRD.


title: Opioid

text: Opioid-induced hyperalgesia – where individuals using opioids to relieve pain paradoxically experience more pain as a result of that medication – has been observed in some people. This phenomenon, although uncommon, is seen in some people receiving palliative care, most often when dose is increased rapidly. If encountered, rotation between several different opioid pain medications may decrease the development of increased pain. Opioid induced hyperalgesia more commonly occurs with chronic use or brief high doses but some research suggests that it may also occur with very low doses.


title: Opioid

text: Side effects such as hyperalgesia and allodynia, sometimes accompanied by a worsening of neuropathic pain, may be consequences of long-term treatment with opioid analgesics, especially when increasing tolerance has resulted in loss of efficacy and consequent progressive dose escalation over time. This appears to largely be a result of actions of opioid drugs at targets other than the three classic opioid receptors, including the nociceptin receptor, sigma receptor and Toll-like receptor 4, and can be counteracted in animal models by antagonists at these targets such as J-113,397, BD-1047 or (+)-naloxone respectively. No drugs are currently approved specifically for counteracting opioid-induced hyperalgesia in humans and in severe cases the only solution may be to discontinue use of opioid analgesics and replace them with non-opioid analgesic drugs. However, since individual sensitivity to the development of this side effect is highly dose dependent and may vary depending which opioid analgesic is used, many patients can avoid this side effect simply through dose reduction of the opioid drug (usually accompanied by the addition of a supplemental non-opioid analgesic), rotating between different opioid drugs, or by switching to a milder opioid with a mixed mode of action that also counteracts neuropathic pain, particularly tramadol or tapentadol.


title: Opioid

text: Clinical studies have consistently associated medical and recreational opioid use with hypogonadism (low sex hormone levels) in different sexes. The effect is dose-dependent. Most studies suggest that the majority (perhaps as much as 90%) of chronic opioid users develop hypogonadism. A 2015 systematic review and meta-analysis found that opioid therapy suppressed testosterone levels in men by about 165 ng/dL (5.7 nmol/L) on average, which was a reduction in testosterone level of almost 50%. Conversely, opioid therapy did not significantly affect testosterone levels in women. However, opioids can also interfere with menstruation in women by limiting the production of luteinizing hormone (LH). Opioid-induced hypogonadism likely causes the strong association of opioid use with osteoporosis and bone fracture, due to deficiency in estradiol. It also may increase pain and thereby interfere with the intended clinical effect of opioid treatment. Opioid-induced hypogonadism is likely caused by their agonism of opioid receptors in the hypothalamus and the pituitary gland. One study found that the depressed testosterone levels of heroin addicts returned to normal within one month of abstinence, suggesting that the effect is readily reversible and is not permanent. , the effect of low-dose or acute opioid use on the endocrine system is unclear. Long-term use of opioids can affect the other hormonal systems as well.


title: Opioid

text: Persons performing any safety-sensitive task should not use opioids. Health care providers should not recommend that workers who drive or use heavy equipment including cranes or forklifts treat chronic or acute pain with opioids. Workplaces which manage workers who perform safety-sensitive operations should assign workers to less sensitive duties for so long as those workers are treated by their physician with opioids.


title: Opioid

text: People who take opioids long term have increased likelihood of being unemployed. Taking opioids may further disrupt the patient's life and the adverse effects of opioids themselves can become a significant barrier to patients having an active life, gaining employment, and sustaining a career.


title: Opioid

text: Opioid use may increase accident-proneness. Opioids may increase risk of traffic accidents and accidental falls.


title: Opioid

text: Opioids have been shown to reduce attention, more so when used with antidepressants and/or anticonvulsants.


title: Opioid

text: Infrequent adverse reactions in patients taking opioids for pain relief include: dose-related respiratory depression (especially with more potent opioids), confusion, hallucinations, delirium, urticaria, hypothermia, bradycardia/tachycardia, orthostatic hypotension, dizziness, headache, urinary retention, ureteric or biliary spasm, muscle rigidity, myoclonus (with high doses), and flushing (due to histamine release, except fentanyl and remifentanil).


title: Opioid

text: Both therapeutic and chronic use of opioids can compromise the function of the immune system. Opioids decrease the proliferation of macrophage progenitor cells and lymphocytes, and affect cell differentiation (Roy & Loh, 1996). Opioids may also inhibit leukocyte migration. However the relevance of this in the context of pain relief is not known.


title: Opioid

text: Physicians treating patients using opioids in combination with other drugs keep continual documentation that further treatment is indicated and remain aware of opportunities to adjust treatment if the patient's condition changes to merit less risky therapy.


title: Opioid

text: The concurrent use of opioids with other depressant drugs such as benzodiazepines or ethanol increases the rates of adverse events and overdose. despite this, opioids and benzodiazepines are concurrently dispensed in many settings. As with an overdose of opioid alone, the combination of an opioid and another depressant may precipitate respiratory depression often leading to death. These risks are lessened with close monitoring by a physician, who may conduct ongoing screening for changes in patient behavior and treatment compliance.


title: Opioid

text: Opioid effects (adverse or otherwise) can be reversed with an opioid antagonist such as naloxone or naltrexone. These competitive antagonists bind to the opioid receptors with higher affinity than agonists but do not activate the receptors. This displaces the agonist, attenuating or reversing the agonist effects. However, the elimination half-life of naloxone can be shorter than that of the opioid itself, so repeat dosing or continuous infusion may be required, or a longer acting antagonist such as nalmefene may be used. In patients taking opioids regularly it is essential that the opioid is only partially reversed to avoid a severe and distressing reaction of waking in excruciating pain. This is achieved by not giving a full dose but giving this in small doses until the respiratory rate has improved. An infusion is then started to keep the reversal at that level, while maintaining pain relief. Opioid antagonists remain the standard treatment for respiratory depression following opioid overdose, with naloxone being by far the most commonly used, although the longer acting antagonist nalmefene may be used for treating overdoses of long-acting opioids such as methadone, and diprenorphine is used for reversing the effects of extremely potent opioids used in veterinary medicine such as etorphine and carfentanil. However, since opioid antagonists also block the beneficial effects of opioid analgesics, they are generally useful only for treating overdose, with use of opioid antagonists alongside opioid analgesics to reduce side effects, requiring careful dose titration and often being poorly effective at doses low enough to allow analgesia to be maintained.


title: Opioid

text: Naltrexone does not appear to increase risk of serious adverse events, which confirms the safety of oral naltrexone. Mortality or serious adverse events due to rebound toxicity in patients with naloxone were rare.


title: Opioid

text: Opioids bind to specific opioid receptors in the nervous system and other tissues. There are three principal classes of opioid receptors, μ, κ, δ (mu, kappa, and delta), although up to seventeen have been reported, and include the ε, ι, λ, and ζ (Epsilon, Iota, Lambda and Zeta) receptors. Conversely, σ (Sigma) receptors are no longer considered to be opioid receptors because their activation is not reversed by the opioid inverse-agonist naloxone, they do not exhibit high-affinity binding for classical opioids, and they are stereoselective for dextro-rotatory isomers while the other opioid receptors are stereo-selective for levo-rotatory isomers. In addition, there are three subtypes of μ-receptor: μ and μ, and the newly discovered μ. Another receptor of clinical importance is the opioid-receptor-like receptor 1 (ORL1), which is involved in pain responses as well as having a major role in the development of tolerance to μ-opioid agonists used as analgesics. These are all G-protein coupled receptors acting on GABAergic neurotransmission.


title: Opioid

text: The pharmacodynamic response to an opioid depends upon the receptor to which it binds, its affinity for that receptor, and whether the opioid is an agonist or an antagonist. For example, the supraspinal analgesic properties of the opioid agonist morphine are mediated by activation of the μ receptor; respiratory depression and physical dependence by the μ receptor; and sedation and spinal analgesia by the κ receptor. Each group of opioid receptors elicits a distinct set of neurological responses, with the receptor subtypes (such as μ and μ for example) providing even more [measurably] specific responses. Unique to each opioid is its distinct binding affinity to the various classes of opioid receptors ("e.g." the μ, κ, and δ opioid receptors are activated at different magnitudes according to the specific receptor binding affinities of the opioid). For example, the opiate alkaloid morphine exhibits high-affinity binding to the μ-opioid receptor, while ketazocine exhibits high affinity to ĸ receptors. It is this combinatorial mechanism that allows for such a wide class of opioids and molecular designs to exist, each with its own unique effect profile. Their individual molecular structure is also responsible for their different duration of action, whereby metabolic breakdown (such as "N"-dealkylation) is responsible for opioid metabolism.


title: Opioid

text: A new strategy of drug development takes receptor signal transduction into consideration. This strategy strives to increase the activation of desirable signalling pathways while reducing the impact on undesirable pathways. This differential strategy has been given several names, including functional selectivity and biased agonism. The first opioid that was intentionally designed as a biased agonist and placed into clinical evaluation is the drug oliceridine. It displays analgesic activity and reduced adverse effects.


title: Opioid

text: Extensive research has been conducted to determine equivalence ratios comparing the relative potency of opioids. Given a dose of an opioid, an equianalgesic table is used to find the equivalent dosage of another. Such tables are used in opioid rotation practices, and to describe an opioid by comparison to morphine, the reference opioid. Equianalgesic tables typically list drug half-lives, and sometimes equianalgesic doses of the same drug by means of administration, such as morphine: oral and intravenous.


title: Opioid

text: In the 1990s, opioid prescribing increased significantly. Once used almost exclusively for the treatment of acute pain or pain due to cancer, opioids are now prescribed liberally for people experiencing chronic pain. This has been accompanied by rising rates of accidental addiction and accidental overdoses leading to death. According to the International Narcotics Control Board, the United States and Canada lead the per capita consumption of prescription opioids. The number of opioid prescriptions per capita in the United States and Canada is double the consumption in the European Union, Australia, and New Zealand. Certain populations have been affected by the opioid addiction crisis more than others, including First World communities and low-income populations. Public health specialists say that this may result from the unavailability or high cost of alternative methods for addressing chronic pain. Opioids have been described as a cost-effective treatment for chronic pain, but the impact of the opioid epidemic and deaths caused by opioid overdoses should be considered in assessing their cost-effectiveness. Data from 2017 suggest that in the U.S. about 3.4 percent of the U.S. population are prescribed opioids for daily pain management. Calls for opioid deprescribing have led to broad scale opioid tapering practices with little scientific evidence to support the safety or benefit for patients with chronic pain.


title: Opioid

text: Opioids are among the world's oldest known drugs. The earliest known evidence of "Papaver somniferum" in a human archaeological site dates to the Neolithic period around 5,700–5,500 BC. Its seeds have been found at Cueva de los Murciélagos in the Iberian Peninsula and La Marmotta in the Italian Peninsula.


title: Opioid

text: Use of the opium poppy for medical, recreational, and religious purposes can be traced to the fourth century BC, when ideograms on Sumerians clay tablets mention the use of "Hul Gil", a "plant of joy".


title: Opioid

text: Opium was known to the Egyptians, and is mentioned in the Ebers Papyrus as an ingredient in a mixture for the soothing of children, and for the treatment of breast abscesses.


title: Opioid

text: It was valued by Hippocrates ( – ) and his students for its sleep-inducing properties, and used for the treatment of pain. The Latin saying "Sedare dolorem opus divinum est", trans. "Alleviating pain is the work of the divine", has been variously ascribed to Hippocrates and to Galen of Pergamum. The medical use of opium is later discussed by Pedanius Dioscorides ( – 90 AD), a Greek physician serving in the Roman army, in his five-volume work, "De Materia Medica".


title: Opioid

text: During the Islamic Golden Age, the use of opium was discussed in detail by Avicenna ( – June 1037 AD) in "The Canon of Medicine". The book's five volumes include information on opium's preparation, an array of physical effects, its use to treat a variety of illness, contraindications for its use, its potential danger as a poison and its potential for addiction. Avicenna discouraged opium's use except as a last resort, preferring to address the causes of pain rather than trying to minimize it with analgesics. Many of Avicenna's observations have been supported by modern medical research.


title: Opioid

text: Exactly when the world became aware of opium in India and China is uncertain, but opium was mentioned in the Chinese medical work "K'ai-pao-pen-tsdo" (973 AD) By 1590 AD, opium poppies were a staple spring crop in the Subahs of Agra region.


title: Opioid

text: The physician Paracelsus (–1541) is often credited with reintroducing opium into medical use in Western Europe, during the German Renaissance. He extolled opium's benefits for medical use. He also claimed to have an "arcanum", a pill which he called laudanum, that was superior to all others, particularly when death was to be cheated. ("Ich hab' ein Arcanum – heiss' ich Laudanum, ist über das Alles, wo es zum Tode reichen will.") Later writers have asserted that Paracelsus' recipe for laudanum contained opium, but its composition remains unknown.


title: Opioid

text: The term laudanum was used generically for a useful medicine until the 17th century. After Thomas Sydenham introduced the first liquid tincture of opium, "laudanum" came to mean a mixture of both opium and alcohol.


title: Opioid

text: Sydenham's 1669 recipe for laudanum mixed opium with wine, saffron, clove and cinnamon. Sydenham's laudanum was used widely in both Europe and the Americas until the 20th century.


title: Opioid

text: Other popular medicines, based on opium, included Paregoric, a much milder liquid preparation for children; Black-drop, a stronger preparation; and Dover's powder.


title: Opioid

text: Opium became a major colonial commodity, moving legally and illegally through trade networks involving India, the Portuguese, the Dutch, the British and China, among others.


title: Opioid

text: The British East India Company saw the opium trade as an investment opportunity in 1683 AD. In 1773 the Governor of Bengal established a monopoly on the production of Bengal opium, on behalf of the East India Company. The cultivation and manufacture of Indian opium was further centralized and controlled through a series of acts, between 1797 and 1949. The British balanced an economic deficit from the importation of Chinese tea by selling Indian opium which was smuggled into China in defiance of Chinese government bans. This led to the First (1839–1842) and Second Opium Wars (1856–1860) between China and Britain.


title: Opioid

text: In the 19th century, two major scientific advances were made that had far-reaching effects. Around 1804, German pharmacist Friedrich Sertürner isolated morphine from opium. He described its crystallization, structure, and pharmacological properties in a well-received paper in 1817.


title: Opioid

text: Morphine was the first alkaloid to be isolated from any medicinal plant, the beginning of modern scientific drug discovery.


title: Opioid

text: The second advance, nearly fifty years later, was the refinement of the hypodermic needle by Alexander Wood and others. Development of a glass syringe with a subcutaneous needle made it possible to easily administer controlled measurable doses of a primary active compound.


title: Opioid

text: Morphine was initially hailed as a wonder drug for its ability to ease pain. It could help people sleep, and had other useful side effects, including control of coughing and diarrhea. It was widely prescribed by doctors, and dispensed without restriction by pharmacists. During the American Civil War, opium and laudanum were used extensively to treat soldiers. It was also prescribed frequently for women, for menstrual pain and diseases of a "nervous character".


title: Opioid

text: Codeine was discovered in 1832 by Pierre Jean Robiquet. Robiquet was reviewing a method for morphine extraction, described by Scottish chemist William Gregory (1803–1858). Processing the residue left from Gregory's procedure, Robiquet isolated a crystalline substance from the other active components of opium. He wrote of his discovery: "Here is a new substance found in opium ... We know that morphine, which so far has been thought to be the only active principle of opium, does not account for all the effects and for a long time the physiologists are claiming that there is a gap that has to be filled." His discovery of the alkaloid led to the development of a generation of antitussive and antidiarrheal medicines based on codeine.


title: Opioid

text: Synthetic opioids were invented, and biological mechanisms for their actions discovered, in the 20th century. Scientists have searched for non-addictive forms of opioids, but have created stronger ones instead. In England Charles Romley Alder Wright developed hundreds of opiate compounds in his search for a nonaddictive opium derivative. In 1874 he became the first person to synthesize diamorphine (heroin), using a process called acetylation which involved boiling morphine with acetic anhydride for several hours.


title: Opioid

text: Heroin received little attention until it was independently synthesized by Felix Hoffmann (1868–1946), working for Heinrich Dreser (1860–1924) at Bayer Laboratories. Dreser brought the new drug to market as an analgesic and a cough treatment for tuberculosis, bronchitis, and asthma in 1898. Bayer ceased production in 1913, after heroin's addictive potential was recognized.


title: Opioid

text: Several semi-synthetic opioids were developed in Germany in the 1910s. The first, oxymorphone, was synthesized from thebaine, an opioid alkaloid in opium poppies, in 1914.


title: Opioid

text: Next, Martin Freund and Edmund Speyer developed oxycodone, also from thebaine, at the University of Frankfurt in 1916.


title: Opioid

text: In 1920, hydrocodone was prepared by Carl Mannich and Helene Löwenheim, deriving it from codeine. In 1924, hydromorphone was synthesized by adding hydrogen to morphine. Etorphine was synthesized in 1960, from the oripavine in opium poppy straw. Buprenorphine was discovered in 1972.


title: Opioid

text: The first fully synthetic opioid was meperidine (later demerol), found serendipitously by German chemist Otto Eisleb (or Eislib) at IG Farben in 1932. Meperidine was the first opiate to have a structure unrelated to morphine, but with opiate-like properties. Its analgesic effects were discovered by Otto Schaumann in 1939.


title: Opioid

text: built on the work of Eisleb and Schaumann. They developed "Hoechst 10820" (later methadone) around 1937.


title: Opioid

text: In 1959 the Belgian physician Paul Janssen developed fentanyl, a synthetic drug with 30 to 50 times the potency of heroin.


title: Opioid

text: Non-clinical use of opium was criminalized in the United States by the Harrison Narcotics Tax Act of 1914, and by many other laws. The use of opioids was stigmatized, and it was seen as a dangerous substance, to be prescribed only as a last resort for dying patients. The Controlled Substances Act of 1970 eventually relaxed the harshness of the Harrison Act.


title: Opioid

text: In the United Kingdom the 1926 report of the Departmental Committee on Morphine and Heroin Addiction under the Chairmanship of the President of the Royal College of Physicians reasserted medical control and established the "British system" of control—which lasted until the 1960s.


title: Opioid

text: In the 1980s the World Health Organization published guidelines for prescribing drugs, including opioids, for different levels of pain. In the U.S., Kathleen Foley and Russell Portenoy became leading advocates for the liberal use of opioids as painkillers for cases of "intractable non-malignant pain".


title: Opioid

text: With little or no scientific evidence to support their claims, industry scientists and advocates suggested that people with chronic pain would be resistant to addiction.


title: Opioid

text: The release of OxyContin in 1996 was accompanied by an aggressive marketing campaign promoting the use of opioids for pain relief. Increasing prescription of opioids fueled a growing black market for heroin. Between 2000 and 2014 there was an "alarming increase in heroin use across the country and an epidemic of drug overdose deaths".


title: Opioid

text: As a result, health care organizations and public health groups, such as Physicians for Responsible Opioid Prescribing, have called for decreases in the prescription of opioids. In 2016, the Centers for Disease Control and Prevention (CDC) issued a new set of guidelines for the prescription of opioids "for chronic pain outside of active cancer treatment, palliative care, and end-of-life care" and the increase of opioid tapering.


title: Opioid

text: In April 2019 the U.S. Food and Drug Administration announced the launch of a new education campaign to help Americans understand the important role they play in removing and properly disposing of unused prescription opioids from their homes. This new initiative is part of the FDA's continued efforts to address the nationwide opioid crisis (see below) and aims to help decrease unnecessary exposure to opioids and prevent new addiction. The "Remove the Risk" campaign is targeting women ages 35–64, who are most likely to oversee household health care decisions and often serve as the gatekeepers to opioids and other prescription medications in the home.


title: Opioid

text: The term "opioid" originated in the 1950s. It combines "opium" + "-oid" meaning "opiate-like" ("opiates" being morphine and similar drugs derived from opium). The first scientific publication to use it, in 1963, included a footnote stating, "In this paper, the term, 'opioid', is used in the sense originally proposed by George H. Acheson (personal communication) to refer to any chemical compound with morphine-like activities". By the late 1960s, research found that opiate effects are mediated by activation of specific molecular receptors in the nervous system, which were termed "opioid receptors". The definition of "opioid" was later refined to refer to substances that have morphine-like activities that are mediated by the activation of opioid receptors. One modern pharmacology textbook states: "the term opioid applies to all agonists and antagonists with morphine-like activity, and also the naturally occurring and synthetic opioid peptides". Another pharmacology reference eliminates the "morphine-like" requirement: "Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors (including antagonists)". Some sources define the term "opioid" to exclude "opiates", and others use "opiate" comprehensively instead of "opioid", but "opioid" used inclusively is considered modern, preferred and is in wide use.


title: Opioid

text: In 2011, the Obama administration released a white paper describing the administration's plan to deal with the opioid crisis. The administration's concerns about addiction and accidental overdosing have been echoed by numerous other medical and government advisory groups around the world.


title: Opioid

text: As of 2015, prescription drug monitoring programs exist in every state, except for Missouri. These programs allow pharmacists and prescribers to access patients' prescription histories in order to identify suspicious use. However, a survey of US physicians published in 2015 found that only 53% of doctors used these programs, while 22% were not aware that the programs were available to them. The Centers for Disease Control and Prevention was tasked with establishing and publishing a new guideline, and was heavily lobbied. In 2016, the United States Centers for Disease Control and Prevention published its Guideline for Prescribing Opioids for Chronic Pain, recommending that opioids only be used when benefits for pain and function are expected to outweigh risks, and then used at the lowest effective dosage, with avoidance of concurrent opioid and benzodiazepine use whenever possible. Research suggests that the prescription of high doses of opioids related to chronic opioid therapy (COT) can at times be prevented through state legislative guidelines and efforts by health plans that devote resources and establish shared expectations for reducing higher doses.


title: Opioid

text: On 10 August 2017, Donald Trump declared the opioid crisis a (non-FEMA) national public health emergency.


title: Opioid

text: Morphine and other poppy-based medicines have been identified by the World Health Organization as essential in the treatment of severe pain. As of 2002, seven countries (USA, UK, Italy, Australia, France, Spain and Japan) use 77% of the world's morphine supplies, leaving many emerging countries lacking in pain relief medication. The current system of supply of raw poppy materials to make poppy-based medicines is regulated by the International Narcotics Control Board under the provision of the 1961 Single Convention on Narcotic Drugs. The amount of raw poppy materials that each country can demand annually based on these provisions must correspond to an estimate of the country's needs taken from the national consumption within the preceding two years. In many countries, underprescription of morphine is rampant because of the high prices and the lack of training in the prescription of poppy-based drugs. The World Health Organization is now working with administrations from various countries to train healthworkers and to develop national regulations regarding drug prescription to facilitate a greater prescription of poppy-based medicines.


title: Opioid

text: Another idea to increase morphine availability is proposed by the Senlis Council, who suggest, through their proposal for Afghan Morphine, that Afghanistan could provide cheap pain relief solutions to emerging countries as part of a second-tier system of supply that would complement the current INCB regulated system by maintaining the balance and closed system that it establishes while providing finished product morphine to those in severe pain and unable to access poppy-based drugs under the current system.


title: Opioid

text: Opioids can produce strong feelings of euphoria and are frequently used recreationally. Traditionally associated with illicit opioids such as heroin, prescription opioids are misused recreationally.


title: Opioid

text: Drug misuse and non-medical use include the use of drugs for reasons or at doses other than prescribed. Opioid misuse can also include providing medications to persons for whom it was not prescribed. Such diversion may be treated as crimes, punishable by imprisonment in many countries. In 2014, almost 2 million Americans abused or were dependent on prescription opioids.


title: Opioid

text: Tramadol and tapentadol, which act as monoamine uptake inhibitors also act as mild and potent agonists (respectively) of the μ-opioid receptor. Both drugs produce analgesia even when naloxone, an opioid antagonist, is administered.


title: Opioid

text: Some minor opium alkaloids and various substances with opioid action are also found elsewhere, including molecules present in kratom, "Corydalis", and "Salvia divinorum" plants and some species of poppy aside from "Papaver somniferum". There are also strains which produce copious amounts of thebaine, an important raw material for making many semi-synthetic and synthetic opioids. Of all of the more than 120 poppy species, only two produce morphine.


title: Opioid

text: Amongst analgesics there are a small number of agents which act on the central nervous system but not on the opioid receptor system and therefore have none of the other (narcotic) qualities of opioids although they may produce euphoria by relieving pain—a euphoria that, because of the way it is produced, does not form the basis of habituation, physical dependence, or addiction. Foremost amongst these are nefopam, orphenadrine, and perhaps phenyltoloxamine or some other antihistamines. Tricyclic antidepressants have painkilling effect as well, but they're thought to do so by indirectly activating the endogenous opioid system. Paracetamol is predominantly a centrally acting analgesic (non-narcotic) which mediates its effect by action on descending serotoninergic (5-hydroxy triptaminergic) pathways, to increase 5-HT release (which inhibits release of pain mediators). It also decreases cyclo-oxygenase activity. It has recently been discovered that most or all of the therapeutic efficacy of paracetamol is due to a metabolite, AM404, which enhances the release of serotonin and inhibits the uptake of anandamide.


title: Opioid

text: Other analgesics work peripherally ("i.e.", not on the brain or spinal cord). Research is starting to show that morphine and related drugs may indeed have peripheral effects as well, such as morphine gel working on burns. Recent investigations discovered opioid receptors on peripheral sensory neurons. A significant fraction (up to 60%) of opioid analgesia can be mediated by such peripheral opioid receptors, particularly in inflammatory conditions such as arthritis, traumatic or surgical pain. Inflammatory pain is also blunted by endogenous opioid peptides activating peripheral opioid receptors.


title: Opioid

text: It was discovered in 1953, that humans and some animals naturally produce minute amounts of morphine, codeine, and possibly some of their simpler derivatives like heroin and dihydromorphine, in addition to endogenous opioid peptides. Some bacteria are capable of producing some semi-synthetic opioids such as hydromorphone and hydrocodone when living in a solution containing morphine or codeine respectively.


title: Opioid

text: Many of the alkaloids and other derivatives of the opium poppy are not opioids or narcotics; the best example is the smooth-muscle relaxant papaverine. Noscapine is a marginal case as it does have CNS effects but not necessarily similar to morphine, and it is probably in a category all its own.


title: Opioid

text: Dextromethorphan (the stereoisomer of levomethorphan, a semi-synthetic opioid agonist) and its metabolite dextrorphan have no opioid analgesic effect at all despite their structural similarity to other opioids; instead they are potent NMDA antagonists and sigma 1 and 2-receptor agonists and are used in many over-the-counter cough suppressants.


title: Opioid

text: Salvinorin A is a unique selective, powerful ĸ-opioid receptor agonist. It is not properly considered an opioid nevertheless, because:


title: Opioid

text: β-endorphin is expressed in Pro-opiomelanocortin (POMC) cells in the arcuate nucleus, in the brainstem and in immune cells, and acts through μ-opioid receptors. β-endorphin has many effects, including on sexual behavior and appetite. β-endorphin is also secreted into the circulation from pituitary corticotropes and melanotropes. α-neo-endorphin is also expressed in POMC cells in the arcuate nucleus.


title: Opioid

text: met-enkephalin is widely distributed in the CNS and in immune cells; [met]-enkephalin is a product of the proenkephalin gene, and acts through μ and δ-opioid receptors. leu-enkephalin, also a product of the proenkephalin gene, acts through δ-opioid receptors.


title: Opioid

text: Dynorphin acts through κ-opioid receptors, and is widely distributed in the CNS, including in the spinal cord and hypothalamus, including in particular the arcuate nucleus and in both oxytocin and vasopressin neurons in the supraoptic nucleus.


title: Opioid

text: Endomorphin acts through μ-opioid receptors, and is more potent than other endogenous opioids at these receptors.


title: Opioid

text: Plain allosteric modulators do not belong to the opioids, instead they are classified as opioidergics.


title: She-Hulk: Attorney at Law

text: She-Hulk: Attorney at Law is an American television miniseries created by Jessica Gao for the streaming service Disney+, based on the Marvel Comics featuring the character She-Hulk. It is the eighth television series in the Marvel Cinematic Universe (MCU) produced by Marvel Studios, sharing continuity with the films of the franchise. It follows Jennifer Walters, a lawyer specializing in cases involving superhumans, who also becomes the green superhero She-Hulk. Gao serves as head writer with Kat Coiro leading the directing team.


title: She-Hulk: Attorney at Law

text: Tatiana Maslany stars as Jennifer Walters / She-Hulk, alongside Jameela Jamil, Ginger Gonzaga, Mark Ruffalo, Josh Segarra, Mark Linn-Baker, Tess Malis Kincaid, Tim Roth, Megan Thee Stallion, Benedict Wong, Renée Elise Goldsberry, Jon Bass, Rhys Coiro, Griffin Matthews, Patti Harrison, Steve Coulter, Charlie Cox, Brandon Stanley, and Drew Matthews. "She-Hulk" was announced in August 2019, with Gao hired in November. Coiro joined to direct multiple episodes in September 2020, and Maslany was cast. By December, Roth and Ruffalo had joined the cast and Anu Valia was also set to direct. Filming began in mid-April 2021 in Atlanta, Georgia, and lasted until mid-August. The subtitle for the series was added by May 2022.


title: She-Hulk: Attorney at Law

text: "She-Hulk: Attorney at Law" premiered on August 18, 2022, and ran for nine episodes until October 13. It is the last television series of in the MCU. The series received generally positive reviews from critics, with particular praise for Maslany's performance, though reception to the series' visual effects was mixed.


title: She-Hulk: Attorney at Law

text: Jennifer Walters has a complicated life as a single attorney in her 30s who also becomes the green superhero She-Hulk.


title: She-Hulk: Attorney at Law

text: Guest stars include Nicholas Cirillo as Ched, Walters' cousin, Peg O'Keef as Runa, a shape-shifting Light Elf from New Asgard who defrauded Bukowski by impersonating Megan Thee Stallion, Patty Guggenheim as Madisynn King, a drunken victim of Blaze's magic who becomes Wong's friend, Leon Lamar as Cornelius P. Willows, Blaze's sidekick, David Otunga as Derek, one of Walters' dates, and Trevor Salter as Josh Miller, a member of Intelligencia who dates Walters in order to steal a sample of her blood for Phelps. Brian T. Delaney provides the uncredited voice of K.E.V.I.N. (Knowledge Enhanced Visual Interconnectivity Nexus), an artificial intelligence in charge of the Marvel Cinematic Universe's story decisions; the character is a reference to Marvel Studios president Kevin Feige. Feige was asked to voice K.E.V.I.N., but he declined. Gao and fellow series' writers Zeb Wells and Cody Zigler have cameo appearances in the season.


title: She-Hulk: Attorney at Law

text: By July 1989, the character Jennifer Walters / She-Hulk was expected to appear in the television film "The Death of the Incredible Hulk" (1990). The character ultimately did not appear, and a proposed television series featuring She-Hulk at ABC was canceled a year later. In 1991, a film based on the character entered development at New World Pictures with Larry Cohen serving as director, and Brigitte Nielsen set to play She-Hulk. Nielsen participated in a promotional photoshoot, but the film ultimately did not materialize.


title: She-Hulk: Attorney at Law

text: In August 2019, Marvel Studios announced at the D23 conference that "She-Hulk" was being developed for the streaming service Disney+, to be set in their shared universe the Marvel Cinematic Universe (MCU). Shortly after, Jessica Gao was approached to pitch for the series. Gao had previously met with Marvel Studios to pitch for "Captain Marvel" (2019), "Black Widow" (2021), and "Shang-Chi and the Legend of the Ten Rings" (2021), which did not pan out, and had expressed her desire to be approached about a potential She-Hulk project each time. She was one of the first creatives to include the character in her pitches to the studio, doing so in her "Black Widow" one, which Marvel Studios executive Brad Winderbaum felt was more of a She-Hulk film featuring Black Widow. Gao believed her past pitches allowed her to build her relationship with Marvel Studios, so by the time she pitched for "She-Hulk", Feige and the other executives knew the type of writer she was, her humor, and "the quirks and nuances" she put into her scripts. Her pitch for "She-Hulk" had included Bruce Banner and Emil Blonsky / Abomination, despite being unsure if they would be able to appear; her pitch also featured more of Blonsky's trial than what is shown in the series. Gao had also included the Leader in her pitch as a character the series could include, with either Samuel Sterns returning, having been portrayed by Tim Blake Nelson in "The Incredible Hulk" (2008), or creating a new version of the character that possibly could have been related to Sterns; The Leader ultimately did not appear in "She-Hulk". Gao was hired to serve as the head writer in November 2019.


title: She-Hulk: Attorney at Law

text: In September 2020, Kat Coiro was hired to direct the first and final episodes plus four others, and to executive produce the series, while Anu Valia had also joined as a director by December 2020. Valia said she was directing a few episodes of the series and described Coiro as the series' "visionary leader", hoping by joining the series she would be able to add what Gao and Coiro had created and find her "own personal connection to the story". Coiro ultimately directed six episodes, with Valia directing three. In May 2022, Marvel revealed the series would be titled "She-Hulk: Attorney at Law". Banner has a line in the series, "She-Hulk attorney at law, it's got a nice ring to it". While working on the editing of the episodes, Marvel Studios president Kevin Feige heard that line and felt it would be a "great title for a show" and that they should alter the series to it. The title is briefly changed to "She-Hulk: Attorney for Hire" in the second episode, "She-Hulk by Titania" in the fifth, "Just Jen: Attorney at Law" in the sixth, and "The Savage She-Hulk" in the ninth.


title: She-Hulk: Attorney at Law

text: The series consists of nine 30-minute episodes, after originally being announced to be consisting of ten episodes; Feige had previously said these ten episodes would equal approximately six hours of content. Marvel Studios' Feige, Louis D'Esposito, Victoria Alonso, and Winderbaum serve as executive producers along with Coiro and Gao.


title: She-Hulk: Attorney at Law

text: In February 2021, Feige stated that some of their series, including "She-Hulk" and "Moon Knight" (2022), were being developed with the potential to have additional seasons made, in contrast to series like "WandaVision" (2021) which were developed as limited events that led into feature films instead. Coiro echoed this in August 2022, stating the series could get a second season, or the character could appear in films. Gao had an idea and premise for what a second season could entail, but focused on telling a complete story with the first season. She was hopeful some of these ideas and material cut from the first season would be able to appear in future projects.


title: She-Hulk: Attorney at Law

text: Francesca Gailes, Jacqueline J. Gailes, Melissa Hunter, Dana Schwartz, Kara Brown, Zeb Wells, and Cody Ziglar serve as writers on the series, many of whom come from a sitcom background. Francesca Gailes also serves as story editor. Wells and Ziglar contributed their knowledge of comics to the series, such as Wells suggesting the lesser-known villains who appear in his episode, "". Writing began in 2019, and by early May 2020, work on the series' scripts had ended. Feige described the series as a "half-hour legal comedy" that would be faithful to John Byrne's take on She-Hulk in Marvel Comics, with star Tatiana Maslany calling it "this really absurd take on a legal show". Gao added that "She-Hulk: Attorney at Law" was "threading a fine line" of being a sitcom while still existing within the MCU, likening it to the series "Ally McBeal", though that series was not a major influence for the writers given many were not in the right age demographic to have experienced that series when it was originally airing. Gao said it was "tricky" balancing tone of the series between the comedic and meta elements with the expected action and drama being within the MCU. Other influences were "Legally Blonde" (2001) and the series "Seinfeld" and "". The series adapts a "case of the week" procedural format while still featuring some serialized elements that contribute to the season arc; Gao implemented this format due to her wanting the audience to enjoy each episode as a complete story.


title: She-Hulk: Attorney at Law

text: The various comic series featuring the character from Stan Lee, Byrne, Dan Slott, and Charles Soule are referenced in "Attorney at Law", with Gao "cherry-pick[ing]" various elements from each and "fus[ing] it all together so that it really felt simultaneously like a culmination, but also completely its own thing"; most of the series draws from the storyline of Slott's run with elements from Byrne's. Soule, who has a legal background and is also an attorney, served as the series' legal consultant, provide advice on aspects such has how lawyers and judges would behave in a courtroom.


title: She-Hulk: Attorney at Law

text: The series incorporates Jennifer Walters' self-awareness and meta nature from the comics, with Walters gaining the awareness and ability to break the fourth wall in the series following her becoming a Hulk. Coiro said there were "some big surprises" regarding the fourth-wall breaking, with Valia adding it was "very fun, very cool", and Maslany saying it was a good mechanism to "bring the audience in" to the story. Gao, Coiro, and the writers discussed how much of the meta nature should be featured, discussing options such as would she talk to the camera, directly to the audience, or another person "more behind the scenes", and if there was another meta element. Initially Walters was constantly breaking the fourth wall, which Marvel Studios felt was too much, resulting in the writers being asked to do a version with editors' notes, a tool used in the comics to clarify story elements, appearing for Walters to interact with. The editor's notes were ultimately scrapped for her just breaking the fourth wall, but not to the extent that was originally conceived. Gao's initial pitch for the series had included "Fleabag" and "Better Call Saul" as references for how to portray Walters breaking the fourth wall, with Maslany believing the "Attorney at Law" scripts drew from "Fleabag"s "irreverence and sense of humor". The fourth-wall breaks culminated in the final episode of the season, with Walters entering the real world and confronting K.E.V.I.N. (Knowledge Enhanced Visual Interconnectivity Nexus) at Marvel Studios; this was heavily inspired by what Byrne did in his comics run.


title: She-Hulk: Attorney at Law

text: The series takes a "high-concept, extraordinary idea" that becomes grounded in Walters' life, with Gao interested in exploring "that little slice of life" outside the normal huge scale and action of the MCU. Including Walters' family helped keep the series "intimate and centered on" her life, with Gao interested in exploring the family dynamic when a Hulk exists in that family and then a second one gets added to it. With the series also exploring dating for a modern woman, Maslany enjoyed how Walters' dating life "was just as much of a stress as potentially becoming one of the Avengers". Having a majority of women on the writing staff allowed them to take their different points of view to create a "well-rounded female perspective" in the series and discuss what it was like to be a woman, and what that meant if they became a public superhero. Gao explained that "a lot of commonalities and a lot of themes emerge[d]" that the writers were able to put into the series. Gao crafted a season arc for Walters' about accepting her new life as She-Hulk, describing the season as the character's "origin story", which allowed her in future appearances to be "so much more confident".


title: She-Hulk: Attorney at Law

text: The series addresses and incorporates many real-life misogynistic and Internet troll comments made about Marvel and female superheroes. Gao called these comments "very tired and unoriginal" given the writers were able to "predict" what the reaction to the series would be when they started writing in 2019.


title: She-Hulk: Attorney at Law

text: "Attorney at Law" is set "a relatively short amount of time" after "Shang-Chi and the Legend of the Ten Rings" in the MCU. Gao avoided discussing the Blip given other films and series have "already covered that territory" and the events have been accepted and people of the MCU are moving on. The first four episodes and the final episode feature mid-credits scenes. They were derived from Gao's love of end credit scenes, not just within the MCU, since they reward audience's patience and are "like an extra special little treat". Additionally, it allowed the writers to include more jokes into the episodes. An original pitch for these scenes was to have them be a "running plot with bad guys".


title: She-Hulk: Attorney at Law

text: Mark Ruffalo, who portrayed Bruce Banner / Hulk in the MCU films, said in November 2019 that he planned to meet with Feige about making an appearance in the series. In March 2020, Ruffalo confirmed that he was in talks to reprise his role in the series. That September, "Deadline Hollywood" reported that Tatiana Maslany had been cast in the lead role of Walters, but Maslany denied being cast and said the report was "a press release that's gotten out of hand" and "not actually a thing". "The Hollywood Reporter" reaffirmed Maslany's casting in November 2020, and Feige officially confirmed it the next month. Maslany was initially hesitant to join large-scale or franchise projects given her desire to perform in ones "focused on character" and tended to "guarantee" collaboration. Deciding to audition to the role, Maslany enjoyed Gao's script and was excited by the challenge the role could bring to her and believed it would bring "a little bit of a shift" in her life. She later stated she "flat-out lied" about denying her casting as she was unsure what she was allowed to say. Feige also confirmed in December 2020 Ruffalo's involvement and the casting of Tim Roth in the series. Ruffalo was reported to have a "small role" in the series. Roth reprises his role as Emil Blonsky / Abomination from "The Incredible Hulk" (2008). Marvel Studios approached Roth to appear in the series after he returned to provide vocal work for the Abomination in "Shang-Chi and the Legend of the Ten Rings", and the role in the series appealed to Roth's "anarchy" within himself and having his career "being chaos".


title: She-Hulk: Attorney at Law

text: In January 2021, Ginger Gonzaga was cast as Nikki Ramos, Walters' best friend, and Renée Elise Goldsberry was cast that April as Mallory Book. Jameela Jamil was cast in June 2021 as Titania, with Josh Segarra joining the following month as Augustus "Pug" Pugliese. In May 2022, Benedict Wong was revealed to be reprising his MCU role as Wong, while Jon Bass was revealed to be part of the cast as Todd Phelps.


title: She-Hulk: Attorney at Law

text: Nicholas Cirillo, David Otunga, and Griffin Matthews were revealed to be part of the cast in May 2022. That July, Drew Matthews was revealed to be playing Dennis Bukowski. The following month, Mark Linn-Baker was revealed to be playing Morris Walters, Patty Guggenheim was revealed as Madisynn King, and Rhys Coiro, Kat's husband, was revealed as Donny Blaze. In August, Megan Thee Stallion was revealed to have a cameo appearance in the series as herself. Her inclusion in the series was suggested by Jamil, after the two had worked together on the television series "Legendary".


title: She-Hulk: Attorney at Law

text: Feige also teased appearances from other MCU characters given Walters' work as a lawyer for superheroes, with Maslany confirming there would be "some really fun characters" in the series that Walters was defending or going up against in court. The majority of the cameos in the series are characters from the comics that have yet to appear in the MCU. Charlie Cox was revealed to be appearing in the series in his MCU role of Matt Murdock / Daredevil in July 2022, which Coiro called the series' "biggest surprise". He had been approached by Feige in June 2020 to reprise his role from Marvel's Netflix television series for this and the film "" (2021). In August 2022, Brandon Stanley was revealed as Eugene Patilio / Leap-Frog. Nick Gomez and Justin Eaton appear as Wrecker and Thunderball, respectively, members of the Wrecking Crew, while David Pasquesi appears as Craig Hollis / Mr. Immortal. Additional characters include Nathan Hurd as Man-Bull, Joseph Castillo-Midyett as El Águila, Terrence Clowe as Saracen, and Jordan Aaron Ford as Porcupine. Wil Deusner provides motion-capture for Skaar, Hulk's son. Gao was unaware if Marvel Studios planned to have Deusner remain in the role for Skaar's future appearances.


title: She-Hulk: Attorney at Law

text: Ann Foley served as the costume designer, after previously working on the Marvel Television series "Agents of S.H.I.E.L.D." Gonzaga provided input into Nikki's wardrobe since she enjoys and knows fashion. She said that Nikki's wardrobe "can't be too crazy" given she works in an office, but was able to make it "cool and edgy". Gonzaga felt most comfortable portraying Nikki when she was wearing "something a little defiant or something that she shouldn't be wearing at work or something that's a little too high fashion". Additionally, Gonzaga sold some of her own personal clothing to the series to wear as Nikki. Speaking to Titania's look in the series, Jamil said the creatives wanted "to go for eleven [with] her style and everything about her", noting her "hair is so big and her outfits are so extra". It was important to Jamil that Titania looked "very fake in every way", so she wore a padded butt to replicate buttock augmentation and did her own make up to make it seem like Titania had plastic surgery by "overlining my lips and chiseling down my nose and overdoing my cheekbones". Daredevil's costume is similar to the red one he wore in Marvel's Netflix series, but with an updated color scheme to include the yellow helmet and accents from the character's debut comics design in "Daredevil" #1. Cox's original suit was used as a reference and for his costume fitting for the one featured in "She-Hulk". Marvel Studios had clear intentions as to what his costume would look like for the series. Cox was excited that "She-Hulk" was using this suit, also understanding the fans and viewers would equally be excited that the character was able to wear that suit.


title: She-Hulk: Attorney at Law

text: Elena Albanese served as production designer. The series' end credits are in the style of courtroom sketches and are drawn by Kagan McLeod, who worked with Aspect on them.


title: She-Hulk: Attorney at Law

text: Filming began on April 12, 2021 at Trilith Studios in Atlanta, Georgia, with Coiro and Valia directing episodes of the series, and Florian Ballhaus and Doug Chamberlain serving as cinematographers for Coiro and Valia, respectively. The series was filmed under the working titles "Libra", "Clover", and "Big Lady". Filming was previously expected to begin on July 6, 2020, but was postponed to March 2021, due to the COVID-19 pandemic.


title: She-Hulk: Attorney at Law

text: Coiro worked to visually keep the comedy of the series balanced with the expected cinematic scope of the MCU, stating, "We obviously are exploring themes and we're exploring tone and we're exploring very everyday comedic moments, but we still need it to feel like it's part of the MCU." Roth initially found it difficult to return to the character but was able to approach the role with more humor after watching and beginning to work alongside Ruffalo. Coiro worked to find a balance when portraying sex in the series, without it going "too far" or being "taboo", while still making it accessible and enjoyable for general audiences. She noted that Maslany felt the sex positivity of the character was "very important to her" and was a main contributor to the conversations about the sexualization in the series.


title: She-Hulk: Attorney at Law

text: Jamil said she would be filming her scenes until the week of August 15, and filming for the series wrapped by that date. During filming, Coiro partnered with the environmental nonprofit Habits of Waste and their "Lights, Camera, Plastic" campaign, to avoid featuring single-use plastics on screen when possible and replacing them with reusable and eco-friendly items.


title: She-Hulk: Attorney at Law

text: Visual effects for the series were created by Digital Domain, FuseFX, Soho VFX, Trixter, Wētā FX, and Wylie Co. Coiro discussed the digital character of She-Hulk, believing some of the initial negative reactions to it in the marketing was because "she is so different" than other digital characters, as she does not have the same "grisliness, harshness, [or] bulkiness" as characters like Thanos or Hulk do. She added that the creatives were focused on achieving detail in She-Hulk's facial expressions and her "nuances of reaction", and credited Alonso for her "incredible eye" in helping to design the character. As well, the creative team focused on strength over aesthetics, studying musculature and woman athletes rather than bodybuilders. Coiro explained, "So she doesn't have a bodybuilder's physique, but she absolutely has a very strong physique that can justify the actions that she does in the show. I think people expected a bodybuilder and for her to have these big, massive muscles but she looks more like Olympians."


title: She-Hulk: Attorney at Law

text: Gao noted that, despite Feige encouraging her and the writers to feature She-Hulk as much as possible in the series, when it came time to start filming, it was requested that some of the scenes with She-Hulk be changed to ones with Walters. She added that "a lot of things... had to be changed at the last minute" because of this shift, and even while editing the episodes, a number of shots were cut that featured She-Hulk due to budget constraints. Digital Domain drew inspiration from the ripening of a strawberry when designing Walters' transformation into She-Hulk.


title: She-Hulk: Attorney at Law

text: Amie Doherty was revealed to be composing the score for the series in July 2022. Doherty wanted her main theme to work for both Walters in the courtroom, and then be able to transition into "this big superhero world" for She-Hulk. The She-Hulk part of the theme Doherty described as "big and bombastic" and one that would fit in the "well-established sound" of the MCU and found Walters' portion more challenging to fit alongside the MCU sound while still being unique. She watched legal dramas like "Ally McBeal", "The Good Wife", and "The Good Fight" for inspiration. Doherty wanted to bring a "modern" sound to her score alongside the orchestra, looking at songs from Megan Thee Stallion, Billie Eilish, and other artists in the top 40. Woodwind instruments were intentionally left out of the score, with Doherty using synths to fill the frequencies they would have provided; brass and strings were also recorded for the score.


title: She-Hulk: Attorney at Law

text: The score for the series will be released digitally by Marvel Music and Hollywood Records in two volumes: music from the first four episodes was released on September 16, and music from the last five episodes was released on October 19. The series' main theme was released as an eponymous single on August 18.


title: She-Hulk: Attorney at Law

text: The first footage of the series debuted on Disney+ Day on November 12, 2021. The teaser ends with Walters saying to the audience, "Don't make me angry; you wouldn't like me when I'm angry" alongside Ruffalo as Banner, which is a homage to an episode of the 1970s live-action television series "The Incredible Hulk" in which Bill Bixby, who portrayed David Banner, says the line; Ruffalo was in a similar pose and costume as Bixby. Feige and Maslany debuted the trailer for the series on May 17, 2022, at Disney's upfront presentation. The trailer was criticized for its visual effects, with many fans online expressing their disappointment. Despite this, Charles Pulliam-Moore of "The Verge" called it "simply smashing" and highlighted the trailer's visual effects, adding that "the show's clearly going to be Jennifer's to own as she embarks on her own path to heroism". Zachariah Kelly of "Gizmodo Australia" felt the trailer "does not disappoint at all", calling the scene where She-Hulk cradles "her Tinder date like a baby... absolutely hilarious", and enjoyed having more context to the clips first seen in the Disney+ Day footage. Meanwhile, Richard Trenholm and Joan E. Solsman from "CNET" described the trailer as "hilarious" and wrote that it "sells the playful tone of the upcoming show". "TechRadar" Stephen Lambrechts meanwhile opined that the trailer was faithful to comic book runs of the character, though he acknowledged criticism surrounding the use of visual effects. The trailer was viewed 78 million times in the 24 hours after it was released, which was the second most views for an MCU Disney+ trailer in a 24-hour time-frame, only behind "The Falcon and the Winter Soldier" Super Bowl LV trailer.


title: She-Hulk: Attorney at Law

text: The series was promoted at the 2022 San Diego Comic-Con with Coiro, Valia, Gao, Maslany, Gonzaga, and Jamil alongside the release of the second trailer. Andrew Webster of "The Verge" felt the trailer had "more lighthearted tone than the first [one]... [with] some legal drama". Edidiong Mboho of "Collider" stated that the trailer set the "comedic tone mixed with the epic" of the series. Jacob Sarkisian of "Digital Spy" found She-Hulk's fourth-wall breaking the "eye-catching feature of the trailer". Similarly, Daniel Chin of "The Ringer" highlighted the "comedic tone that's true to the fourth-wall-breaking nature of its source material" of the trailer and felt it revealed more about the plot. A poster also released at Comic-Con featured a hotline number that had a pre-recorded message from Walters describing the services her law firm provided superpowered individuals. An episode of the series "" was released on August 10, 2022, exploring Banner using footage of his MCU film appearances. Disney created an ad on Tinder meant to represent a dating profile for Walters, while a faux commercial for Walters' law firm Goodman, Lieber, Kurtzberg & Holliway was released ahead of the series' premiere, which Cameron Bonomolo from "ComicBook.com" described as a ""Better Call Saul"-style advertisement".


title: She-Hulk: Attorney at Law

text: Ahead of the release of the second episode, a Twitter account for Titania was created, while a video was released of Jamil in character covering real-world posters for the series on Sunset Boulevard with her own and spray-painting her name on them. This was after Titania's brief appearance at the end of the first episode, with Jamil believing there was "something so iconic" and "very desperate" about someone promoting themselves after such a brief appearance. Jamil also appeared in character in New York City in September 2022 for a "L'Officiel" party and Kourtney Kardashian's Boohoo fashion show. Jamil chose to make these appearances in character as a way to pay homage to how the series breaks the fourth wall. At that time, a message from Titania appeared on the hotline number replacing the previous one. Following the season finale, the hotline number featured a new message from Mallory Book and Pug, advertising the superhuman law services from GLK&H and touting the various famous clients they worked with, such as Megan Thee Stallion, Blonsky, and Wong.


title: She-Hulk: Attorney at Law

text: A QR code was included in each episode linking viewers to a website to access free digital comics featuring She-Hulk that updated weekly, a program which was first introduced in "Moon Knight". The comics released for the episodes, in order, were "Savage She-Hulk" #1, "She-Hulk" (2004) #1, "Savage She-Hulk" #2, "West Coast Avengers Annual" #4, "She-Hulk" (2004) #10, "West Coast Avengers" #46, "Tales to Astonish" #48, "She-Hulk" (2014) #9, and "Sensational She-Hulk" #50. The "Marvel Must Haves" merchandise program, which reveals new toys, games, books, apparel, home decor, and other merchandise related to each episode of "She-Hulk" following an episode's release, started for the episodes on August 19 and concluded on October 15, 2022.


title: She-Hulk: Attorney at Law

text: "She-Hulk: Attorney at Law" held its world premiere at El Capitan Theatre in Los Angeles on August 15, 2022. The series debuted on Disney+ on August 18, 2022, and consisted of nine episodes, concluding on October 13. It was originally scheduled to debut on Wednesday, August 17 with releases weekly on Wednesdays, before moving to weekly releases on Thursdays. It is the final series in of the MCU.


title: She-Hulk: Attorney at Law

text: The review aggregator website Rotten Tomatoes reported an approval rating of 85%, with an average score of 7.7/10, based on 600 reviews. The site's critic's consensus states: "Whether she's fighting bad guys, defending a client, or managing her messy social life, "She-Hulk: Attorney at Law" passes the bar for bingeworthy viewing." Metacritic, which uses a weighted average, assigned the series a score of 67 out of 100 based on 26 critics, indicating "generally favorable reviews".


title: She-Hulk: Attorney at Law

text: The series' first four episodes were reviewed by critics before they debuted. Daniel Fienberg at "The Hollywood Reporter" called these episodes "broad, bright and eager to serve the audience with a wink and a nudge" though lacking "stakes or a distinctive style". He felt the series' writing for characters previously seen in more dramatic situations, and the Easter eggs and cameos would be divisive with viewers. Writing for "Rolling Stone", Alan Sepinwall said attempting to be a half-hour comedy series produced "mixed but mostly positive" results, but believed the series had a harder time distinguishing itself within the MCU than the character's comic series because the MCU had a lighter tone already compared to the other comics being published around She-Hulk's runs, which made the contrast of her comics more apparent. He also noted the MCU was "drastically less populated" in regards to characters that could be featured, with Slott having an "enormous toy box" in the comics to feature a wide array of characters. Sepinwall said the humor of "Attorney at Law" was "softer than what you find in the more overtly ridiculous MCU films like "" or "Guardians of the Galaxy"" and did not become consistently funny until the fourth episode.


title: She-Hulk: Attorney at Law

text: Joelle Monique at "TheWrap" called the series "a delightful break from the cutesy family fun and intense heroic introspection" of the previous Marvel Studios Disney+ series, praising Maslany's performance and noting it was "incredibly rewarding as a long-time fan of the franchise" as well as those who enjoy legal television series. Richard Roeper from the "Chicago Sun-Times" gave the episodes 3 out of 4 stars, praising Maslany and believing "She-Hulk: Attorney at Law" "plays like a 21st century take on a 1980s TV show" and felt like "one of those 'cameo every week' kind of shows, with gratuitous but entertaining fight sequences sprinkled in between the courtroom antics and the comedic byplay". "The Verge"s Charles Pulliam-Moore said the series a "surprisingly refreshing spin" on the Marvel Studios Disney+ series, one that felt "like the precursor to something new yet familiar". Arezou Amin of "Collider" gave the first four episodes an "A", saying they were a "delightful ride" and was hopeful the final five episodes would be equally charming.


title: She-Hulk: Attorney at Law

text: Caroline Framke of "Variety" said in her review that the series was "charming enough as it bounces from one hijink to the next, especially in Maslany's capable hands. But between its obligations to the larger Marvel Cinematic Universe, a far more limited budget than its film peers, and attempts to infuse Jen's story with dated #girlboss energy, "She-Hulk" also represents an unsteady balancing act that needs more time than it likely has to settle into its own groove." She also noted having Walters be able to have more control over She-Hulk than Banner with Hulk because of her daily experiences as a woman keeping her emotions in check was "an undeniably effective way to make the She-Hulk experience markedly, urgently different from that of" Hulk's. Framke also called the story's approach to Walters' job and dating life, and the series' costumes, "several steps out of date", and wished for a more innovative approach to the fourth-wall breaking, that has become more commonplace in media since Byrne introduced it to the character in the comics back in the 1980s. Giving the series 2.5 stars out of 4, "USA Today"s Kelly Lawler said "She-Hulk: Attorney at Law" "oh-so-close to being a great show, but doesn't fully commit to any of the three or four different shows it's attempting", wishing it committed better to the legal comedy, with more fourth-wall breaking and the examinations of regular humans in the MCU. Despite this, Lawler felt Walters was "a very appealing protagonist", with praise also going to Maslany, and that the series had "some well-placed humor", believing if "Attorney at Law" "leans into its strengths, it could be a really unique, fun take" on the MCU. Kirsten Howard from "Den of Geek" enjoyed that the woman characters were portrayed as "smart, strong, and girlbossing it", but, like Framke, added it was "a rather rote narrative" that felt "dated as all hell, [and] speaks to how far behind the MCU is with female superhero representation that it feels the need to catch up in such a lazy and clichéd way". They also felt the second, third, and fourth episodes were "too fluffy [and] too hackneyed", criticizing the comedy, procedural elements, and infrequent fourth-wall breaking that ended up being "jarring".


title: She-Hulk: Attorney at Law

text: The response to the series' visual effects were mixed, with some reviewers feeling it was an improvement over what was featured in the trailers, while others called it distracting and entering the uncanny valley. Some were critical of it, but believed it did not detract from the series, with Howard stating some visual effects in the later episodes leaned towards ""Polar Express" territory". Howard also felt it would have been "a pretty powerful statement on its own" to have a fully realized She-Hulk character model against the Hulk model.


title: She-Hulk: Attorney at Law

text: In a review of the entire series, Amelia Emberwing from "IGN" gave "She-Hulk: Attorney at Law" an 8 out of 10, praising the approach from Gao, Coiro, and Maslany. She enjoyed the humor Gao and the writers were able to find in moments that highlight "some of the most ridiculous parts of everyday life as a woman" against the struggle of suddenly gaining superpowers along with the sitcom format and the fourth-wall breaks. However, both the sitcom format and fourth-wall breaks "fall apart" in the finale, which was "unable to reconcile with its tone" and did not adequately resolve "the abject humiliation Jen experiences" in the penultimate episode. Despite this "little bit of a bobble" at the end of the series, Emberwing found "Attorney at Law" to be "completely fresh to the Marvel Cinematic Universe", particularly in bringing "female sexuality front and center" and its approach to toxic masculinity. Emberwing's colleague Alex Stedman felt "Attorney at Law" was a successful first sitcom in the MCU, praising Maslany's performance, though feeling the 30 minute runtimes were at times too short, and sometime wishing multiple episodes had been released each week. "Polygon"s Matt Patches called the series "easily one of the horniest shows currently streaming on Disney Plus, and for that, one of the most refreshing".


title: She-Hulk: Attorney at Law

text: In February 2021, the documentary series "Marvel Studios: Assembled" was announced. The specials go behind the scenes of the MCU films and television series with cast members and additional creatives. The special of this series, "Assembled: The Making of She-Hulk: Attorney at Law", was released on Disney+ on November 3, 2022.


title: She-Hulk: Attorney at Law

text: In November 2019, Feige stated that after She-Hulk was introduced in the series, the character would cross over to the MCU films.


title: Akkadian Empire

text: The Akkadian Empire () was the first ancient empire of Mesopotamia after the long-lived civilization of Sumer. It was centered in the city of Akkad () and its surrounding region. The empire united Akkadian and Sumerian speakers under one rule. The Akkadian Empire exercised influence across Mesopotamia, the Levant, and Anatolia, sending military expeditions as far south as Dilmun and Magan (modern Saudi Arabia, Bahrain, and Oman) in the Arabian Peninsula.


title: Akkadian Empire

text: The Akkadian Empire reached its political peak between the 24th and 22nd centuries BC, following the conquests by its founder Sargon of Akkad. Under Sargon and his successors, the Akkadian language was briefly imposed on neighboring conquered states such as Elam and Gutium. Akkad is sometimes regarded as the first empire in history, though the meaning of this term is not precise, and there are earlier Sumerian claimants.


title: Akkadian Empire

text: Nimrod's historical identity is unknown or debated, but Nimrod has been identified as Sargon of Akkad by some, and others have compared him with the legendary Gilgamesh, king of Uruk. Today, scholars have documented some 7,000 texts from the Akkadian period, written in both Sumerian and Akkadian. Many later texts from the successor states of Assyria and Babylonia also deal with the Akkadian Empire.


title: Akkadian Empire

text: Understanding of the Akkadian Empire continues to be hampered by the fact that its capital Akkad has not yet been located, despite numerous attempts. Precise dating of archaeological sites is hindered by the fact that there are no clear distinctions between artifact assemblages thought to stem from the preceding Early Dynastic period, and those thought to be Akkadian. Likewise, material that is thought to be Akkadian continues to be in use into the Ur III period.