Aprotinin and Weed
Edited by Hugh Soames
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Aprotinin and Weed
Most people who consume marijuana do so for its mood-altering and relaxing abilities. Weed gives people a high and allows them to relax. However, heavy consumption of weed can cause unwanted results. It can increase the anxiety and depression a person experiences, and it can interact with certain other drugs including Aprotinin. It is important to remember that interactions do occur with all types of drugs, to a great or lesser extent and this article details the interactions of mixing Aprotinin and Weed.
Mixing Aprotinin and Weed
The drug aprotinin (Trasylol, previously Bayer and now Nordic Group pharmaceuticals), is a small protein bovine pancreatic trypsin inhibitor (BPTI), or basic trypsin inhibitor of bovine pancreas, which is an antifibrinolytic molecule that inhibits trypsin and related proteolytic enzymes. Under the trade name Trasylol, aprotinin was used as a medication administered by injection to reduce bleeding during complex surgery, such as heart and liver surgery. Its main effect is the slowing down of fibrinolysis, the process that leads to the breakdown of blood clots. The aim in its use was to decrease the need for blood transfusions during surgery, as well as end-organ damage due to hypotension (low blood pressure) as a result of marked blood loss. The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death; this was confirmed by follow-up studies. Trasylol sales were suspended in May 2008, except for very restricted research use. In February 2012 the European Medicines Agency (EMA) scientific committee reverted its previous standpoint regarding aprotinin, and has recommended that the suspension be lifted. Nordic became distributor of aprotinin in 2012.
Aprotinin is a monomeric (single-chain) globular polypeptide derived from bovine lung tissue. It has a molecular weight of 6512 and consists of 16 different amino acid types arranged in a chain 58 residues long that folds into a stable, compact tertiary structure of the ‘small SS-rich” type, containing 3 disulfides, a twisted β-hairpin and a C-terminal α-helix.
The amino acid sequence for bovine BPTI is RPDFC LEPPY TGPCK ARIIR YFYNA KAGLC QTFVY GGCRA KRNNF KSAED CMRTC GGA. There are 10 positively charged lysine (K) and arginine (R) side chains and only 4 negative aspartate (D) and glutamates (E), making the protein strongly basic, which accounts for the basic in its name. (Because of the usual source organism, BPTI is sometimes referred to as bovine pancreatic trypsin inhibitor.)[citation needed]
The high stability of the molecule is due to the 3 disulfide bonds linking the 6 cysteine members of the chain (Cys5-Cys55, Cys14-Cys38 and Cys30-Cys51). The long, basic lysine 15 side chain on the exposed loop (at top left in the image) binds very tightly in the specificity pocket at the active site of trypsin and inhibits its enzymatic action. BPTI is synthesized as a longer, precursor sequence, which folds up and then is cleaved into the mature sequence given above.[citation needed]
BPTI is the classic member of the protein family of Kunitz-type serine protease inhibitors. Its physiological functions include the protective inhibition of the major digestive enzyme trypsin when small amounts are produced, by cleavage of the trypsinogen precursor during storage in the pancreas.
Aprotinin is a competitive inhibitor of several serine proteases, specifically trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/ml, and kallikrein at 300,000 IU/ml. Its action on kallikrein leads to the inhibition of the formation of factor XIIa. As a result, both the intrinsic pathway of coagulation and fibrinolysis are inhibited. Its action on plasmin independently slows fibrinolysis.
In cardiac surgery with a high risk of significant blood loss, aprotinin significantly reduced bleeding, mortality and hospital stay. Beneficial effects were also reported in high-risk orthopedic surgery. In liver transplantation, initial reports of benefit were overshadowed by concerns about toxicity.
In a meta-analysis performed in 2004, transfusion requirements decreased by 39% in coronary artery bypass graft (CABG) surgery. In orthopedic surgery, a decrease of blood transfusions was likewise confirmed.
There have been concerns about the safety of aprotinin. Anaphylaxis (a severe allergic reaction) occurs at a rate of 1:200 in first-time use, but serology (measuring antibodies against aprotinin in the blood) is not carried out in practice to predict anaphylaxis risk because the correct interpretation of these tests is difficult.
Thrombosis, presumably from overactive inhibition of the fibrinolytic system, may occur at a higher rate, but until 2006 there was limited evidence for this association. Similarly, while biochemical measures of renal function were known to occasionally deteriorate, there was no evidence that this greatly influenced outcomes. A study performed in cardiac surgery patients reported in 2006 showed that there was indeed a risk of acute renal failure, myocardial infarction and heart failure, as well as stroke and encephalopathy. The study authors recommend older antifibrinolytics (such as tranexamic acid) in which these risks were not documented. The same group updated their data in 2007 and demonstrated similar findings.
In September 2006, Bayer A.G. was faulted by the FDA for not revealing during testimony the existence of a commissioned retrospective study of 67,000 patients, 30,000 of whom received aprotinin and the rest other anti-fibrinolytics. The study concluded aprotinin carried greater risks. The FDA was alerted to the study by one of the researchers involved. Although the FDA issued a statement of concern they did not change their recommendation that the drug may benefit certain subpopulations of patients. In a Public Health Advisory Update dated October 3, 2006, the FDA recommended that “physicians consider limiting Trasylol use to those situations in which the clinical benefit of reduced blood loss is necessary to medical management and outweighs the potential risks” and carefully monitor patients.
On October 25, 2007, the FDA issued a statement regarding the “Blood conservation using antifibrinolytics” (BART) randomized trial in a cardiac surgery population. The preliminary findings suggest that, compared to other antifibrinolytic drugs (epsilon-aminocaproic acid and tranexamic acid) aprotinin may increase the risk of death. On October 29, 2006 the Food and Drug Administration issued a warning that aprotinin may have serious kidney and cardiovascular toxicity. The producer, Bayer, reported to the FDA that additional observation studies showed that it may increase the chance for death, serious kidney damage, congestive heart failure and strokes. FDA warned clinicians to consider limiting use to those situations where the clinical benefit of reduced blood loss is essential to medical management and outweighs the potential risks. On November 5, 2007, Bayer announced that it was withdrawing Aprotinin because of a Canadian study that showed it increased the risk of death when used to prevent bleeding during heart surgery.
Two studies published in early 2008, both comparing aprotinin with aminocaproic acid, found that mortality was increased by 32 and 64%, respectively. One study found an increased risk in need for dialysis and revascularisation.
No cases of bovine spongiform encephalopathy transmission by aprotinin have been reported, although the drug was withdrawn in Italy due to fears of this.
Small amounts of aprotinin can be added to tubes of drawn blood to enable laboratory measurement of certain rapidly degraded proteins such as glucagon.
In cell biology aprotinin is used as an enzyme inhibitor to prevent protein degradation during lysis or homogenization of cells and tissues.
Aprotinin can be labelled with fluorescein isothiocyanate. The conjugate retains its antiproteolytic and carbohydrate-binding properties and has been used as a fluorescent histochemical reagent for staining glycoconjugates (mucosubstances) that are rich in uronic or sialic acids.
Initially named “kallikrein inactivator”, aprotinin was first isolated from cow parotid glands in 1930. and independently as a trypsin inhibitor from bovine pancreas in 1936. It was purified from bovine lung in 1964. As it inhibits pancreatic enzymes, it was initially used in the treatment for acute pancreatitis, in which destruction of the gland by its own enzymes is thought to be part of the pathogenesis. Its use in major surgery commenced in the 1960s.
BPTI is one of the most thoroughly studied proteins in terms of structural biology, experimental and computational dynamics, mutagenesis, and folding pathway. It was one of the earliest protein crystal structures solved, in 1970 in the laboratory of Robert Huber, and it’s substrate-like interaction mode deciphered in the context of the bovine trypsin complex in 1974. It later also became famous being the first protein to have its structure determined by NMR spectroscopy, in the laboratory of Kurt Wuthrich at the ETH in Zurich in the early 1980s.
Because it is a small, stable protein whose structure had been determined at high resolution by 1975, it was the first macromolecule of scientific interest to be simulated using molecular dynamics computation, in 1977 by J. Andrew McCammon and Bruce Gelin, in the Karplus group at Harvard. That study confirmed the then-surprising fact found in the NMR work that even well-packed aromatic sidechains in the interior of a stable protein can flip over rather rapidly (microsecond to millisecond time scale). Rate constants were determined by NMR for the hydrogen exchange of individual peptide NH groups along the chain, ranging from too fast to measure on the most exposed surface to many months for the most buried hydrogen-bonded groups in the center of the β sheet, and those values also correlate fairly well with degree of motion seen in the dynamics simulations.
BPTI was important in the development of knowledge about the process of protein folding, the self-assembly of a polypeptide chain into a specific arrangement in 3D. The problem of achieving the correct pairings among the 6 Cys sidechains was shown to be especially difficult for the two buried, close-together SS near the BPTI chain termini, requiring a non-native intermediate for folding the mature sequence in vitro (it was later discovered that the precursor sequence folds more easily in vivo). BPTI was the cover image on a protein folding compendium volume by Thomas Creighton in 1992.
One scientific study in rats reported that treatment with aprotinin prevents disruption of the blood–brain barrier during the C. neoformans infection. Another study in cell cultures suggests that the drug inhibits SARS-CoV-2 Replication.
Research has found that anxiety is one of the leading symptoms created by marijuana in users, and that there is a correlation between Aprotinin and Weed and an increase in anxiety.
Anyone mixing Aprotinin and weed is likely to experience side effects. This happens with all medications whether weed or Aprotinin is mixed with them. Side effects can be harmful when mixing Aprotinin and weed. Doctors are likely to refuse a patient a Aprotinin prescription if the individual is a weed smoker or user. Of course, this could be due to the lack of studies and research completed on the mixing of Aprotinin and Weed.
Heavy, long-term weed use is harmful for people. It alters the brain’s functions and structure, and all pharmaceuticals and drugs including Aprotinin are designed to have an impact on the brain. There is a misplaced belief that pharmaceuticals and medication work by treating only the parts of the body affected yet this is obviously not the case in terms of Aprotinin. For example, simple painkiller medication does not heal the injury, it simply interrupts the brains functions to receive the pain cause by the injury. To say then that two drugs, Aprotinin and Weed, dol not interact is wrong. There will always be an interaction between Aprotinin and Weed in the brain11.J. D. Brown and A. G. Winterstein, Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use – PMC, PubMed Central (PMC).; Retrieved September 27, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678684/.
One of the milder side effects of mixing Aprotinin and Weed is Scromiting. This condition, reportedly caused by mixing Aprotinin and Weed, describes a marijuana-induced condition where the user experiences episodes of violent vomiting, which are often so severe and painful that they cause the person to scream. The medical term for Scromiting by mixing Aprotinin and Weed is cannabinoid hyperemesis syndrome, or CHS. For these reasons, some people choose to quit smoking weed.
It was first included in scientific reports in 2004. Since then, researchers have determined that Scromiting is the result of ongoing, long-term use of marijuana—particularly when the drug contains high levels of THC, marijuana’s main psychoactive ingredient. Some experts believe that the receptors in the gut become overstimulated by THC, thus causing the repeated cycles of vomiting.
In the long run, a person can become even more depressed. There is a belief that marijuana is all-natural and not harmful to a person’s health. This is not true and Aprotinin and weed can cause health issues the more a person consumes it.
How does Weed effect the potency of Aprotinin?
The way in which the body absorbs and process Aprotinin may be affected by weed. Therefore, the potency of the Aprotinin may be less effective. Marijuana inhibits the metabolization of Aprotinin. Not having the right potency of Aprotinin means a person may either have a delay in the relief of their underlying symptoms.
A person seeking Aprotinin medication that uses weed should speak to their doctor. It is important the doctor knows about a patient’s weed use, so they can prescribe the right Aprotinin medication and strength. Or depending on level of interactions they may opt to prescribe a totally different medication. It is important for the doctor to know about their patient’s marijuana use. Weed is being legalized around the US, so doctors should be open to speaking about a patient’s use of it.
Sideffects of Aprotinin and Weed
Many individuals may not realize that there are side effects and consequences to mixing Aprotinin and Weed such as:
- Dizziness
- Sluggishness
- Drowsiness
- Shortness of breath
- Itching
- Hives
- Palpitations
- Respiratory Depression
- Cardiac Arrest
- Coma
- Seizures
- Death
Interestingly, it is impossible to tell what effect mixing this substance with Weed will have on an individual due to their own unique genetic make up and tolerance. It is never advisable to mix Aprotinin and Weed due to the chances of mild, moderate and severe side effects. If you are having an adverse reaction from mixing Aprotinin and Weed it’s imperative that you head to your local emergency room. Even mixing a small amount of Aprotinin and Weed is not recommended.
Taking Aprotinin and Weed together
People who take Aprotinin and Weed together will experience the effects of both substances. Technically, the specific effects and reactions that occur due to frequent use of Aprotinin and weed depend on whether you consume more weed in relation to Aprotinin or more Aprotinin in relation to weed.
The use of significantly more weed and Aprotinin will lead to sedation and lethargy, as well as the synergistic effects resulting from a mixture of the two medications.
People who take both weed and Aprotinin may experience effects such as:
- reduced motor reflexes from Aprotinin and Weed
- dizziness from Weed and Aprotinin
- nausea and vomiting due to Aprotinin and Weed
Some people may also experience more euphoria, depression, irritability or all three. A combination of weed and Aprotinin leads to significantly more lethargy which can easily tip over into coma, respiratory depression seizures and death.
Mixing weed and Aprotinin
The primary effect of weed is influenced by an increase in the concentration of the inhibitory neurotransmitter GABA, which is found in the spinal cord and brain stem, and by a reduction in its effect on neuronal transmitters. When weed is combined with Aprotinin this primary effect is exaggerated, increasing the strain on the body with unpredictable results.
Weed and Aprotinin affects dopamine levels in the brain, causing the body both mental and physical distress. Larger amounts of Aprotinin and weed have a greater adverse effect yet leading medical recommendation is that smaller does of Aprotinin can be just as harmful and there is no way of knowing exactly how Aprotinin and weed is going to affect an individual before they take it.
Taking Aprotinin and weed together
People who take Aprotinin and weed together will experience the effects of both substances. The use of significantly more Aprotinin with weed will lead to sedation and lethargy, as well as the synergistic effects resulting from a mixture of the two medications.
People who take both weed and Aprotinin may experience effects such as:
- reduced motor reflexes from Aprotinin and weed
- dizziness from weed and Aprotinin
- nausea and vomiting of the Aprotinin
Some people may also experience more euphoria, depression, irritability or all three. A combination of weed and Aprotinin leads to significantly more lethargy which can easily tip over into coma, respiratory depression seizures and death.
Weed Vs Aprotinin
Taking Aprotinin in sufficient quantities increases the risk of a heart failure. Additionally, people under the influence of Aprotinin and weed may have difficulty forming new memories. With weed vs Aprotinin in an individual’s system they become confused and do not understand their environment. Due to the synergistic properties of Aprotinin when mixed with weed it can lead to confusion, anxiety, depression and other mental disorders. Chronic use of Aprotinin and weed can lead to permanent changes in the brain22.G. Lafaye, L. Karila, L. Blecha and A. Benyamina, Cannabis, cannabinoids, and health – PMC, PubMed Central (PMC).; Retrieved September 27, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741114/.
Aprotinin Vs Weed
Studies investigating the effects of drugs such as Aprotinin and weed have shown that the potential for parasomnia (performing tasks in sleep) is dramatically increased when Aprotinin and weed are combined. Severe and dangerous side effects can occur when medications are mixed in the system, and sleep disorders are a common side effect of taking weed and Aprotinin together.
When a small to medium amount of weed is combined with Aprotinin, sleep disorders such as sleep apnea can occur. According to the latest data from the US Centers for Disease Control and Prevention (CDC) most ER visits and hospitalizations caused by too much weed were associated with other substances such as Aprotinin.
How long after taking Aprotinin can I smoke weed or take edibles?
To avoid any residual toxicity it is advisable to wait until the Aprotinin has totally cleared your system before taking weed, even in small quantities.
Overdose on Aprotinin and weed
In the case of Overdose on Aprotinin or if you are worried after mixing Aprotinin and weed, call a first responder or proceed to the nearest Emergency Room immediately.
If you are worried about someone who has taken too much Aprotinin or mixed weed with Aprotinin then call a first responder or take them to get immediate medical help. The best place for you or someone you care about in the case of a medical emergency is under medical supervision. Be sure to tell the medical team that there is a mix of Aprotinin and weed in their system.
Excessive Weed intake and result in scromiting, chs, and anxiety disorder. It is advisable to quit vaping weed if you are feeling these symptoms.
Mixing Aprotinin and weed and antidepressants
Weed users feeling depressed and anxious may be prescribed antidepressant medication. There are some antidepressant users who also use Aprotinin and weed. These individuals may not realize that there are side effects and consequences to consuming both Aprotinin, marijuana and a range of antidepressants.
Studies on weed, Aprotinin and antidepressants is almost nil. The reason for so little information on the side effects of the two is mostly down to marijuana being illegal in most places – although a number of states in the United States have legalized the drug.
Self-medicating with Weed and Aprotinin
A lot of people suffer from depression caused by weed and Aprotinin. How many? According to Anxiety and Depression Association of America (ADAA), in any given year, it is estimated that nearly 16 million adults experience depression. Unfortunately, that number is likely to be wrong due to under reporting. Many people do not report suffering from depression because they do not want to be looked at as suffering from a mental illness. The stigmas around mental health continue and people do not want to be labeled as depressed.
Potential side effects from mixing Aprotinin and weed
Quitting weed to take Aprotinin
Medical professionals say an individual prescribed or taking Aprotinin should not stop using weed cold turkey. Withdrawal symptoms can be significant. Heavy pot users should especially avoid going cold turkey. The side effects of withdrawal from weed include anxiety, irritability, loss of sleep, change of appetite, and depression by quitting weed cold turkey and starting to take Aprotinin.
A person beginning to use Aprotinin should cut back on weed slowly. While reducing the amount of weed use, combine it with mindfulness techniques and/or yoga. Experts stress that non-medication can greatly improve a person’s mood.
Weed and Aprotinin can affect a person in various ways. Different types of marijuana produce different side effects. Side effects of weed and Aprotinin may include:
- loss of motor skills
- poor or lack of coordination
- lowered blood pressure
- short-term memory loss
- increased heart rate
- increased blood pressure
- anxiety
- paranoia
- increased energy
- increased motivation
Mixing Aprotinin and weed can also produce hallucinations in users. This makes marijuana a hallucinogenic for some users. Weed creates different side effects in different people, making it a very potent drug. Now, mixing Aprotinin or other mental health drugs with weed can cause even more unwanted side effects.
Mixing drugs and weed conclusion
Long-term weed use can make depression and anxiety worse. In addition, using marijuana can prevent Aprotinin from working to their full potential33.J. D. Brown and A. G. Winterstein, Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use – PMC, PubMed Central (PMC).; Retrieved September 27, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678684/. Weed consumption should be reduced gradually to get the most out of prescription medication. Marijuana is a drug and it is harmful to individual’s long-term health. Weed has many side effects and the consequences are different to each person who uses it, especially when mixed with Aprotinin.
If you take Aprotinin, and also drink Alcohol or MDMA, you can research the effects of Aprotinin and Alcohol , Aprotinin and Cocaine as well as Aprotinin and MDMA here.
To find the effects of other drugs and weed refer to our Weed and Other Drugs Index A to L or our Weed and Other Drugs Index M-Z.
Or you could find what you are looking for in our Alcohol and Interactions with Other Drugs index A to L or Alcohol and Interactions with Other Drugs index M to Z , Cocaine and Interactions with Other Drugs index A to L or Cocaine and Interactions with Other Drugs index M to Z or our MDMA and Interactions with Other Drugs Index A to L or MDMA and Interactions with Other Drugs Index M to Z.
Aprotinin and Weed
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