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Vasopressin

Vasopressin

Note: As of 2015, Vasopressin is no longer included in the Advanced Cardiac Life Support (ACLS) guidelines. Clinical studies have shown that both epinephrine and vasopressin improve the chances to restore spontaneous circulation during cardiac arrest. With vasopressin creating no added benefit compared with administering epinephrine alone, it was removed to simplify the algorithm.

Vasopressin: An overview

Vasopressin (also called arginine vasopressin, argipressin, or antidiuretic hormone) is a hormone synthesized from the AVP gene as a peptide prohormone in the hypothalamus and is converted to AVP. Synthetically produced vasopressin plays a role in treating diabetes insipidus, resulting from a lack of naturally occurring pituitary hormone.

Vasopressin injections control frequent urination, increased thirst, and water loss caused by diabetes insipidus (DI), a condition that leads to excessive loss of water from the body, which results in dehydration. Vasopressin is an effective injection in preventing abdominal or stomach distension, which is a common event post-surgery. The medicine is available in solution form only and can be purchased only via a doctor’s prescription.

It is pertinent to mention here that the success rate of resumption of spontaneous circulation during cardiac arrest increases considerably post epinephrine and vasopressin administration. However, since it was discovered that administering epinephrine alone produced the similar results, vasopressin administration was of little use. For this reason, vasopressin has been removed from the ACLS cardiac arrest algorithm. The removal simplifies the algorithm. Epinephrine remains the primary vasopressor used to treat cardiac arrest.

Vasopressin Uses

Synthetic vasopressin finds multiple uses in the medical field. This section briefly describes some of these uses.

Today, the most common use for vasopressin is in the treatment of diabetes insipidus (DI). While the hormone is produced naturally in the human body, low levels of this hormone can produce DI. The medicine used for this condition is commonly available as Pressyn.

However, this is not the only reason vasopressin is used. For example, vasopressin agonists are sometimes used to treat gastrointestinal bleeding, ventricular tachycardia, and ventricular fibrillation. The long-acting synthetic analog of vasopressin, i.e., desmopressin, is used for treating bleeding in conditions like von Willebrand disease and haemophile A.

Analogues like terlipressin play the role of vasoconstrictors. Such analogs have been used in the medical field since 1970. Previously, vasopressin was used in combination with epinephrine for returning spontaneous circulation during cardiac arrest. But as of 2015, it has been removed from the ACLS algorithm since epinephrine can get the job done alone.

Today, the vasopressin analogs are used as the hemodynamic support of catecholamine-refractory, hyperdynamic septic shock. The arginine vasopressin (AVP) and terlipressin (TP) can increase the mean arterial pressure and reduce the catecholamine demand in this particular scenario. However, there remains a risk of the relevant hemodynamic side effects. Some of these side effects include cardiac output reduction, oxygen delivery resistance, and mixed-venous oxygen saturation. The consequence of these side effects is impaired tissue perfusion and ischemic tissue injury. Furthermore, the decrease in platelet count and increase in aminotransferases activity and bilirubin concentration are also related to V1 agonists. Research studies from 2008 are focused on finding the clinical relevance of these changes.

Physiology & Receptors

Now we will look at the physiology of the arginine vasopressin hormone, as well as the receptors on which it binds. Understanding the physiology of vasopressin is critical for understanding the possible effects and drug interactions of synthetic vasopressin.

Vasopressin is a nine-amino acid peptide, first synthesized as the preprohormone in the hypothalamus. The vasopressin precursor travels along magnocellular neuron axons, then through the pituitary stalk, and finally to the post-pituitary gland. There it is stored in the intracellular compartment. Post stimulation, only up to 20% of the amount of vasopressin is released into blood circulation. Blood volume and pressure are the key regulators of this hormone’s natural secretion.

As for the main properties of the hormone, it has a plasma half-life of only five to fifteen minutes. The clearance of vasopressin primarily depends on renal and liver vasopressinases.

Let us shift our focus to the receptors. Vasopressin binds to 3 receptor subtypes. All of these receptors belong to the family of membrane-bound, G protein-coupled receptors. A brief overview of these receptors is as follows:

The binding of vasopressin to these different receptors triggers different changes. For example, the activation of V1a receptors leads to platelet aggregation, and activation of extra-renal V2 receptors induces the release of coagulation factors. Similarly, oxytocin and vasopressin also work in combination and produce their respective effects. In the case of synthetic drug vasopressin, different scenarios are presented before the healthcare professionals.

Let’s take a closer look at signaling. The ligand-based stimulation of these vasopressin receptors induces receptor subtype-specific interactions with G-protein-coupled receptor kinases, as well as the protein kinase C. These interactions are mediated via specific motifs present in the carboxyl termini of the vasopressin receptors. It is pertinent to mention that Guanine nucleotide-binding proteins, commonly known as the G-proteins, play the role of signal transducers in this signaling. They are linked with the cell surface membrane, which receptors to effectors. Researchers have characterized the G-proteins as Gs, Gi/o, Gq/11, and G12/13. This characterization indicates that a single receptor can activate multiple second messenger pathways, courtesy of the interactions with one or more G-proteins.

Key Actions of Vasopressin

Osmoreceptors are the special nerve cells that are very sensitive to the changes in serum osmolality. Interestingly, these cells have a close association with the same cells concerned with the production and secretion of vasopressin. Minor changes in the serum osmolality (amounting to even one percent increase or decrease) can change the secretion levels of vasopressin.
 

 

 

 

 

 

 

 

 

 

 

 

 

Take the example of a person suddenly feeling dehydrated, i.e., water loss resulting from excessive perspiration. The serum osmolality is increased. As a result, the vasopressin molecules are separated from the neurophysin molecules, to which they are loosely attached in the secretory cells. The vasopressin is then released from the posterior pituitary gland, which leads to renal water retention.

Consider an event of the opposite nature, where a person becomes overhydrated, say, from drinking too much water. As a result, vasopressin release is depressed, and water excretion increases. The osmoreceptors above are also associated with the thirst center. High serum osmolality stimulates it; low serum osmolality inhibits it.

Now, let us look at things from a renal point of view. Vasopressin acts on the collecting duct cells in the kidneys. These cells have specific receptors for the vasopressin hormone, which connect to aquaporins. Aquaporins are special water channels; they fuse with particular cell membrane regions when vasopressin stimulates the cells. These cell membrane regions are exposed to urine, and facilitate water entry into cells. The water then reverts to circulation. As a result, urine volume decreases and mineral content increases. The phenomenon is known as urine concentration.

Vasopressin also has a key role in response to a decrease in blood volume. Our carotid sinus has special pressure sensors called baroreceptors. These receptors are designed to detect arterial blood pressure. It is pertinent to mention that each carotid sinus is associated with the carotid arteries in the neck and the left atrium of the human heart. In an event where blood volume increases, the carotid sinus’s tissues are stretched. As a result, the baroreceptor nerves are stimulated, transmitting the impulse to inhibit vasopressin secretion. Hence, water excretion is amplified. The exact reverse process happens when the blood volume decreases, and as a result, water retention increases.
 

Things to Keep in Mind Before Using Vasopressin

Before seeking treatment with vasopressin, the user needs to ensure that they aren’t allergic to chlorobutanol or vasopressin. The healthcare provider(s) must be informed if the patient has ever encountered any of the following diseases or symptoms related to the following diseases:

  1. Coronary artery disease
  2. Kidney disease
  3. Severe headache/migraine
  4. Epilepsy
  5. Anaphylactic reactions

It is important to inform the doctors in advance because conveying this information becomes impossible in an emergency. Pregnant women need to inform the doctor about their pregnancy status, since the drug can lead to premature labor contractions. This holds for the second and third trimesters of pregnancy in particular. An adjusted dose of vasopressin can be administered to pregnant women if the injection becomes extremely important. Breastfeeding mothers must not breastfeed for at least 90 minutes post-treatment with vasopressin. Any milk collected via a breast pump during this time must be discarded.

Using Vasopressin

Vasopressin is administered by trained health professionals in a healthcare facility (i.e. a clinic or hospital). It is an intramuscular or intravenous shot that is administered under the skin and can be administered to multiple different areas of the body. Patients who suffer from diabetes insipidus can be given the shot at home if they are not admitted to the hospital. If the patient has to use the medicine themselves, a trained healthcare professional will instruct the patient on the preparation and injection of the vasopressin.

Understanding the procedure to the fullest is critical for every patient. Injecting vasopressin to a different body area every single time is highly recommended, and it is necessary to implement a shot rotation policy. The goal is to reduce the risk of a skin reaction or allergy. Furthermore, a new needle and syringe must be used every time vasopressin is injected. Doctors may limit the fluid intake for patients taking vasopressin. Following the guidelines provided by the healthcare professional is important for preventing any unwanted effects.

Dose

Vasopressin dose differs from patient to patient. When self-administered, it is best for patients to follow the dose recommended by a doctor. In the event where a doctor’s recommendations aren’t available, it is best to follow the directions printed on the label. No changes in the dose must be made without an opinion from a doctor (preferably the one who has been working with the patient long term).

It is pertinent to mention that the amount of medicine to be taken is directly proportional to the strength of the medicine. The number of doses, the time between the doses, and the duration of treatment with the medication all depend on the nature of the medical situation. The usual injection dosage for the treatment of diabetes insipidus is as follows:

Missed Dose

For patients who will take vasopressin for longer durations of time, it is best to design a schedule in advance and follow it strictly. But in an event where a patient misses one dose, taking it as soon as possible is highly recommended. If the gap period is too big, skipping the missed dose and sticking with the regular dosing schedule is recommended. Double dosing vasopressin is not recommended in such an instance, since it can lead to unpleasant side effects.

Storage

Vasopressin should be stored in a closed container at room temperature. External elements like heat, moisture, direct light, and extremely low freezing temperatures can affect the medicine’s composition. Instructions for disposing of the medicine must be sought from healthcare professionals. Used needles must be discarded in a hard, closed container out of the reach of children and animals.

Precautions

Closely monitoring the patient while vasopressin is being given is important. This is commonly considered standard practice since it allows the doctors to monitor the efficiency of the medicine in real time. Decisions about further administration can be made based on these observations.

As part of this procedure, blood and urine tests are prescribed to ensure there are no side effects. Vasopressin can lead to an anaphylactic reaction, so it is important to monitor the patient closely (especially in the early days of treatment). Reversible diabetes insipidus is another possibility, so informing the doctor of side effects is extremely important. Taking any other medicines without informing the doctor can lead to complications. This includes over-the-counter medicines, vitamin supplements, and traditional herbal and natural oils.

What are the Side Effects of Vasopressin?

While vasopressin is a great option for treating a number of conditions, it may cause some unwanted effects as well. It is pertinent to mention that a patient may or may not experience some or all of these side effects.

Here are some of the main side effects:

Some of the other side effects of vasopressin are as follows:

Some users may experience certain side effects that are not listed here.

Possible Drug Interactions

At least 279 drugs are known to interact with vasopressin. In this list, 59 drug interactions are categorized as major drug interactions by healthcare professionals, 217 are classified as moderate, and three are deemed minor. To avoid any complications that might arise from these drug interactions, it is advisable to inform the healthcare provider about all medications a vasopressin user is currently taking.

While the list of all possible drug interactions is too lengthy to include here, the most important drug interactions for any healthcare provider to know are:

Frequently Asked Questions (FAQs)

Here are the most common questions healthcare providers and ACLS practitioners have about Vasopressin.

While vasopressin was originally included in the ACLS algorithm for cardiac arrest, it has since been removed because epinephrine was found to be sufficient for improving the chances of returning spontaneous circulation. Otherwise, vasopressin (also called the antidiuretic hormone) plays a critical role in maintaining osmolality, hence maintaining water volume in the extracellular fluids. It is critical in blood pressure regulation, sodium homeostasis, and renal functioning.

The diuretic action of vasopressin on the collecting ducts is its direct action.

Vasopressin plays a key role in systemic vascular resistance during the phases where the body is deprived of water. This maintains blood pressure during such dehydrating phases.

If the time elapsed since the missed dose is less than half of the normal gap between doses, taking the dose as soon as possible is recommended. However, if the time until the next scheduled dose is less than half of the normal gap, it’s best to wait until the next scheduled dose. You do not want to double dose on vasopressin.

Feelings of weakness, drowsiness, and headache are possible side effects of overdosing on vasopressin. However, the chance of overdose is low because the medicine is usually administered in a healthcare facility under the observation of a fully qualified healthcare professional.

Alcohol can make vasopressin less effective, so it is advisable for patients to avoid drinking alcohol for the duration of their vasopressin treatment.

In the event of an emergency or where fluid restriction fails, one option that can be considered in case of an emergency is Demeclocycline, a tetracycline antibiotic.

Vasopressin is a powerful vasoconstrictor. However, unlike other vasoconstrictors, the hormone also has vasodilatory properties.

Vasopressin is released in response to hypotension. Hence, the chances of this injection leading to hypotension are extremely low.

It is quite possible that vasopressin can contribute to hypertension via the hormone’s antidiuretic effects. Similarly, vasopressin V2 receptor antagonists can lower blood pressure.

Conclusion

Vasopressin is an extremely effective drug for patients suffering from diabetes insipidus and certain other complications. While it has been officially removed from the ACLS algorithm, it is still important to understand its effects in case it ever becomes relevant in a life-support discussion or real-world scenario. It is also important to understand the mechanism of action, noting the key drug interactions and side effects.

If you would like to learn more about the drugs, ECG rhythms, clinical scenarios, and other topics related to ACLS, AMRI has study materials that can help you develop your understanding. Accredited by the National Board of Emergency Care Certifications (NBECC), AMRI has helped more than one million medical professionals earn their ACLS, BLS, and PALS certifications or recertifications since 1983.

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