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Essay: Ecstasy

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What is ecstasy? Ecstasy is the common street name for 3,4-methylenedioxymethamphetamine (MDMA) . This is a synthetic chemical, which mimics stimulants and causes hallucinations . The drug became more commonly used in parties (Fig. 7) to enhance the pleasurable experiences. Today, it remains on the list of drugs prohibited from sale or use (Patterson 2017). Absorption: “ECSTASY” reaches its peak plasma concentration about 2 hours after oral administration (Kalant 2001). The chemical structure of ecstasy allows it to reach the brain quickly after ingestion. The pill is ingested in the mouth and moves down the oesophagus. Once it reaches the stomach, some of the molecules are absorbed in the bloodstream, but most of them move to the small intestine to be absorbed. Afterwards, the molecules move to the liver. In the liver, some of the substance is metabolized to inactive compounds, but the remaining of the substance travels to the heart. The heart pumps oxygenated blood carrying the ecstasy substances to organs and the brain. The MDMA manages to cross the blood brain barrier, as it is non-polar, in just about 15 minutes. (if taken on an empty stomach) (Fig. 8). Metabolism: The drug is broken down metabolically, mainly in the liver. MDMA acts by increasing the release of the neurotransmitters; serotonin (euphoria, sexual arousal), noradrenaline (increased heart rate and blood pressure) and dopamine (euphoria, increased energy). Effects: The effects vary according to the dose, frequency and duration of use. – Short term:  increase in wakefulness and endurance of energy  sexual arousal  sweating  nausea  hallucinations (Patterson 2017)  postponement of fatigue and sleepiness  psychological effects: sense of euphoria, well-being, greater sociability (Sherlock et al. 1999) http://www.drugfreeworld.org/drugfacts/ecstasy/short-long-term-effects.html (cite this here) – Long term:  Depression  Kidney failure  Psychosis  Brain damage One of the most important side effect is sweating, which results from vigorous physical activity (increased muscle activity) and increase in body temperature (Cohen 1995). Large amounts of sodium can be lost in sweat and if this is accompanied by vast amounts of water, the result is haemodilution leading to hyponatremia. Also, inappropriate secretion of the antidiuretic hormone (ADH) released from the posterior part of the pituitary gland in the hypothalamus of the brain, leads to retention of water by the kidneys (Holden & Jackson 1996). Hence, water passes from the blood to the tissues, including the brain. Vasopressin-Antidiuretic hormone: (Klabunde 2016) Vasopressin (antidiuretic hormone, ADH) is a peptide hormone which is secreted from the posterior part of the pituitary gland in the hypothalamus of the brain. The primary function of ADH is to regulate extracellular fluid volume. This is done when osmoreceptors in the hypothalamus detect changes in water volume in the body. If the volume of water is low, then there is an increase in the release of ADH which increases water permeability in the collecting ducts of the nephron, leading to less urine formed. Ecstasy causes an increase in the ADH, hence the water levels increase, sodium levels decrease and hence decreasing the blood plasma osmolarity. Serotonin pathway: (National Institute on Drug Abuse 2017) Serotonin pathway is the predominantly affected nerve pathway by ecstasy. Serotonin is a neurotransmitter and regulates several processes in the brain; emotions, sleep, appetite and perceptions. Electrical impulses traveling down the axon towards the terminal bouton cause the release of serotonin from small vesicles into the synaptic cleft. When in the synaptic space, the serotonin binds to receptors, on the membrane of the postsynaptic which causes a change in the electrical properties of the receiving neuron. (Fig. 9) Ecstasy molecules bind to the serotonin receptors on the postsynaptic neurons, resulting in serotonin staying in the synaptic cleft. (Fig. 10) Therefore, more serotonin receptors are activated inducing a euphoric effect. After ecstasy is eliminated from the body, the decreased release of serotonin causes much less receptors to be activated, hence producing depression. (Fig.11) Legal status: Ecstasy is classified as a Class A drug under the Misuse of Drugs Act. The Misuse of Drugs Act divides drugs into: Class A: cocaine and crack, ecstasy, heroin, LSD, methadone, methamphetamine (crystal meth). Class B: amphetamine, barbiturates, codeine, ketamine, synthetic cannabinoids such as Spice and cannabis. Class C: anabolic steroids, minor tranquillisers or benzodiazepines. The law defines a series of offences, as it is illegal to be in possession of the drug or supply it. Ecstasy cannot be prescribed by doctors. The maximum penalties for possession of ecstasy is 7 years imprisonment plus a fine, and for supply is life imprisonment plus a fine (The Advisory Council on the Misuse of Drugs 1971).  FLUID BALANCE AND ION CONCENTRATION Fluid Volume and ion concentration are both maintained in very narrow limits, even though there are wide variations in the metabolic activity and environmental stresses of a person. (Lewis 2016) The process responsible for maintaining these factors in their optimum levels is called homeostasis and the major key organ responsible is the kidneys. Total body water (TBW) is about 60% of body weight in men and 50% in women. Two thirds of TBW is in the intracellular compartment (intracellular fluid or ICF); the remaining is in the extracellular compartment (extracellular fluid or ECF). Normally, about 25% of the ECF is in the intravascular compartment; the rest is interstitial fluid. Osmolarity and Osmolality: (Erstad 2003) Osmolarity is the number of milliosmoles/liter (mOsm/L) of solution, ie the concentration of an osmotic solution. Osmolality is the number of milliosmoles/ kg (mOsm/kg) of solvent, ie the concentration of the particles that is dissolved in a fluid. Osmosis occurs when water crosses cell membranes from areas of low solute concentration to areas of high solute concentration. This in turn, allows osmolality to be equal across body fluid compartments. Body Fluid Intake and Losses: (Fig.12) The average intake of body fluids of a person in a day is 2.5L. Figure 12 [showing intake and losses of body fluids ] Osmolarity: (Ashworth Rachel, 2017) Sources of Intracellular Osmolarity:  Charged Macromolecules and their counter ions  Smaller metabolites and their counter ions  Small inorganic ions Donnan Effect: ions will get into the cell, decreasing the water potential in the cell. This results to water diffusing into the cell by osmosis and eventually rupturing the cell. The role of Na+/K+ ATPase: This pump is used to actively pump inorganic ions in and out of a cell; Na+ ions are pumped outside, K+ ions are pumped inside to counteract the Donnan Effect. Additionally, the pump has a role to generating cell membrane’s voltage. Tonicity: Iso-osmotic/isotonic solutions: When body fluids have an osmolarity of 275-290 mOsm/L, there is no water movement since the osmotic pressure of the two fluid compartments is equal. Hypotonic solutions: Water from the ECF will move into the cell, since the cell has a lower water potential (decreased osmolality). This, in turn, causes swelling of the cells and lysis. Hypertonic solutions: Water from the cell moves out to the ECF, since the ECF has a lower water potential (decreased osmolality). This, in turn, causes the cells to shrink. Regulation of Body Fluid: (Ashworth Rachel, 2017) The kidneys provide homeostatic control mechanisms to regulate the urinary excretion of sodium and water. The nephron (Fig. 13) filters the blood plasma to form urine; sodium ions are reabsorbed in distal convulated tubule by aldosterone and water is reabsorbed in the collecting duct by the antidiuretic hormone (ADH) Blood Osmolarity: 1. Osmoreceptors in the hypothalamus detect an increase in the osmolarity of the blood 2. The hypothalamus triggers thirst and the release of the antidiuretic hormone (ADH) 3. ADH increases
the permeability of the collecting duct to retain water and hence prevent further osmolarity increase 4. Thirst makes the person to drink more water and hence decrease blood osmolarity Blood Volume: 1. The juxtaglomerular apparatus (JGA) responds to low blood volume or blood pressure caused by dehydration or loss of blood 2. JGA produces renin which converts angiotensinogen to angiotensin II 3. Angiotensin II causes arteriole constriction hence increasing blood pressure or causes the adrenal gland to release aldosterone 4. The release of aldosterone increases sodium and water reabsorption in the distal tubules, hence increasing the blood volume  SIGNS AND SYMPTOMS IN THE SCENARIO-HYPONATREMIA Low sodium levels (hyponatremia): Hyponatremia may result from not eating enough foods containing sodium, too much sweating and urinating or being over-hydrated. When sodium levels are low, aldosterone causes kidneys to retain sodium and water hence decreasing the amount of water in the body. Ecstasy causes the release of ADH which further retains water. (van Dijken et al. 2013) Symptoms of hyponatremia:  Confusion  Headache  Nausea  Coma Severe hyponatremia (sodium levels less than 125mmol/L) must be corrected immediately because it can lead to cerebral edema, irreversible neurologic damage, respiratory arrest, brainstem herniation and death. Treatment of hyponatremia includes the use of saline (>3%). (Braun & Barstow 2015)  CT SCAN AND OTHER MEDICAL IMAGING What is medical imaging? Medical imaging is the technique to create visual representations of the interior body parts and the function of organs or tissues (Radiological Society of North America 2016). CT Scan (Computerised Tomography): How does it work: (National Institute of Biomedical Imaging and Bioengineering 2017) • A motorized table moves the patient through a circular opening and starts to rotate him/her. • During rotation, the X-ray source produces a narrow beam of X-rays that passes through a section of the patient’s body. • Detectors, found opposite the X-ray source, detect the X-rays passing through the patient’s body as a snapshot and create an image. Many different “snapshots” (at many angles) are collected during one rotation. • The image data is sent to a computer to reconstruct the “snapshots” into one or multiple cross-sectional images of the internal organs and tissues. What do they show: (Health 2017) CT Scans produce cross sectional images of the body with lighter areas showing denser tissue and darker areas showing lighter tissue. This is because the denser tissues have absorbed more X-rays and hence less X-rays hit the detector, and vice versa. CT Scans detect: (RadiologyInfo.org 2017)  bleeding or leaking aneurysm, brain injury and fractures  blood clots in the brain  brain tumors  enlarged brain cavities (ventricles) in patients (hydrocephalus)  diseases or malformations of the skull Other medical imaging techniques: (Robson Lesley 2017) (Khalil et al. 2011)  X-ray: visualizing the skeletal system and some disease processes in soft tissues.  DEXA Scan (Dual Energy X-ray Absorptiometry): using two low energy X-ray sources (increased accuracy).  MRI (Magnetic Resonance Imaging): using non-ionising radiation to get both structural and functional information  Ultrasound: using sound waves  Molecular Imaging; such as SPECT (Single Photon Emission Computer Tomography) and PET (Positron Emission Tomography): provide images at a cellular and molecular level In this scenario A C.T. scan revealed cerebral odema with evidence of brain herniation. (Fig.14)  ORGAN DONATION Organ Donor Register (ODR): (NHS Blood and Transplant 2017) It is a confidential list of people who wish to donate their organs and/or tissue. By joining the register, it is easier to find out potential donors, but also consent is established. When registering, the person must inform his/her family, since if she/he dies, family will be asked to confirm the registration. Anyone who has the capability of making decision (ie mental capacity) and lives in the UK can register. Having a medical condition may prevent you from becoming a donor; Creutzfeldt-Jakob Disease (CJD), cancer or HIV. Organ Transplant: It is an operation that removes an organ or tissue from one person and places it in another. Organ Donation: It is when someone allows his/her organs or tissues to be removed and transplanted to someone else. Different ways to donate: (LifeCenter Northwest 2017) 1. Brain stem death-when a person has no longer brain stem activity; no consciousness and no capacity to breathe 2. Circulatory death-loss of function of the heart and lungs usually after cardiac arrest 3. Living donation-whilst still alive, donations may include: kidney, small section of liver In this scenario: Leah has passed away due to brain stem death.  CONCLUSION: The scenario underlines the action of the illegal drug, Ecstasy, on the body. The cascade of events that occurred to Leah, show that she was feeling hot and drunk lots of water, resulting in the release of ADH (due to ecstasy pharmacological effects) and aldosterone to increase sodium levels. Hyponatremia in this case showed to be deadly as cerebral oedema and brain herniation were evident in the CT scan. Leah was signed up for organ donation as she was brain stem dead.

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