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Cholesterol Lowering
Why is high cholesterol a health problem?
Cholesterol is a fat that is produced by the liver but also comes from our diet. We all need some cholesterol for normal body functions, such as making cell membranes, producing and transporting hormones, and building protective nerve sheaths. Eating a lot of fatty foods in your diet can increase your blood cholesterol levels above healthy levels. Since cholesterol is not water-soluble, it circulates in the blood attached to proteins called lipoproteins. Excess cholesterol is deposited in the arteries causing them to become blocked and hardened, which narrows the arteries and restricts blood flow. This condition, called atherosclerosis, increases your risk of developing cardiovascular disease, including heart attack, angina, and stroke.
How do cholesterol-lowering medications work?
Cholesterol-lowering medications are used to reduce high cholesterol and triglyceride levels. They are classed according to how they work and include:
- Statins that block the production of cholesterol by the liver but have no effect on dietary cholesterol, such as atorvastatin, simvastatin, and rosuvastatin
- Cholesterol absorption inhibitors that block the absorption of cholesterol in the intestines, such as ezetimibe
- Fibrates that regulate the amount of lipoprotein produced to carry cholesterol in the blood, such as fenofibrate
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Stomach / Intestines
Peptic ulcers and reflux
Gastric acid is needed for digestion of food. Gastric reflux or gastroesophageal reflux disease (GORD) is when the acidic contents of the stomach flow back into the oesophagus causing heartburn (a burning feeling from the stomach towards the neck) and dyspepsia (indigestion and abdominal pain). Reflux disease, as this condition is commonly known, is usually due to damage or loss of normal function of the sphincter muscle at the junction of the oesophagus and stomach that normally acts as a one-way valve and prevents backflow of stomach contents. Reflux can also damage the oesophagus causing oesophagitis or inflammation of the oesophagus.
Peptic ulcers are damage to the stomach lining (gastric ulcers) or the lining of the upper intestine (duodenal ulcers) and are caused by excess gastric acid production due to use of nonsteroidal anti-inflammatory drugs (NSAID) or by infection of the stomach with the bacterium Helicobacter pylori.
Medications used to treat reflux and ulcers are based on reducing the amount of gastric acid produced and released into the stomach, and fall into two categories:
- Proton pump inhibitors like omeprazole, esomeprazole, rabeprazole and lansoprazole, which block the enzyme involved in producing gastric acid by stomach lining cells.
- H2-receptor antagonists like ranitidine, which block the gastric H2-receptor preventing the normal stimulation by histamine of gastric acid production.
Ulcer protection
Another treatment for peptic ulcers is using a cytoprotectant like sucralfate that forms a protective barrier over the ulcer from the damaging effects of gastric acid and digestive enzymes.
Gastroparesis
Gastroparesis is when the stomach muscles do not work properly causing a partial paralysis of the stomach and delayed emptying of the contents. The result is that food stays too long in the stomach before emptying into the small intestine and this can put extra pressure on the esophageal sphincter. Gastroparesis is usually due to nerve damage and can be treated using a serotonin (5HT) receptor agonist like cisapride. This action stimulates stomach muscle contraction so that food can be moved out into the small intestine.
Stomach muscle spasm
Muscle spasm in the stomach can be caused by a variety of GI disorders, including peptic ulcers, reflux disease, infection or food intolerance. Muscle spasm can be treated symptomatically using an antispasmodics medication like propantheline that works as an anticholinergic by blocking the action of the neurotransmitter acetylcholine that is involved in regulating intestinal smooth muscle contraction. This action allows the smooth muscle to relax, reducing muscle spasm.
Nausea
Nausea and vomiting are symptoms of several different conditions, including, gastrointestinal disorders, migraine, chemotherapy and radiotherapy for cancer treatment, reaction to surgical anaesthetic and dysmobility, which is when the intestinal or stomach muscles do not work efficiently and movement of food through the GI tract slows down. The vomiting reflex originates in the chemoreceptor trigger zone (CTZ) of the area postrema of the brain sending nerve messages to the vomiting centre of the brain. Medications used to relieve nausea and vomiting include two types of antiemetic:
- Serotonin receptor-antagonists like ondansetron that work by binding to specific 5HT3 receptors in the intestine and in the CTZ and block the transmission of nerve messages from the intestines and from the CTZ to the vomiting centre in the brain, which prevents the vomiting reflex from being triggered.
- Dopamine antagonist like domperidone and metoclopramide that work by binding to dopamine receptors in the CTZ blocking the transmission of nerve messages to the vomiting centre in the brain, which prevents the vomiting reflex from being triggered. They also have gastrokinetic action by interacting with nervous control of muscle contraction in the stomach and upper intestine, which helps relieve symptoms of dysmobility (when food processing slows down) and this also helps prevent vomiting.
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Psoriasis Treatments
What is psoriasis?
Psoriasis is a non-allergic, chronic skin condition that has a genetic predisposition and can affect anyone at any age. It is characterised by red scaly patches of skin ranging from mild, with a few patches usually at the backs of the knees and elbows, and minimal discomfort, to severe with psoriatic lesions covering large areas of the body and causing extreme itching, pain and discomfort. Psoriasis is thought to be an automimmune disease, where certain cells of the immune system (T lymphocytes) are triggered to overproduce inflammatory chemicals, particularly TNF alpha, a cytokine that stimulates excessive growth and proliferation of keratinocytes (epidermal skin cells), causing thickening and scaling of the skin as well as inflammation.
Treatment for psoriasis
Calcipotriol is a derivative of calcitriol or Vitamin D (also known as 1,25 dihydroxycholecalciferol or 1,25(OH)2D3). Vitamin D is primarily involved regulating calcium metabolism but has other actions including inhibition of cell proliferation, stimulation of cell differentiation and immunomodulation. Calcipotriol binds to the same receptor in skin cells as Vitamin D and has the same activity in regulating cell growth and differentiation but is less effective in terms of calcium metabolism. Calcipotriol is used as a topical treatment for psoriasis and helps to prevent over production of hardened keratinocytes and restores normal cell growth and behaviour to the epidermal skin cells.
Tazarotene is a retinoid pro-drug of Vitamin A that affects skin cell behaviour and helps reverse abnormal changes in keratinocyte behaviour; it also has anti-inflammatory properties.
Both medications reduce the inflammation, scaling and thickening of psoriatic plaques and relieve symptoms of psoriasis.
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Cold Sore Treatments
What are cold sores?
Herpes Simplex Virus (HSV) is a virus that infects mucous membrane cells and exists in two forms;HSV I that infects the lips, mouth and face, and HSV-II that infects the genitals. A cold sore is the result of an infection with HSV I and early warning signs of active virus include a tingling sensation on the lips or face. If untreated at an early stage the virus will multiply rapidly and within 24 hours a cold sore will form, starting as small blisters on the surface of the skin, which join up to form a weeping sore. This is when the virus is contagious and can spread to form more cold sores or can infect others by direct contact. Eventually the immune system kicks in to kill the virus and the cold sore crusts over to form a scab as it heals.
Once infected with HSV it is always possible that re-infection will occur, as the virus can persist undetected by travelling down a nerve fibre and lying dormant or inactive in a nerve cell, to be reactivated under certain conditions, such as by stress, illness, sunlight or a compromised immune system.
Treatments for cold sores
Acyclovir is an antiviral drug that can be used to treat infection with HSV-1. It is a nucleoside analogue, which means that it becomes incorporated into the viral DNA within the host cell and replaces building blocks needed for viral DNA synthesis. This inhibits the action of viral DNA polymerase and prevents normal viral DNA synthesis, without affecting normal processes of the host cells, which prevents the virus replicating and therefore stops the growth and spread of the virus. If applied to the skin within 24 hours of the first tingle, acyclovir can prevent a cold sore from developing. However, it can be used at any stage of infection, to prevent spread of infection, reduce and relieve painful symptoms, and speed up the heeling process to help heal blisters and sores caused by the infection. Acyclovir can also be taken orally to suppress recurrent infection of HSV and to prevent infection in people who are immunocompromised. Valacyclovir is a similar antiviral to acyclovir and is a prodrug of acyclovir that is more readily absorbed and is converted to acyclovir by the liver.
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Erectile Dysfunction
What causes ED?
The natural process of sexual stimulation activates a series of biochemical reactions that relaxes blood vessels in the penis and allows blood flow into the corpus cavernosum, which is the spongy erectile tissue of the penis that fills with blood causing an erection. Loss of an erection is due to the activity of an enzyme called phosphodiesterase type 5 (PDE5) that breaks down the chemical responsible for relaxing blood vessels, cyclic guanosine monophosphate (cGMP), which results in contraction of the blood vessels, preventing blood flow. If the natural processes do not function properly due to physical or psychological problems, this can lead to erectile dysfunction or ED.
Medications for ED
The medications available for treating ED are used to increase blood flow into the penis, working by different mechanisms. These are:
- Phosphodiesterase type 5 (PDE5) inhibitors
- Prostaglandins
Phosphodiesterase type 5 (PDE5) inhibitors
Phosphodiesterase type 5 (PDE5) inhibitors block the action of the enzyme PDE5 that prevents blood flow into the penis and this action allows blood to remain in the penis, which maintains an erection. This resolves ED by allowing the natural process of sexual stimulation to activate the mechanism for achieving and maintaining an erection. However, PDE5 inhibitors only work when sexually aroused and do not work otherwise; their effect lasts for around four hours. These medications include sildenafil, tadalafil, vardenafil.
Prostaglandins
Prostaglandin E1, also known as alprostadil, is a naturally occurring chemical that has many functions including relaxation of smooth muscle in various tissues, including the corpus cavernosum and blood vessel walls. Prostaglandin E1 is used to treat ED by direct injection into the penis resulting in widening of the cavernosal arteries in the penis and relaxation of trabecular smooth muscle in the penis. This increases blood flow into the penis causing an erection.
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