Chemotherapy PDF

CHEMOTHERAPY DR WALID THEIB ABU ADAS PHD  WHAT IS CHEMOTHERAPY? Cytotoxic chemotherapy agents are used to treat cancers, leukaemia's and lymphomas. There are over 50 such drugs, which can be used as single agents, or in combination, orally, IV and subcutaneously.  Cytotox...

CHEMOTHERAPY DR WALID THEIB ABU ADAS PHD  WHAT IS CHEMOTHERAPY? Cytotoxic chemotherapy agents are used to treat cancers, leukaemia's and lymphomas. There are over 50 such drugs, which can be used as single agents, or in combination, orally, IV and subcutaneously.  Cytotoxic chemotherapy refers to agents whose mechanisms of action cause cell death or prevent cell growth, generally through inhibiting microtubule function, protein function, or DNA synthesis.  Cytotoxic chemotherapy mechanisms of action may be cell cycledependent—arresting cancer cell growth at specific phases in the cell cycle.  HOW DOES CHEMOTHERAPY KILL CANCER CELLS? In the centre of each living cell is the nucleus, this is the control centre of the cell. It contains chromosomes, which are made up of genes.  Chemotherapy damages the genes inside the nucleus of cells A combination of chemotherapy drugs is often used. This will include drugs that damage cells at different stages in the process of cell division.  GOALS Curative (eradication) Induction: Given with the intent of inducing complete remission. Consolidation: Repetition of induction chemotherapy, aim to prevent relapse. Maintenance: Long term, low dose, single or combination chemotherapy in a patient who has achieved complete remission, again prevent relapse  Palliative Provide comfort Improve/prolong quality of life SIDE EFFECTS OF CHEMOTHERAPY The goal of chemotherapy is to destroy cancer cells. Traditional chemotherapies work by killing cells that divide rapidly. But as they wipe out fast-growing cancer cells, they can also damage fastgrowing healthy cells.  Damage to healthy blood cells can lead to side effects such as fatigue or infection. Chemotherapy can also damage the cells that line mucous membranes throughout the body, including those inside the mouth, throat and stomach. This can lead to mouth sores, diarrhoea or other issues with the digestive system. And damage to cells at the hair roots, or follicles, can lead to hair loss.  SIDE EFFECTS CLASSIFICATIONS Immediate Occurs within thirty minutes of administration. Venous pain Facial/body flushing Cardiac Arrhythmias Short to medium term Occurs within hours and up to seven days of administration. Discoloration of urine Nausea and vomiting mucositis CNS Toxicity Anorexia  Medium to long term Occurs later than seven days and may be cumulative in nature. Bone Marrow depression Alopecia Liver dysfunction Bone marrow depression is a temporary cessation of the bone marrow’s ability to produce blood cells.  TUMOR LYSIS SYNDROME TUMOR LYSIS SYNDROME Tumour lysis syndrome (TLS) is an oncology emergency. It is a serious and potentially life-threatening complication of cancer therapy. It occurs when cancer treatments cause the destruction (or lysis) of a large number of rapidly dividing cancer cells, overwhelming the body’s ability to excrete the end products of cell deat  THROMBOCYTOPAENIA SYMPTOMS Blood in stools Epistaxis Bleeding Gums Prolonged bleeding after trauma Haematuria  CONCLUSION Chemotherapy causes damage to both healthy cells and the cancerous cells we are aiming to destroy, this leads to multiple complications following chemotherapy, these often require medical intervention.  Pain Number one reason people take medication Generally is related to some type of tissue damage and serves as a warning signal  25 million people suffer acute pain related to surgery or injury. Chronic pain affects 250 million Americans Is a multibillion dollar industry. Opioid receptors—binding sites not only for endogenous opiates but also for opioid analgesics to relieve pain. Several types of receptors: Mu, Kappa, Delta, Epsilon and Sigma.  Location: CNS incl. brainstem, limbic system, dorsal horn of spinal cord Morphine sulfate and morphine  Narcotic Analgesics Can be given orally, IM, sub q, IV or even transdermally Orally are metabolized by liver, excreted by kidney—caution if compromised Morphine and meperidine produce metabolites Widespread effects: CNS, Resp., GI  Narcotics—Mechanisms of Action Bind to opioid receptors in brain and SC and even in periphery acting on receptors located on neuronal cell membranes. The presynaptic action of opioids to inhibit neurotransmitter release is considered.  Indications for Use Before and during surgery Before and during invasive diagnostic procedures During labor and delivery Tx acute pulmonary edema Treating severe, nonproductive cough  Contraindications to Use Respiratory depression Chronic lung disease Chronic liver or kidney disease BPH Increased intracranial pressure Hypersensitivity reactions  Management Considerations age-specific considerations Morphine often drug of choice Use non-narcotic when able Combinations may work by different mechanisms thus greater efficacy  Route selections Oral preferred IV most rapid Epidural, or local injection Can use rectal suppositories  Scheduling Give narcotics before encouraging turning, coughing and deep breathing in post-surgical patients Automatic stop orders after 72h In acute pain, narcotic analgesics are most effective when given parenterally and at start of pain  Cancer Give on a regular schedule Oral, rectal and transdermal are preferred over IV  Management of Withdrawal Symptoms Methadone Clonidine (norepinephrine) Gradually decrease dosing so not to cause withdrawal  NSAIDs on-steroidal anti-inflammatory drugs (NSAIDs) are medicines that are widely used to relieve pain, reduce inflammation, and bring down a high temperature The main types of NSAIDs include: ibuprofen naproxen diclofenac  Peptic ulcers and gastrointestinal bleeding Long-term or high-dose use of NSAIDs could also lead to ulcers developing peptic ulcers  Toradol (ketoralac) is used only for pain. Is the only NSAID that can be given by injection. Use limited to 5 days as can cause bleeding.  Effects of Nonsteroidals on Other Drugs Decrease effects, beta blockers and diuretics Affect sodium and water retention  Acetaminophen Poisoning Toxicity occurs with 20g or more. Treatment—gastric lavage, charcoal, antidote is Mucomyst (acetylcysteine  dosaging Acetaminophen (paracetamol) 325 to 500 mg orally every 4 hours or 500 to 1000 mg every 6 to 8 hours (maximum 3 g per day) Tramadol Start with 25 mg orally once daily May increase daily dose by 25 to 50 mg after 3 to 7 days; give in 3 or 4 divided doses Age ≤75 years: Maximum 400 mg daily Age >75 years: Maximum 300 mg daily  Morphine Start with 2.5 to 10 mg orally every 4 hours as needed (an oral solution is available for initial low doses; lowest tablet strength available in the United States is 15 mg) After 3 to 7 days, determine 24-hour Corticosteroids DR WALID ABU ADAS PHD  corticosteroids Commonly referred to as steroids, corticosteroids are a type of anti-inflammatory drug. They are typically used to treat rheumatologic diseases, like rheumatoid arthritis, lupus or vasculitis (inflammation of the blood vessels). Specific corticosteroids include the medications cortisone and prednisone.  Corticosteroids are man-made drugs that closely resemble cortisol, a hormone that adrenal glands produce naturally. Corticosteroids are often referred to by the shortened term "steroids."  Some corticosteroid medicines include cortisone, prednisone and methylprednisolone. Prednisone is the most commonly used type of steroid to treat certain rheumatologic diseases (like rheumatoid arthritis or lupus)  Steroid medications are available in several forms that vary in how easily they dissolve or how long they stay in the body. Steroids might be given locally, to the precise place where a problem exists, or systemically, which means throughout the "system" or body.  Examples of local steroid treatments include joint injections, eye drops, ear drops and skin creams. Systemic steroid treatments include oral medicines (given by mouth) or medicine that is delivered directly into a vein (intravenously or IV) or muscle (intramuscularly). Systemic steroids circulate through the bloodstream to various body sites.  TYPES Cortisol, a glucocorticoid whose functions include immunosuppression. Sex steroids:Progestogens: – Progesterone, which regulates cyclical changes in the endometrium of the uterus and maintains a pregnancy Androgens: – Testosterone, which contributes to the development and maintenance of male secondary sex characteristics  Estrogens: – Estradiol, which contributes to the development and maintenance of female secondary sex characteristics  How do steroids work? Steroids work by decreasing inflammation and reducing the activity of the immune system. Inflammation is a process in which the body's white blood cells and chemicals can protect against infection and foreign substances such as bacteria and viruses. In certain diseases, however, the body's defense system (immune system) doesn't function properly. This might cause inflammation to work against the body's tissues and cause damage. Signs of inflammation includ  This might cause inflammation to work against the body's tissues and cause damage. Signs of inflammation include Redness. Swelling. Pain. Steroids reduce the production of chemicals that cause inflammation. This helps keep tissue damage as low as possible. Steroids also reduce the activity of the immune system by affecting the way white blood cells work  Steroids are used in the treatment for certain rheumatologic inflammatory conditions, such as: Systemic vasculitis (inflammation of blood vessels). Myositis (inflammation of muscle). Rheumatoid arthritis (chronic inflammatory arthritis). Systemic lupus erythematosus (a generalized disease caused by abnormal immune system function).  When inflammation threatens to damage critical body organs, steroids can be organ- saving and in many instances, life-saving. For example, steroids may prevent the worsening of kidney inflammation, which could lead to kidney failure in people who have lupus or vasculitis. For these patients, steroid therapy might eliminate the need for kidney dialysis or transplantation.  What are the possible side effects of steroids? Increased appetite. Weight gain. Changes in mood. Muscle weakness. Blurred vision. Increased growth of body hair.  Withdrawal Steroid use cannot be stopped abruptly; tapering the drug gives the adrenal glands time to return to their normal patterns of secretion. Withdrawal symptoms and signs (weakness, fatigue, decreased appetite, weight loss, nausea, vomiting, diarrhea, abdominal pain) can mimic many other medical problems  Mother who decided to stop steroid cream for facial eczema after it permanently damaged one eye reveals how the years-long withdrawal left her covered in agonising itchy skin and it even hurt to breathe Drug Treatment of Diabetes Mellitus DR WALID THEIB PHD  There are two types of diabetes mellitus Type 1, in which the body's immune system attacks the insulin-producing cells of the pancreas, and more than 90% of them are permanently destroyed Type 2, in which the body develops resistance to the effects of insulin  General treatment of type 1 diabetes requires lifestyle changes, including healthy diet and exercise. People with type 1 diabetes require insulin injections and frequent monitoring of glucose levels. General treatment of type 2 diabetes also requires lifestyle changes, including weight loss, healthy diet, and exercise. A few people with type 2 diabetes can control blood glucose levels with only diet and exercise, but most people require drugs to lower blood glucose levels, sometimes including insulin  People with type 1 diabetes almost always require insulin therapy and will become very sick without it. Many people with type 2 diabetes require insulin as well. Usually, insulin is injected under the skin. For certain people, inhaled insulin is also available, although it is not used commonly. Insulin currently cannot be taken by mouth because insulin is destroyed in the stomach. New forms of insulin, such as forms that can be taken by mouth, are being tested.  Insulin is injected under the skin into the fat layer, usually in the arm, thigh, or abdomen. Small syringes with very thin needles make the injections nearly painless. An insulin pen, which contains a cartridge that holds the insulin, is a convenient way for many people to carry and use insulin, especially for people who take several injections a day outside the home.  Another device is an insulin pump, which pumps insulin continuously from a reservoir through a small cannula (hollow plastic tube) left in the skin. The rate of insulin administration can be adjusted depending on the time of day,  Pump therapy is considered in some people who require more than three injections per day.  Insulin is available in four basic forms, divided by speed of onset and duration of action:  Rapid-acting insulin includes lispro, aspart, and glulisine insulins. They are the fastest of all, reaching maximum activity in about 1 hour and working for 3 to 5 hours. Rapid-acting insulins are injected at the beginning of a meal  Short-acting insulin, such as regular insulin, begins acting slightly more slowly and lasts longer than rapid-acting insulin. Regular insulin reaches its maximum activity in 2 to 4 hours and works for 6 to 8 hours. It is injected 30 minutes before eating a mea  Intermediate-acting insulin, such as neutral protamine Hagedorn (NPH) or U-500 insulin, starts to work within 0.5 to 2 hours, reaches its maximum activity in 4 to 12 hours, and works for 13 to 26 hours depending on which intermediate-acting insulin is used. This type of insulin may be used in the morning to provide coverage for the first part of the day or in the evening to provide coverage during the night.  Long-acting insulin, such as insulin glargine, insulin detemir, U-300 insulin glargine or insulin degludec, has very little effect during the first few hours but provides coverage for 20 to 40 hours depending on which of these types is used.  Inhaled insulin is available for use in some situations for people who are unable or unwilling to take insulin injections. Inhaled insulin is available as an inhaler (similar to an asthma inhaler), and people inhale the insulin into the lungs for absorption. Inhaled insulin works similar to short-acting insulin and needs to be taken several times per day  Allergic reaction to insulin Insulin injections can affect the skin and underlying tissues. An allergic reaction, which occurs rarely, causes pain and burning, followed by redness, itchiness, and swelling around the injection site for several hours  Oral Antihyperglycemic Drugs Oral antihyperglycemic drugs can often lower blood glucose levels adequately in people with type 2 diabetes. However, they are not effective in type 1 diabetes. There are several types, but oral antihyperglycemic drugs work in four major ways:  Insulin secretagogues stimulate the pancreas to produce more insulin Insulin sensitizers do not affect the release of insulin but rather increase the body’s response to it delay absorption of glucose by the intestine increase glucose excretion in the urine  Insulin secretagogues include sulfonylureas (for example, glyburide) and meglitinides (for example, repaglinide). Insulin sensitizers include biguanides (for example, metformin) and thiazolidinediones (for example, pioglitazone). Drugs that delay absorption of glucose by the intestine include alpha-glucosidase inhibitors (for example, acarbose and miglitol).  Drugs that increase glucose secretion in the urine include sodium-glucose co-transporter-2 (SGLT2) inhibitors (for example, canagliflozin, dapagliflozin, and empagliflozin). Facts about antidepressants DR WALID THEIB PHD  Antidepressants are not addictive Antidepressants are not stimulants or tranquilizers and do not make you "high" Antidepressants are not the same as antipsychotic medications Antidepressants have a balancing effect on the neurotransmitters in the brain  Antidepressants do not work immediately: A depressive episode does not disappear overnight, even if you are taking an effective medication Antidepressants do not work immediately after taking them Usually it takes 2 to 6 weeks of taking antidepressant medication on a daily basis before you experience an improvement  Antidepressants should not be stopped suddenly: It is important to continue taking the antidepressants WHICH have been prescribed, even after experience improvements An early and sudden stop to antidepressant treatment increases the risk of depression coming back To reduce the risk of depression coming back, antidepressants should be taken for 4 to 9 months after the start of the first episode Depending on the specific situation, medication may need to be continued for more than 9 months  Selective serotonin reuptake inhibitors (SSRIs) SSRIs are the most commonly prescribed class of antidepressants. An imbalance of serotonin may play a role in depression. These drugs fight depression symptoms by decreasing serotonin SRIs treat depression by increasing levels of serotonin in the brain  SSRIs include: sertraline (Zoloft) fluoxetine (Prozac, Sarafem) citalopram (Celexa) escitalopram (Lexapro) paroxetine (Paxil, Pexeva, Brisdelle) fluvoxamine (Luvox)  Common side effects of SSRIs include: nausea trouble sleeping nervousness tremors sexual problems  Serotonin and norepinephrine reuptake inhibitors (SNRIs) SNRIs help improve serotonin and norepinephrine levels in the brain. This may reduce depression symptoms.  desvenlafaxine (Pristiq, Khedezla) duloxetine (Cymbalta) levomilnacipran (Fetzima) venlafaxine (Effexor XR) In addition to treating depression, duloxetine may also relieve pain. This is important because chronic pain can lead to depression or make it worse  Tricyclic antidepressants (TCAs) TCAs are often prescribed when SSRIs or other antidepressants don’t work. It isn’t fully understood how these drugs work to treat depression. Tricyclic antidepressants usually have more of an effect on norepinephrine levels than on serotonin levels  TCAs include: amitriptyline amoxapine clomipramine (Anafranil) desipramine (Norpramin) doxepin imipramine (Tofranil) nortriptyline (Pamelor) protriptyline trimipramine (Surmontil)  Common side effects of TCAs can include: constipation dry mouth fatigue The more serious side effects of these drugs include: low blood pressure irregular heart rate seizures  Tetracyclic antidepressant Maprotiline is used to treat depression and anxiety. It also works by balancing neurotransmitters to ease symptoms of depression Tetracyclic antidepressants are used to treat major depressive disorder with symptoms such as depressed mood, feelings of worthlessness, nervousness, trouble sleeping, loss of pleasure, low energy, and suicidal thoughts  Common side effects of this drug include: drowsiness weakness lightheadedness headache blurry vision dry mouth  Dopamine reuptake blocker Bupropion (Wellbutrin, Forfivo, Aplenzin) is a mild dopamine and norepinephrine reuptake blocker. It’s used for depression and seasonal affective disorder. It’s also used in smoking cessation. blocking the action of the dopamine transporter---IMPROVE DOPAMIN LEVEL  Common side effects include: nausea vomiting constipation dizziness blurry vision  5-HT1A receptor antagonist The drug in this class that’s used to treat depression is called vilazodone (Viibryd). It works by balancing serotonin levels and other neurotransmitters. decrease blood pressure and heart rate via a central mechanism, by inducing peripheral vasodilation, and by stimulating the vagus nerve Side effects can include: nausea vomiting trouble sleeping  Monoamine oxidase inhibitors (MAOIs) MAOIs are older drugs that treat depression. They work by stopping the breakdown of norepinephrine, dopamine, and serotonin. They’re more difficult for people to take than most other antidepressants because they interact with prescription drugs, nonprescription drugs, and some foods. They also can’t be combined with stimulants or other antidepressants.  MAOIs include: isocarboxazid (Marplan) phenelzine (Nardil) selegiline (Emsam), which comes as a transdermal patch tranylcypromine (Parnate) Central Nervous System (CNS) Stimulants DR WALID THEIB PHD  Central nervous system stimulants used for attention deficit disorder, narcolepsy or excessive sleepiness A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation They are drugs which increase the muscular (motor) and the mental (sensory) activities.  Classification of CNS stimulants 1. Cerebral stimulants. 2. Psychomotor stimulants e.g. Amphetamine 3. Spinal cord stimulants.  General signs and symptoms of CNS stimulation: ↑ Heart rate. ↑ Respiratory rate. Instability & restlessness. Muscle twitching (tremors). Hair erection. Convulsion but at high dose may lead to death.  Classification of CNS stimulants according to their site of action: Cerebral stimulants. Medullary stimulants. Spinal cord stimulants  Cerebral Stimulants: --Examples Caffeine and Cocaine Site of action Cerebral cortex MOA 1-Stimulates CNS and heart → excitation. Relaxes smooth muscles. 2. A2 receptors antagonist → CNS stimulation & smooth muscles relaxation  Medullary Stimulants Examples Picrotoxin, Cardiazol, Coramine Site of action Medulla oblongata MOA Noncompetitive GABAA receptors blocker which is a chloride dependent → no hyperpolarization → excitation.  Spinal Cord Stimulant Example Strychnine. Site of action Spinal cord MOA Block the postsynaptic inhibitory response to glycine by blocking glycine receptors. Glycine is the main inhibitory transmitter acting on motor neurons. Amphetamine A CNS stimulant and sympathomimetic agent indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD Caffeine A stimulant present in tea, coffee, cola beverages, analgesic drugs, and agents used to increase alertness. It is also used in to prevent and treat pulmonary complications of premature birth. Lisdexamfetamine A central nervous system (CNS) stimulant used to treat attention deficit hyperactivity disorder (ADHD) and moderate to severe eating disorders  Metamfetamine A sympathomimetic agent used in the treatment of attention deficit hyperactivity disorder (ADHD) and exogenous obesity Megestrol acetate A progestin that is administered orally to treat anorexia and cachexia or serious unexplained weight loss and is also used as an antineoplastic agent to treat certain types of malignancy. Doxapram A short acting respiratory stimulant used to treat acute respiratory insufficiency in COPD patients.  Psychomotor stimulants Psychomotor stimulants are drugs that stimulate the central nervous system to increase motor activity and to produce euphoria, excitement, and a feeling of having lots of energy. Unfortunately, some drugs of abuse, like methamphetamine or cocaine, belong to this class of substances  Amphetamines (including ecstasy or methylenedioxymetamphetamine) Armodafinil. Atomoxetine. Cocaine. Methylphenidate.  Medical Indications Attention deficit hyperactivity disorder (ADHD) Narcolepsy Asthma Obesity Nasal and sinus congestion Hypotension due to anesthesia  increase catecholamine levels  Administration The primary method of administration for stimulants is oral intake. Recreational administration of stimulants also occurs by intramuscular and/or intravascular injection, smoking, and intranasal administration.  Contraindication There are numerous relative contraindications to the use of stimulants. Patients with advanced arteriosclerosis should use minimal stimulants given the elevated risk of myocardial infarction, as stimulants elevate cardiac demand. Also, patients with severe hypertension will exacerbate their existing elevated high blood pressure when using stimulants and, therefore, should minimize their use. Untreated hyperthyroidism, glaucoma, and a recent stroke are also relative contraindications to stimulant use  Younger patients under the age of 12 and pregnant patients should avoid using stimulants.  Farzam K, Kidron A, Lakhkar AD. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Aug 11, 2020. Adrenergic Drugs. [PubMed]  Parkinson's disease is a brain disorder that leads to shaking, stiffness, and difficulty with walking, balance, and coordination. Parkinson's symptoms usually begin gradually and get worse over time. As the disease progresses, people may have difficulty walking and talking  Parkinson's disease occurs when nerve cells, or neurons, in an area of the brain that controls movement become impaired and/or die. Normally, these neurons produce an important brain chemical known as dopamine. When the neurons die or become impaired, they produce less dopamine, which causes the movement problems of Parkinson's  Medicines for Parkinson's Disease Drugs that increase the level of dopamine in the brain Drugs that affect other brain chemicals in the body Drugs that help control nonmotor symptoms  The main therapy for Parkinson's is levodopa, also called L-dopa. Nerve cells use levodopa to make dopamine to replenish the brain's dwindling supply. Usually, people take levodopa along with another medication called carbidopa. Carbidopa prevents or reduces some of the side effects of levodopa therapy—such as nausea, vomiting, low blood pressure, and restlessness— and reduces the amount of levodopa needed to improve symptoms.  Dopamine agonists to mimic the role of dopamine in the brain MAO-B inhibitors to slow down an enzyme that breaks down dopamine in the brain MAO-B (Monoamine Oxidase-B) Inhibitors  Rasagiline ------Azilect (tablets) Selegiline --Eldepryl (tablets) ----Zelapar (tablets that dissolve on the tongue) Safinamide ----Xadago (tablets)