LEC 2 - Antihistamine PDF

A ll e r g ie s An ti h is ta m in es An t ia ll e rg ic s  ALLERGY TERMS ANTIHISTAMINE URTICARIA A medication...

A ll e r g ie s An ti h is ta m in es An t ia ll e rg ic s  ALLERGY TERMS ANTIHISTAMINE URTICARIA A medication that blocks the effects of histamine AKA hives, it is a skin by binding to H1 receptors. This helps reduce symptoms of allergies, such as itching, swelling, condition characterized by and runny nose. raised, itchy welts or hives. It RHINITIS is often caused by an allergic H2-RECEPTOR Inflammation of the nasal reaction but can also be ALLERGY A receptor in the stomach mucous membranes, causes triggered by other factors. when the immune system reacts that helps control acid symptoms like a runny/stuffy to a foreign substance that gets production. When histamine nose, sneezing, and itching. It inside the body that is usually binds to it, more stomach can be allergic (allergic ANAPHYLAXIS harmless to others. acid is produced. H2 blockers rhinitis) or non-allergic (such are medicines that reduce as viral rhinitis). A severe, potentially life- threatening allergic reaction ALLERGEN stomach acid by blocking that requires immediate this receptor. They’re used to A substance that causes an treat heartburn and ulcers. ERYTHEMA medical attention. Symptoms allergic reaction. (pollen, dust can include difficulty breathing, Redness of the skin caused swelling, mites, animal dander, certain by increased blood flow to foods, and insect stings. the capillaries in the H1-RECEPTOR affected area. It can be due ANTIGEN to inflammation, irritation, binds to histamine. When A substance that triggers an immune response. Antigens are histamine binds to H1 or infection HISTAMINE often proteins found on the surface receptors, it causes symptoms A chemical released by the of pathogens (bacteria & viruses) of allergic reactions like itching, immune system during swelling, and redness. DERMATITIS allergic reactions and found mostly in bronchioles ANTIBODY Inflammation of the skin inflammatory responses. It A protein produced by the immune that causes redness, causes symptoms such as H1 receptor antagonists system in response to an antigen. swelling, and itching. It can itching, swelling, and redness (antihistamines) are used to Antibodies bind to antigens to treat allergies. be caused by allergies, by dilating blood vessels neutralize or mark them for irritants (eczema) destruction by other immune cells.  ANTIHISTAMINE - GENERAL INFO Histamine is a biogenic amine involved in various physiological functions, including regulation of COMPETITIVE ANTAGONISM gastric acid secretion, neurotransmission, and Antihistamines work by competitively immune response. blocking the H1 receptors, preventing histamine from binding to these sites and It primarily exerts its effects through histamine receptors: exerting its effects. H1 RECEPTORS TYPES OF ANTIHISTAMINES Primarily involved in allergic responses, causing symptoms such as itching, sneezing, and 1ST GENERATION 2ND GENERATION bronchoconstriction. Examples: Diphenhydramine (Benadryl), Examples: Loratadine (Claritin), Cetirizine Chlorpheniramine, Doxylamine. (Zytrec) , Fexofenadine (Allegra). H2 RECEPTORS Characteristics: These can cross the blood- Characteristics: These are less likely to Involved in gastric acid brain barrier and often cause sedation as a cross the blood-brain barrier, resulting in secretion. side effect due to their central nervous fewer sedative effects. system effects. MOA: Primarily block peripheral H1 H3 & H4 RECEPTORS MOA: Block H1 receptors both peripherally receptors, reducing allergic symptoms Have roles in neurotransmission and centrally, leading to reduced allergic with minimal sedation. and immune function, but are less symptoms and sedation. relevant to allergy treatment. 1ST GENERATION 2ND GENERATION cetirizine - reactine desloratadine - aerius fexofenadine allergra  ANAPHYLAXIS ANAPHYLAXIS AND HYPOTENSION TREATMENT During anaphylaxis, a severe allergic reaction, 1. Epinephrine: a massive release of histamine and other First-line treatment for anaphylaxis. It works by causing inflammatory mediators occurs. vasoconstriction (narrowing of blood vessels), reversing the effects of histamine-induced vasodilation and raising blood This can lead to systemic vasodilation, pressure. causing a rapid and life-threatening drop in blood pressure (shock). 2. Antihistamines: These block the action of histamine at H1 and H2 receptors, Symptoms of anaphylaxis include difficulty helping to reduce symptoms of the allergic reaction. breathing, swelling, hives, and hypotension. If However, they are less effective in treating hypotension untreated, hypotension can progress to and should be used as supportive therapy alongside circulatory collapse, which is a medical epinephrine. emergency. 3. IV Fluids: In cases of severe hypotension, intravenous fluids can help increase blood volume and improve blood pressure.  Action of Histamine VASCULAR EFFECTS CARDIAC EFFECTS dilation of capillaries - transient rapid heart beat causes capillaries (small blood vessels) to expand - leads to redness and at high levels - cause swelling arrhythmias hypotension by dilating blood vessels erythema in skin EXTRAVASCULAR redness of the skin due to increased blood flow to the area (dilated blood SMOOTH MUSCLE vessels) contraction of smooth muscles (intestines or bronchioles) leaky capillaries - fluid & proteins escape causing irritation of nasal GI upset membranes or hives Histamine increases the permeability of capillaries, allowing fluid and proteins to leak into surrounding tissues. This leak causes swelling (edema) and irritation, nasal congestion, runny nose, or hives (urticaria).  Indications for Antihistamines 3 1. ACUTE ALLERGIC REACTIONS hay fever, insect bites, pet dander, minor food/drug allergies 2. DRY NASAL SECRETIONS often in cough/cold products anticholinergic component 3. SLEEP AIDS 4. REDUCTION OF NAUSEA due to sedative properties & VOMITING & MOTION can have morning grogginess SICKNESS Walls of Hollow Organs: Smooth Muscle Tissue Stomach: Helps with mixing and churning food during digestion. Intestines: Aids in the movement of food (peristalsis) through the digestive tract. LOCATION Bladder: Controls the expulsion of urine. Uterus: Involved in contractions during childbirth. Blood Vessels: Arteries and veins: Smooth muscle in the vessel walls helps regulate blood pressure by contracting or relaxing to control the diameter of the vessels. Respiratory Tract: Bronchi and bronchioles: Regulates airflow in and out of the lungs by controlling the diameter of the airways. Urinary Tract: Ureters: Helps propel urine from the kidneys to the bladder. Bladder: Assists in the storage and controlled release of urine. Reproductive Tract: Uterus: Involved in the menstrual cycle and childbirth. Vas deferens and fallopian tubes: Assists in the movement of sperm and eggs. Eyes: Iris: Controls the size of the pupil, regulating the amount of light that enters the eye. Ciliary muscles: Controls the shape of the lens for focusing. Skin: Arrector pili muscles: Small smooth muscles attached to hair follicles, responsible for causing "goosebumps."  Smooth Muscle Tissue WHERE ITS NOT Skeletal Muscles: responsible for voluntary movements like walking, lifting, and talking. These muscles are under conscious control and are made of striated muscle fibers, not smooth muscle. Heart: made of cardiac muscle, which is also striated but functions involuntarily, like smooth muscle CNS (Central Nervous System): brain and spinal cord Skin's Epidermis: The epidermis, the outermost layer of skin, is made up of epithelial cells However, the underlying dermis has small smooth muscles like the arrector pili (which cause goosebumps). Bones and Joints: Movement of the bones is controlled by skeletal muscles attached to them. Lymphatic Vessels: While large lymphatic vessels may have some smooth muscle to help move lymph fluid, small lymphatic vessels (capillaries) do not contain smooth muscle. Lungs' Alveoli: The alveoli (air sacs where gas exchange occurs in the lungs) However, smooth muscle is present in the bronchioles and bronchi, which are responsible for regulating airflow before it reaches the alveoli. Drug Interactions older generation antihistamines have a prominent sedating effect Sedation is greatly increased when antihistamines taken in combination with: hypnotics zolpidem (Ambien), eszopiclone (Lunesta) sedatives diazepam (Valium), lorazepam (Ativan) anxiolytics buspirone (Buspar), clonzapam (Klonopin) alcohol narcotic analgesics morphone (MS Contin), oxycodone (OxyContin) Muscle Relaxants baclofen (Lioresal), cyclobenzaprine (Flexeril) other CNS depressants  1st Gen Antihistamine Characteristics SEDATING ANTICHOLINERGIC SHORTER DURATION OF EFFECTS ACTION Central Nervous System Effects: They often cross the blood-brain barrier, Drying Effects: They have which can lead to drowsiness and anticholinergic properties, which They often require more sedation. This is a common side can lead to dryness of the mouth, frequent dosing compared to effect. throat, and eyes, and can cause second-generation constipation and urinary retention. antihistamines.  Advantages of 2nd gen Antihistamines HELPS REDUCE SIDE EFFECTS COMMONLY ASSOCIATED WITH OLDER ANTIHISTAMINES MORE SELECTIVE FOR MAY BE USEFUL FOR PERIPHERAL H1 RECEPTORS PATIENTS REFRACTORY LONGER HALF LIFE They target histamine receptors TO OLDER AGENTS outside the (CNS), which helps may be dosed once daily minimize sedation because they don’t They may be effective for patients cross the blood-brain barrier as easily who do not respond well to first- which can improve adherence as first-gen antihistamines. generation antihistamines. to treatment. therefore less sedating and drying (have fewer anticholinergic side effects) Why do Antihistamine have Anticholinergic Properties EFFECTS ON THE AUTONOMIC NERVOUS CHEMICAL STRUCTURE SYSTEM Many 1st gen antihistamines share a By blocking muscarinic receptors, chemical structure similar to tricyclic these antihistamines can inhibit the antidepressants and other actions of the parasympathetic anticholinergic agents. This similarity nervous system, which uses allows them to bind to and block acetylcholine as its primary muscarinic receptors, which mediate neurotransmitter. the effects of acetylcholine in the body. NON-SELECTIVE RECEPTOR BINDING CNS EFFECTS 1st gen antihistamines are non-selective, By blocking the action of meaning they can interact with various acetylcholine in the brain, these receptors beyond H1 receptors, including antihistamines can affect cognitive muscarinic acetylcholine receptors. This function and alertness, adding to their broad binding profile is what gives them sedative properties. their anticholinergic properties.  Side Effects ANTIHISTAMINES COMMON LESS COMMON (SEEN IN OVERDOSE) drowsiness & Sedation dry mouth (xerostomia) hypotension dry mucous membranes urinary retention (difficulty emptying bladder) *first gen antihistamine have a higher potential for all rapid heartbeat (tachycardia) three antihistamines 1ST GEN CLASSES  1st generation antihistamines Ethanolamines Alkylamaines phenothiazines most sedating, highest highest potential for Rx ONLY anticholinergic effects CNS stimulation, high anticholinergic effects, medium for epigastric moderate sedation dimenhydrinate - Gravol (OTC) distress diphenhydramine - promethazine - prescribed Benadryl (OTC) chlorpheniramine (OTC) when OTC options not effective for maintenance hydroxyzine (Atarax) - rx only, very sedating, often prescribed for puritis/urticaria related reactions  2nd gen OTC designed to be less sedating than first-generation antihistamines, as they have a reduced ability to cross the blood-brain barrier work by selectively blocking H1 histamine receptors desloratidine Cetrizine fexofenadine loratidine Clarinex, Aerius Zytrec Claritin New on the Allegra market 2nd generation Reactine Alavert PRODRUG Antiallergic Agents  Cromolyn Sodium AKA Sodium cromoglycate 1 MEchanism of Action 2 indications involves inhibiting the release of Degranulation of mast cells: prophylactic in (prevent histamine and other inflammatory refers to the process by which disease/condition, rather than mediators from mast cells. By mast cells release their stored treat): preventing the degranulation of mast granules containing various chronic bronchial asthma cells. By stabilizing the cell chemicals (histamine and (oral/inhaled) membrane, cromolyn sodium blocks other inflammatory allergic rhinitis (nasal inhaler) calcium influx into mast cells, which is mediators) into surrounding food allergies (oral) essential for the release of these tissues. occurs when mast allergic conjunctivitis (eye mediators. cells are activated by certain drops) stimuli, such as allergens, Preventative strategy only injury, or infections. Understanding Terminology What is the difference an antiallergic and an antihistaminic drug? Drugs that prevent mast cells from releasing histamine (as well as other substances) are antiallergic drugs or mast cell stabilizers. Drugs that are administered to relieve signs and symptoms of acute reactions in which histamine has already been released are called antihistaminic drug Erythema Erythema is redness of the skin vs that is often the result of capillary dilation. Dermatitis Dermatitis is an inflammatory condition of the skin associated with itching, burning, and edematous vesicular formations Any process or drug that prevents the onset of symptoms (or disease) as a result of Prophylaxis exposure before the reactive process can take place KNOWLEDGE WHERE IS HISTAMINE LOCATED IN THE BODY? WHAT STIMULATES HISTAMINE RELEASE? Histamine is found throughout the body within mast cells and basophilic white blood cells. When antigens come into contact with the skin or lungs or enter the bloodstream of sensitized individuals (previously exposed to the antigen), the mast cells and basophils immediately release histamine into the blood WHAT ARE THE EFFECTS OF HISTAMINE ON VARIOUS TISSUES? Histamine produces vasodilation of capillaries, contraction of muscle in the intestine, constriction of smooth muscle of the bronchioles, increased heart rate, and secretion of gastric acid. Effects of histamine on the capillaries within the skin produce the characteristic allergic responses of redness, swelling (edema), and itching or pain.  HOW DOES CROMOLYN SODIUM PRODUCE ITS ANTIALLERGIC RESPONSE? WHEN IS CROMOLYN SODIUM USED? Cromolyn sodium prevents the release of histamine from the mast cells, so an allergic response is avoided. It has no effect on histamine receptors or smooth muscle tone to interrupt an allergic reaction; therefore, cromolyn must be given prophylactically, before histamine release has begun. HOW DO THE ANTIHISTAMINICS PREVENT THE ACTION OF HISTAMINE? WHAT RECEPTORS ARE INVOLVED IN ALLERGIC REACTIONS? Antihistaminic drug’s molecules interact with (occupy) histamine receptors and block histamine from producing its usual responses. Two types of known histamine receptors are H1- and H2-receptors. Allergic responses produced by histamine are mediated through the H1-receptors located in the smooth muscle of blood vessels, bronchioles, intestine, and skin capillaries.  WHAT OTHER PHARMACOLOGICAL ACTIONS DO ANTIHISTAMINICS PRODUCE? In addition to inhibiting the actions of histamine, antihistaminics possess local anesthetic and anticholinergic activity. They can relieve vertigo, motion sickness, and nausea; are commonly found in over-the-counter products for relief of symptoms associated with common colds; and produce sedation. WHY ARE ANTIHISTAMINICS FOUND IN OVER-THE-COUNTER PRODUCTS? WHAT ARE TWO EXAMPLES? Dimenhydrinate (Dramamine) can relieve vertigo, motion sickness, and nausea. Antihistaminics that relieve symptoms associated with the common cold include Tylenol Cold and Flu. Nonprescription sleeping aids include Nytol (diphenhydramine). Diphenhydramine is sometimes used as an antiemitic too. ADVERSE EFFECTS CONTRAINDICATIONS ANTIHISTAMINE drowsiness or sedation anticholinergics, (because antihistaminics anticoagulants, antidepressants, depress the CNS) corticosteroids, drugs that produce CNS dry mouth depression (alcohol, hypotension barbiturates, hypnotics, rapid heartbeat narcotic analgesics, anorexia phenothiazines, epigastric distress tranquilizers), urinary retention. MAO inhibitors.  SCENARIO 1 Nasalcrom (cromolyn sodium) does not block histamine that has already been released. It may take a while for the Mrs. Lewis calls the clinic where you are working. Nasalcrom to take effect, and Mrs. Lewis She says when she was in the clinic 2 days ago, should allow several days to see benefit. In the doctor diagnosed her with allergic rhinitis the meantime, she should take the Chlor- and gave her prescriptions for cromolyn sodium inhalation and Chlor-Trimeton. She claims she Trimeton to control her symptoms. Taking has used cromolyn for the past 48 hours without it at bedtime should allow her relief at any relief of her nasal symptoms. “My nose is night, when drowsiness should not be a running like a faucet with this pollen count so problem. During the day, Mrs. Lewis may high. I didn’t fill the Chlor- Trimeton prescription benefit from one of the less sedating because I have to work and can’t tolerate the antihistaminics. You should discuss another drowsiness.” What should you tell her? antihistaminic with the doctor and get back to her.  SCENARIO 2 Explain to her that Nasalcrom is used to prevent histamine release in allergic conditions, such as hay fever, and will be Six months later, during cold season, Mrs. Lewis calls the office for a refill on her of no benefit for a cold (a viral Nasalcrom prescription. She says she has a condition). Suggest that she ask her terrible cold with a runny nose and the pharmacist for a recommendation for cromolyn worked so well when she used it an over-the-counter cold product, or during hay fever season she wants to use it inform her that you will ask the doctor now. What should you do? to suggest a cold preparation and get back to her.  SCENARIO 3 Explain to her that Nasalcrom is used to prevent histamine release in allergic conditions, such as hay fever, and will be Six months later, during cold season, Mrs. Lewis calls the office for a refill on her of no benefit for a cold (a viral Nasalcrom prescription. She says she has a condition). Suggest that she ask her terrible cold with a runny nose and the pharmacist for a recommendation for cromolyn worked so well when she used it an over-the-counter cold product, or during hay fever season she wants to use it inform her that you will ask the doctor now. What should you do? to suggest a cold preparation and get back to her.  SCENARIO 4 The powder from the capsule should be dissolved into a glass of hot water and the resulting solution consumed. This A patient has just received a medication should be taken on an prescription for Gastrocrom. What empty stomach. Juice, milk, and food should be included in his should not be taken within 30 minutes instructions for proper of taking the medication. administration? CONTRAINDICATIONS ANTIHISTAMINE USE ANTICHOLINERGIC ANTIHISTAMINE DURING PREGNANCY Cardiovascular disease hypertension predisposition to NO developing: an increase because their safety in intraocular pressure has not yet been established. urinary retention  Asthma vs COPD COPD Chronic Obstructive Pulmonary Disease Asthma smoking can easily immediate cause damage and lead to this condition Today's lesson will help you: EMPHYSEMA PROSTAGLANDINS HISTAMINE Emphysema destroys alveoli, a group of lipid which are air sacs in the lungs. When the immune compounds The air sacs weaken and system encounters an They mediate the eventually break, which allergen (like pollen, inflammatory dust, or certain foods), reduces the surface area of response, histamine is released the lungs and the amount of oxygen that can reach the contributing to pain, from mast cells. This bloodstream. This makes it redness, swelling, and causes classic allergic harder to breathe, heat. symptoms  FIRST-GENERATION VS. PRIMARY ACTION SECOND-GENERATION Antihistamines block H1 receptors to inhibit First-generation antihistamines can cause sedation the action of histamine, thereby alleviating due to their central effects. symptoms of allergic reactions and Second-generation antihistamines are less sedating respiratory conditions. and primarily act peripherally. CLINICAL APPLICATIONS EXTRA NOTES Allergic rhinitis (hay fever) Some antihistamines also have Allergic conjunctivitis anticholinergic properties, leading to Urticaria (hives) additional effects such as dry mouth, Anaphylaxis (as adjunctive treatment) urinary retention, and constipation. Insomnia (some first-generation antihistamines due to This is more common in first- their sedative properties) generation antihistamines. Sedation: Many (diphenhydramine & chlorpheniramine), can cause significant drowsiness and sedation. Caution is advised when driving or operating heavy machinery. Anticholinergic Effects: can cause dry mouth, blurred vision, urinary retention, constipation, and confusion, especially in older adults. Use with caution in individuals with glaucoma, prostate enlargement, or urinary retention. Drug Interactions: can interact with alcohol, benzodiazepines, and other central nervous system depressants, increasing the risk of sedation and respiratory depression. Use in Older Adults: Increased sensitivity and higher risk of side effects (e.g., confusion, dizziness) in elderly patients. Consider using lower doses or opting for second-generation antihistamines. Avoidance in Certain Conditions: asthma, chronic obstructive pulmonary disease (COPD), or other respiratory issues, as they can thicken secretions. Less Sedating, but Not Sedation-Free: While are less likely to cause sedation, some individuals may still experience drowsiness (e.g., cetirizine). Heart Conditions: Fexofenadine has been associated with a risk of QT interval prolongation, so caution is advised in patients with pre- existing heart conditions or on medications that affect heart rhythm. Pregnancy and Lactation: Always consult a healthcare provider before using any antihistamine during pregnancy or while breastfeeding Many antihistamines can pass into breast milk, which means that a nursing infant may be exposed to the medication Liver and Kidney Function: Dose adjustments may be necessary for individuals with impaired liver or kidney function, particularly for cetirizine and loratadine. Drug Interactions: Although second-generation antihistamines have fewer interactions compared to first-generation, caution is still needed when taken with other medications, especially those that may also cause drowsiness.