PHAR 100 - Module 5
Non-prescription drugs
· Drugs that can be sold to the public without prescription (e.g. over the counter drugs)
o Prescription drugs
· Drugs restricted to the sale by prescription only
o Over-the counter drugs (OTC)
· Sold on the premise that the public can diagnose mild symptoms and select the appropriate agents to treat them
o Guidelines for using an OTC drugs
· Not a replacement for prescription drugs
· In case of mild illness and/symptoms
· In case of adverse effects, stop using the OTC drug
à Can have drug interactions with herbal and prescription drugs
· Consultation with pharmacist for aid in choosing OTC drug
à Should not self-medicate for over 2 weeks without medical consultation
o Safety and efficacy of OTC drugs
· Sale is controlled by Foods and drugs Act
· Older OTC drugs that have been in the market for decades were not subjected to random clinical trials because of grandparenting (new regulations does not apply to products already on the market)
à Because of no randomized trials, those drugs may not be very effective and have serious toxicities.
o Selection of appropriate OTC drugs
· Proven efficacy and known toxicities
· Simple formulations and ingredients
· Brand vs Generic
à Generics are usually as effective as brand name ones but with a cheaper price
· Appropriate and effective dose
à Drug will come in appropriate dosage form (e.g. liquid for children)
à Will have a therapeutically effective dose of the active ingredient
o Common OTC drugs
· Internal analgesics
à Provide pain relief
à Internal vs topical analgesics
¨ Topical diclofenac is a effective analgesic for minor sprains pain
à Mechanism of action
¨ Tissue damage occurs
¨ Arachidonic acid is released
¨ Can be converted by COX-1 enzyme into protective prostaglandins or COX-2 into inflammatory prostaglandins
¨ Inflammatory prostaglandins cause pain, inflammation, fever and degreased platelets aggregation
¨ Analgesic block some or both Cox enzymes
à Acetylsalicylic acid (Aspirin)
¨ Relieves pain (analgesic), fever (antipyretic) and inflammation (anti-inflammatory)
- ASA inhibits the synthesis of prostaglandins
¨ Low doses can prevent stroke and heart attack
- ASA inhibits platelet aggregation hence clot formation
¨ Adverse effects
- Gastric irritation (2% of pop) : breaks down the mucosal protective layer of the stomach
- Tinnitus: ringing of the ear in high doses
- Reye’s syndrome: when given to children during a fever; rare illness that affects the CNS
- Allergic reactions: rare
à Acetaminophen
¨ Comprises of more than 50% of the market
¨ Inhibits the synthesis of prostaglandins
¨ Relieves pain (analgesic) and fever (antipyretic) but not inflammation
¨ Drug of choice for children
¨ Adverse effects
- Overdose (5 to 10 grams – 20 tablets) leads to fatal liver injury
- Susceptibility to liver toxicity in individuals with liver disease and alcohol use disorder
à NSAIDs (e.g. ibuprofen and naproxen)
¨ Relieves pain (analgesic), fever (antipyretic) and inflammation (anti-inflammatory)
¨ More effective than ASA in all the types of relief
¨ Adverse effects
- Gastric irritation (less than ASA),
- Skin rash
- Dizziness
- Blurred vision
- Fluid retention
· Antihistamines
à Use for treatment of allergy symptoms
à Are CNS depressants and therefore can interact with others
à Blocks histamine receptors which inhibit binding of histamine to its receptor; it decreases allergy symptoms
à First-generation agents
¨ Cause sedation and drowsiness
à Second-generation agents
¨ Less sedating and preferred agents
· Drugs for excess stomach acid
à Neutralizes or decrease stomach acid secretion
à Antiacids
¨ Neutralizes stomach acid secretion
¨ Systemic antiacids
- Given orally and absorbed by GI tract
- Can cause hypercalcemia or systemic alkalosis in high doses
¨ Non-systemic antiacids
- Given orally and not absorbed by GI tract
- Can cause decrease phosphate absorption, decrease in other drugs absorption and constipation
- Does not cause systemic alkalosis as it is not absorbed
à H2 receptor antagonist
¨ Decreases stomach acid secretion
¨ Normal case: Histamine receptors (H2 – different from allergy ones) activate which cause increase proton pump release of H+ and take K+
¨ With antagonist: Antagonist blocks H2 receptors which cause decrease proton pump release of H+
¨ Can cause skin rashes, headaches and confusion
à Proton pump inhibitors (PPIs)
¨ Decreases stomach acid secretion
¨ Permanently binds to proton pump hence inhibiting acid secretion by 90%
¨ Most effective at suppressing acid secretion
¨ Can cause diarrhea, headache and abdominal pain
· Decongestants
à Congestion is caused by dilation of blood vessels which causes fluid leakage from the vessels and into the extracellular space
à Causes constrictions of blood vessels, preventing accumulation of fluid
à Best are a nose solution with 0.5% phenylephrine or oral tablet of pseudoephedrine
à Can cause chronic rhinitis (congested runny nose) and irritation after long term use
· Cough suppressants
à Cough is a complex event involving signals from the bronchioles which is process the cough center in the medulla of the brain
à Productive cough (clears the airways of mucous) should not be suppressed
à Non-productive cough (dry cough – no mucous) should be suppressed
à Centrally acting cough suppressants
¨ Blocks the processing of information to the brain hence reducing frequency of cough (e.g. Dextromethorphan HBr)
à Peripheral cough suppressants
¨ Blocks the nerve endings in the throat and bronchioles hence inhibiting the stimulus of cough
· Sleeping aids
à Helps an individual fall asleep
à Melatonin is common
· Laxative
à Increase excretion of soft-formed stool by increasing gut motility or hydration of the stool
à Stimulants
¨ increases gut motility
¨ increases secretion of mucous, water and electrolytes into the intestine
¨ can cause cramping, water and electrolyte imbalance
à Bulk-forming and osmotic
¨ Bulk forming agents maintain the stool soft because it binds to water to form a viscous solution
¨ Osmotic agents draw water into the stool
¨ Are preffered laxatives
¨ can cause water and electrolyte imbalance
· Antidiarrheals
à Used to control diarrhea
à Absorbents
¨ Add bulk to the GI tract and may absorb toxins
¨ Used to control acute symptoms of diarrhea that will resolve on its own (self-limiting diarrhea)
à Loperamide
¨ Synthetic opioid that does not penetrate into the CNS
¨ Inhibits the gut motility by acting on opioid receptors
¨ Effective in mild to moderate diarrhea with no fever or blood (Non-infectious travelers diarrhea)
¨ Drug of choice
· Hydrocortisone cream
à Topical anti-inflammatory agent composed of 0.5% or 1% hydrocortisone
à Used for poison ivy, poison oak and any inflammatory condition that can be treated topically
· Sunscreen
à Best at broad-spectrum with a SPF of at least 30
à Chemical
¨ Contains compounds that absorb UV rays before they get to the skin
à Physical
¨ Contains minerals that block and scatter UV rays before they can enter the skin
o Other drugs with OTC preparations
· ASA and Oral anticoagulants
à May produce bleeding
à Both prevents platelets from coagulating and hence stop a cut from bleeding
· Antiacids
à Can interfere with the absorption of other drugs
o Herbal drugs
· Refers to lants or plants part that are used to prevent or treat illness or improve health
· General public
à Desire from the public to use natural products that they believe are safer than conventional medications
· Manufacturers and retailers
à They promote these products for financial gain
· Brief history
à Before the 1940s, medicine depended largely on natural products
o Classifications of medicinal/herbal products
· Allopathic medicine
à Drugs used by the mainstream medicine
à Drugs have a drug identification number (DIN) from health Canada
à Has undergone full testing for safety and efficacy
· Herbal medicine
à Refers to plant products being sold to treat a condition and do not have a DIN
à Often lacks phase 3 clinical trial data
· Phytopharmaceuticals
à Refers to drugs obtained from plants which are purified and used at therapeutic doses with scientific evidence and documented toxicity
· Allopathic phytopharmaceuticals
à Refers to drugs obtained from plants that are purified and meet all the requirement of a drug
o Problems associated with herbals: lack of efficacy and safety data
· Lack of randomized trials evaluating the safety or efficacy of herbals
o Problems associated with herbals: Interpreting the literature
· Literature aimed for the public overstates the efficacy of herbal preparations
· Literature has to be interpreted carefully
o Additional problems associated with herbals
· Lack of standardization
à Legislation should address the problem of quality control
· Intentional adulteration
à Addition of substances other than the herbal
· Differing global standards
à Manufacturing facilities in other countries may not use the same standard used in Canada
· Drug interaction with allopathic medicine
o Overview of herbal drugs
· St. John’s Wort
à Likely effective for mild to moderate depression
à Recommended to treat mild to moderate depression and to heal wounds
à Has hypericin and hyperforin which have antidepressant activity
à Less effective than other antidepressant but more effective than the placebo
à Toxicities
¨ A syndrome has been associated with the herb that manifests as confusion, agitation, shivering, fever, sweating, diarrhea, muscle spasms, and tremor
¨ Can cause phototoxicity (if drug goes on the skin and the skin goes in contact with the sunlight, can cause skin reaction)
· Aloe Vera
à Possibly effective for cold sores and minor skin irritations
à Recommended for healing of wounds and burns
à Active ingredients are mannans and anthraquinones
à Toxicities
¨ If ingested, diarrhea
· Devil’s Claw
à Possibly effective for osteoarthritis and back pain
à Recommended for a number of ailments ranging
from migraine to kidney disease; mainly used for the
treatment of inflammatory condition
à Active ingredient believed are the iridoid glycosides.
à Needs further research for effectiveness
à Toxicities
¨ Diarrhea
· Panax Ginseng
à Possibly effective for thinking and memory, erectile dysfunction, multiple sclerosis related fatigue, sexual arousal and reducing the risk of contracting influenza
à Active ingredients are ginsenosides and panaxosides
à Toxicities
¨ Headache
¨ High blood pressure
¨ Bleeding
¨ Raise insulin levels
· Echinacea
à Possibly effective for the common cold
à Recommended for treatment for wound healing and as a anti-inflammatory agent
à Active ingredients are echinacein, cichoric acid, and caffeic acid
· Valerian
à Possibly effective for mild insomnia
à Recommended for treatment of anxiety and panic attacks
à Active ingredients are valepotriates
à Toxicities
¨ Liver toxicities
o Vitamins
· Substance essential for the maintenance of normal metabolic functions but is not made by the body (except vitamin K and D)
· Water-soluble
à Vitamin C and eleven vitamins in the B group are water-soluble
· Fat soluble
à Vitamins A, D, E, and K are fat-soluble
o Vitamins as supplements
· Need for increase nutrition
· Absorption disturbances
· Inadequate nutritional intake
o Approaches to vitamin therapy
· Nutritional approach
à Individuals that selects a diet aimed at supplying the recommended dietary
allowance (RDA) for each vitamin
· Megavitamin approach
à individuals ingest vitamins in excess of the RDA
o Overview of vitamins
· Vitamin A
à Food sources
¨ Only found in animal products (e.g. liver, milk fat and egg yolk)
¨ Carotene can be converted to vitamin A by the body
à Functions
¨ Growth and development
¨ For normal structure of the mucous membranes
and epithelial cells
¨ Is constituent of a complex molecule in the rods of the eye, called rhodopsin, which is required for night vision
à Use and effects
¨ Administered in periods of increased requirement (e.g. infancy)
¨ Vitamin A deficiency can result in a delay of growth and development, night blindness and drying of the surface of the eye and bad changes in cells lining the bronchioles
¨ Excessive vitamin A intake can result in dry itchy skin, vomiting, headache, and an enlarged liver and spleen
· Vitamin D
à Food sources
¨ found in meat, fish, and mushrooms
à Functions
¨ increases the absorption of calcium and phosphate from the intestine, which is needed for new bone formation
¨ involved in the regulation of blood calcium level and in the removal of calcium from older bone
à Use and effects
¨ Used in the prevention of osteoporosis
¨ Vitamin D deficiency can result in decreased absorption of calcium and phosphate from the intestine, and therefore a decreased blood calcium level
¨ Vitamin D deficiency can also lead to the removal of calcium from bone
¨ Excessive vitamin D intake can result in elevated calcium levels in the blood.
¨ Excessive vitamin D intake may also cause excess removal of calcium from bone and fatigue, nausea, vomiting, diarrhea, and impaired kidney function
· Vitamin E
à Food sources
¨ present in vegetable oils and some green leafy vegetables as tocopherols
à Functions
¨ role as an antioxidant
¨ protects cells in the cardiovascular system and other tissues from the damaging effects of free radicals.
à Use and effects
¨ Useful in the treatment of premature babies with an uncommon
type of hemolytic anemia
¨ Vitamin E deficiency may occur in conditions of a malabsorption syndrome
¨ Excessive vitamin E intake can inhibit platelet aggregation
· Vitamin B12 (cobalamin) & vitamin B9 (Folate and Folic Acid)
à Food sources
¨ Vitamin B12 is found in meats and dairy products
¨ All food groups are rich in folate, however, fresh green vegetables, liver, and yeast are especially high in folate
à Functions
¨ Folic acid and vitamin B12 work together in the synthesis of red blood cells
à Use and effects
¨ Absorption of vitamin B12 decreases with age
¨ The RDA for folic acid increases in pregnant women to help prevent deficiencies that may lead to neural tube defects
¨ Alcohol misuse or malabsorption syndromes can lead to deficiencies of both vitamin B12 and folate.
¨ Certain drugs (e.g., oral contraceptives, some anticonvulsants, and folate antagonists used in cancer chemotherapy) may result in folate deficiency
· Vitamin C
à Food sources
¨ found in fruits and vegetables
à Functions
¨ contributes to the framework that holds cells together, is required for the formation of bone and teeth, functions as an antioxidant, and helps absorb iron
à Use and effects
¨ used to prevent and treat scurvy
¨ Excessive vitamin C intake can result in diarrhea, formation of kidney stones, and rebound scurvy.
o Food additives
· substances that are added to food to improve the appearance, texture, and storage
of food
· include substances added during the processing of food or added to improve nutritive value (e.g., addition of vitamins and minerals to certain foods)
o Classes of food additives (broad - intentional and unintentional)
· Intentional
à substances that are added to food to improve the appearance, texture,
and storage of food
· Unintentional
à Substances added inadvertently because of the growing, manufacturing, and storage processes of food. (e.g. contaminants)
o Food additives regulation in Canada
· conducted by the Food and Drug Regulations under the authority of Health Canada. All permitted food additives and their conditions of use are listed in the Lists of Permitted Food Additives
· Reasons why it is so regulated
à Food additives are consumed without our knowledge
à are taken for a lifetime by the entire population
à Healthcare professionals are not involved with food additives and are, therefore, not available to give advice regarding food additives
à Young children are exposed during vulnerable periods
à are not essential for life
o Determining toxicity of a food additive
· risk/benefit ratio of additives must be determined
· technique used to determine risk/benefit is to study the toxicity in animals and then extrapolate the results to humans but there are limits to the technique
à Exposure
¨ extent of exposure in humans is difficult to replicate in animals; humans is lifetime whilst animal is 1-2 years
à Assumption of risk
¨ The acceptable human dose is taken as 1/100 or 1/1000 of the maximum no-effect dose in animals
¨ assumption made is that studying high doses in animals will mimic low-dose, lifetime exposure in humans.
o Food additives as carcinogens
· If compound found positive, compound is usually not allowed as a food additive
o Rational use of food additives
· Function
à Use of additives is justified if they enhance or maintain the quality or acceptability of food
· Quantity
à Additives should be used only in quantities sufficient to obtain stated ends
· Purity
à should be pure
· Toxicological evaluation
à should be undertaken. This information should be gathered and utilized to determine potential risk of the food additive
· Special groups
à Should be considered (e.g. heavy drinkers and cobalt chloride - Risk assessments determined that individuals would need to consume 24 beers every day for long periods of time to receive a toxic dose of cobalt chloride.)
o Classes of food additives
· Flavouring
à Types of flavouring agents
¨ flavouring agents and enhancers, essence of smoke, and synthetic flavours.
à Evaluation
¨ difficult to evaluate such a large number of substances
à Toxicity
¨ very few flavourings have demonstrated toxicities (e.g. flavour
enhancer monosodium glutamate (MSG)
· Colours
à organic dyestuffs added to give food an appetizing appearance.
à most common allergic reaction is to tartrazine, a yellow food colour
· Texture agents
à added to improve or impart a specific texture to a product.
à Silicates are added to flour and flour products to keep them free flowing
à Emulsifying and thickening agents (e.g., gums, agar) are added to a number of frozen foods
· Preservatives
à Allows for the delivery of food to distant destinations and ensures the appropriate quality of the food for the consumer
à Antibacterial
¨ Smoke
¨ Antibiotics
¨ Sodium nitrite
à Antioxidants
¨ prevent the oxidation and, thus, rancidity and discolouration of foods.
¨ Water-soluble
- are added to foods to reduce the oxidation of carbohydrates
(e.g., browning of fruit). The agents most used are ascorbic and citric acid
¨ Lipid-soluble
- are added to foods to prevent fats from becoming rancid (i.e., oxidizing).
· Sweeteners
à Sugar is the most common
à Saccharin
¨ first artificial sweetener developed and was added to numerous products. The use of saccharin was restricted in Canada based on studies that demonstrated a potential for it to cause
cancer.
¨ Health Canada Food Directorate removed the restriction, allowing saccharin to be in tabletop sweeteners
à Aspartame
¨ Replaces Saccharin
¨ individuals with a condition known as phenylketonuria cannot tolerate phenylalanine, one of the amino acids in aspartame