Final Exam Flashcards
1
Q
Explain the history behind drug use and development
A
Drugs have been used since before recorded history as shown evidenced by early written records from China and Egypt which provide a glimpse into agent traditions of drug use.
Ancient Civilizations: healers existed historically in all traditions and cultures of ancient times.
- Greece: Theophrastus wrote a textbook on the therapeutics that included opium, obtained from the opium poppy (palaver somniferum). Serturner, A pharmacist in Germany, isolated crystals of morphine from opium and tested the pure substance on himself and three companions to discover its pain relieving capabilities. Opium contains two important substances which are 10% morphine and 0.5% codeine. The name morphine comes from Morpheus, god of dreams. It can relieve pain a very great intensity. Coding is also widely used for pain relief and does it constitute of Tylenol-3.
- Egypt: Egyptian history was recorded on papyri. One of these papyri, the Ebers Papyrus, why is a textbook of drug use for medical students containing many true observations, particularly on purgatives, which are drugs used to cause bowel movements. One of the drugs recommended was senna which is still used today.
- China: Shen Nung classified all drugs according to taste. For example, Ma Huang was classified as a medium drug widely used for coughs and influenza. And the modern error, ephedrine has been isolated from Ma Huang to treat asthma and produce a derivative for decongestion.
Poisons: The use of poisons has resulted in the discovery of drugs still used today. All substances are poisons, there’s none which is not a poison, the right dose differentiates a poison and a remedy.
- Curare: A plant-derived drug that was historically used by indigenous people in various regions of the Amazon rainforest. As a poison, arrows were dipped in curare to use as a poison for hunting as it acted upon voluntary muscles causing paralysis and eventually death by respiratory paralysis. As a drug it was used by anaesthetists during surgery for muscle relaxation. Newer derivatives are still used by anesthetists today
- Ergot: A poisonous fungus that grows on the heads of rye, particularly during wet seasons. In the middle ages, ergot was ground together with rye, finding its way into bread. This resulted in terrible epidemics that killed over 20,000 people in one region of Russia. As a poison, ergot targets the nervous system resulting in symptoms of mental frenzy, hallucinations, and convulsions. It affects the cardiovascular system by causing constriction of the blood vessels that lead to the fingers, toes, and limbs. In the reproductive system, it causes violent contractions of the uterus. In the early 16th century, midwives used this to hasten labor. However, if not used appropriately it can result in death. As a drug, the ergotamine derivative is useful in treating migraines by preventing the pulsation of blood vessels. Ergonovine was used to Hazenbirth, but now is used to arrest uterine bleeding after childbirth.
Religion: in ancient societies, traditional healers acted as both physicians and priests, resulting in therapy being heavily influenced by religion and magic. In most parts of the world, plants containing intoxicating substances were used by traditional healers to alter the state of consciousness and facilitate communication with their gods. An example of this is peyote from the peyote cactus which was widely used to achieve a mystical state linked to spiritual and realistic use. It contains a potent substance, mescaline, which causes hallucinations, a feeling of well-being, and distortion similar to LSD.
2
Q
What are drugs? What are the two major categories of drugs?
A
A drug is any substance received by a biological system that is not received for nutritive purposes, and which influences the biological function of the organism, meaning that chemicals, biological agents, and herbal products are all considered drugs.
About 25% of drugs used today are derived from plant sources where the active substances are purified and potentially modified to be either more effective or less toxic.
Drugs acting on the brain: Drugs that act on the brain alter the normal chemical signalling in the brain.
-LSD: Albert Hoffman tried to synthesize improved pharmaceutical products based on components of ergot but instead synthesized LSD, similar in chemical structure. The discovery of the psychedelic effects of LSD supported the idea that mental illnesses might be due to the production of potent substances in the brain that could produce psychic disturbance. This research stopped in the 1970s and the drug was classified as a controlled substance. Recently, however, evidence indicates that derivatives of LSD might be effective in treating depression, anxiety, and addiction.
Drugs acting against infectious disease: an infectious disease is any disease caused by an organism such as bacteria, viruses, fungi, or parasites.
1900: Organoarsenicals - arsenic and organic molecules can be selectively bound to parasites. This idea was applied to infectious disease to cure syphilis.
1930: Silva Drugs - Synthetic drugs for the treatment of bacterial disease as anti-bacterial compounds.
1940: Penicillin - During the second world war, penicillin was used in therapy of gram-positive bacterial disease.
1950: Streptomycin - antibiotic for tuberculosis and gram-negative bacterial diseases.
3
Q
What is the process to drug development?
A
1) Drug discovery: Basic drug research is done through identification of the target, where a target for a new potential drug such as a receptor is found and it’s binding compound is identified and studied to determine pharmacological effects at the molecular, cellular, organ, and animal level; and studying the target, where the binding compound shows promise as a lead compound and enters detailed studies for safety and efficacy.
2) Pre-clinical studies: after the target has been discovered and studied, drugs enter pre-clinical studies which are conducted prior to testing in humans in range from molecular to tissue and animal studies. Pre-clinical studies can be pharmacology studies, which determine the detailed mechanism of action of the new drug, or toxicology studies, which determine the potential risks or harmful effects of the drug. These studies look at acute toxicity, chronic toxicity, and effects of reproductive, carcinogenic, and mutagenic potential.
If a manufacturer wants to test a new drug on humans, three steps are required before they can proceed. This includes proof of safety and efficacy, which must be submitted, from several animal species, to the government regulatory agency in the particular country concerned (Canada - Health products and food branch, USA - FDA), methodology, where the methods of the proposed clinical trial of humans is required, and investigation, where the submission is evaluated by qualified scientists that can give permission to highly qualified investigators like clinical pharmacologists to begin investigation of the drug in humans.
3) Phase 1 clinical trial: carefully evaluate the absorption, distribution, illumination, and adverse effects of the new drug. These trials test one or two doses of the drug to determine the tolerability on a limited number of healthy volunteers (20 - 80). The efficacy of the drug is not assessed.
4) Phase 2 clinical trial: determination of whether the drug is effective in treating the condition for which it is recommended in a limited number of patients with the disease (100 - 500). They also pay careful attention to the safety of the drug.
5) Phase 3 clinical trial: often called a randomized controlled trial‘s (RCT), are the main studies for licensing and marketing of the drug. These studies determine how safe and effective the drug is compared to no treatment or the current recommended therapy. It is tested on a larger number of people to obtain information about the drug in a diverse population. They are also conducted at centres in many cities, as one centre usually does not have the required number or diversity of patients. These trials are the most expensive part of drug development costing upwards of 50 million dollars.
6) Health Canada’s Review: the manufacture will submit to the regulatory body a new drug application containing detailed results of clinical trials. The results are again reviewed by regulatory scientists and, if deemed effective and the toxicity is acceptable, it will be granted approval.
7) Manufacturing: Manufacturers come up with a drug name and a brand name for the drug because chemical names are too complex for general use. Generic names are given to drugs that show promise. Around the same time that that is done, the manufacturer will apply for a patent with a brand name for the drug giving the company exclusive rights to market the drug for 20 years. That 20 year life begins when the patent is filed during pre-clinical development phase, so the effective patent life is in the range of 10 to 12 years. After a patent on a drug expires, other manufacturers can make copies of the original brand-name drug and sell it under their own brand name. The original brand-name drug and any generic versions will all contain the identical active ingredient gradient in the same amount and dosage form. These regulations are in place to ensure that all market of drugs are as effective as the original brand-name drug and or bioequivalent which is achieved by studying comparative bioavailability between blood levels after administration of the original and new brand-name drugs to healthy volunteers under controlled conditions.
8) Post market surveillance (Phase 4 clinical trial): The dragon is carefully watched even after being put on the market. If unexpected changes are seen in patients, there are changes to the drug labels to add warnings or advice about how to take the drug.
4
Q
What is the design of phase 3 clinical trials?
A
Please three clinical trials can be divided into three large stages:
1) Enrollment: the people the new drug is tested on have to carefully be defined. The target population is the group of patients for whom the drug is intended. The study population is a subset of the target population that meets all required criteria. Two factors influence who can be included in the study population. This includes inclusion/exclusion criteria, which find characteristics of the patients to be included in the study to determine who is eligible for the trial in order to illuminate variables other than the drug under study that may influence results well also representing the target population. Severity of disease is important to consider and other present diseases as well. However, comorbidities are often included to be representative of the target population. Consent is the other criteria. Before a person can participate, informed consent must be obtained where the patient signs a document written in non-scientific language that outlines the purpose, procedures, and all potential risks and benefits that may occur. These consent documents are reviewed by an independent institutional ethics review board and at any time, or participant can revoke their consent.
2) Treatment: Studies are conducted in a double blind manner where neither the investigator nor the study subject is aware of the treatment the subject is assigned to. This is done to avoid any bias that could occur if the subject believes the drug will work or if the investigator is expecting positive results. Patients recruited for study are assigned to experimental treatment groups or a control group. To ensure these groups are similar, patients are assigned by randomization which ensures that confounding variables are distributed equally between experimental and control groups, removing potential bias. The efficacy and safety of the experimental drug has to be compared to a controlled drug which can either be placebo or a gold standard drug. A placebo does not contain any active drug but has identical in appearance, color, taste, and administration. Placebos can be very efficient in sick and anxious patients. A gold standard drug is a drug acceptable by the medical community has the best available treatment for that disease at that time. If a gold standard drug is a variable, that is what the control group receives so that all patients are receiving some sort of treatment.
3) Results: to determine if the experimental treatment was more or less effective than the control, and outcome of the trial which measures how much the drug worked in each participant is measured and compared in a reliable and objective manner. Factors which can influence the interpretation of a clinical trial must be considered when analyzing results. These include compliance, where patient compliance is tested by having participants bring back orally administered drugs or checking that the nurse signed off on intravenous drugs, quality of life, where the impact on patient quality of life is assessed, and statistics, where the measured outcome is compared to the measured outcome for the control drug using statistics to determine whether the difference is real or by chance.
5
Q
What are drug targets?
A
Drugs are designed to interact with a selected target in the body which is commonly a receptor, but there can be other targets in the body.
Receptors: A molecule or complex of molecules on the outside or inside of a cell that has a regulatory or functional role in the organism. Many copies of the same receptor exist on or within a single cell, and many of the same cell types exist in an organ that all work together. This means thousands of the same receptors are within an organism. Receptors are normally bound to an activated by endogenous ligands, which are substances found in the body such as hormones and neurotransmitters. The location of receptors determines where a drug will act and whether the response that results is beneficial or detrimental.
Chemical Reactions: Commonly used antacids neutralize stomach acid through a simple acid-base neutralization reaction.
Physical Chemical Forces: Cholestyramine works by chemically binding the bile acids in the gastrointestinal tract to prevent reabsorption and increase the elimination of bile salts that are used to make cholesterol.
Most drags mimic or block the effect of a ligand at a receptor to stimulate the receptor as an agonist, or block the response as an antagonist.
6
Q
How is drug response considered?
A
The intensity of the pharmacological effects produced by a drug increases in proportion to the dose. This is called the dose response relationship, reduce is defined as the amount of drag taken. To compare the effects of two different drugs you must consider the quantity, frequency of use, user demographics, and environmental factors.
For a drug to achieve its desired response, many receptors need to be activated at once. At low doses, very little response is observed as not many receptors are activated. The dose of the drug increases more receptors are activated until the desired response is seen. This is where a threshold exists. Once the threshold is reached a small increase in does result in a large increase in response. The response will increase until reaching a maximal effect where increasing the amount of drug will have no increase in therapeutic response. These can be seen on a dose response-curve.
7
Q
Define efficacy and potency
A
Efficacy: the maximum pharmacological response that can be produced by a specific drug in that biological system.
Potency: the dose of drug required to produce a response of a certain magnitude, usually 50% of the maximum response for that drug.
8
Q
What is therapeutic range?
A
Therapeutic range is the range of doses that achieve the therapeutic effect by keeping the blood concentration above the minimum which produces the desired response, but below the concentration that produces a toxic response.
9
Q
What must happen for a drug to reach its desired effect?
A
To produce its desired effect, a drug must reach the cellular site of action at the right concentration, exert it’s a fact, and then be removed from the body.
10
Q
Define pharmacokinetics
A
Pharmacokinetics is a term that refers to the movement of a drug into, through, and out of the body.
11
Q
What are the different routes of administration?
A
Topical: drugs are applied directly to a particular place on or in the body by administration on the skin, through the skin, or through inhalation. Drugs applied to the skin treat mild to moderate severity conditions such as eczema, acne, and infection. These drugs, applied for a local affect, can be absorbed and produce a systemic affect. Transdermal drug delivery is the application of a drug to the skin for absorption into the general circulation for a systemic effect. This method of delivery is convenient, delivers a steady drug supply for several days, and bypasses the enzymes of the stomach, intestine, or liver. Drugs administered by inhalation can be rapidly absorbed from the lungs for local and systemic effect. An advantage of inhalation is that the quantities of drugs are smaller than that required for a systemic effect, thus avoiding toxicity associated with oral administration. A disadvantage is that the method requires proper use by the patient.
Enteral: administration via the gastrointestinal tract either through the mouth or an artificial opening. This administration enters the blood through the gastrointestinal tract then is delivered to the liver where enzymes decrease the amount of active drug left to enter the general circulation. This is called the first pass effect. These can be administered by mouth which is commonly used, most convenient, least expensive, and non-invasive, but absorption is variable due to differences in intestinal motility and disease. They can also be administered into the rectum for a systematic or local effect in patients who are nauseated or vomiting. An advantage is that the digestive enzymes of the stomach are bypassed but a disadvantage is that there is only a limited number of medication available for rectal administration and absorption from the rectum mucosa is slow, incomplete, and variable. Sublingual and buccal administration bypasses enzymes of the stomach, intestines, and liver but not all drugs are adequately absorbed this way and if the drug is swallowed, it just behaves as if it were taken orally.
Parenteral: administration bypassing the gastrointestinal tract through intervenous, intramuscular injection, or subcutaneous injection. In intravenous administration, the drug is placed directly into the blood and has immediate effects for drugs that are poorly absorbed, provided that they can be made into a solution in purified water. It must also be considered that the response is irreversible and administration require significant human resources and sterility. In intramuscular administration, the drug is injected deep into a muscle where the volume of drug is limited to 2 to 3 mL in an adult. In subcutaneous administration, the drug is injected into the deepest layer of the skin allowing for the modification of drug preparation to control the timing of release of that drug from the injection site.
12
Q
Why is there not always a good relationship between the dose of drug and the concentration of drug in the blood?
A
During absorption, not all of the drug ends up in the blood. This is because bioavailability differs between drugs.
13
Q
Define bioavailability
A
Bio availability is defined as the fraction of an administered dose that reaches the systemic circulation in an active form.
14
Q
What are the four processes involved in pharmacokinetics?
A
1) absorption: The movement of a drug from the site of administration into the blood. For a drug to be absorbed and distributed two sites of action, it must be able to cross biological membranes. This can be done by diffusion through aqueous pores across a concentration gradient, diffusion through lipids dissolving into the lipid membrane and passing down a concentration gradient, or active/carrier mediated transport where carrier membrane complexes grasp the molecule move through the membrane and release the molecule on the other side.
2) distribution: The movement of a drug from the blood to the side of action and other tissues. Most drugs reach all tissues and organs regardless of the target site of action. The concentration of a drug at the site of distribution is an equilibrium with its concentration in the blood. The rate at which drugs distribute in and out of a particular organ depend on the blood flow to that organ. After administration, drug distribution to the target site allows a response to occur. However, once the concentration begins to reach equilibrium, moving into other tissues and organs, the concentration at the active site begins to decrees and the effect of the drug has been terminated.
3) metabolism: also known as bio transformation, the conversion of a drug to a different chemical compound in order to eliminate it. The products of metabolism are called metabolites which are usually devoid of pharmacological action. To be eliminated from the body by the kidneys, a drug must be water soluble so most drugs are converted to more water soluble compounds. The liver is where most biotransformation reactions occur, but some metabolism occurs in the kidneys, intestines, lungs, skin, and most other organs.
- Phase 1: functional groups are added or unmasked on the drug to prepare it for the addition of a large water soluble molecule.
-Phase 2: Add a large water soluble moiety, usually glucuronic acid or sulfate, making the metabolite water soluble for excretion by the kidney.
4) excretion: includes moving the drug and it’s metabolites out of the body through all bodily fluids.
-kidney: The majority of drugs are eliminated by the kidney. Drugs of sufficient water solubility will be excreted in the urine while lipid soluble drugs can be reabsorbed back in blood.
-G.I. tract: Some drugs are excreted in faeces after undergoing biotransformation in the liver.
-lungs: Volatile or gaseous drugs can be excreted by the lungs.
-breast milk: Drugs are often found in the breastmilk of nursing parents which can expose nursing infants to a therapeutic or toxic dose of the drug.
-saliva and sweat: drugs can be found in saliva and sweat, often in the presence of drug misuse.
15
Q
What is P450?
A
P450s are enzymes capable of biotransforming drugs. They are in most tissues, but are present in high concentrations in the liver. The cytochrome P450 family of enzymes biotransforms the vast majority of clinically used drugs.
16
Q
Why is there variation of drug response?
A
As drugs undergo five events after administration including absorption, distribution, target interaction, metabolism, and excretion, there are many possible influences at any stage which can contribute to variability in the observed response among patients. Some examples include genetic factors, environmental factors, disease states, physiological states, and the presence of other drugs.
Genetic: variability exists in the receptors to which the drug binds and in the manner in which the body handles and eliminates drugs. The activity of enzymes involved in bio transformation can vary between individuals due to genes that encode for those enzymes. Some individuals are slow biotransformers and others are fast biotransformers.
Environmental: exposure to certain chemicals can increase enzymes in the liver responsible for biotransformation of drugs. This makes these people illuminate the drug more rapidly.
Other disease states: the presence of a disease state may alter the manner in which drugs are handled by the body.
Altered physiological states: as we age, we lose the reserve or redundancy in Nuro function and drugs have a greater affect than expected. Liver and kidney function also decrease with age reducing the rate at which elderly eliminate drugs. Another example is during pregnancy due to increased blood volume, cardiac output, and rate of renal excretion.
Other drugs present: when multiple drugs are taken together it is possible for one drug to change the biological effect of a second, leading to variability in drug response.
17
Q
What are the adverse effects of drugs?
A
An adverse drug reaction is defined as any effect produced by a drug in a patient that is not the intended effect.
Extension of therapeutic effect: occurs when there is too much of the drug in the blood (overdose).
Unrelated to main drag action: drugs can cause effects that are unrelated to the intended action like causing nausea. These may or may not be expected.
Allergic reaction: this is mediated by the immune system from an antigen-antibody combination which provokes an adverse reaction in the patient. These can be very mild or very severe.
Withdrawal an addiction: unwanted physiological and psychological effects of the drug can occur.
Teratogenesis: when a drug produces defects in a developing fetus.
Adverse biotransformation reaction: occurs when a drug is converted to a chemically reactive metabolite that combine to tissue components and cause tissue or organ damage.
18
Q
Why is it difficult to predict adverse drug reactions?
A
Rarity of occurrence: the toxic reaction may be rare, making it difficult to predict the adverse drug reaction.
Length of usage: toxic reaction my only appear after prolonged use.
Detect ability and animals: the toxic effect may not be detectible in animals and only appear once the drug is being tested in humans.
Time period specificity: the toxic affect maybe unique to a particular period in time.
19
Q
What is the therapeutic index?
A
Therapeutic index tells you how safe the drug is relating the dose of the drag required to produce a beneficial effect to the dose required to produce an undesirable or adverse effect. The higher the therapeutic index the safer the drug. When a drug has a low therapeutic index, it is more likely that toxicities will be observed. It is calculated by dividing toxic dose 50 by effective dose 50.
20
Q
What is toxic dose 50? What is effective dose 50?
A
TD50: dose of drug that is toxic in 50% of the population.
ED50: dose of drug that is effective in 50% of the population.
21
Q
Discuss drug-drug interactions
A
A drug to drug interaction occurs when one drug changes the pharmacological effect of a second. These can occur at many points during the drugs journey through the body.
Absorption: add drag can increase intestinal movement, speeding the passage of a second drug through the intestine and decreasing contact of the second drug with the intestinal wall, thereby decreasing absorption.
Metabolism: a drug can block the inactivation of a second drug in the liver, increasing the blood level and pharmacological effect of the second drug.
Excretion: a drug can facilitate the expression of a second drug by the kidney, decreasing the blood level and pharmacological effect of the second drug.
22
Q
Discuss drug-food interactions
A
Drag the food interactions involves interference of food with drugs taken concurrently.
Tyramine: found in well matured cheeses and a variety of other foods. It is capable of raising blood pressure and is broken in the liver by an enzyme known as MAO. One class of anti-depressant drugs are inhibitors of MAO, preventing tyramine from being broken down to inactive products. This causes the blood pressure raising effects of tyramine to be greatly intensified.
Grapefruit: alter the absorption of drugs by inhibiting enzymes that bio transform drugs, resulting in a greater amount of the active drug being absorbed. The higher blood levels of the drug can potentially lead to overdose.
23
Q
What is the cerebral cortex?
A
The cerebral cortex, also known as the cerebrum, is the largest part of the brain and is very rich in neurons. The overall functions of the cerebral cortex are: sensory and motor coordination, mental processes, intelligence, memory, vision, judgment, thought, speech, emotions, and consciousness. The neurons in the cerebral cortex can be stimulated or depressed by drugs.
24
Q
What is the limbic system?
A
The limbic system is a region of the brain that integrates memory, emotion, and reward. This area of the brain, together with the hypothalamus, controls emotion and behavior. The limbic system contains the dopaminergic reward centers, which are targets for commonly misused drugs and are associated with addiction.
25
Describe neurons
Neurons are the functional unit of the brain capable of generating and transmitting electrical signals. The brain contains about 90 billion neurons that differ from each other and shape and size. New neurons are generated continuously through neurogenesis and the connection between neurons is constantly reshape through neuroplasticity.
Dendrites: Short and can have highly complex branching patterns that function as receiving antenna for incoming information and except information through receptors located on the dendritic membranes. Upon receiving this information, and electric current is generated and directed down the neuron.
Cell Body: Also known as the soma, is the largest part of the neuron and contains the nucleus and surrounding cytoplasm. The cytoplasm contains abundant prepackaged neurotransmitters that can be secreted.
Axon: Single fibre that extends from the cell body and ends at the synapse. The axon continues to carry the incoming information away from the dendrites and cell body by way electrical impulses. This information is in passed onto subsequent neurons.
26
What is the synapse?
An electrical impulse Hass to be somehow communicated across the junction of one neuron to another to produce a further effect. The junction between two neurons is the synapse, and is the area where one neurons axon ends and another neurons dendrite or cell body begins.
27
What is synaptic transmission?
Synaptic transmission is the passage of a signal from one neuron to another. It can also be called neural transmission which is very rapid and usually chemical in nature, meaning a substance is quickly released that activates the next neuron. The chemicals that transmit a signal between two neurons are called neurotransmitters.
28
How are neurotransmitters removed from the synaptic cleft?
1) neurotransmitters, like norepinephrine, are taken back into the presynaptic neuron with transporters.
2) Neurotransmitters, like Acetylcholine, are broken down by enzymes.
3) Neurotransmitters, Like glutamine, are taken by glial cells.
29
What are the steps to synaptic transmission?
At the end of an axon an electrical impulse causes vesicles with neurotransmitters to fused with the presynaptic membrane, releasing neurotransmitters into the synaptic cleft. These neurotransmitters diffuse across the synaptic cleft and bind with the postsynaptic neuron receptors. Activation of receptors causes a change in the permeability of the postsynaptic membrane, allowing ions to move into the postsynaptic neuron, generating an action potential. This transmission continues through neurons until it reaches the target organ in order to cause and effect. The neurotransmitters in the synapse are terminated in one of three ways and the postsynaptic membrane can re-polarized before the next signal.
30
What are the neurotransmitters and receptors?
Glutamate: primary excitatory neurotransmitter in the CNS and is found in almost all neurons acting on a family of receptors called the glutamatergic receptors. Neurons that release glutamate, termed glutamtergic neurons are important for learning.
Catecholamines: dopamine and norepinephrine are catecholamines that are similar in structure. Dopaminergic pathways are involved in the control of hormonal systems, motor coordination, and motivation and reward. Alterations in dopamine mediated motivation and reward systems are involved in addiction. Norepinephrine can bind to a large number of receptor types, but the two main classes are alpha and beta. Activation of these receptors usually leads to excitation of the cell. This pathway is targeted by CNS stimulants.
GABA: gamma-amino butyric acid is the primary inhibitory neurotransmitter in the CNS. Neurons that release GABA and GABA receptors are found in high concentrations in the cerebral cortex and other areas. A number of CNS depressants enhance GABA receptor function.
Serotonin: in the CNS, hyperactivity of the serotonergic system is involved in anxiety, and hyperactivity has been implicated in depression. CNS stimulants act by increasing serotonin at the synapse.
Acetylcholine: produces an excitatory response in the CNS. Two types of cholinergic receptors include nicotinic receptors, which are found in certain regions of the brain and can be stimulated by acetylcholine or nicotine, or muscarinic receptors, Which are found in many regions of the brain and are involved in learning, memory, and cognitive function. Muscarinic receptors can be stimulated by acetylcholine or muscarine. Drugs that block the action of acetylcholine at these receptors produce amnesia. Lots of these culinergic Neurons is thought to be associated with Alzheimer’s disease.
Opioid peptides: three classes of endogenous opioid peptides exist which are enkephalins, endorphins, and dynorphin‘s. They have varying degrees of selectivity for the three opioid receptors mu, delta, and kappa. All opioids interact with these receptors.
31
How has historical use of chemicals contributed to the advancement of pharmacology?
Use of sulfa drugs led to the development of the first synthetic antibacterial compounds.
32
Phase 3 clinical trials can employ a placebo. What is a placebo?
A placebo is defined as an inert substance masquerading as a drug.
33
Drug A can only relieve pain of mild intensity. Drug B, on the other hand, relieves pain a very marked intensity. What can you conclude?
Drug B has greater efficacy than drug A.
34
 The ultra short duration of action of thiopental is due to what?
Redistribution of the drug from the brain to muscle and fat.
35
What should be considered when selecting the most appropriate dosage for a patient’s situation?
Differences in bioavailability need to be carefully considered.
36
Penicillin can combine with proteins to form antigens. And a small percentage of the population receiving penicillin experiences adverse effects. What is this adverse effect?
A drug allergy.
37
What is the primary excitatory neurotransmitter in the brain?
Glutamate
38
Describe chemical transmission.
Chemical transmission is due to the notion that most synaptic transmission is chemically mediated.
39
What is an SUD?
SUD, also known as substance use disorder, is defined and diagnosed by a number of criteria. A minimum of two criteria must be met to be classified as having a mild SUD. The more criteria met, the more severe the SUD.
40
What are the criteria of an SUD?
Social impairment: the individual fails to fulfil major roles and has persistent social or interpersonal problems where social, occupational, or recreational activities are given up or reduced.
Risky use: the individual may use the substance in physically hazardous situations or use the substance despite physiological or psychological problems.
Impaired control: The individual may have persistent craving for the substance
Withdrawal: The individual may experience a withdrawal syndrome after stopping use of the substance.
Tolerance: the individual may develop tolerance to the substance.
41
What is addiction?
Addiction is a state in which stopping or abruptly reducing the dose of a given drug produces non-physical symptoms.
42
What is the hypothesis used to explain addiction?
The dopamine hypothesis explains addiction through effect on reward systems and dopamine increase. It suggests that misused drugs increase dopamine in the reward systems of the brain. These dopaminergic systems are responsible for natural rewards and stimulus related rewards, so drugs associated with addiction caused exaggerated increase in dopamine, altering brain communication.
43
What are the three characteristics of addictive drugs?
Increase dopamine: substances that increase dopamine in the brain reward systems including CNS stimulants, opioids, alcohol, and cannabis.
Produce novelty: substances that produce a novel feeling including LSD, and ecstasy.
Reduce anxiety: substances that reduce anxiety including CNS depressants like benzodiazepines and barbiturates.
44
What is drug withdrawal?
Drug withdrawal is a physiological state produced by repeated administration of a drug that causes withdrawal syndrome when the drug is discontinued or the dose is decreased. The severity of withdrawal syndrome increases with the speed of drug withdrawal, as the biological processes that accommodate to the presence of the drug do not have time to reverse themselves.
Withdrawal symptoms are usually opposite to the effects of a drug. For stimulants, withdrawal symptoms include sleepiness, muscle pain, anxiety, tremors, low mood, suicidal ideation‘s, and cardiovascular problems. For opioids, withdrawal symptoms include sweating, muscle aches, agitation, diarrhea, abdominal cramping, and vomiting.
45
What is drug tolerance?
Drug tolerance is expressed as a shortened duration of action and decreased magnitude of effect. The extent and rate of tolerance is specific for each drug. Drug tolerance can also be reversible among drug discontinuation.
46
What is cross tolerance?
Cross tolerance occurs between pharmacologically similar drugs. It is the resistance or tolerance to one drug because of the resistance or tolerance to a pharmacologically similar drug.
47
What factors influence SUD?
Genetic factors: predispose an individual to SUD
Pre-existing disorders: individuals with major affective disorder, anxiety disorder, or schizophrenia are hire at risk for SUD
Environmental factors: environments can increase the likelihood of drug missuse and SUD. These include family dynamics, trauma, and social groups
Developmental factors: individuals are more vulnerable during certain developmental time frames like adolescence and early adulthood
48
What is harm reduction?
Harm reduction is an approach to prevent negative consequences of substances and improve health without judgement or discrimination. The goal is to decrease morbidity, mortality, lost productivity, apprehension of children, and criminal activity.
49
What is Misuse potential?
Misuse potential is the tendency of a drug to be misused. It varies from drug to drug, as well as from individual to individual.
Nature of the drug: pleasurable affects produced by a drug increase the probability that the drug will be taking again.
Route of administration: drugs administered by routes that give rapid absorption and a facts have a greater potential for misuse.
Amount of use: the greater the dose and frequency, the greater the potential for development of tolerance, withdrawal, and addiction.
Availability: the more widespread a drug, the more likely it will be misused.
Inherent harmfulness: if a drug is perceived to be a serious risk to life and health, it will not be used even if widely available.
50
Which class of drugs is thought to result in addiction but not withdrawal?
Hallucinogens
51
What are amphetamines?
Amphetamines are drugs of widespread missuse and are controlled substances. These include amphetamine, dextroamphetamine, and methamphetamine. They are synthetic organic compounds that are structurally similar to the neurotransmitters norepinephrine and dopamine. amphetamines can be synthesized readily, resulting in illicit manufacturing where the purity is variable and may contain side products of the chemical reaction, unreacted chemicals, and filler agents.
Methylphenidate (Ritalin): used to treat attention deficit hyperactivity disorder (ADHD)
MDMA (ecstasy): A derivative of methamphetamine that fosters the feeling of intimacy and empathy while improving intellectual capacities. It is neurotoxic, causing neuronal damage and death.
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What are the effects of amphetamines?
Amphetamines affect the CNS by:
1) Decreased threshold for transmitting sensory input to the cerebral cortex, leading to CNS excitation.
2) A feeling of euphoria and reward.
3) Temperature regulation and feeding centre modifications leading to appetite suppression.
4) An increase in aggressive behaviour in mood swings.
Increased CNS excitation will lead to increased alertness, a feeling of power, reduced fatigue, and increased responsiveness. However, it also results in increased heart rate and blood pressure.
Short term effects: chest pain, heart attack, cardiovascular collapse, increased respiratory rate.
Long-term effects: chronic sleeping problems, poor appetite, anxiety, psychosis, aggressive behavior, abnormal cardiac rhythm, and elevated blood pressure.
Overdose: seizure, high fever, or stroke.
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What are the therapeutic uses of amphetamines?
Amphetamines, like Methylphenidate, can help treat narcolepsy, a chronic sleep disorder, or ADHD, a disorder consisting of hyperactivity and difficulty controlling attention. Amphetamines improve attention and control, enhancing task completion and performance.
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How are amphetamines most commonly taken?
Amphetamines are typically taken orally, injected, or are smoked. However, occasionally they are sniffed or snorted.
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Discuss the potential for misuse and SUD of amphetamines.
The misuse potential is extremely high as amphetamines produce euphoria and water soluble salt forms allow for large doses that are readily injectable for a rapid response. The inherent harmfulness does not appear to be a deterrent to misuse.
Tolerance: develops to the euphoria and mood elevating effects, the anoretic effects, the cardiovascular and respiratory stimulatory effects, and the lethal effects of the drugs. However, it does not develop to therapeutic effects or drug induced psychosis.
Withdrawal: cessation of use results in mood depression that may be profound, prolonged sleep, appetite, lack of energy, and fatigue.
Addiction: amphetamines are self administered to produce euphoria and abrupt awakening. These effects act as rewards that give a craving sensation for the effects.
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What is cocaine?
Cocaine is classified as a local anaesthetic and a CNS stimulant. It is one of the most popular recreational drugs as a narcotic. Cocaine is almost indistinguishable from amphetamine and it’s a cute effects and toxicity. It has a shorter duration of action, usually less than an hour, and is commonly sniffed or smoked.
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How does cocaine act in the body?
Cocaine causes generalized CNS stimulation by inhibiting the active reuptake of dopamine and serotonin, increasing the concentration of these neurotransmitters in the synaptic cleft to increase the activation of postsynaptic neuron receptors.
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What is the therapeutic use of cocaine?
Cocaine is used as a local anaesthetic for the mouth and throat, but is rarely used as there are better local anaesthetics that do not have associated potential for misuse and SUD.
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What are the long-term effects of cocaine?
Toxic psychosis, paranoia, hallucinations, impaired sexual function, permanent brain damage, high blood pressure, irregular heart rhythm, and changes to nasal mucosa.
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Discuss the potential for misuse and SUD of cocaine.
Cocaine has one of the highest misuse liabilities due to powerful euphoria which can be rapidly reached by injection or smoking the freebase. The inherent harmfulness does not appear to deter misuse.
Tolerance: develops toward the mood elevating affect but not the drug induced psychotic affect. Tolerance does not develop as readily to hallucinatory and behavioural effects of cocaine as compared to amphetamines.
Withdrawal: withdrawal symptoms are very similar to those associated with amphetamines.
Addiction: addiction can occur as the behavioural effects are usually perceived as pleasurable and rewarding.
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What is the ADME of nicotine?
Nicotine is the ingredient in tobacco products responsible for smoking addiction.
1) Absorption: nicotine exists in smoke in small particles, and when inhaled, droplets are rapidly absorbed. Nicotine can be absorbed from the G.I. tract, oral mucosa, and across the skin. The dose is controlled by the depth of inhalation and frequency of smoking.
2) Distribution: nicotine is distributed through the body and rapidly gains access to the brain.
3) metabolism: nicotine is rapidly metabolized in the liver.
4) Excretion: metabolites are excreted in the urine. The half life is about two hours.
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What is the mechanism of action for nicotine?
Nicotine stimulates nicotinic receptors at synapses to increase psychomotor activity, cognitive function, attention, and memory. In large doses, nicotine causes agitation, tremors, and seizures.
The effects in the CNS are mediated by the nicotinic receptor-mediated release of the CNS neurotransmitters dopamine and serotonin.
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What are the therapeutic uses of nicotine?
The only therapeutic use of nicotine is in smoking cessation programs where nicotine is administered through chewing gum, transdermal patches, or buccal spray to maintain blood nicotine levels and satisfy the craving for a cigarette.
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What are the short-term effects of smoking?
Regular smoker: mild euphoria, arousal, concentration, relaxation, increased heart rate, increased blood pressure, and suppressed appetite.
Non-regular smoker: dizziness, headache, nausea, vomiting, abdominal cramps, coughing, and gagging.
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What are the long-term effects of smoking?
Tobacco smoke contains over 4000 compounds including nicotine, carbon monoxide, carcinogenic aromatic hydrocarbons, tars, and products of combustion. The long-term effects are related to these products of combustion and not nicotine itself.
Cardiovascular disease: higher risk of death due to cardiac causes from nicotine. Also: carbon monoxide reduces the capacity of red blood cells to carry oxygen, increasing the incidence of atherosclerosis and thrombi.
Lung disease: smokers syndrome is characterized by difficulty breathing, wheezing, chest pain, congested lungs, and lung infections. There is also increased risk of emphysema and other chronic obstructive lung diseases.
Cancer: 30% of all cancers are caused by cigarette smoke which increases the risk of lung, oral cavity, throat, bladder, and uterus cancers.
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What are alternative effects of smoking?
Passive smoke increases risk of cardiovascular disease and cancer, specifically in children, increasing the incidence of bronchitis, pneumonia, asthma, and sudden infant death syndrome.
During pregnancy, smoking affects the developing foetus with a 2 to 3 fold increase in the incidence of the foetus being small or born preterm. This can be reversed if the pregnant woman stopped smoking early in pregnancy. Exposure to passive smoke also increases the chance of a low birthweight neonate due to decreased oxygen delivery to the fetus.
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What is the potential for missuse and SUD for nicotine?
Tolerance: does not appear to a great extent as smokers continue to keep nicotine blood levels at a certain range (30-40ng/mL)
Withdrawal: involves symptoms such as irritability, restlessness, anxiety, insomnia, fatigue, and the inability to concentrate. This is felt in the morning when smokers are in a state of nicotine withdrawal.
Addiction: occurs and manifests as an extreme urge to smoke.
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What is the pharmacology of caffeine?
Caffeine is found in tea, coffee, chocolate, and cola drinks. As well, it is found in over-the-counter stimulants, analgesics, and diuretics. The average cup of coffee contains 100 mg of caffeine, well energy drinks have over 300 mg of caffeine.
The lethal dose of caffeine Is equal to about 10 g of caffeine.
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What is the ADME of caffeine?
Caffeine predominantly affects the CNS and cardiovascular system as a stimulant.
1) absorption: taken orally, caffeine is rapidly and completely absorbed. Blood levels are significant at 30 minutes and peak 2 hours after ingestion?
2) distribution: caffeine distributes to all parts of the body and freely crosses into the brain and placenta.
3) metabolism: genetics determine the rate at which we metabolize and excrete caffeine, which is why drinking coffee at night keeps some people awake but not others.
4) elimination: the half-life varies from 2.5 hours to 10 hours.
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What is the mechanism of action of coffee?
100 to 250 mg of caffeine increases mental performance and motor activity while decreasing drowsiness and fatigue.
Without caffeine, Tennessee and receptors stimulate GABAergic neurons that inhibit dopamine release.
With caffeine, adenosine receptors are completely blocked in the brain causing an increase in dopamine release and stimulating the CNS.
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What are the short term effects of caffeine?
CNS: mood elevation, reduced fatigue, clearer thought, nervousness, irritability, agitation, reduced sleep.
Cardiovascular: construction of cerebral blood vessels, increased peripheral blood flow, stimulated cardiac muscle with rapid and irregular heartbeats.
Respiration: stimulation of the respiratory rate and relaxation of bronchial smooth muscle.
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What is the clinical use of caffeine?
Caffeine is used to stimulate breathing in pre-term newborns. This helps the immature brains and lungs remember how to breathe.
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What are the long-term effects of caffeine?
Restlessness, nervousness, insomnia, increased urinary output, gastric upset, rambling speech, and rambling thought.
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What are the effects of caffeine in special circumstances?
Smoking: cigarette smoke increases the metabolism of caffeine.
Pregnancy: large doses of caffeine increase the risk of stillbirth, decreased foetal growth rate, and slightly increase the chances of miscarriage. Metabolism of caffeine is slower in pregnant people, extending the duration of action by two times in the second trimester, and three times in the third trimester.
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What is the potential for Misuse and SUD for caffeine?
Misuse: potential is low as caffeine is not a reinforcer due to only mild euphoria. Inherent harmfulness is very low.
SUD:
-Tolerance: some tolerance does develop
-Withdrawal: abrupt cessation will result in headache, fatigue, and drowsiness
-Addiction: mild addiction can occur
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Why are amphetamines used in sports?
Amphetamines increase the feelings of euphoria, reward, increased respiration, insomnia, and psychoses. These effects increase endurance and speed, or cause appetite suppression which is helpful in sports that benefit from weight loss.
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Why are anabolic steroids used in sports?
Anabolic steroids are used to increase muscle mass and strength with reduced androgenic affects and maintained anabolic affects.
Anti catabolic: reduced breakdown of protein allows athletes to maintain muscle mass
Anabolic: produce more protein to increase muscle mass
Motivation: aggressive behavior, known as roid rage, is beneficial for competitive sports.
Anabolic steroids have greater effects in individuals with lower basil circulating levels of testosterone. With low to moderate doses there are modest effects, While large doses yield significant increases in lean body mass, weight, and strength.
Anabolic steroids increase mood swings, develop severe acne, increase cardiovascular disease with low density Lipo proteins, alter liver function, and reduce testosterone by blocking the release of gonadotropin which can cause infertility, libido, and impotence. In females, there is an increase in body hair, lowered voice, enlarged clitoris, increased libido, and amenorrhea.
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Why are benzodiazepines used in sports?
Benzodiazepines reduce stress and anxiety during competition but can also impair psychomotor coordination and focus at higher doses, so benefits are closely weighed with potential impairments in performance.
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What is blood doping and erythropoietin?
Blood doping is the re-infusion of an athletes blood cells, well erythropoietin is a hormone that increases the amount of red blood cells produced in the body. Both methods increase oxygen carrying to increase sport performance.
Inappropriate use of erythropoietin can result in thrombotic events.
Blood doping is detected by measuring the age of red blood cells, well erythropoietin is detected in urine.
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Why are diuretics used in sports?
Diuretics increase exccretion of salt and water through the kidneys in order to reduce body water and allow that athlete to compete in lower weight classes. These can also increase the speed of excretion of other band drugs to avoid detection.
Toxicities include excess electrolyte and water depletion.
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Why were performance-enhancing drugs banned in sports?
Athlete protection: to protect athletes under pressure to perform well.
Unfair advantage: to make a level playing field between all competitors.
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What are sedative hypnotic agents?
Sedative hypnotic agents are CNS depressants that produce different affects at particular doses.
Antianxiety: used for anxiety disorders like general anxiety disorder and obsessive compulsive disorder.
Sedation: used to relieve anxiety, decreased activity, moderate excitement, and calm the individual.
Hipnosis: produce drowsiness and aid in the onset and maintenance of sleep.
General anesthesia: induce a state of unconsciousness with the absence of pain sensation.
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What are the mechanisms of action of sedative hypnotics?
Without: excitatory neurons release the neurotransmitter glutamate when excitatory inputs exceed inhibitory inputs.
With: inhibitory signals from GABA neurons increase with most sedated hypnotics, decreasing glutamate nerve firing.
GABA selectively opens chloride channels to allow chloride ions to flow into the cell when signalled to open. Chloride ions flow into the postsynaptic neuron, making it hard for the postsynaptic neuron to transmit incoming messages to other neurons. This depresses the CNS signalling.
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What are benzodiazepines?
Benzodiazepines are taken as a capsule or tablet, but can be available for intravenous or intranasal use. They increase the frequency of the opening of the chloride channel. Therapeutic effects include relaxation, calmness, skeletal muscle relaxation, and anticonvulsant effects.
Benzodiazepines are the most commonly used drugs in overdose, following ingestion of enormous doses, rapid intervenous injection, or drug combination.
An antidote for benzodiazepines is flumazenil, a benzodiazepine receptor antagonist that blocks the effects of benzodiazepines.
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What are the short-term effects of benzodiazepines?
CNS: drowsiness, lethargy, fatigue, and impairment of thinking or memory.
Breathing: respiratory depression is seen with rapid intervenous administration.
Motor coordination: impairment of motor coordination and driving.
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What are the long-term effects of benzodiazepines?
Long-term effects very between individuals as some people can take large amounts for long periods without any major evidence of intoxication. Others demonstrate symptoms of chronic sedated hypnotic intoxication like impaired thinking, poor memory and judgment, disorientation, in coordination, and slurred speech.
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What are the effects of Benzodiazepines in special populations?
Pregnant: benzodiazepines cross the placenta and distribute into the foetus resulting in risk for abnormalities. When breast-feeding, benzodiazepines are exposed to infants with therapeutic or toxic doses which can result in sedation or death.
Older adults: benzodiazepines produce cognitive disfunction and are metabolized more slowly which can lead to oversedation, falls, and injury.
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What is the potential for misuse and SUD with benzodiazepines?
Misuse of benzodiazepines for recreation occurs typically with combination of alcohol in order to enhance CNS depression effects.
Misuse potential: weaker reinforcing properties than other drugs with a low inhernt harmfulness.
Tolerance: can develop to summative affects and impairment of coordination, the anxiolytic effect, or euphoric effects. However, the magnitude does not produce clinical concerns. Cross tolerance can occur with other sedative hypnotic drugs.
Withdrawal: mild but distinct withdrawal occurs with anxiety, headache, and insomnia. With chronic use, discontinuation causes agitation, paranoia, seizures, and delirium.
Addiction: may develop in some individuals but not all, depending on factors of genetics and the environment.
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Discuss barbiturates.
Barbiturates are sedative hypnotics classified according to the duration of action. They can be long acting, 1 to 2 days, short acting, 3 to 8 hours, and ultra short acting, 20 minutes. They are an older class of drugs that has been replaced by safer and more effective sedative of hypnotics.
Route of administration: administered in different ways depending on what they’re used to treat. For epilepsy they are administered orally, for anesthesia, they are administered intravenously.
Mechanism of action: activation of barbiturate receptor increases the duration of the opening of the chloride channel, demonstrating the full spectrum of those dependent CNS depression.
Therapeutic use: In low doses, barbiturates result in tranquillity and relaxation, while also inducing sleep. Ultra short acting and short acting can be used to induce anaesthesia well long acting agents can be used as antiepileptics.
Lethality: Low therapeutic index and potential for Leith Aliti due to depression of respiration, especially when combined with alcohol. Lethal dose of barbiturates varies between individuals, no antidote exists, and death can occur from withdrawal.
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What are the short term effects of barbiturate use?
Barbiturate suppress REM type sleep which is essential to wake up feeling well rested.
Short-term use induces a fax like mild euphoria, reduced interest, dizziness, impairment of motor coordination, intoxication, and a depressed cardiovascular system.
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What are the long-term effects of Barbiturate use?
Long-term use of barbiturates is chronic inebriation where memory, judgment, and thinking are all impaired. Individuals also exhibit hostility and mood swings that include depression.
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What is the potential for miss use and SUD of barbiturates?
Barbiturates are prescribed Less frequently but illicit use continues to be a problem.
Potential for misuse: Equal to or greater than alcohol due to the significant degree of reinforcement from pleasurable effects. Inherent harmfulness is very high due to risk of death from respiratory depression or withdrawal.
Tolerance: can develop, along with a high degree of cross tolerance between barbiturates and others sedatives.
Withdrawal: occurs after discontinuation of chronic use with tremors, anxiety, weakness, insomnia, and postural hypotension that can produce to seizures, delirium, visual hallucinations, and high body temperature. Barbiturates must be withdrawn slowly under medical supervision.
Addiction Colin can result from regular use, ear respective of the dose. Addiction includes the craving of the drug and a feeling of panic without adequate supply. Craving persists long after use.
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What are benzodiazepine-like drugs?
Benzodiazepine like drugs are sedative hypnotics used to treat anxiety or difficulty sleeping. Zopiclone and zolpidem bind to GABA receptors and cause sedation. These drugs act similarly to benzodiazepine but disturb sleep patterns even less.

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What is Buspirone?
Buspirone is an xanxiolytic as it does not act on the GABA receptor, but on a serotonin receptor. It is used in generalized anxiety states and has an advantage as it does not appear to have additive effects with other sedated hypnotic drugs. This drug is prescribed instead of benzodiazepine when the individual is already taking another CNS depressant drug.
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What is alcohol?
Alcohol is one of the three most used non-medical drugs in Canada that produces more health problems and deaths than all illicit drugs combined. The reason for extensive use is it’s ready availability and the permissive attitudes of society.
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What is the ADME of alcohol?
Alcohol is a CNS depressant that works by slowing down brain functioning and neural activity.
1) Absorption: ethanol is absorbed rapidly from the stomach, 20%, and the upper small intestine, 80%, with absorption rate affected by stomach emptying time, ethanol concentration in the G.I. tract, and the presence of food. To reach maximal blood alcohol concentration, the time is 30-90 minutes.
2) Distribution: ethanol distributes throughout total body water and right away Gaines access to the brain. It can also transfer a cross the placenta and distribute throughout a developing fetus.
3) Metabolism: ethanol is converted to acetyl aldehyde by ADH (rate limiting step); MEOS, Part of the cytochrome P450 system Call and contributes to the metabolism of ethanol at full capacity; acetyl aldehyde is converted to acetate by the enzyme ALDH; acetate is metabolized into carbon dioxide and water by tissues. Genetic variance exist, so some individuals rapidly convert alcohol to acetyl aldehyde as a protective agent against alcoholism from unpleasant side effects. Alcohol is metabolized at a constant rate, irrespective of blood alcohol concentration.
4) excretion: over 95% of ethanol is eliminated by bio transformation in the liver. The remaining 5% is excreted in the breath, urine, and sweat.
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What are the medical uses of alcohol?
Alcohol sponge to treat fever, skin disinfectant, antidote for methanol poisoning, and hand sanitizer.
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What is the mechanism of action of alcohol?
Alcohol affects a large number of membrane proteins by binding to the chloride ion channel and augmenting GABA mediated neuronal inhibition. Interaction of alcohol with chloride ion channels in reward areas explain the reinforcing effects of the drug.
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What are the short term effects of alcohol?
Cardiovascular: Low doses create vasodilation, I’ll high doses depress the cardiovascular system altering the normal rhythm of the heart.
Stomach: low doses increase gastric secretion, while high doses irritate the lining of the stomach to cause inflammation and erosion that increases vomiting and abdominal pain or aggravates ulcers.
Liver: low doses have no adverse effects, well high doses inhibit glucose production and lead to hypoglycemia.
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What are the adverse effects of binge drinking?
Memory loss, depression, irritability, oversedation, overdose from respiratory depression or coma
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What are the long-term effects of alcohol use?
CNS: neurological and mental disorders occur such as alcoholic dementia, with a decrease in cognitive functioning from damaged axons and neurons in the brain.
Cardiovascular: alcoholic cardiomyopathy and increased incidence of hypertension and stroke.
Liver: alcoholic liver disease causes hospitalization and death, but can be reversible at early stages with abstinence.
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What happens with alcohol and pregnancy?
Chronic use of high dose ethanol in pregnancy can produce tetragenic effects of the foetus that manifest postnatally as fetal alcohol spectrum disorder (FASD).
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Discuss alcohol and drug interactions.
During drug therapy, ethanol leads to additive or synergistic effects of the CNS depression, and the inhibition of metabolism can occur.
Chronically drinking alcohol but abstaining before drug therapy can increase the activity of metabolizing enzymes in the liver, but only occurs without liver injury.
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What is the potential for misuse and SUD for alcohol?
Potential for misuse: with significant reinforcing properties, miss use potential is moderate from the ease of availability and social acceptance. Inherent harmfulness is moderate as death can occur from high doses, and chronic ingestion can have long-term effects on health.
Tolerance: tolerance to chronic consumption occurs. Individuals can also develop tolerance to ethanol induced impairment performance if they repeat the task repeatedly under the influence.
Cross tolerance: with sedative hypnotics a higher dose of sedative hypnotic drug is required for the therapeutic affect. For general anesthetic’s, a higher dose of anaesthetic agent is required for surgical anaesthesia for someone with alcohol tolerance.
Withdrawal: produces compensatory excitation of the CNS with delirium tremens, convulsions,coma, and death.
Addiction: compulsive desire to seek, obtain, and drink ethanol exists as a powerful factor in chronic use.
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What drug can aid in the treatment of alcohol withdrawal?
Benzodiazepines suppress withdrawal syndrome from cessation of alcohol use due to its similar mechanism of action.
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What drug can treat alcohol use disorder?
Naltrexone diminishes the craving for ethanol and assists in the maintenance of abstinence by blocking the activation of dopaminergic reward pathways in the brain.
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What step of alcohol metabolism is rate limiting?
Conversion of alcohol to acetyl aldehyde by alcohol dehydrogenase.
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What is cannabis?
Cannabis is a drug containing forms of the hemp plant, cannabis sativa, a herbaceous annual. There are 60 chemical compounds found in cannabis sativa which are cannabinoid‘s. Of these, THC is the most potent psychoactive agent in cannabis that accounts for most of the psychoactive effects.
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Explain the history of cannabis.
2700 BCE to 1800 BCE: cannabis plants were used for manufacturing rope and mild intoxicating effects.
1920’s: public concern raised in North America over effects of cannabis on individuals and society. Legislation was enacted to outlaw the use of cannabis as it was considered a narcotic.
1960’s: use of cannabis increased, driven by Cold War and the changing political and cultural climate.
1978: a USA sponsored project using herbicide paraquat was initiated to destroy cannabis crops in Mexico. Because paraquat produces lung toxicity.
1997: Ontario dismiss charges related to possession of cannabis on the basis that the individual was using it to control epilepsy not controlled by conventional drug therapy. The law allowed cultivation of varieties of cannabis with small amount of THC to manufacturer rope, clothing, and other hemp products.
2005: Health Canada supported trials on the medical use of cannabis.
2012: recreational use of cannabis was legalized in Washington.
2018: recreational cannabis became legal in Canada.
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How is cannabis classified?
Cannabis can be classified pharmacologically, as a CNS depressant, euphoriant, and hallucinogen. It can also be classified legally, being legal in Canada as of October 17, 2018.
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How is cannabis administered?
Cannabis is a dried flowering plant that is typically smoked or inhaled. Extracts with cannabinoids in oil form can be administered by vaping or through oral consumption.
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What is the mechanism of action of cannabis?
THC binds specifically to receptors in the brain and spinal cord called CB1 receptors. When CB1 receptors are activated, they inhibit the release of excitatory neurotransmitters to reduce cognitive function and cause CNS depressant effects.
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What are the two cannabinoid receptors?
CB1: Found in brain. In the cerebral cortex, receptors mediate the distortions of time, color, sound, and taste well also mediating the decrease in cognitive function in concentration. In the hippocampus, they account for changes in memory and learning. Even though THC is not a very effective agonist, a large number of receptors exist to produce a response.
CB2: found outside the CNS and are not involved in psychoactive effects of THC but can be involved in inflammation. The binding of THC to receptors on lymphocytes is responsible for immunosuppressive properties.
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What is the ADME of THC?
1) Absorption: THC is inhaled or ingested. If inhaled, absorption is rapid and onset is immediate, with a fax lasting 3 to 4 hours. If ingested, THC is absorbed more slowly and incompletely with the onset being delayed 30 to 60 minutes, and having an effect less than that from smoking.
2) Distribution: THC rapidly distributes throughout the body, especially to tissues with high blood perfusion such as the lung, heart, brain, and liver. THC also rapidly crosses the placenta and is highly lipid soluble to be stored in adipose tissues.
3) Metabolism: THC is metabolized slowly.
4) Excretion: THC has a half-life of approximately 30 hours but elimination from adipose tissue can take longer.
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What are the short term effects of cannabis use?
CNS: relaxation, drowsiness, euphoria, impaired motor coordination, increased appetite, and pseudo hallucinations.
Cardiovascular system: increased heart rate, increased blood flow to extremities, postural hypotension.
G.I. tract: increased appetite, dryness of the mouth, and dryness of the throat.
Other: reduced sex drive in males from reduce testosterone, disruption of the ovarian cycle, and a hangover.
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What are the long-term effects of cannabis?
Psychological: With high doses, problems occur with short term memory, concentration, and the ability in abstract thinking. A motivational syndrome is also characterized with a loss of ambition and emotional flatness, appearing upon cessation of drug use. Permanent effects are currently unknown.
Cardiovascular: changes in blood pressure are not serious, but an increase in heart rate can be a potential problem for those with heart disease.
Respiratory: bronchitis, asthma, sore throat, chronic irritation, damage to membranes of the respiratory tract, and lung cancer or obstructive pulmonary disease. Smoking cannabis is damaging because of higher concentration of tar and carcinogens in the smoke.
Fertility: decreased sperm count, follicle stimulating hormone and aluminizing hormone reduced, menstrual cycles without ovulation, developmental delays for fetuses, cognitive deficits, impulsiveness, and attention, and hyperactivity for fetuses.
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What are the medical uses of cannabis?
Healthcare practitioners may authorize the use of cannabis for the relief of symptoms that do not respond to conventional medical treatments. Medical cannabis is prescribed for prevention of nausea and vomiting associated with anti-cancer drugs.
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What is the potential for misuse and SUD for cannabis?
The misuse potential is low to moderate as euphoria and reinforcement are less compared to other drugs. The inherent harmfulness is also low, especially within frequent use.
Tolerance: occurs to psychoactive properties, effects on the cardiovascular system, and impairment of performance and cognitive function.
Withdrawal: mild withdrawal occurs with sleep disturbance, irritability, loss of appetite, nervousness, mild agitation, upset stomach, and sweating.
Addiction: develops as a persistent craving for the drug. The risk is more evident in those who use cannabis to control psychological distress.
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Does cannabis affect the presynaptic or postsynaptic neuron?
Cannabis binds to CB1 receptors on the presynaptic neuronal membranes in the brain.
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What receptor does THC bind to?
Cannabinoid receptors
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What are opioids?
Opioids are class of drugs naturally found in the opium poppy plant, Papaver somniferum. Initially opium was used as a crude extract but is now used as a purified substance to produce clinically used drugs like morphine and codeine. Morphine is one of the most useful drugs known to pharmacologists but is renowned for causing opioid use disorder.
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What are the different classes of opioids?
An opioid is any natural or synthetic substance that exerts actions on the body through binding to opioid receptors.
Endogenous opioids: opioids made in the body that bind to opioid receptors and exert analgesic effects. Three families are enkephalins, dynorphin’s, and beta endorphins. These affect the perception of pain and emotional response to pain, while also influencing mood and associating with reward pathways.
Natural opioids: derived from the opium poppy plant. Morphine binds directly to opioid receptors to treat severe acute and chronic pain or cause euphoria. Codeine is converted to morphine by liver enzymes and is a prescribed drug that is commonly used.
Semi-synthetic opioids: altered versions of morphine that are chemically changed to obtain different pharmacological properties. Hydromorphone is used for analgesia. diacetylmorphine is used as an injectable opioid agonist therapy to manage OUD.
Synthetic opioids: Chemically synthesize to bind to opioid receptors and illicit similar pharmacological responses or be used for other clinical purposes. fentanyl was designed for treatment of secure acute and chronic pain. Loperamide leverages constipation and treats diarrhoea by staying in the intestine. Methadone is used for analgesia And can be used to treat OUD, preventing withdrawal symptoms while not causing euphoria.
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What are the different opioid receptors?
Mu: Present in brain and spinal cord to mediate analgesia And are responsible for morphine mediated depression of respiration in the brainstem.
Kappa: Involved in analgesia, dysphoria, and miosis.
Delta: involved in analgesia at the level of the spinal cord and brain, well also modulating emotional response to opioids.
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What is the mechanism of action of opioids?
Opioids block pain pathways in the spinal cord and brain through activation of mu opioid receptors. They prevent pain signals from travelling by reducing neurotransmitter release from presynaptic neurons and reducing the effect on postsynaptic neurons. They reduce emotional reaction through modulation of the limbic system.
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What are the short term effects of opioids?
Analgesia, sedation, suppression of cough center, respiratory depression, endocrine effects, miosis, heart rate, thermoregulation, and decreased intestinal motility.
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What are the therapeutic uses of opioids?
Relief of severe pain: mitigate post surgical pain and pain experienced by terminally ill patients.
Treatment of diarrhea: Loperamide does not produce withdrawal but it’s useful and controlling diarrhea.
Cough suppression: all opioids suppress cough.
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What is the potential for misuse for opioids?
Opioids are usually taken alone but can be found in combination with other drugs like cocaine and methamphetamine.
Misuse potential: powerful euphoric effects with large risk of misuse. Not high inherent harmfulness for low doses, but life-threatening for high doses.
Risk of injections: injection sites can develop abscesses and infections.
Overdose: overdose produces profound respiratory depression that can cause death. Treatment consists of antagonist and support of respiration. Antagonist known as naloxone is primarily used to treat overdose. While naltrexone is an opioid antagonist that treats alcohol use disorder.
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What is the risk of opioid use disorder?
Tolerance: occurs to most pharmacological effects, except constriction of the pupils and constipation. Develops more slowly to respiratory depression then to analgesic affects of opiates. Tolerance can reverse in a few days. Cross tolerance occurs if opioids act on the same receptor.
Withdrawal: withdrawal depends on track, pattern reviews, daily dose, route of administration, and concurrent use of other drugs. Symptoms include restlessness, anxiety, insomnia, sweating, fever, chills, increased respiratory rate, cramping, vomiting, and diarrhea.
Addiction: craving and compulsion for opioids develops from euphoric action resulting in powerful reinforcement. Use of opioids and other psychoactive drugs occur in an attempt to achieve greater euphoria.
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Discuss opioid use during pregnancy.
Mother dependent on opioids during pregnancy faces increased risk of premature delivery and a low birthweight infant. At birth, the infant undergoes an abrupt termination of opioid exposure resulting in withdrawal reaction with irritability, sleep disturbances, poor feeding, and occasional seizures. This can last weeks to months.
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How is opioid use disorder treated?
Buprenorphine Is a long acting synthetic opioid that binds to mute opioid receptors as an agonist to prevent withdrawal symptoms. In Canada it is combined with naloxone to block opioid receptors and prevent withdrawal symptoms.
If taken sublingually, naloxone is broken down before getting into circulation and has no significant effects.
Methadone is a synthetic opioid that is effective following oral administration with a long duration of action. With a much lower misuse potential, it is used to remove potential risks of injections, decrease euphoria, and avoid withdrawal.
Psychosocial supports like counselling and treatment of concurrent physical and mental health issues should be considered to optimize recovery.
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Why is methadone used in the treatment of opioid use disorder?
It transfers individuals with opioid use disorder to an opioid that is long acting and doesn’t cause euphoria.
132
Discuss drugs used to treat infections.
Drugs used to treat infections are the most dramatic examples of modern medicine. Diseases that were associated with a high death rate in 1940 are now curable with a few tablets.
The development of drugs to treat infections is based on the concept of selective toxicity to harm an invading organism without harming the host. Antibiotics, antifungals, and antivirals all fall under this class, with antibiotics being the most abundant.
133
What is an antibiotic?
An antibiotic is a chemical substance that suppresses the growth of bacteria, and may eventually destroy them. The term antibiotic refers specifically to chemical substances produced by microorganisms. The purpose of an antibiotic is to stop a bacterial infection through bacteriostatic or bactericidal effects.
134
What is special about the structure of bacterial cells?
Unlike human cells, bacterial cells have a rigid outer layer called the cell wall, which surrounds the cytoplasmic membrane. The cell wall contains a peptidoglycan layer, which is a complex, cross-linked polymer of polysaccharides and polypeptides. These cross-links give structural rigidity and are responsible for maintaining the cell’s shape, integrity, and
preventing cell lysis from high osmotic pressure.
135
What is the difference between gram-positive and gram-negative bacteria?
Gram-Positive: have a thick peptidoglycan layer and no outer membrane.
Gram-Negative: have a thin peptidoglycan layer and an outer membrane.
136
How are antibiotics classified on a spectrum?
Narrow Spectrum: only useful against particular species of microorganisms (ex. penicillin G is only effective against Gram-positive bacteria).
Broad Spectrum: are effective against a wider range of microorganisms, including both
Gram-positive and Gram-negative bacteria (ex. tetracyclines).
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How are antibiotics classified by biochemical pathways?
Antibiotics utilize the concept of selective toxicity by targeting and interfering with essential components of biochemical reactions in bacteria.
Cell Wall Synthesis Inhibitors: stop the proper formation of the bacterial cell wall and/or membrane, influencing the structural integrity of the cell. (penicillins and cephalosporins)
DNA Synthesis Inhibitors: inhibit DNA replication in bacteria, preventing bacterial growth. (fluoroquinolones)
Protein Synthesis Inhibitors: inhibit protein translation within bacteria. (tetracylines and
macrolides)
Metabolic Inhibitors: block the formation of key bacterial metabolic substrates needed
for bacteria to survive and reproduce. (antifolate drugs)
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What are the different penicillins?
The fact that Penicillium mould could produce and excrete an antibacterial substance was first
discovered by Alexander Fleming in 1929, but penicillin wasn’t successfully isolated from
the mould until the Second World War by Florey and Chain.
In general, two types of penicillins, which are cell wall synthesis inhibitors, exist: natural (penicillin G) and semisynthetic (modified penicillin G).
Penicillin G: narrow spectrum antibiotic extracted and purified from Penicillium mould to destroy Gram-positive bacteria. It is useful in the treatment of pneumonia, middle ear
infections, skin infections, and meningitis. It is also very useful in the treatment of syphilis.
Methicillin: penicillinase is produced by organisms to break down penicillin and become
resistant to penicillin G. Methicillin is an antibiotic that is resistant to penicillinase.
Ampicillin/Amoxicillin: antibiotics that have a broader spectrum of antibacterial activity and are useful against a range of infections caused by Gram-negative bacteria (urinary tract infections).
Amoxicillin/Clavulanic Acid: a combination of a semisynthetic penicillin plus an inhibitor of
penicillinase that was introduced to combat penicillinase-producing strains of bacteria.
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What is the mechanism of action of penicillin?
Penicillin is closely related to D-alanyl-D-alanine, a chemical component necessary for the formation of new bacterial cell walls. So penicillin interferes with new bacterial cell wall formation and the resulting cells, protoplasts, are formed without cell walls, becoming fragile and ready to burst. Human cells do not have cell walls and are therefore unaffected by penicillin. Thus, penicillin is selectively toxic to bacteria.
140
What are the adverse effects of penicillin?
The most common adverse effect to penicillin
is gastrointestinal distress due to disturbance of healthy gut flora.
Another adverse effect is penicillin allergy. 1-10% of the population is allergic to
penicillin. With symptoms of a rash, fever, face and tongue swelling, and itchy hives, or in rare cases, severe difficulty breathing and a marked fall in blood pressure
141
What are cephalosporins?
Cephalosporins inhibit cell wall synthesis but are more resistant to penicillinase than the penicillin group. Cephalosporins are divided into five generations depending on their spectrum of activity.
142
What are the adverse effects of cephalosporins?
Similar to penicillins, adverse effects include gastrointestinal side effects such as nausea and diarrhea, and the potential for a person who is allergic to penicillin to also be allergic to cephalosporins.
143
What is the mechanism of action of cell wall synthesis inhibitors?
In bacterial cell wall synthesis, 2 glycopeptide chains are connected by transpeptidase to forms a stable cell wall, releasing D-alanine. Penicillin and cephalosporins resemble D-Alanine compete for the binding spot on the
transpeptidase, thus inhibiting the enzyme.
Without this crosslinking, the cell wall is not functional. If the bacterial cell cannot form a proper cell wall, it will not be able to maintain its internal environment and will break open and die.
144
What are Fluoroquinolones?
Fluoroquinolones are a chemically distinct class of antibiotics that inhibit bacterial DNA synthesis.
Ciprofloxacin: used for oral or intravenous
therapy of infections caused by a wide variety of Gram- positive and Gram-negative microorganisms
145
What are tetracyclines?
Tetracyclines were one of the first broad spectrum antibiotics developed. Because of widespread use for many years, many bacteria have become resistant. Specifically, tetracyclines are protein synthesis inhibitors.
Mechanism of Action: bind to the 30S subunit of the mRNA-ribosome and prevent the addition
of amino acids to the protein chain to inhibit protein synthesis.
Adverse Effects: gastrointestinal effects such as nausea, vomiting, and diarrhea, as well as, discolouration of teeth and diminished bone growth.
Use in Special Populations: have a strong affinity for calcium, therefore they are not used during pregnancy or in children under 12.
Storage: can deteriorate into toxic degradation products if stored for long periods of time so
it is important to discard outdated supplies.
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What are macrolides?
Macrolides are protein synthesis inhibitors that are active against several bacterial infections caused by Gram-positive microorganisms. When an individual is allergic to penicillin, a macrolide may be an effective alternative.
Erythromycin: effective in treating infections caused by some Gram-negative bacteria.
Mechanism of Action: bind to the 50S ribosomal subunit on tRNA and block peptide bond formation.
Adverse Effects: nausea, vomiting, and diarrhea
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What is the mechanism of action of protein synthesis inhibitors?
Step 1: the charged tRNA carrying amino acid 6 binds to the acceptor site on the ribosome.
Step 2: the peptidyl tRNA, with amino acids 1 through 5 then binds the amino acid chain to amino acid 6, increasing the peptide chain.
Step 3: the uncharged tRNA is released.
Step 4: the new 6 amino acid peptide moves into position with its new tRNA, and the process
repeats.
Tetracyclines bind to the 30S ribosomal subunit and prevent the binding of the charged t6 tRNA to stop protein synthesis.
Macrolides bind to the 50S ribosomal subunit and block peptide bond formation.
148
What are metabolic inhibitors?
Antifolates are inhibitors of folate metabolism in bacteria.
A folate, Tetrahydrofolic acid, is essential for bacteria to synthesize DNA and protein. If tetrahydrofolic acid is not formed, bacterial growth will slow.
Sulfonamides: competitively inhibits an upstream step in the synthesis of tetrahydrofolic acid, by inhibiting para-aminobenzoic acid (PABA) incorporation into dihydropteroic acid. Susceptible bacteria must synthesize tetrahydropfolic acid from PABA, but, mammalian cells use preformed tetrahydrofolic acid from their surroundings.
Trimethoprim: inhibits the enzyme dihydrofolic acid reductase, thus inhibiting tetrahydrofolic acid formation. Trimethoprim is selectively toxic to bacteria because it has greater inhibitory actions on the bacterial enzyme.
149
Discuss combination antifolates.
A combination product containing sulfamethoxazole and trimethoprim was developed to inhibit sequential steps in the metabetabolic pathway.
Co-trimoxazole: useful in the treatment of
urinary, respiratory, and gastrointestinal tract infections
150
What are the pros and cons of using antibiotics in combination?
Pros:
- Therapy of a severe infection where the microorganism responsible is not known or the infection is so dangerous that one cannot wait to determine by tests
- Treatment of a mixed bacterial infection where no single antibiotic could eliminate all the bacteria responsible
- Treating tuberculosis, where emergence of resistant mycobacterium is an important hazard (antitubercular drugs decrease emergence of resistant tubercle bacilli).
- Infections treated by two antibiotics that act synergistically.
Cons:
- Unnecessary additional cost.
- Increased chance of toxicity.
- Enhanced opportunity for resistant bacteria when the combination is not effective.
- Decreased number of normal populations of different bacteria, removing their inhibitory
influence on dangerous bacteria
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Discuss antimicrobial resistance.
Emergence of resistant strains is a long standing problem with antimicrobials as
bacteria can mutate and evolve to become resistant to antibiotics. WHO outlined the seriousness of this as some infections are not treatable with available antibiotics.
When you have a bacterial infection, the initial bacterial population is composed of diverse bacteria with different traits caused by mutations. When an antibiotic is taken, the subset of bacteria that are sensitive to its effects will die, while bacteria resistant to its effects will not. Over time, resistant bacteria will replicate and the trait giving them antibiotic resistance will become common to the entire population.
Two major factors are associated with the development of antibiotic resistance: evolution of bacteria, and clinical and environmental factors.
Over-Prescription: over-prescribed antibiotics as used due to a lack of diagnostic equipment or pressure from drug companies and patients.
Inappropriate Use: premature discontinuation of treatment or using drugs prescribed to others. Additionally, some countries allow the sale of antibiotics over the counter, contributing to inappropriate use.
Use in Agriculture: can expose animals to an unnecessary antibiotic which increases the risk of drug-resistance development.
152
Can you use antibiotics for everything?
No, many times antibiotics are prescribed when they aren’t really needed, causing side effects that include a rash, dizziness, nausea, diarrhea, yeast infections, and Clostridium difficile. Antibiotics can also lead to antibiotic resistance, making future infections harder to treat.
Antibiotics do not work on viruses such as those that cause colds and the flu, bronchitis, or runny noses. Antibiotics also won't help some
common bacterial infections, including many sinus infections, and some ear infections.
When you have an infection caused by bacteria and your doctor prescribes antibiotics, take them exactly as prescribed.
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How do organisms become resistant to antibiotics?
Uptake: Small molecules gain access to the inside of the microorganism by moving through pores. Mutation or lack of these pores makes the organism resistant.
Target: A mutation in the target for the antibiotic can reduce the binding of the drug.
Inactivation: Microorganisms develop an enzyme that inactivates the antibiotic (penicillinase).
Efflux Pumps: Some microorganisms will over express transporters that
pump the drug out of the microorganism before the cell can be injured.
154
What are antifungal drugs?
Fungal infections are increasing in patients
who are required to take immunosuppressive drugs.
Echinocandins: act by inhibiting the
synthesis of the cell wall. Micafungin and caspofungin are very well tolerated in patients and are only available for IV administration.
Imidazoles (Azoles): Ketoconazole and fluconazole are effective when taken orally or intravenously for systemic fungal infections. They inhibit a fungal cytochrome P450 to
inhibit ergosterol synthesis which is critical for cell wall function and survival. The selective toxicity lies in the higher affinity fungal P450. Miconazole is available as over-the-counter drugs for yeast infections.
155
What is a virus?
A virus is a small, infectious agent that is only able to multiply within the living cells of other
organisms, including animals, plants, and bacteria. Viruses are infectious particles that take over the operation of a cell for the sole purpose of manufacturing new viruses.
There are many different types of viruses, but they all are specific in the types of cells that they infect, dependent upon the types of receptors that are found on the surface of the target cell.
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What is the viral life cycle?
1) Attachment: virus use receptor proteins to target specific cells for infection.
2) Entry: genetic material of the virus, like DNA which contains the information to replicate, enters the host cell is D N A.
3) Replication: once inside the cell, the instructions in the DNA are transcribed to RNA.
4) Biosynthesis: protein-building machinery of the host cell translates these instructions into the components of a new virus.
5) Assembly: parts are assembled into new viruses within the host cell.
6) Release: when ready, new viruses emerge from the host cell, often killing it in the
process. As they emerge, some viruses retain the host cell membrane, forming an envelope for protection from the immune system.
Each new virus is now capable of infecting another host cell and repeating the process of virus replication.
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What are two types of antivirals?
Oseltamivir (Tamiflu): a neuraminidase inhibitor used to treat influenza. Neuraminidase is an enzyme that allows the spread of the virus from cell to cell. These drugs prevent neighbouring cells from being infected with the virus.
Acyclovir: taken into infected cells, and activated by the virus activates to inhibit viral DNA replication. Thus, acyclovir is selective for cells that are infected with the virus. Acyclovir is the drug of choice for treatment of infections caused by herpes simplex virus or the varicella-zoster virus that causes chickenpox and shingles. Long-term use will decrease the frequency of recurrence of genital herpes.
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What is the difference between antivirals and vaccines?
The major difference between vaccines and antivirals are their general mechanism of action and when they are administered.
Vaccines introduce non-functional fragments of the virus to the body prior to viral infections, such that the adaptive immune system is able to recognize and destroy the virus if it is introduced into the body. They are preventative, while antivirals treat infections already occurring in the body.
159
Which penicillin is resistant to penicillinase?
Methicillin
160
Co-trimoxazole is a combination of what drugs?
Trimethoprim and sulfamethoxazole
161
Discuss the monthly ovarian cycle.
1) At the beginning of the menstrual cycle, the levels of estradiol and progesterone in the blood are low and the endometrium is sloughed. This is known as menstruation.
2) In response to the low levels of estrogen
and progesterone, the hypothalamus secretes gonadotropin releasing hormone, which stimulates the pituitary to release FSH and LH.
3) In response to FSH, ovarian follicles, each containing one ovum, begin to enlarge.
4) After five or six days, one follicle develops rapidly, while the others regress. The maturing follicle begins to secrete estradiol in increasing amounts, then larger amounts cause the
endometrium to thicken.
5) Around day 14, levels of estrogen, LH, and FSH peak, stimulating the maturing ovarian follicle to grow more rapidly. The follicle swells and bursts, releasing the ovum. This is known as the follicular phase.
6) The corpus luteum releases progesterone, which stimulates the endometrium to secrete nutrients that are needed to support the
fertilized ovum when it arrives in the uterus. Progesterone is the hormone supporting the endometrium in this second half of the cycle.
7) If there is no fertilized ovum, then after 10 or 12 days, the corpus luteum ceases to function, progesterone secretion diminishes, and the endometrium loses hormonal support, leading to sloughing of the endometrium. This is known as the luteal phase
162
What are the mechanisms of action for hormonal contraceptives?
Inhibit Hormone Release: inhibit the release of GnRH from the hypothalamus to inhibit the release of FSH and LH, resulting in no follicular maturation and the inhibition of ovulation.
Inhibit Sperm Migration: progestins alter the secretions of the endocervical gland to a scant, thick fluid not optimal for sperm migration.
Inhibit Ovum Implantation: cause the endometrium to not fully develop making it unsuitable for implantation of a fertilized ovum
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What are oral contraceptives?
Oral contraceptive refers to a product containing both an estrogen and a progestin. The oral contraceptives vary in the amount and type of hormones present in the pill, as well as how often the pill is taken.
Fixed Combination: have a fixed combination of estrogen and progestin. One preparation is intended to be taken for 21 days out of a 28 day cycle with menses occurring during the 7 day pill-free/placebo period. The first product, Enovid-E, became available in Canada in 1961.
Some fixed combination pill regimens are taken for 28 days each cycle with no or very infrequent drug free periods. The advantage of this preparation is that menstruation is eliminated for the duration of therapy, which is particularly useful for women who have difficult or problematic menstruations.
Multiphasic: contain a fixed amount of estrogen and variable amounts of progestin; the progestin increases from week to week. These “phasic” preparations are currently
the oral contraceptives of choice.
With this method of oral contraceptive, the hormone dose is kept to a minimum and adverse events are reduced as compared to the fixed-dose combination. Another advantage
of a multiphasic approach is that the hormonal sequence more closely mimics the pattern of
hormones released in the normal ovarian cycle.
Progestin Only Pill: also known at the mini-pill, contain a daily low dose of progestin taken as
long as the drug is needed. Patient acceptability is less than with the estrogen-progestin
combinations, since breakthrough bleeding is often a problem. Efficacy in preventing pregnancy is slightly less than with the combination products.
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What are the adverse effects of combination oral contraceptives?
Mild:
* Nausea, caused by estrogen
* Edema, as estrogen and progestin cause water retention.
* Headache
Moderate:
* Breakthrough bleeding
* Weight gain
* Increased skin pigmentation due to estrogen
* Acne and hirsutism from progestin with androgenic properties
* Increased vaginal and uterine infections
* Post-drug amenorrhea
Severe:
* Blood Clots: estrogens induce the production of factors for blood coagulation
* Heart Attack: progestins are associated with a small increased risk for heart attack. The risk is greater if the patient is obese, or smokes.
* Stroke: increased risk for cerebrovascular disease (stroke). The risk is greater if the patient is over 35.
* Hypertension: more prevalent in women over 35.
* Cancer: endometrial and ovarian cancer risks are reduced and there is no increased risk of developing breast cancer. No clear decision has been made with respect to cervical cancer, as it is complicated by HPV infection.
Due to these adverse effects, women should not be taking a combined estrogen-progestin oral contraceptive if they have: thromboembolic disease, cerebrovascular disease, impaired liver function or overt liver disease, carcinoma of the breast or estrogen-dependent neoplasia, undiagnosed bleeding, migraines with auras, and/or pregnancy or suspected pregnancy.
Oral contraceptives during pregnancy may be associated with congenital limb deformities, masculinization, and cryptorchidism.
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What are non-contraceptive benefits of oral contraceptives?
* Reduced risk of ovarian cysts.
* Reduced risk of ovarian and endometrial cancer.
* Reduced incidence of ectopic pregnancy.
* Less iron deficiency anemia
* Less acne and hirsutism from newer progestins with less androgenic effects.
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What is depo-provera?
Depo-Provera, also known as “the shot”, is a contraceptive injection where progestin is injected IM every three months.
Adverse Effects:
Depo-Provera is progestin-only, resulting in breakthrough bleeding between periods, increasing LDL, and decreasing HDL.
167
What are IUDs?
IUDs are implanted into the uterus by
a medical professional to release levonorgestrel for 5 years.
Adverse Effects:
heavy menstrual flow, pelvic discomfort,
and increased uterine infections.
168
What is the transdermal contraceptive patch?
Transdermal contraceptive patches contain estrogen and progestin in a patch that is applied to the skin, delivering the drug at a constant rate for seven days. Three patches are required per cycle and the mechanism of action is the same as for combined oral contraceptives.
169
Discuss the efficacy of hormonal contraceptives.
IUDs are the most effective contraceptives. Efficacy is measured based on perfect use effectiveness and typical rate effectiveness to show the efficacy in both user scenarios. Usually, the typical rate efficacy is lower than the perfect use.
170
Discuss male contraceptives.
Male contraceptives, which can be taken orally or injected, have not reached the Canadian market as attempts to inhibit spermatogenesis have been largely unsuccessful, resulting in unacceptable rates of fertility.
Spermatogenesis: the hypothalamus releases GnRH, which stimulates the pituitary gland
to release FSH and LH. In males, FSH stimulates the seminiferous tubules to produce sperm, while LH stimulates the Leydig cells to produce testosterone, which is responsible for secondary sex characteristics and the inhibition of the hypothalamus.
Attempts to create male contraceptives by inhibiting the release of GnRH, and thus spermatogenesis, also decrease testosterone
production, which leads to the adverse effect of a decrease in sex drive. Four main compounds have been tested for use as male contraceptives
Androgen-Based: androgens inhibit the release of GnRH in an injectable form. However only 80% of the subjects responded with a lowering of sperm count and the excess androgen enhanced aggression.
Estrogens: suppress GnRH release, however, testosterone production and sex drive decreases, and men develop feminine characteristics. Small amounts of androgens were added, but only 60% of the subjects became infertile, and adverse effects from estrogen were numerous.
Progestin and Androgen: a synthetic progestin is used to inhibit the release of GnRH. This results in loss of spermatogenesis as well as testosterone production, decreasing male secondary sex characteristics. Androgen is added to replace the lost testosterone and maintain the secondary sex characteristics.
Finding the appropriate dose of the exogenous androgen is a major challenge.
Gossypol: obtained from cottonseed to destroy elements of the seminiferous tubules, decreasing sperm production, but not altering sex drive or functions of testosterone. The drug has undergone extensive clinical trials and led to infertile sperm counts in 99% of the subjects. Recovery of sperm count after discontinuing use of gossypol is not always guaranteed. However, it is more apt to occur if the sperm count does not fall too low and the duration of treatment does not exceed two years.
Hypokalemia has been the major problem reported, resulting in transient paralysis. The drug was undergoing clinical trials in North America, but has now been abandoned.
171
What is the difference between prescription and non-prescription drugs?
Prescription Drugs: drugs restricted to sale by prescription only.
Non-Prescription Drugs: drugs that can be sold to the general public without a prescription.
172
What are over-the-counter drugs?
OTC drugs are sold without a prescription based on the premise that the general
public is able to diagnose mild symptoms and to select appropriate agents to treat those symptoms.
OTC drugs are not a replacement for prescription drugs or care by a healthcare professional, and should only be used in certain circumstances.
Illness and/or Symptoms: be familiar with the mild symptoms
Adverse Events: if adverse events occur, stop taking the drug immediately. OTC drugs can cause toxicities on their own, as well as cause
drug interactions with other drugs, including herbal and prescription drugs.
Consultation: if in doubt, your local pharmacist can assist you with choosing an appropriate OTC drug.
Self-medication: should not exceed two weeks without consulting a physician.
173
Discuss the safety of efficacy of OTC drugs.
The sale of OTC drugs is controlled by a section of the Food and Drugs Act which controls the
safety, efficacy, advertising, and sale of these products. All new OTC products are subjected to rigorous preclinical testing for safety. Post-market safety surveillance is also conducted on all products. A number of recent OTC additions were available by prescription before being released onto the OTC market. For these products, extensive clinical trials were conducted for the initial market approval
174
What is grandparenting?
A process where new regulations do not apply to products that have already been on the market. (acetaminophen)
175
How do you select the appropriate OTC drug?
Proven Efficacy and Known Toxicity: the best OTC drug will have proven efficacy for the condition and a known level of toxicity.
Simple Formulations and Ingredients: the best OTC drug will have the simplest formulation.
Brand vs Generic: the best OTC drug will not necessarily be the brand name product. Generics are usually cheaper than the name brand product and are just as effective.
Appropriate and Effective Dose: the best OTC drug will come in the appropriate dosage form and have a therapeutically effective dose of the active ingredient.
176
What are internal analgesics?
Analgesics provide relief from pain. These include acetylsalicylic acid, acetaminophen, and non-steroidal anti-inflammatory drugs.
177
Discuss acetylsalicylic acid (ASA).
ASA is the generic name for Aspirin. It is an effective analgesic, antipyretic, and anti-inflammatory. In addition, low doses can prevent stroke and heart attack.
Mechanism of Action: inhibits the synthesis of prostaglandins, which are endogenous substances that enhance the mediation of pain and fever, and have a role in inflammation.
Stroke and Heart Attack Prevention: inhibits platelet aggregation and clot formation.
Adverse Effects:
- Gastric Irritation: most common toxicity as ASA breaks down the mucosal protective barrier in the stomach, leading to irritation
and increased bleeding. It is most effective to use an analgesic and antacid as separate entities.
- Tinnitus: ringing in the ears at high doses.
- Reye’s Syndrome: occurs when ASA is given to children during a fever. Reye’s syndrome is a rare but serious illness affecting the central nervous system. As such, acetaminophen is the drug of choice in children with fever.
- Allergic Reactions: these people may
also be allergic to tartrazine, yellow food colouring.
178
Discuss acetaminophen.
Acetaminophen, named Tylenol, is the most widely used OTC analgesic, comprising more than 50% of the market.
Mechanism of Action: inhibition of prostaglandin synthetases, cyclooxygenase I and II, which are the enzymes responsible for the formation of prostaglandins.
Therapeutic Uses: effective analgesic and antipyretic, however, acetaminophen is not an effective anti-inflammatory medication.
Acetaminophen is available in a liquid preparation and is, thus, convenient and suitable for children and infants. It is the drug of choice in cases where ASA causes gastric irritation and in febrile conditions in children and young adults, as acetaminophen is not associated with Reye’s syndrome.
Adverse Effects: overdose (5-10g) can lead to fatal liver injury. Individuals with alcohol use disorder or liver disease are more susceptible to the liver toxicity. In addition, some evidence indicates that liver injury can occur with large therapeutic doses if taken for a long time. One of the issues surrounding acetaminophen is that it is found in multiple products. An individual may overdose by simultaneously using two or three cold preparations all containing acetaminophen
179
Discuss NSAIDs.
Non-steroidal, anti-inflammatory drugs include ibuprofen (Advil) and naproxen (Aleve).
Therapeutic Uses: effective analgesic, antipyretic, and anti-inflammatory compounds. A 200 mg dose of ibuprofen is more effective than a 325 m g dose of ASA in a number of conditions, including dental pain and menstrual pain. Moreover, ibuprofen and naproxen are among the most effective OTC anti- inflammatory agents available.
Adverse Effects: gastric irritation (less than uncoated A S A), skin rash, dizziness, blurred vision, and fluid retention.
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What is the mechanism of action of internal analgesics?
When tissue damage occurs, arachidonic acid is released. Arachidonic acid can be converted by the enzyme COX-1 into protective prostaglandins, which are involved in many beneficial effects such as gastroprotection, platelet aggregation, renal protection, vasodilation, and bronchodilation.
Arachidonic acid can also be converted by the enzyme COX-2 into inflammatory prostaglandins, causing detrimental effects such as inflammation, pain, fever, and decreased platelet aggregation.
Analgesics work by blocking one or both of the cyclooxygenase enzymes, decreasing the production of prostaglandins involved in inflammation, pain, and fever, which is beneficial, but they also decrease the production of the protective prostaglandins, which contributes to adverse effects. These drugs do not all block the cyclooxygenase enzymes the same way, so the effects are not all the same between the drugs.
181
What is a topical analgesic?
Most pain is best treated with an internal analgesic, but some topical products are available for the relief of pain associated with minor sprains and joint pain. Topical diclofenac is one topical analgesic and anti-inflammatory with proven efficacy.
182
What are antihistamines?
Antihistamines are used for the treatment of allergy symptoms such as hay fever. These drugs block histamine receptors, thereby inhibiting the binding of histamine to its receptor, decreasing allergy symptoms.
Antihistamines are classified into first- and second-generation agents due to slight differences in their pharmacology.
First-generation antihistamines (diphenhydramine): cause sedation and
drowsiness.
Second-generation antihistamines (cetirizine): less sedating
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What are drugs for excess stomach acid?
Drugs for excess stomach acid are designed to either neutralize stomach acid or decrease stomach acid secretion. Acid secretion is an active process where protons are transferred into the stomach in exchange for potassium. This process is carried out by the proton pump.
Antacids: hold the pH of gastric contents at about four. All antacids neutralize gastric acid by an acid-base chemical reaction.
- Systemic: given orally and are absorbed by the gastrointestinal (GI) tract. (calcium carbonate rapidly neutralizes stomach acid and is well
tolerated, but large ingestion can cause hypercalcemia, and systemic alkalosis)
- Non-Systemic: given orally, but are not absorbed and thus do not cause systemic
alkalosis. (Aluminum hydroxide coats the mucosal lining of the stomach, protecting it from the acid. It is one of the more popular antacids and has a fast onset of action, but can decrease phosphate absorption, decreases absorption of other prescription drugs, and causes constipation).
H2 Receptor Antagonists:
- Without H2 Receptor Antagonist: when the histamine receptors in the acid secreting cells of the stomach are activated, the proton pump is turned on and acid secretion is increased.
- With H2 Receptor Antagonist: block the H2 receptors, reducing the amount of acid secreted. These agents are more effective than antacids and are free of major adverse effects,
although skin rashes, headache, and confusion
are infrequently reported.
Proton Pump Inhibitors: omeprazole permanently binds to the proton pump, inhibiting acid secretion by 90% or more. They are the most effective drugs available for suppressing acid secretion. The frequency of adverse effects is low and includes diarrhea, headache, and abdominal pain. These drugs were only available by prescription until recently.
184
What are decongestants?
Congestion is caused by the dilation of small blood vessels, which allows fluid to leak from the vessels into the spaces between cells. Decongestants cause constriction of blood vessels, preventing the accumulation of fluid and thereby reducing congestion.
A nose drop solution containing 0.5% phenylephrine or an oral tablet of pseudoephedrine are the drugs of choice.
Long-term use leads to local irritation and chronic rhinitis. Therefore, use should not exceed three days. Other common adverse effects include rebound congestion and
potential alteration of blood pressure.
185
When should cough suppressants be used?
Cough is a complex event involving signals from the bronchioles, which are processed by the
cough centre in the medulla of the brain.
In general, a productive cough should not be suppressed, but a non-productive cough should
be suppressed.
186
What are cough suppressants?
Centrally-acting Cough Suppressants: block
the processing of information in the brain, reducing the frequency of the cough. Codeine is present in some OTC cough suppressants. An alternative OTC cough suppressant is dextromethorphan hydrobromide (20-30mg/6hrs).
Peripheral Cough Suppressants: block the nerve endings in the throat and bronchioles, inhibiting the stimulus to cough. In these agents, camphor and menthol are added to vaporizers or rubbed on the throat and chest. The efficacy is questionable as they may exert a small response to inhibit peripheral nerves in the throat but the placebo response is likely to be the reason for any efficacy observed.
187
What are sleep aids?
Sleep aid preparations are intended to help an individual fall asleep or to relieve sleeplessness.
Melatonin: a hormone that plays a key role in the body’s internal sleep-wake cycle. Melatonin in a purified drug form can be used to help combat jet lag after travelling across time zones or adjust sleep-wake cycles
Many night-time preparations of OTC drugs also exist, like NyQuil and Aleve PM. These preparations have added first generation antihistamines (diphenhydramine) in an attempt to produce sedating effects.
188
What are laxatives?
Laxatives increase excretion of a soft-formed stool by increasing gut motility or hydration of the stool. This may be necessary to relieve constipation, prior to radiological examination, prior to bowel surgery, or for patients suffering from cardiovascular disease or hemorrhoids, as any straining would make these conditions worse.
Stimulant (bisacodyl): increase motor activity of the intestine and increase secretion of mucus, water, and electrolytes into the intestine
- Adverse effects: cramping, water and electrolyte disturbances, and functional disturbances in the GI tract with long-term use.
Bulk Forming and Osmotic Laxatives: bulk-forming laxatives (methylcellulose) swell in water to form an emollient gel or viscous solution that maintains soft stool. These indigestible bulk substances may also indirectly stimulate peristalsis. Osmotic laxatives (polyethylene glycol 3350) draw water into the stool, resulting in softer stool. Full effect for both occurs 2 to 3 days after therapy has begun.
- Adverse effects: water and electrolyte disturbances
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What are antidiarrheal agents?
Antidiarrheal agents are used to control diarrhea. The major concern with diarrhea is dehydration, especially in young children and the elderly. Antidiarrheals should not be used if the diarrhea is accompanied by fever or if blood
or mucus is in the stool.
Adsorbents: add bulk to the GI tract and may absorb toxins. They are useful to control the acute symptoms of self-limiting diarrhea (e.g., Pepto-Bismol).
Loperamide: a synthetic opioid that does not penetrate into the CNS. It inhibits gut motility by acting on opioid receptors in the GI tract, reducing peristaltic activity. It is effective for mild to moderate non-infectious traveller’s diarrhea, as it inhibits cramps. It is the drug of choice.
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What is hydrocortisone cream?
0.5% or 1.0% hydrocortisone is a topical anti-inflammatory agent used for exposure to poison ivy, poison oak, poison sumac, insect bites, and any inflammatory condition that is treated topically.
Calamine lotion: commonly used and gives temporary relief, if exposure is mild, by preventing itching, but does not modify the inflammatory response.
191
Discuss sunscreens.
It has been estimated that about 75% of some forms of skin cancer are caused by UV radiation
emitted by the sun. Use of a good sunscreen is recommended for everyone older than 6 months of age everyday when going outside, which reduces the risk of common skin cancers by 40-50%.
Chemical: contain compounds that absorb UV rays before they can penetrate into your
skin, such as avobenzone and octisalate.
Physical: contain minerals, such as titanium dioxide and zinc oxide, that block and scatter UV rays before they can enter lower layers of the skin
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What drug interactions can occur with OTC preparations?
Antihistamines interact with other CNS depressants, such as alcohol, sedative-hypnotics, and opioids.
ASA given with oral anticoagulants may produce bleeding. ASA prevents platelets from adhering to each other, which is necessary to stop a cut from bleeding.
Antacids change the pH of the stomach acid and coat the stomach lining, so they interfere with the absorption of some drugs
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What are herbal drugs?
Herbal drugs refer to plants or plant parts that are used to prevent or treat illness, or improve health. Approximately 80% of the world’s population is reported to use herbal drugs for treatment of illness and disease. The use of herbal drugs is gaining popularity in Canada.
General Public: the desire of the general public to use natural products, which they believe are safer than conventional or allopathic medications. However, botulinum toxin, produced naturally by a microorganism, is one of the most toxic substances known to science.
Manufacturers and Retailers: promote these products for financial gain.
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What is the history of herbal drugs?
The practice of medicine prior to the 1940s depended on a large number of natural products, including opium.
The 1950s heralded the era of the purified natural product (morphine). The pharmaceutical industry developed thousands of synthetic drugs.
Many of today’s drugs are still derived from these natural sources.
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What are the classifications of medicinal products?
Allopathic Medicine: drugs used by mainstream medicine. These drugs have a drug identification number from Health Canada and have undergone full testing for safety and
efficacy.
Herbal Medicine: plant products being sold to treat a condition and do not have a DIN. These products, which are unpurified, often lack phase 3 clinical trial data.
Phytopharmaceuticals: drugs obtained from plants which are purified and used at
therapeutic doses with scientific evidence of efficacy and documented toxicity.
Allopathic Phytopharmaceuticals: drugs obtained and purified from plants that meet all the requirements of a drug, and therefore have full status as a drug.
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What is the value of plants for pharmaceuticals?
Plants have a number of uses in the preparation of both herbal and allopathic drugs. They are a direct source of some therapeutic agents. Plants also provide a source of raw material for the manufacture of modified semi-synthetic compounds with altered properties, such as increased efficacy.
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What are the problems with herbals?
One of the problems with herbals is the lack of RCT evaluating efficacy and safety of herbals. In 2004, Canada introduced new regulations that began the process of better regulations for herbal products to ensure their efficacy and safety.
Another problem associated with herbals is having to carefully interpret the literature. The
literature aimed at the general public often overstates the efficacy of herbal preparations. The Natural Medicines Comprehensive Database provides evidence-based information
on herbal medicines, rating the effectiveness of herbal products on a scale.
Lack of Standardization: current legislation should address the problem of quality control during the manufacture of herbal products. compliance with appropriate standards of purity and content will depend on the extent of inspections by Health Canada.
Intentional Adulteration: the addition of substances other than the herbal (inactive
materials and dyes to increase weight, and allopathic drugs to increase the effectiveness of the drugs, such as cocaine, NSAIDs, estrogens, and/or sildenafil).
Differing Global Standards: facilities and processes in other countries may not be inspected using the same standards used in Canada.
Drug Interactions with Allopathic Medicines: drug-drug interactions occur between prescription and herbal drugs. Therefore, it is
important to inform physicians of the use of any herbal medications.
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What is St. John's Wart?
St. John’s Wort is likely effective
for mild to moderate depression. Herbalists recommend St. John’s Wort to treat mild to moderate depression and to heal wounds.
The active ingredients are hypericin and hyperforin, which have true antidepressant activity. St. John’s Wort is less effective
than other antidepressants, however, it is superior to placebo in mild to moderate depression.
Toxicities:
* confusion, agitation, shivering, fever, sweating, diarrhea, muscle spasms, and tremor.
* phototoxicity.
* serotonin syndrome.
* products with St. John’s Wort and ephedra cause additive CNS excitation
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What is Aloe Vera?
Aloe vera is possibly effective for cold sores and minor skin irritations. Herbalists recommend aloe vera to be applied topically in a gel or
cream as an aid in the healing of wounds and burns.
The active ingredients are mannans and anthraquinones. The mechanism of action in wound healing is thought to be an increase in the microcirculation of the skin.
Upon ingestion, aloe vera causes severe diarrhea. Therefore, ingestion
should be avoided
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What is Devil's Claw?
Devil’s claw is possibly effective for osteoarthritis and back pain. There is
insufficient evidence for all other suggested indications. Herbalists recommend devil’s claw for a number of ailments ranging from migraine to kidney disease. However, it is mainly used for the treatment of inflammatory conditions.
The active ingredients are iridoid glycosidesthat have some anti-inflammatory properties, but they are inactivated in the acid of the stomach.
Toxicities: the most common is diarrhea.
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What is Panax Ginseng?
Panax ginseng is possibly effective for thinking and memory, erectile dysfunction, multiple-sclerosis related fatigue, sexual arousal, and
reducing the risk of developing influenza. Panax ginseng is said to enhance memory, learning, productivity, and the immune system. It is also claimed to reduce blood sugar in a diabetic person.
The active ingredients are ginsenosides and panaxosides.
Toxicities: headache, high blood pressure, and bleeding. Ginseng can also increase insulin levels in the blood. Therefore a diabetic taking insulin should not also take ginseng.
202
What is Echinacea?
Echinacea is possibly effective for the common cold. Herbalists recommend echinacea for the prevention and treatment of the common cold, for wound healing, and as an anti-inflammatory
agent.
The active ingredients are echinacein, cichoric acid, and caffeic acid. Echinacea extracts can
stimulate T-lymphocytes for immunity.
Toxicities: rare but include allergic reactions and patients with autoimmune disease (lupus) should not use this herbal, as any effect on the immune system could make conditions worse.
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What is Valerian?
Valerian is possibly effective for mild insomnia. Herbalists recommend valerian for the treatment of anxiety and panic attacks.
The active ingredients are a group of compounds known as valepotriates.
Toxicities: liver toxicity and CNS depressant properties can impair the ability to operate a motor vehicle.
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What are vitamins?
A vitamin is a substance essential for the maintenance of normal metabolic functions but is not made in the body and, therefore, must be provided from an outside source. Vitamins
participate in a diverse array of metabolic pathways.
Vitamins are classified into two main categories:
Water-Soluble: Vitamin C and eleven vitamins in the B group are water-soluble.
Fat-Soluble: Vitamins A, D, E, and K are fat-soluble.
When a person obtains vitamins from a healthy diet, the vitamins in the food are not considered drugs. However, when vitamins are consumed as a tablet in a chemically pure form, they are considered drugs.
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When are vitamins used as dietary supplements?
Need for Increased Nutrition: nutritional requirements may be necessary during periods of growth, hard physical work, pregnancy, chestfeeding, menstruation, or stress. Increased requirements may also be caused by hyperthyroidism, fever, tissue wasting disorder or long-term immobilization.
Absorption Disturbances: disturbances in GI absorption can be due to prolonged diarrhea, surgery involving an absorptive area of the intestine, or liver disease. Absorption disturbances may also occur due to an individual taking antibiotics that alter intestinal bacteria, as vitamin K and biotin require synthesis by intestinal bacteria into usable forms within the body.
Inadequate Nutritional Intake: associated with individuals who consume an inadequate diet
for a variety of reasons, including poverty and/or geograpy, individuals with SUD who have inadequate food intake, and individuals on restricted diets.
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What are the approaches to vitamin therapy?
Nutritional Approach: an individual selects a diet aimed at supplying the recommended dietary allowance for each vitamin, or a multivitamin preparation that supplies the RDA of each vitamin.
Megavitamin Approach: individuals ingest vitamins in excess of the RDA. Consuming vitamins in this way has a few consequences. The excess of some water-soluble vitamins is
rapidly excreted in the urine, but overdosing of
vitamin B6 (pyridoxine) can cause nerve injury.
In addition, it is clear that taking high doses of the fat-soluble vitamins A, D, and E can accumulate in body fat and can cause severe toxic effects.
207
Discuss vitamin A.
Vitamin A is a fat-soluble vitamin.
Food Sources: only in animal products, such as liver, milk fat, and egg yolk. Other compounds, such as carotene found in carrots, are pro-vitamin A, as they have to be converted to vitamin A in the body.
Functions: required for growth and development, for normal structure of the mucous membranes and epithelial cells, and as a constituent of a complex molecule in the rods of the eye, called rhodopsin, which is required for night vision.
Uses and Effects: vitamin A has several important therapeutic uses. Additionally, vitamin A deficiency or excessive intake of vitamin A are associated with negative effects.
- Therapeutic Uses: infancy, pregnancy, and
lactation, the treatment of acne and other skin diseases including psoriasis and skin cancers.
- Deficiency: result in a delay of growth and development, night blindness and drying of the surface of the eye, changes in cells lining the bronchioles in the lung which enhances the
opportunity for respiratory infection, and dry, thick, and horny skin.
- Excessive Intake: result in dry itchy skin, vomiting, headache, and an enlarged liver
and spleen.
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What are retinoids?
Retinoids are vitamin A derivatives. Retinoids, specifically oral forms, are associated with a number of serious adverse effects, including damage to an unborn child, depression, diabetes, and liver disease. For these reasons, the use of retinoids must be monitored by a clinician.
209
Discuss vitamin D.
Vitamin D is a fat-soluble nutrient.
Food Sources: meat, fish, and mushrooms. In several countries, milk is fortified with vitamin D.
Function: increases the absorption of calcium and phosphate from the intestine, which is needed for new bone formation. It is also involved in the regulation of blood calcium level and in the removal of calcium from older bone.
Uses and Effects: vitamin D is an important nutrient for bone health.
- Therapeutic Uses: prevention of osteoporosis.
- Deficiency: 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 in an attempt to maintain blood calcium levels. As a result, defective bone growth occurs in infants and children leading to bowleggedness or rickets.
- Excessive Intake: result in elevated calcium levels in the blood. Calcium is deposited
in several tissues, including the kidney, heart, lungs, blood vessels, and skin. During pregnancy, the fetus also suffers from the high blood calcium level. This is particularly concerning for individuals with kidney or heart disease. Excessive vitamin D intake may also cause excess removal of calcium from bone and fatigue, nausea, vomiting, diarrhea, and impaired kidney function.
210
Discuss vitamin E.
Vitamin E is a group of fat-soluble compounds.
Food Sources: naturally occurring tocopherols that are present in vegetable oils and some green leafy vegetables.
Function: essential for a number of biochemical reactions, including a role as an antioxidant and
protecting cells in the cardiovascular system and other tissues from the damaging effects of free radicals.
Uses and Effects: vitamin E acts as an antioxidant.
- Therapeutic Uses: useful in the treatment of premature babies with an uncommon type of hemolytic anemia.
- Deficiency: rare as the tocopherols are so prevalent in our diets. It may occur in conditions of a malabsorption syndrome (Crohn’s disease).
- Excessive Intake: inhibit platelet aggregation and contribute to the anticoagulant effect of warfarin.
211
Discuss vitamin B12.
Vitamin B12 (cobalamin) is water-soluble. Folate or folic acid is vitamin B9 and is found in many foods.
Food Sources: vitamin B12 is found in meats and dairy products. Fresh green vegetables, liver, and yeast are especially high in folate.
Function: work together in the synthesis of red blood cells.
Uses and Effects: ingestion of vitamin B12 and folic acid is associated with health benefits
as well as harmful effects.
- Therapeutic Uses: absorption decreases with age, so elderly individuals may need to
increase vitamin B12 intake. The RDA for folic acid increases in pregnant women to help prevent deficiencies that may lead to
neural tube defects (spina bifida) in the unborn child. It is recommended that any woman
anticipating pregnancy should begin taking prenatal vitamins before they become pregnant.
- Deficiency: alcohol misuse or malabsorption syndromes can lead to deficiencies of both vitamin B12 and folate. If vitamin B12 cannot be absorbed from the intestines, a condition known as pernicious anemia can occur. Certain drugs may result in folate deficiency.
- Excessive Intake: no significant toxic effects have been associated with vitamin B12.
Folic acid is generally considered non-toxic when taken as a supplement. However, it can mask undiagnosed pernicious anemia, leading to a delay in treatment. In addition, since antifolate medications are now used in cancer chemotherapy, further research regarding the safety of folic acid supplements is required.
212
Discuss vitamin C.
Vitamin C (ascorbic acid) is water-soluble.
Food Sources: fruits and vegetables.
Function: 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.
Uses and Effects: used to prevent and treat scurvy.
- Therapeutic Uses: prevention and treatment of scurvy. Under one special circumstance (very fit), supplementation with vitamin C may be beneficial for the cold. It has long been claimed that the antioxidant activity of vitamin C may be of use in preventing cancers, as it may be useful in combination with other proven anticancer drugs.
- Deficiency: result in scurvy. Symptoms of scurvy include weakness, bruising, anemia,
loose teeth, and bleeding gums.
- Excessive Intake: result in diarrhea, formation of kidney stones, and rebound scurvy
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A supplement of which of the vitamins is recommended for women of childbearing age to decrease the incidence of neural tube defects such as spina bifida in their offspring?
Folic acid
214
What are food additives?
Food additives are substances that are added to food to improve the appearance, texture, and storage of food. This may include substances added during the processing of food or added to improve nutritive value.
Intentional: substances that are added to food to improve the appearance, texture, and storage of food.
* Vitamins and minerals
* Flavours
* Colours
* Preservatives
* Texture agents
Unintentional: added inadvertently as a result of the growing, manufacturing, and storage processes of food. These are contaminants and the amount present in food is limited by regulations.
* Fertilizers
* Pesticides
* Heavy metals
* Biohazardous contamination
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What are the food additive regulations in Canada?
The regulation of food additives in Canada is 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.
If a particular food additive is not on this list, the manufacturer is required to submit information on the proposed use, evidence of safety, and information on the effectiveness of the additive. The submission is then evaluated by Health Canada scientists before approval is granted.
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Why is the safety of food additives important?
* Consumed without our knowledge
* Taken for a lifetime by the entire population.
* Healthcare professionals are not involved
* Young children are exposed
* They are not essential for life.
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How is the toxicity of a food additive determined?
The efficacy of a food additive is easily determined, but a number of problems are associated with assessing toxicity. The risk/benefit ratio of additives must be carefully determined. The technique used to determine risk/benefit is to study the toxicity in animals and then extrapolate the results to humans.
Exposure: extent of exposure in humans is difficult to replicate in animals. Additives are administered to animals for one or two years, while humans can be exposed their entire lives.
Assumption of Risk: the acceptable
human dose is then taken as 1/100 or 1/1000 of the maximum no-effect dose in animals. The
assumption made is that studying high doses in animals will mimic low-dose, lifetime exposure
in humans. The human exposure is based on estimates of the intake of that particular food.
Fortunately, the assumptions tend to overestimate the actual risk.
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What is the rationale for the use of food additives?
Function: use is justified if they enhance or maintain the quality or acceptability of food.
Quantity: should be used only in quantities sufficient to obtain stated ends.
Purity: should be pure.
Toxicological Evaluation: should be undertaken for information be gathered and utilized to determine potential risk.
Special Groups: should be considered.
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Discuss a specific population that is impacted by food additives.
In the 1960s, a number of deaths due to cardiac causes occurred in a group of individuals with
no apparent risk factors for heart disease. The causative factor was found to be cobalt chloride, a compound which inhibited the heart muscles from functioning. Cobalt chloride was added to beer to control the amount of foam.
Individuals would need to consume 24 beers every day for long periods of time would receive a toxic dose of cobalt chloride.
220
What are flavouring agents?
Flavouring agents are quite prevalent in foods. With thousands of flavouring agents in use, testing has not been as thorough as other food additives. However, toxicity issues remain quite rare.
Types: substances such as flavouring agents and enhancers, essence of smoke, and synthetic flavours. Since 1975, there has been a large increase in the use of simulated
flavours. These additives are mixtures of artificial flavours.
Evaluation: difficult to evaluate such a large number of substances. Four to five thousand flavourings are in use and most have not been adequately tested, but are approved due to the experience obtained over years of use.
Toxicity: very few flavourings have demonstrated toxicities. However, the flavour
enhancer monosodium glutamate causes a tightening of muscles in the face and neck,
accompanied by headache, nausea, and giddiness.
221
What are colouring agents?
Colouring agents are organic dyestuffs added to give food an appetizing appearance. Most are well evaluated.
Allergic reactions have occurred to food colours. The most common reaction is
to tartrazine, a yellow food colour. If an individual is allergic to aspirin, they may also be allergic to tartrazine.
Canada allows only 10 food colours to be used, the USA allows 11, and some countries allow much more (Denmark allows 33). Canada has banned the use of Red Dye No. 2, as it produced cancers in experimental animals at high doses
222
What are texture agents?
Texture agents are added to improve or impart a specific texture to a product. These substances are found in foods in relatively high concentrations of up to 1-3% of the product. As a class, these agents possess little or no toxicity.
Silicates: added to flour and flour products to keep them free flowing.
Emulsifying/Thickening: added to a number of frozen foods.
223
What are preservatives?
The use of agents to preserve the quality of food is one of the more rational uses of additives. It allows for the delivery of food to distant destinations and ensures the appropriate quality of the food for the consumer. In most cases, the benefit outweighs the risk.
Antibacterials:
* Smoke: age-old method of preserving meat. The major concern is that natural smoke carries a small carcinogenic risk. Some of the currently used smoke flavouring products have had the carcinogens removed.
* Antibiotics: not used in Canada to prevent the emergence of antibiotic resistant organisms.
* Sodium Nitrite: added to meat to impart a pleasing red colour to prepared meats and to inhibit growth of Clostridium botulinum. An adverse effect of sodium nitrite is the formation of nitrosamines, which are known carcinogens.
Antioxidants: prevent oxidation, rancidity, and discolouration of foods. They improve
storage and quality of the product.
*Water-Soluble: added to foods to reduce the oxidation of carbohydrates (ascorbic and citric acids).
*Lipid-Soluble: added to foods to prevent fats from becoming rancid
Some of the antioxidants have been shown to cause liver damage. Tocopherols (vitamin E) are also used as antioxidants. They are less effective than some of the other antioxidants used, but possess a lower toxicity risk.
224
What are sweeteners?
While sugar is the most common sweetener in food, two common agents that have been used in addition to sugar are saccharin and aspartame.
Saccharin: first artificial sweetener developed and was added to numerous products. Use was restricted in Canada based on studies that demonstrated a potential for it to cause
cancer. However, in 2016 the Health Canada Food Directorate completed a detailed safety assessment on saccharin and removed the restriction, allowing saccharin to be in tabletop sweeteners.
Aspartame: only toxicity of note associated with aspartame is that individuals with phenylketonuria cannot tolerate phenylalanine, one of the amino acids in aspartame.
225
What are environmental toxicants?
An environmental toxicant can be defined as a chemical that is released into the environment and that can produce adverse health effects on living organisms.
226
Whats the difference between acute and chronic toxicity?
Acute Toxicity: associated with a single exposure to a chemical and often a large
dose of the chemical.
Chronic Toxicity: associated with repeated exposure to small doses of a chemical over a
long period of time.
Example: Aflatoxin B1 is a common food contaminant. Acute toxicity of aflatoxin B1 can result in liver necrosis, liver failure, and death, while chronic toxicity of aflatoxin B1 can cause liver cancer.
227
What is air pollution?
Human contribution to air pollution has a long and complicated history. This toxicant can be divided into two main categories: particulate matter and gaseous air pollutants. They can be attributed to both natural and anthropogenic sources.
1273: first anti-pollution law was established by Edward I, King of England. He made it illegal to burn coal while the punishment was decapitation.
1900s: first automobiles were manufactured and the number of vehicles went from zero to millions. The gasoline internal combustion
engines became, and still are, a major source of air pollution.
1952: “Killer smog” in London, England was responsible for an estimated 4000 deaths, where the main causes of death were bronchitis, pneumonia, and other respiratory illnesses. This event demonstrated the lethality of air pollution and led to the Clean Air Act.
1956: the Clean Air Act introduced a number of measures to reduce air pollution. One measure was to shift the source of home-heating towards cleaner coals, electricity, and gas, thereby reducing the amount of smoke pollution released from household fireplaces.
Particulate Matter: a mixture of tiny particles composed of non-gaseous pollutant. Can be solids or liquid droplets.
Gaseous Air Pollutants: carbon monoxide, carbon dioxide, nitrogen oxides, sulfur oxides, hydrogen sulfide, and ozone
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What are sources of air pollutants?
Natural Air Pollutants: include volcanoes, forest and prairie fires, and dust storms.
Anthropogenic Air Pollutants: man-made air pollutants.
* Heating and Power: combustion of fossil fuels releases carbon dioxide, carbon monoxide, sulfur oxides, and nitrogen oxides. Coal is the largest contributor to the human-made increase of carbon dioxide in the air.
* Automobiles: exhaust releases smoke, lead particles, carbon monoxide, and nitrogen oxides. In the late 20th century, governmental regulations forced the decrease of emissions, particularly with the use of low-lead or unleaded gasoline. More recently, emission testing and green vehicles have helped
to reduce the impact of automobile emissions.
* Industrial Processes: release a wide variety of pollutants. The types of pollutants depend on the manufacturing processes. Examples include acids, solvents, chlorine, ammonia gas, and metals.
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How does air pollution impact human health?
The predominant health effect associated with air pollution is chemical irritation of the respiratory tract. Certain subpopulations are particularly susceptible to air pollution, including very young children, older adults, and people with cardiorespiratory diseases such as asthma.
In most cases, the health problems are due to the combined action of particulates and sulfur oxides, but no single pollutant seems to be responsible.
230
What is tobacco smoke?
Tobacco smoke is another important environmental toxicant. Environmental tobacco smoke, or secondhand smoke, is the combination of mainstream smoke and sidestream smoke.
Secondhand Exposure: exposure to secondhand tobacco smoke can cause lung cancer. Exposure to environmental tobacco smoke carries the same health risks as directly smoking. Since non-smoking adults and children may be involuntarily exposed to
environmental tobacco smoke, numerous bylaws have begun to be put in place to restrict the areas where a person is allowed to smoke in public.
231
What are pesticides?
Pesticides are used to intentionally kill organisms. Insecticides and herbicides are the two major classes of pesticides that act as environmental toxicants
232
Discuss insecticides.
Insecticides are chemicals used to kill insects or to make insects unable to reproduce or develop
normally.
Organochlorine Insecticides: increase the sensitivity of neurons, resulting in increased CNS stimulation that manifests as tremors, convulsions, and eventually, death.
-Health Risk: can present long-term
problems that are not completely understood.
-DDT: originally introduced in 1945 to control malaria-containing mosquitoes. It was very effective and widely used until the 1970s, when use stopped because: Insects were developing resistance, bird and fish populations were decreasing, soil and water concentrations were increasing, and levels of DDT in food was increasing
Organophosphorus Insecticides: first synthesized during World War II to be used as
potential warfare agents. Since then, selective organophosphorus insecticides have been developed (Malathion) that require metabolic activation to work. This occurs rapidly in
insects. These agents are relatively unstable and break down in the environment. Therefore, they are considered to have a small impact on the environment, overall.
- Toxicity: very toxic to humans. They are absorbed through the skin and are the leading cause of poisoning in the agricultural sector.
- Mechanism of Action: irreversibly inhibit acetylcholinesterase for breaking down acetylcholine in the synaptic cleft.
- Effects: If AchE is inhibited, then acetylcholine
is no longer broken down, leading to an increase in acetylcholine in the nervous tissue.
This results in increased acetylcholine-mediated
neuronal firing throughout the body, resulting in decreased heart rate, severe difficulty breathing, fecal and urinary incontinence, and
blurred vision. Death can occur due to
respiratory failure.
233
Discuss herbicides.
Herbicides are chemicals capable of killing or injuring plants.
Agent Orange: a mixture that was used extensively in the Vietnam War as a defoliant to make it easier to spot targets hidden by tree cover. It acts by mimicking plant growth hormones, causing uncontrolled, unsustainable growth, leading to plant death.
- TCDD: introduced during the manufacturing process of Agent Orange. TCDD binds to the aryl hydrocarbon receptor, which is involved in the expression of many genes required for normal cellular functioning. Toxicity manifests as chloracne, impairment of liver, decreased CNS function, an increased occurrence of certain cancers, and birth defects or stillbirths.
Paraquat: the most widely used herbicides, however, it is highly toxic when ingested. Causes cellular damage and, when ingested, it causes immediate burns to the mouth and stomach. Regardless of the route of entry, the primary target of paraquat toxicity is the lungs, where cellular damage results in the development of fibrous tissue that inhibits the ability to breathe. Ingestion of as little as two teaspoons can cause death due to lung damage.
234
Discuss lead toxicity.
Lead is a ubiquitous, naturally-occurring element found in the environment and in many different chemical compounds. The two main toxic compounds containing lead are lead oxide and tetraethyl lead.
Lead Sources:
* Old Paint: in the 1950s, lead was used to make paint dry quickly, wear well over time, and to make colours vibrant. This was especially problematic for young children because of their tendency to put everything into their mouths and they are more susceptible to lead toxicity
as they absorb 35-50% of ingested lead
* Industry: lead-acid car batteries account for the most significant proportion of global lead consumption. Industries that use lead release lead emissions into the air, both in the workplace and in the surrounding area. Some of the airborne lead emissions can ends up in the soil where it can contaminate fruits and vegetables. As well, children may be exposed to lead when eating dirt.
* Leaded Gasoline: up until the 1970s, tetraethyl lead was used as an additive in gasoline to increase engine compression, thereby increasing fuel economy. During fuel combustion, the lead was oxidized to form lead oxides which were released into the atmosphere.
Lead Toxicity: affects the functioning of multiple systems in the body.
* CNS: decrease in
appetite, irritability, and fatigue. Permanent brain damage, known as lead encephalopathy,
can occur. This results in learning deficits, epilepsy, and blindness.
* PNS: degeneration of the motor nerves occurs which results in the loss of coordination and the appearance of being clumsy.
* Kidneys: dysfunction is due to the impairment of energy metabolism involving the mitochondria within the kidney.
* Blood: decreases the biosynthesis of heme, the iron-containing component of hemoglobin, leading to decreased lifespan of red blood cells. This results in anemia.
235
Discuss mercury toxicity.
Mercury is another naturally-occurring element that poses health risks to humans. Mercury can be found in the water and in the air. The main contamination source of mercury is the industry, where it is used in the preparation
of chlorine and sodium hydroxide as an electrode.
Individuals may be exposed to mercury in the air, where it exists as mercury vapour, or through food. The major source of exposure for humans is ingesting fish from mercury-contaminated water, as mercury in the water is accumulated and concentrated through the aquatic food chain. The bioamplification of mercury levels in common fish.
Mercuric Mercury: inhalation of vapours containing mercury. Only 15% of mercuric mercury is absorbed into the body. However, it accumulates in the kidneys and is very toxic to these organs.
Methyl Mercury: converted to methyl mercury by bacteria and fish in water. Methyl mercury is the most toxic form of mercury. 90% of it is absorbed from food after eating. Methyl mercury targets the CNS, where it enters the brain, binds to nerve cell proteins, and leads to
nerve cell death.
- Acute toxicity: irritability, numbness and tingling, vision and hearing loss, tremor, and paralysis.
- Chronic toxicity: coma and death.
Treatment: chelating agents work for mercuric
mercury poisoning. Methyl mercury poisoning can be treated with charcoal if the mercury was recently ingested, which will prevent the methyl mercury from being absorbed into the body.
236
Discuss Bisphenol A toxicity.
Bisphenol A (BPA) is an industrial chemical used to make polycarbonate which has been used in many consumer products including reusable water bottles and baby bottles. BPA is also found in epoxy resins, which act as a protective lining on the inside of metal-based food and beverage cans.
Source: through the diet where minute quantities of BPA can leach out of containers and into the water or food. The rate at which this occurs increases with heating, leading to concern over the effects of microwaving containers composed of BPA.
BPA Toxicity: can bind to estrogen receptors and mimic some effects of estrogen. It has been proposed that synthetically-derived estrogen compounds such as BPA could play a role in reproductive cancers, fertility problems, and
altered brain development in infants.
Addressing Toxicity:
* General Population: controversy has arisen over whether BPA is toxic to humans. The current dietary exposure to BPA is not expected to pose a health risk to the general population, including newborns and infants.
* Infants: newborns and infants are at the
greatest risk of exposure due to their small size.
* Environment: accumulation in bodies of water would harm fish and other organisms. Regulations to limit the maximum concentration of BPA that can be released into the environment.
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What are the adverse effects of pharmaceuticals in the environment?
Unlike other environmental pollutants, the potential adverse effects of pharmaceuticals on human health are well known, as preclinical and clinical studies have established both the beneficial and toxic effects on humans prior to marketing. Thus, it is possible to predict the adverse effects of pharmaceuticals in drinking water on the human population. It is more difficult, however, to predict the effects on aquatic animal and plant life.
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How do pharmaceuticals enter the environment?
Use in Agriculture: increased levels of antibiotics in groundwater and soils as pharmaceuticals are used to treat farm animals, the agent is excreted, and the resulting manure is spread on the fields as fertilizer. This leads to the contamination of soil, ground water, and eventually, waterways.
Treatment of Pets: pharmaceuticals will be metabolized and excreted as they are in humans, and will find their way into surface and groundwater systems.
Disposal of Medication: 25% of unused drugs are washed down the sink or flushed down the toilet, which find their way into sewage discharge. About 30% of all unused drugs are thrown into the garbage and disposed of in a landfill, which can contaminate groundwater.
Aquaculture: antibiotics in aquaculture is extensive as they are used to prevent disease and to promote rapid growth to maturity. As aquaculture is concentrated at certain locales, high local concentrations of the antibiotics may exist.
Human Prescriptions: administration and excretion of prescription drugs is one of the major sources of pharmaceuticals in the environment. A percentage of all drugs consumed by humans are excreted unchanged or as active metabolites. These excreted drugs are passed into the municipal wastewater systems. Treatment of sewage may or may not remove the pharmaceuticals.
Manufacturing Processes: discharge from manufacturing plants have a major effect in local surface and groundwater. The impact of this source of pharmaceutical release on the environment will increase over time, as the chemical facilities are moving to developing countries that have less environmental standards than North America.
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Discuss neuroactive drugs in the environment.
The use of neuroactive drugs has increased by 60% over the last decade. These drugs have been detected in surface water, groundwater, and soils.
Sewage treatment plants reduce but do not effectively remove this group of drugs from the effluent. As with most other pharmaceuticals, the exposure of humans to neuroactive drugs in the environment appears to be minimal.
One concern is that concentrations of SSRIs present in surface waters have had deleterious effects on the reproduction and physiological development of fish.
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Discuss steroid hormones in the environment.
The steroid hormones of most concern are estrogenic compounds. Sources of estrogens in the environment include ethinyl estradiol from oral contraceptives and excretion of natural estrogens by animals, including humans.
The concentrations of steroid hormones in the environment and in drinking water are in the ng/L range, which is well below the level where effects are observed.
Additive Effect: human exposure to estrogens and endocrine disrupting agents.
Reproduction and Maturation: deleterious effect of low concentrations of steroid hormones on the reproductive capacity and sexual maturation of aquatic animals.
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Discuss antibiotics in the environment.
The major source of antibiotics in the
environment is their use in agriculture, where these agents are added to feed to enhance
animal growth.
The use of antibiotics in agriculture can result in the development of resistant strains of bacteria and the transfer of these resistant bacteria to human infections. Another concern is the biomagnification of antibiotics in edible plants and animals, leading to low-level exposure of antibiotics to humans.
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Discuss antihypertensive drugs in the environment.
Approximately 30% of Canadians are treated daily for hypertension. This number will increase as the population ages.
While most antihypertensive medications have been measured in surface water, the concentrations are in the n g/L range, which is well below levels that would be toxic to humans.
The questions that remain to be answered are whether these compounds are biomagnified in the food chain, and what concentrations are present in the seafood we eat
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Discuss analgesics in the environment.
Ibuprofen, naproxen, and ASA are the most commonly observed in the environment, due to their high frequency of use.
The concentration of analgesics in drinking water do not pose a risk to human health and the acute toxicity of analgesics in the environment appears to be minimal on aquatic species.
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What are the sources of human exposure to pharmaceuticals in the environment?
The two potential sources of human exposure to pharmaceuticals in the environment are drinking water and bioaccumulation in food sources.
While standards for permissible levels of pesticides in drinking water exist, no such regulations exist for pharmaceuticals.
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What determines the concentration of pharmaceuticals in the environment?
* Extent of use
* Dose administered
* Persistence in the environment
* Ability of sewage treatment to remove
The minimum therapeutic dose is used for determining the risk of various concentrations of a pharmaceutical in the environment to humans.
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How can you reduce the risk of pharmaceuticals in the environment?
1. Reduce discharge from factories bwith etter regulations
2. The potential effect of pharmaceuticals on the environment should be considered as part of the licensing process.
3. Municipal sewage treatment plants have to be designed to remove pharmaceuticals in
wastewater.
4. Unused pharmaceuticals must not be discharged into the sewers and landfills. There is a requirement for “take back programs” at pharmacies for proper disposal.
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Which organism is at the greatest risk from pharmaceuticals in the environment?
Fish
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What is cancer?
Cancer refers to a group of diseases that primarily affects Canadians 50 years of age and older. In fact, 45% of males and 43% of females will develop cancer at some point in their lives.
In addition, about 30% of all deaths in Canada are due to cancer. The most common types of cancer in Canada are lung, breast, colorectal, and prostate, with lung cancer being the leading cause of cancer death.
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What are the key features of cancer cells?
Cancer is a generic term for a large number of diseases that involve abnormal groups of cells.
Cell Growth & Division: ability to proliferate indefinitely.
Invasion: ability to invade surrounding normal tissue.
Metastasis: ability to spread throughout the body.
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What are the main causes of cancer?
Genetics: genetic makeup contributes to a variation in response to carcinogens. For example, people who have Xeroderma pigmentosum have a genetically-based
deficiency in DNA repair. As a result, these people are prone to mutations and, therefore, have a high incidence of skin cancer.
Environmental Factors: include all non-genetic elements such as environmental chemicals, diet, and infections. These factors are modifiable, meaning a person can decrease the risk of exposure to detrimental environmental factors.
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What are the steps in carcinogenesis?
1) Initiation: starts with a procarcinogen, and ends with either a normal cell or a cancer cell.
* Procarcinogen: environmental carcinogens are inactive chemicals that undergo metabolic activation by drug metabolizing enzymes in the body.
* Ultimate Carcinogen: highly reactive forms of chemicals react irreversibly with a DNA molecule, damaging the DNA.
* Normal Cell: the DNA returns to as it was and the cell remains a normal cell.
* Cancer: if the DNA is repaired incorrectly or is not repaired at all, permanent DNA damage occurs, causing a change in the chemistry of the gene.
The cells must divide (cell proliferation) to make the genetic change, or mutation, permanent.
2) Promotion: once a cell has been mutated by an initiator, it is susceptible to the effects of promoters. These compounds promote division and proliferation of the cell, giving rise to
many cells with the same genetic defect as the original initiated cell. Promoters typically have no or minimal effect on uninitiated cells.
3) Progression: the rapid growth of tumours once they are established, increasing the malignancy of the tumour. In general, cancer is characterized by a long latent period between the time of exposure and the development of the disease. (lung cancer doesn’t develop until about 20 years after a person starts smoking)
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How does tobacco use impact cancer risk?
Smoking causes many cancers, including lung, esophageal, bladder, and pancreatic cancers. In addition to genetic factors, whether smoking results in the development of cancer will depend upon the tar content of the cigarettes smoked, the frequency of smoking, and the duration of the habit.
Smokers are eight times more likely to develop lung cancer than non-smokers. Passive smoking is also a risk factor for cancer. In fact, more than 800 Canadians who do not smoke die from secondhand smoke every year.
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How does diet impact cancer risk?
Saturated animal fat and red meat are strongly linked to cancer of the colon, rectum, and prostate. High intake of salt has been linked to stomach and other cancers.
Skimping on fresh fruits and vegetables can contribute to many different types of cancer. It is thought that fruits and vegetables contain constituents that block cancer-inducing chemicals produced in the body
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How does occupation impact cancer risk?
In the developed world, strict control measures have cut down on cancer caused by occupational exposure to carcinogens. However, these measures are not as well instituted in developing countries, making it likely that carcinogens in the workplaces are a major hazard.
Asbestos - Lung: Brake-lining, shipyard, insulation, and demolition workers
Benzene - Leukemia: Painters, furniture finishers, rubber workers, petrochemical
workers
Formaldehyde - Nose: Hospital and laboratory workers, and manufacturers of wood products, paper, and textiles
Ionizing Radiation - Bone Marrow: Nuclear materials, medicinal products and procedures
Soot - Skin: Chimney sweeps and cleaners, firefighters, bricklayers
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How are bacteria and viruses linked to cancer?
Bacteria: Helicobacter pylori, the bacterium responsible for causing stomach ulcers, is strongly associated with stomach cancer.
Viruses: Hepatitis B and C can cause liver cancer. It is estimated that, globally, up to 80% of liver cancer is caused by hepatitis. Human papillomavirus (HPV), which is sexually transmitted, can cause cervical cancer.
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How can you prevent cancer?
Avoid Excessive Sunlight: decreases risk of skin cancers. If you are exposed, be sure to protect yourself with sunscreen.
Monitor Alcohol Intake: alcohol is associated with an increase in a number of cancers, including mouth and liver cancers.
Eliminate Tobacco Use: decrease the risk of developing lung cancer and other cancers associated with tobacco use.
Eat Healthy: maintain an adequate diet of fruit and vegetables, and moderate your consumption of saturated fats and red meats.
Be Active: maintaining a healthy lifestyle will ensure that your body is in its best form to combat the carcinogens.
Get Vaccinated: vaccinations for HepB and HPV are available in Canada.
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What are the goals of cancer treatment?
The goals of cancer treatment differ based on the type and severity of the cancer.
Prevent the Cancer: treatment is given to prevent cancer cell growth, or to remove precancerous cells that could turn into cancer.
Cure the Cancer: primary goal of treatment. However, a cure has been achieved in only a few cancers; for example, testicular cancer, Hodgkin’s disease, and childhood leukemias.
Control the Cancer: when a cure is not possible, the goal is to control the cancer, stopping it from growing and spreading, and prolonging patient survival.
Relieve Symptoms: when curing or controlling the cancer is not possible, it is important to make the patient as comfortable as possible.
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What are chemotherapeutic drugs?
The main types of cancer treatments are surgery, chemotherapy, radiation, and bone marrow transplantation.
Chemotherapeutic drugs act by slowing the growth of rapidly dividing cells. In general, these drugs inhibit DNA synthesis, protein synthesis, or cell division by a variety of ways. Newer agents act directly against abnormal protein in cancer cells and are, therefore, a more targeted therapy than the traditional chemotherapeutic drugs.
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What are the classes of chemotherapeutic drugs?
Alkylating Agents: bind to and interfere with DNA replication.
Mitotic Inhibitors: affect microtubule function and the formation of the mitotic spindle, thereby preventing cell division.
Hormones and Hormone Antagonists: treat hormone sensitive tumours by suppressing
cell division.
Biologicals: inhibit cell replication by blocking cytokines, which normally control cell growth. Some drugs are also antibodies to these cytokines.
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How do chemotherapeutics have selective toxicity?
Cancer cells divide continuously, whereas most normal cells are in a non-dividing state. Therefore, one way to target cancer cells is to target continuously dividing cells.
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What must be considered when designing a chemotherapy regimen?
Benefit-Risk Assessment: must weigh the possible benefits of chemotherapy versus the adverse effects of treatment in each clinical situation. The cells lining the gastrointestinal tract will be harmed, resulting in nausea, vomiting, and ulceration. Hair roots will also be harmed, resulting in hair loss. In addition, each type of cancer chemotherapeutic is associated with its own toxicities. The decision whether or not to continue chemotherapy will need to be re-evaluated prior to each treatment.
Combination Chemotherapy: chemotherapeutic drugs are frequently used in combination for a couple of reasons.
- Development of Resistance: cancer cells are less likely to develop resistance when attacked by a variety of drugs that act in different ways.
- Occurrence of Toxicities: drugs have low TI. If a single drug was used, it would not be possible to increase the dose beyond a certain level because the toxicities would be too great. Using
a combination of drugs allows for the selection of chemotherapeutics with different toxicities. The dose of each chemotherapeutic drug and the schedule for taking the drugs are carefully evaluated and designed to maximize the anticancer effects while minimizing toxicity.
