Module 4 - PS268

THERAPEUTIC DRUGS, PREVENTION AND TREATMENT

What is Health Canada's role in regulating Natural Health Products (NHPs)?

Health Canada regulates the safety and quality of all foods and drugs under the Food and Drugs Act and Food and Drug Regulations, including NHPs.

Examples of NHP’s

• vitamins,

• minerals

• herbal remedies

• homeopathic medicines

• tarditional medicines

• probiotics

• amino acids

• omega-3s

Concerns about NHPs in 1990s

NHPs were classified as foods, so only purity and safety had to be proven—not effectiveness or side effect

Natural Health Products Directorate (NHPD)

• established in 2004 to regulate NHPs

• defines them as products to treat or prevent diseases or promote health

• ensures they meet safety standards similar to OTC drugs

What is required under Traditional Use Evidence

Documented use for at least 50 years, including details on condition treated, dosage, and preparation method.

what is St. Johns Wort used for and what does research say about it?

used for anxiety, depression, restlessness and sleep issues

• A review of 29 trials found it more effective than placebo and comparable to antidepressants, with fewer side effects.

Risks of St, Johns Wort

Dangerous interactions with many prescription drugs (e.g., contraceptives, warfarin, antidepressants); has caused psychiatric side effects in some users.

SAMe

S-adenosyl-L-methionine is a natural compound in the body used to support healthy mood balance.

• Studies show it may be as effective as tricyclic antidepressants.

Ginkgo Biloba

Marketed to improve memory and circulation; evidence is mixed and often weak.

• It has blood-thinning properties that can interact dangerously with drugs like aspirin.

Caffeine in NHPs

Found in guarana, green tea, and coffee bean extracts; used in weight-loss and energy products.

• Dosage and safety vary widely.

Herbal sleep aids

herbal or natural products used to promote relaxation or sleep, efficacy and safety depend on ingredients

Natural Male Enhancement Products

claim to maximize erection potential but without clear scientific backing

• ex: Enzyte

  • lack scientific support

  • contain unregulated ingredients

OTC drugs

over-the-counter drugs

• Nonprescription medications that are self-selected and self-administered for symptom relief of self-diagnosed conditions.

Nonmedicinal Ingredients (NMIs)

substances included in a product that do not have medicinal properties but may serve other functions like stabilizers or fillers.

Concerns with Nonmedicinal ingredients

NMI’S

Food and Drugs Act (FDA)

Canadian law governing drug safety and food quality. It aims to ensure that products are safe for consumers.

Controlled Drugs and Substances Act (CDSA)

Canadian legislation that regulates the production, distribution, and possession of controlled substances, aiming to prevent drug misuse and ensure public safety.

Schedule 1 (NAPRA)

• Prescription-only drugs

• Tylenol 3 (30mg codeine)

Schedule 2 (NAPRA)

• Nonprescirption drugs sold BEHIND the counter

  • pharmacist must assist

  • tylenol 1 (8mg codeine)

Schedule 3 (NAPRA)

• Nonprescription drugs available OTC

Why are some OTC drugs kept behind the counter (Schedule II)?

To allow pharmacist supervision and reduce misuse or adverse effects. Example: Tylenol #1 (8 mg codeine).

What determines whether a drug is prescription-only or OTC?

Depends on toxicity, administration method, dosage, and potential for misuse

What early ingredients were used in OTC sleep aids like Compoz?

Scopolamine (acetylcholine blocker) + methapyrilene (antihistamine). Both were later removed due to safety concerns.

What is the purpose of Antihistmaines in sleep aids?

used in sleep aids to promote sedation by blocking histamine receptors in the brain, which can help induce sleep.

Why was methapyrilene withdrawn from OTC use?

It caused cancer in lab animals and was pulled after 1979.

current main ingredient in most OTC sleep aids in Canada?

Diphenhydramine (either hydrochloride or citrate).

How does diphenhydramine induce sleep?

It acts as an inverse agonist at CNS H1 histamine receptors, causing sedation.

common brand names for OTC diphenhydramine sleep aids?

Nytol and Sleep-Eze D.

2 main drugs classes for pain relief

1. anaesthetics (blocks all sensations)

2. analgesics (selectively reduce pain)

What types of pain are opioids and salicylates best for?

• Opioids: Visceral pain (organs)

• Salicylates (e.g., Aspirin): Somatic pain (muscle, joints, headache)

How does aspirin work as an analgesic?

It blocks COX-1 & COX-2, preventing prostaglandin synthesis and reducing pain/inflammation.

Asprin’s main effects

• Analgesic (mild–moderate pain)

• Antipyretic (fever reducer)

• Anti-inflammatory (e.g., arthritis)

What are key risks of aspirin?

• GI irritation & bleeding

• Increased bleeding time

• Reye’s syndrome risk in under-20s with viral illness (serious/fatal)

Reye’s syndrome

a rare but serious condition that causes swelling in the liver and brain, primarily affecting children and teenagers recovering from viral infections.

Acetaminophen

a common pain reliever and fever reducer that is used for mild to moderate pain.

how does acetaminophen compare to aspirin

• Equal in pain and fever relief

• Less stomach irritation

• Not anti-inflammatory

• Overdose = liver damage

nonsteroidal anti-inflammatory drugs (NSAID’s)

a class of medications that reduce inflammation, pain, and fever. They work by inhibiting COX enzymes like aspirin

• ibuprofen

What are common NSAID side effects?

GI upset, nausea, and cramps; overdose can damage the liver

What’s the limit for OTC codeine in Canada?

8 mg or less (e.g., Tylenol #1, 222) — combined with ASA or acetaminophen and caffeine.

Why is codeine use under review?

Due to growing safety concerns and addiction risk; may shift all products to prescription-only.

What causes the common cold?

Viruses (mostly rhinoviruses, coronaviruses); spread via hands → face contact

What are the 3 main symptom-targeting ingredients in cold remedies?

• Antihistamines (e.g., chlorpheniramine)

• Decongestants (e.g., phenylephrine)

• Analgesic-antipyretics (e.g., acetaminophen)

What ingredient is commonly used as a cough suppressant?

Dextromethorphan

What OTC remedy treats both sinus pressure and headache?

Products with phenylephrine + acetaminophen (e.g., Dristan, Benylin Cold & Sinus)

How does Health Canada regulate OTC product safety?

It approves active ingredients, not every formulation — so consumers must read labels.

What are the 6 key active ingredients in OTC cold/allergy meds?

• ASA (aspirin)

• Acetaminophen

• Chlorpheniramine

• Diphenhydramine

• Dextromethorphan

• Phenylephrine

Why is Dextromethorpan sometimes abused by teens?

At high doses, DM causes hallucinations and altered states by acting on sigma receptors.

Dextromethropan

A common cough suppressant that, at high doses, can cause hallucinations and altered states of consciousness

chloral hydrate

A sedative and sleep-inducing (anxiety reducing) medication often used for its calming effects

Mickey Finn

bartender added it to drinks to incapacitate victims and rob them

What is the active metabolite of chloral hydrate?

Trichloroethanol, which causes CNS depression.

risks of chloral hydrate

• tolerance develops within 5-14 days

• withdrawal is very intense

• gastric irritation

• used as a rape date drug

Paraldehyde

CNS depressant which was used to treat convulsive disorders as well as alcoholism

• common in mental hospitals before 1950s due to effectiveness

What were the pros and cons of paraldehyde?

Pros: Effective sedative with wide safety margin
Cons: Horrible taste and strong odour

Bromides

are sedative agents used historically to treat anxiety and insomnia (sleep aid)

• very low doses in OTC meds till 1960s

Main risk of Bromide

• bromide salts accumulate in body

• causes gradual CNS depression over days

• neurological/psychiatric effects like psychosis

When were barbiturates first introduced?

1903 – became widely prescribed for anxiety and insomnia.

Barbituates

first CNS depressants prescribed widely for anxiety, relaxation and sleep disorders

• largely replaced by safer drugs benzodiazepines

How are barbiturates grouped?

grouped according to their duration of action

• short-acting, intermediate-acting, and long-acting categories.

What is the main mechanism of barbiturates?

CNS depression by enhancing GABA activity (indirectly).

decline in barbiturates use

• high overdose risk

• addiction risk

• severe tolerance and withdrawals

  • was later replaced in 1950s

Phenobarbital

long acting barbiturate

• sedative (low doses)

Secobarbital

short acting barbiturate

• sleeping pill

Amobarbital

intermediate acting barbiturate

• sedative/sleep aid

short acting barbiturates

• onset = 15 mins

• duration = 2-3 hours

  • more likely to produce withdrawal symptoms

long acting barbiturates

• onset = 1 hour

• duration = +8 hours

what does CNS depressant mean?

substances that reduce the activity of the central nervous system, leading to decreased alertness, relaxation, and sedation.

• reduces brain activity

Low doses of long acting barbiturates

• 30-50mg

• used for daytime anxiety relief

  • ex: phenobarbital

High doses of short acting

• 100-200mg

• used as sleeping pills

  • ex: secobarbital

What determines the addiction potential of barbiturates?

Speed of onset and duration — fast, short-acting drugs are most addictive.

Meprobamate (Miltown)

A drug used for anxiety relief; it has sedative properties and was widely prescribed in the mid-20th century (1950s)

Why was meprobamate seen as a breakthrough in the 1950s?

Marketed as safer than barbiturates for anxiety and muscle pain.

Why was 282-MEP withdrawn in Canada?

Risks (dependence, overdose) outweighed benefits; withdrawn in 2013.

did meprobamate replace barbiturates

yes, it was marketed as a new CNS depressant, safer than barbiturates

Methaqualone

was introduced as a sedative-hypnotic and marketed as a safer alternative to barbiturates for insomnia and anxiety treatment.

• marketed as a love drug

effects of methaqualone

• alcohol like disinhibtion

  • motor incoordination

• sedation

• quick euphoria → highly addictive

  • psychological and physical dependance

Why was methaqualone banned?

high doses led to

• physical dependance

• psychosis during withdrawls

• seizures

• tolerance building rapidly

What was the first benzodiazepine?

Chlordiazepoxide (Librium) in 1960, followed by diazepam (Valium).

What makes benzodiazepines safer than barbiturates?

Benzodiazepines have a lower risk of overdose and dependence compared to barbiturates, primarily because they do not significantly depress respiratory function at therapeutic doses.

What factors increase dependence risk with benzodiazepines?

Fast onset, short duration, and high doses.

What are common uses of benzodiazepines?

Anxiety, insomnia, seizures, alcohol withdrawal, agitation, and muscle spasticity.

What is Canada’s most prescribed benzo today?

Lorazepam (Ativan)

What is Rohypnol and why is it controversial?

A benzodiazepine linked to date-rape drug use due to sedation + amnesia (not sold in Canada/US).

half life

The duration a drug remains active in the body before its effects diminish significantly, influencing dosing schedules.

What determines onset speed and half-life of benzodiazepines?

Lipid solubility and metabolic pathways (active metabolites = longer effect).

Which benzodiazepine has the longest half-life?

Diazepam (20–100 hours)

What is sodium pentathol used for?

Anesthesia, “truth serum,” and lethal injection protocols.

Why is thiopental controversial in lethal injections?

There are concerns regarding its potential for causing pain and suffering during execution, as well as the ethical implications of using a drug initially intended for anesthesia.

What are Z-drugs and examples?

Nonbenzodiazepines used for insomnia:

• Zolpidem (Ambien)

• Zopiclone (Canada)

• Zaleplon, Eszopiclone (Lunesta)

How do Z-drugs work and how are they scheduled?

Similar to benzos (GABAergic); classified as Schedule 4 substances.

Ambien CR

extended-release for all night sleep

Intermezzo

sublingual tablet for middle-of-the-night awakenings

How do benzodiazepines work?

They enhance GABA’s inhibitory action by increasing chloride ion flow at the GABAA receptor.

Where do benzodiazepines bind?

Between the α1 and γ2 subunits on the GABAA receptor.

What happens when GABA binds to its receptor?

Chloride ions enter the neuron, causing hyperpolarization and inhibition.

Do benzodiazepines directly activate GABA receptors?

No—they only enhance GABA’s effect.

What is zolpidem (Ambien) used for?

It's a nonbenzodiazepine hypnotic used to treat insomnia.

What are risks of hypnotics like zolpidem?

Sleepwalking, sleep-driving, and increased depression risk.

What replaced barbiturates for sleep post-1976?

Benzodiazepines, especially triazolam (Halcion).

What is a safer alternative to sleeping pills?

Behavioral strategies for managing insomnia.