Week 8

Kia ora, in our previous session, we delved into an exploration of pharmacology, covering specific terminology and its meanings, along with an exploration of pharmacokinetics (how our bodies affect a drug). This week, we will shift our focus to the other arm of pharmacology, pharmacodynamics (how a drug affects our bodies).

Pharmacokinetics recap

But, before then, let’s quickly check your knowledge of pharmacokinetics in the following six-question pātaitai (quiz).

Pharmacodynamics

Pharmacodynamics looks at how a drug affects or interacts with the body to produce a specific effect.

Mechanisms of drug action

Mechanisms of drug action refer to the sites or specific targets in the body where drugs exert their effects. The three primary mechanisms of drug action include:

1. Cell receptors (drug-receptor interactions) 
2. Ion channels (alteration of cell transport processes)
3. Enzymes (alteration of enzyme function).

It is important to note that a drug can modify the function of a cell or its rate of function, but it cannot give it a new function. This means that a drug’s effect will depend on what the cell normally does.

Receptor mechanisms

Receptors are specialised proteins or molecules found on cell surfaces or within cells. 

These receptor sites play a role in the binding of chemical messengers such as hormones and neurotransmitters. Chemical messengers are known by the term ligands. 

When ligands bind to receptors, they either activate a signalling process that prompts the cell to respond in a particular way or block this signalling process to stop the cell from responding.

1. Ligands that activate a receptor are called agonists.
2. Ligands that block or inhibit a receptor are called antagonists.

Different cells in the body may respond to a chemical messenger in different ways.

Example

For example, the naturally occurring ligand adrenaline (a neurotransmitter) can cause different cells in the body to respond in the following ways:

• When adrenaline binds to receptors on nerve cells, an electrical impulse is generated that travels along the nerve.
• When adrenaline binds to receptors on heart muscle cells, it causes muscle contraction.
• When adrenaline binds to beta receptors in the lungs, it causes smooth muscle relaxation. 
• When adrenaline binds to receptors on liver cells, it causes glycogen stored in the cell to be broken down into glucose.

Cell receptor (drug-receptor interactions)

The most common way that drugs work is to mimic the body’s naturally occurring ligands.

As you read each of the following points, refer to the illustration above to help visualise the different drug-receptor interactions in action.

• A drug that binds to a receptor and activates it is an agonist.
  • Once the drug binds to its receptor, a messenger is released to cause an action.
  • Agonist drugs cause a cell to respond in its usual way.
• A drug that binds to a receptor and blocks it is an antagonist.
  • The drug binds to the receptor to prevent agonists from activating the receptors. This means the agonist is unable to produce a response.
  • Antagonist drugs prevent the cell from responding.

Example

Salbutamol is an example of a drug that acts on cell receptors, specifically acting as a beta-2 adrenergic receptor agonist. By binding to and activating beta-2 adrenergic receptors located on the surface of smooth muscle cells, salbutamol causes relaxation of smooth muscle cells.

Salbutamol primarily acts on the receptors in the respiratory system. This results in bronchodilation to make breathing easier and manage the symptoms of asthma, COPD and other respiratory conditions.

Non-selective and selective drugs

A non-selective drug acts on a range of receptors to cause many different effects.

The more selective a drug is about which receptors it binds to, the more predictable and specific its effects are, with fewer unwanted effects.

Types

There are three types of beta (β) adrenoreceptors:

1. β1 - found mainly in the heart, kidneys, and fat cells.
2. β2 - found in the bronchioles of the lungs and the arteries of the skeletal muscle.
3. β3 - found in the gall bladder, urinary bladder and brown adipose (fat) tissue. 
    

If a non-selective beta blocker is given to a patient, then all these receptors are affected, so the effects will be much greater than what is wanted.

Beta-blockers are mainly used for the heart and so should be β1 selective. Otherwise, there will be too many unwanted effects, particularly for asthmatics, as β2 receptors will also be affected.

Example

An example of a beta-1 selective blocker used for the heart is metoprolol, which targets beta-1 adrenergic receptors in the heart. This makes it suitable for managing conditions like hypertension and certain heart diseases without significantly affecting beta-2 receptors in the lungs.

If a beta-2 adrenergic receptor agonist, such as salbutamol, is used as a bronchodilator in an asthma attack, it may also cause an increased heart rate.

Watch: Agonist vs. Antagonist (3:35 minutes)

Mātakitaki mai, watch this video for a summary of agonist and antagonist drugs with examples.

Challenge yourself to answer the review questions by pausing the video at 3 minutes 14 seconds. The answers are given at 3 minutes 19 seconds, so be quick to press pause!

Ion channels (alteration of cell transport processes)

Ion channels are proteins that form pores in the cell membrane. The channels can open and close, allowing ions (charged particles) to pass into or out of the cell through the cell membrane.

Ion channels are typically specific to certain ions. Different ion channels allow the passage of specific ions based on factors like size, charge, and other molecular properties.

Example

For example, sodium (Na+), calcium (Ca++), potassium (K+), and chloride (Cl-) ions may each have dedicated ion channels that selectively permit their passage. 

This graphic illustrates the ions passing through these ion channels in the cell membrane. 

Depolarisation

The passage of ions across the cell membrane results in a change in the electrical charge between the inside and outside of the cell. The difference in charge is known as depolarisation.

Depolarisation is essential for various cellular functions, including the communication between nerve cells and muscle contraction, such as the contraction of the heart muscle.

Interactions

In pharmacology, drugs can interact with ion channels to alter their activity. Drugs may act on ion channels in different ways:

• Activation: Some drugs can bind to ion channels and promote their opening, allowing ions to flow through. This can lead to an increased cellular response.
• Inhibition: Other drugs can block ion channels, preventing ions from passing through. This inhibition can decrease cellular activity.
• Modulation: Some drugs can alter the sensitivity of ion channels, making them more or less responsive to natural signals.

Calcium channel blockers

These drugs block calcium ion channels in cardiac muscle and blood vessels to stop the entry of calcium into the cell. This results in a reduction in muscle contraction.

In the heart, this means a decrease in cardiac output (i.e. how strongly the heart beats). In blood vessels, this causes vasodilation, resulting in blood pressure dropping.

Here, you can see the calcium channel blocker acting like a locked gate, preventing the internal calcium stores from entering the cell cytosol. 

Prescriptions

Calcium channel blockers are prescribed for:

• The treatment of hypertension
• The prevention of angina
• Controlling arrhythmias (abnormal heart rhythms).

Examples

• Amlodipine
• Diltiazem
• Felodipine
• Nifedipine

Watch: Calcium channel blockers […] (3:32 minutes)

This video reviews the action of calcium channel-blocking drugs. Āta mātakitaki, watch carefully as you will use this information to support a patient in the activity that follows. You can also give the recall activity at 3:00 minutes a go to supercharge your retention!

Sodium channel blockers

These drugs act by blocking the flow of sodium into cells. This reduces cell excitability and reduces the speed of conduction.

In the heart, this means slowing of the heart rate and a reduction in the conduction of electrical signals through the heart.

In the nervous system, this means stabilising the electrical activity in the brain and also decreasing the transmission of signals along nerve fibres, which may have effects on pain perception.

Prescriptions

Sodium channel blockers are prescribed for:

• Treating cardiac arrhythmia.
• Controlling and preventing seizures in individuals with epilepsy.
• Alleviating nerve pain caused by damage or malfunction of the nerves.

They may also be prescribed to help prevent migraines or reduce their frequency.

Examples

• Lamotrigine
• Lidocaine
• Flecainide.

Enzymes (alteration of enzyme function)

Enzymes are substances that help a chemical reaction occur. Most drugs that act on enzymes inhibit their action, resulting in the reaction reducing and slowing, causing a decrease in the amount of the final product. This results in decreased activity.

Drugs that alter enzyme function

ACE inhibitors (angiotensin-converting enzyme inhibitors)

• Angiotensin-converting enzyme converts angiotensin I into angiotensin II.
• Angiotensin ll is a strong vasoconstrictor (it narrows the walls of blood vessels and increases blood pressure). 
• Inhibiting ACE results in reduced levels of angiotensin ll, therefore less vasoconstriction. The result will be a drop in blood pressure. 

In this graphic, you can visualise the effect that ACE inhibitors have on preventing the angiotensin-converting enzyme from converting angiotensin I into angiotensin II.

Watch: How do ACE inhibitors work? (2:11 minutes)

This video illustrates the mode of action of ACE inhibitors and touches on the common use of this type of medication. Complete the five-question pātaitai (quiz) that follows to check your retention and understanding.

Prescriptions

ACE inhibitors are prescribed for the:

• Treatment of hypertension
• Management of heart failure
• Protection of the heart after a heart attack
• Management of kidney diseases.

Examples

Examples of ACE inhibitors are:

• Enalapril
• Lisinopril
• Cilazapril
• Quinapril
• Perindopril
• Ramipril.

Disulfiram (alcohol antagonist)

This drug is used to discourage patients from drinking alcohol.

Ordinarily, alcohol is broken down in the body to acetaldehyde and then to acetate, which is further broken down to carbon dioxide and water and excreted. By inhibiting the aldehyde dehydrogenase enzyme (ALDH), we slow the breakdown of acetaldehyde.

When the patient drinks alcohol, acetaldehyde builds up in the bloodstream, causing extremely unpleasant symptoms like nausea, vomiting and violent flushing.

This graphic illustrates this process.

Summary

This brings us to the end of our exploration of how different drugs interact with the body to produce a specific effect.

We have focused on the following sites of drug action:

1. Cell receptors (drug-receptor interactions) 
2. Ion channels (alteration of cell transport processes)
3. Enzymes (alteration of enzyme function).

This pharmacology knowledge is crucial for pharmacy technicians because it provides a foundational understanding of how medications exert their effects. By comprehending these mechanisms, pharmacy technicians can contribute effectively to patient care by:

• ensuring the safe and appropriate use of medications
• and providing accurate information to patients about how their medications work to help the conditions that they have been prescribed for. 

Bahuta khūba! Well done! You have completed another week of Patient Care.

Introduction

Previously in Patient Care 2, we investigated the structures and functions of the reproductive, urinary system and musculoskeletal systems. In this session, we extend our learning and apply this knowledge to disorders and their treatments, one of which you can see in this image of the female reproductive system above - Polycystic Ovary Syndrome. More on that soon! 

The menstrual cycle

The menstrual cycle refers to the physiological changes that occur in people with female reproductive organs. The length of each phase of the menstrual cycle varies, although the average menstrual cycle is 28 days. Menstrual cycles are counted from the first day of menstrual bleeding.

The menstrual cycle is divided into the following phases:

1. Follicular 
2. Ovulation 
3. Luteal 
    

Let’s explore each phase.

Follicular phase

• Begins on day one of menstrual bleeding to approximately day 14 of the cycle.
• Menstrual bleeding typically lasts from day one to day seven of the cycle, which means there is an overlap between menstrual bleeding and the early stages of the follicular phase.
• The pituitary gland in the brain releases follicle-stimulating hormone (FSH), which stimulates the development of several ovarian follicles within the ovary. After several days, one or two follicles become dominant.
• As the follicles grow and mature, they produce oestrogen.
• The increasing oestrogen levels stimulate the thickening of the endometrium (lining of the uterus) in preparation for a potential pregnancy.

Ovulation

• Usually occurs around day 14 in a 28-day cycle.
• The increase in oestrogen in the follicular phase stimulates the pituitary gland in the brain to release luteinising hormone (LH). 
• This surge in LH triggers the dominant follicle in the ovary to rupture and release the mature egg. The mature egg is now available for fertilisation.

Luteal phase

• This phase begins immediately after ovulation and lasts until the start of the next menstrual period. (Approximately days 15 – 28 of a 28-day cycle.)
• The remains of the ruptured dominant follicle in the ovary become a corpus luteum (meaning ‘yellow body’ as it looks like a mass of yellow tissue).
• The corpus luteum produces large amounts of progesterone. 
  • Progesterone causes changes in the endometrium (uterine lining) to prepare for the potential implantation of an embryo to establish a pregnancy. 
• If implantation does not occur within approximately two weeks, the corpus luteum will collapse, causing a sharp drop in the levels of both progesterone and oestrogen.
• The drop in progesterone and oestrogen causes the uterus to shed its lining in a process termed menstruation.

This illustration shows days 1 to 28 of the menstrual cycle and what is occurring to hormone levels, the ovaries and the endometrium layer throughout the cycle. 

Disorders of the reproductive system

Infertility (Mate matapā)

Infertility is defined as not being able to become pregnant after 12 months of contraceptive-free intercourse or not being able to carry pregnancies to a live birth.

There can be many causes of infertility for both men and women, and sometimes no cause is found.

You may already know or be able to guess some of these possible causes for men and women. Expand each label to check what these include:

Treatment

One of the pharmacological treatments for infertility in women is treatment with clomifene citrate (also spelled as clomiphene citrate).

Polycystic Ovarian Syndrome (PCOS) (Huahua hua kūao)

PCOS is a disorder of the female reproductive system (and the image that we started this week of Anatomy and Physiology with - you can scroll back up to see it). Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of male hormones (androgens), particularly testosterone, either through the release of excessive luteinising hormone (LH) or through high blood insulin levels (hyperinsulinemia).

It is called PCOS because ultrasound scanning shows multiple (poly) immature follicles that look like cysts. The follicles in the ovaries have developed from primordial (beginning) follicles, but their development has stopped due to the disturbed ovarian function.

PCOS affects about 5% - 10% of women of reproductive age and is thought to be one of the leading causes of female infertility. While the causes are unknown, insulin resistance, diabetes, and obesity are all strongly associated with PCOS. Signs and symptoms begin during puberty and worsen with time.

Here, you can see the differences between the follicles developing in normal ovaries as opposed to polycystic ovaries.

Symptoms

Common symptoms and impacts of PCOS include:

• Irregular menstrual periods: Women with PCOS often have irregular or infrequent menstrual cycles.
• Fertility issues: This can be due to various factors such as irregular periods, changes in the endometrium, and hormonal imbalances.
• Ovulatory dysfunction: Ovulation may not occur regularly, leading to fertility issues.
• Hyperandrogenism: Elevated levels of male hormones (androgens) may cause symptoms such as hirsutism (excess hair growth), acne, and male-pattern baldness.
• Insulin resistance: Some individuals with PCOS may experience insulin resistance, which can contribute to metabolic issues and an increased risk of type 2 diabetes.
• Weight gain: Many women with PCOS may find it challenging to manage their weight.
• Skin changes: Skin problems, such as darkening of the skin (acanthosis nigricans), may occur.

Treatments

Benign prostatic hypertrophy (Mate repe tātea)

This condition of the male reproductive system can also be known as benign prostatic hyperplasia. It is a non-cancerous enlargement of the prostate gland, which is a walnut-sized gland located below the bladder and in front of the rectum.

As you can see in the illustration above, the prostate gland surrounds the urethra, the tube that carries urine from the bladder through the penis. The main function of the prostate is to produce seminal fluid, which nourishes and transports sperm during ejaculation. However, as men age, the prostate gland can undergo benign (non-cancerous) growth, leading to an enlargement of the gland. This enlargement can constrict the urethra, causing various urinary symptoms.

Treatment

One pharmacological treatment for BPH involves the use of doxazosin, a medication classified as an alpha-blocker. Doxazosin works by blocking the action of specific natural substances that tighten the muscles. This action leads to the relaxation of smooth muscle cells in the prostate and bladder neck, ultimately alleviating the obstruction caused by an enlarged prostate and enhancing urine flow.

Urinary Tract Infection (UTI) (Pokenga pūaha mimi)

Urinary tract infections affect both men and women. They can affect various parts of the urinary tract, including kidneys, ureters, bladder, and urethra. Cystitis is a common type of UTI that specifically involves localised inflammation in the bladder.

Cystitis

Cystitis is commonly caused by a bacterial infection, with the most common bacteria being Escherichia coli (E. coli). The infection typically occurs when bacteria enter the urethra and travel up into the bladder. Women are more susceptible to cystitis than men because the location of their urethra is close to the anus, increasing the likelihood of bacteria from the anal region entering the urethra and travelling to the bladder. Also, the length of their urethra is shorter, making it easier for bacteria to travel from the external genital area to the bladder.

Symptoms

Symptoms can be similar in both men and women and may include:

• Pain or discomfort in the pelvic region or lower abdomen.
• The need to urinate more often than usual.
• Urgency - a strong, persistent urge to urinate.
• Discomfort or a burning feeling during urination.
• Cloudy or strong-smelling urine.

Treatment

Pharmacological treatment for cystitis may include a urine alkalising agent. Complete this activity to find out more about this treatment. Don’t worry if you don’t get all the questions correct. This activity is designed to introduce you to the content! Use this as an opportunity to take note of the correct answers.

Treatment may also include oral antibiotics such as nitrofurantoin and trimethoprim.

Leaving cystitis untreated

If cystitis is left untreated, it can lead to the development of more severe symptoms such as:

• Fever and chills
• Back pain
• Increased pelvic pain
• Nausea and vomiting
• Confusion
• Low blood pressure.

Complications

• It can also lead to more severe complications, including:
• Spread of infection to the kidneys, causing a condition called pyelonephritis. 
• Become a chronic condition with frequent, recurring episodes of infection.
• In rare cases, severe infections can lead to sepsis, a life-threatening condition where the body's response to infection causes widespread inflammation. Sepsis requires immediate medical attention.
• Pregnant women with untreated cystitis are at an increased risk of complications such as preterm birth and low birth weight.

Erectile Dysfunction (ED)

Erectile dysfunction is a condition affecting the male reproductive system. It occurs when sexual stimulation or arousal fails to generate sufficient blood flow to the penis, preventing the achievement and maintenance of an erection suitable for sexual intercourse, despite the desire. Many people have erection problems at times, and the likelihood increases with age.

The process of achieving an erection involves intricate mechanisms. The brain, influenced by thoughts and sensory stimuli such as touch, hearing, smell, and sight, triggers the release of nitric oxide, a chemical messenger. Nitric oxide, in turn, induces the relaxation of smooth muscle cells in the blood vessel walls that supply the erectile tissue in the penis. This relaxation facilitates dilation of the blood vessels, promoting increased blood flow to the erectile tissue. The heightened blood flow results in the engorgement of the erectile tissue, ultimately leading to an erection.

Causes of ED

There are various causes of ED, including medical, physical, and psychological factors such as:

• Cardiovascular issues such as atherosclerosis can impede blood flow to the penis.
• Disorders such as diabetes can affect hormonal levels.
• Neurological disorders such as multiple sclerosis, Parkinson's disease, and stroke can interfere with nerve signals.
• Peyronie's Disease, which is the development of scar tissue inside the penis, can lead to bending or curvature during erections.
• Certain drugs, including antidepressants, antihypertensives, and prostate cancer treatments, may contribute to ED.
• Trauma or injury to the pelvic area or spinal cord may result in erectile problems.
• Surgical procedures involving the prostate, bladder, or rectum can impact erectile function.
• Lifestyle factors including smoking, excessive alcohol consumption, and drug abuse.
• Psychological causes such as stress, anxiety, and depression.
• Difficulties in relationships or communication can also have a psychological impact.

Read this article from the Daily Mail for more explanations on the pharmacology of Viagra, and then complete the following activity: The science of VIAGRA.

Musculoskeletal system

As a pharmacy technician, your role involves providing patients with accurate information about many different health disorders.

Musculoskeletal recap

Take a moment now to reflect on how you would respond to a patient who asks you: “Is a sprain and a strain the same thing?”

• How would you describe each?
• Can you name the parts of the body involved? 
• What pharmaceutical and self-care advice would you give for each?

Musculoskeletal disorders and their treatments

Let’s now look at musculoskeletal disorders and their treatments, starting with an illustration reminding you of the varied functions of our beloved bones, followed by some fun facts.

Bone facts

• Bones are considered living tissue.
• Throughout the lifecycle, the body continuously breaks down and rebuilds new bone.
• Bones contain the protein collagen and minerals, such as calcium and phosphorus, that make the collagen hard and dense.
• To maintain bone density, the body needs adequate calcium and other minerals as well as certain levels of hormones, including oestrogen in women and testosterone in men.
• Vitamin D is needed so the body can absorb calcium from food and incorporate it into bones.
• Physical activity (especially weight-bearing exercise) also helps bones become dense.
• Bone is stronger than reinforced concrete.

Bone fractures

A fracture is a crack or break in a bone usually caused by trauma. It is usually accompanied by injury to the surrounding tissues. Certain underlying disorders can weaken parts of the skeleton so that breaks are more likely to occur. Such disorders include some infections, benign bone tumours, cancer, and osteoporosis.

As you can see here, there are a variety of bone fractures. 

A closed fracture, also known as a simple fracture, is a type of bone fracture where the broken bone does not penetrate the skin, whereas an open fracture, also known as a compound fracture, is a type of fracture where the broken bone protrudes through the skin, creating an open wound.

Closed fractures typically have less risk of infection compared to open fractures, as the skin remains intact, providing a protective barrier against external contaminants.

Signs and symptoms

These will depend on the type and location. General symptoms may include the following:

• Pain, the intensity of which may vary, but it is usually localised to the injured area.
• Swelling often occurs around the injured area. This is the body's natural response to inflammation.
• Bruising or discolouration of the skin may develop due to bleeding beneath the skin at the site of the fracture.
• In some cases, a broken bone may cause a visible deformity or an abnormal alignment of the affected limb or joint.
• The ability to move the injured area or joint may be restricted, and there may be pain with movement.
• The injured area is likely to be tender to the touch.
• If the fracture involves a weight-bearing bone, it may be challenging or impossible to put weight on the affected limb.

Examples

Expand the labels to read and see an example of a fractured neck of femur and a Colles fracture.

Osteoporosis (Kōiwi ngoikore)

In osteoporosis, the density and quality of bone are reduced. Bone density refers to the amount of bone tissue in a certain volume of bone. It is a key indicator of bone strength and resilience. In this progressive bone disease, bone density is significantly decreased, and bones become porous and brittle, making them more susceptible to fractures, particularly in the hip, spine, and wrist.

Stages of osteoporosis

Check out the four stages of this disease, which are characterised by the severity of bone loss and the likelihood of fractures.

• Stage 1: Normal bone density
  In this stage, the bone density is considered normal, and there are no visible signs of osteoporosis.
• Stage 2: Osteopenia
  This stage is characterised by a loss of bone mass and density, but the bone loss is not yet severe enough to be diagnosed as osteoporosis. Osteopenia is a warning sign that the bones are starting to weaken and is often reversible with appropriate lifestyle changes and medical treatment.
• Stage 3: Osteoporosis
  In this stage, there is a significant loss of bone density, and the bones become weaker, making them more susceptible to fractures. At this stage, bone loss is typically irreversible, and medical intervention is necessary to manage the condition.
• Stage 4: Severe osteoporosis
  This is the most advanced stage of osteoporosis, characterised by a substantial loss of bone density and a high risk of fractures. The bones become fragile and may fracture with minor trauma, leading to chronic pain, disability and loss of independence.

Symptoms

Osteoporosis is often referred to as a "silent disease" because it typically progresses without noticeable symptoms until a fracture occurs. When symptoms do occur, they might include:

• Back pain: Fractures of the spine (vertebrae) can lead to back pain, height loss, and a stooped posture.
• Bone fractures: Osteoporosis increases the risk of fractures, especially in the hip, spine, and wrist. Fractures may occur with minimal trauma or no apparent cause.
• Loss of height: Compression fractures of the spine can result in a gradual loss of height over time.
• Change in posture: As vertebral fractures occur, the spine may curve forward, leading to a hunched or stooped appearance.

Treatment

The goals of treatment are to preserve bone mass, prevent fractures, decrease pain, and maintain function. Prevention and treatment involve the following:

• A healthy diet that is rich in calcium and vitamin D.
• Safe exposure to sunlight for vitamin D.
• Smoking cessation.
• Limiting alcohol intake.
• Vitamin D supplements (for some people).
• Exercises to maximise bone and muscle strength and minimise the risk of falls.
• Bisphosphonates - drugs to reduce the rate of bone loss such as alendronate, risedronate and zoledronate.

And that's a wrap! Buen trabajo, good work. See you next week!