Cellular Interactions Flashcards Preview

PM2C: Therapeutics and Patient Care: Autumn > Cellular Interactions > Flashcards

Flashcards in Cellular Interactions Deck (33):

What is the inflammatory response for?

1. First line of defence that's part of the inate immune system

2. Protects against injury

3. Protects against infections

4. Promotes healing


What are the 5 cardinal signs of inflammation?

1. Redness

2. Heat

3. Swelling
(due to increase blood flow to the area)

4. Loss of function

5. Pain


What is the 3 sections of the skin structure?

1. Epidermis

2. Dermis
- Fatty tissue - connective tissue
- Capillaries

3. Subcutaneous Layer
- Fat
- Larger blood vessel and nerves


What occurs when there's an injury to the surface of the skin?

1. Clots and exudate- neutrophils gather and haemorrhage too

2. Mitosis (dividing cells)
- Fibroblasts- create tissue to heal and create new scar tissue
- New capillaries and macrophages

3. Complex cascade of events occur that recruit many other cell types from the circulation


What is the purpose of inflammation occurring in injury?

1. Protect from invading pathogen

2. Penetration

3. Burn

4. For both part of healing process


What is the purpose of inflammation occurring in insect bite?

1. Protects against infection

2. Heals wound


What clinical problems may an inflammation response have?

1. Insect bite: Hypersensitivity- out of controlled response

2. Contact dermatitis: allergy

3. Atopic Dermatitis (eczema)

4. Urticaria (allergy/adverse reaction)- give someone a drug rash


Give examples of when the inflammation response goes wrong?

1. Hypersensitivity (insect bite)

2. Failure to heal

3. Chronic inflammation (Rheumatoid arthritis- cells attacking themselves and lose function in cell)


How do chemical signals cause cardinal signs of inflammation?

Changing cellular functions and each mediator has slightly different effects by targeting different receptors and cells

2. Many mediators are complex as most act as drug targets
- Receptors
- Enzymes
- Steroid receptors and protein expression


What mediators act as drug targets?

1. Receptors

2. Enzymes

3. Steroid Receptors and protein expression


What are mast cells and give examples of what they release?

1. Cells that contain or make numerous inflammatory mediators (reside in every tissue site of the body)

2. Histamine, 5-HT (serotonin), proteases

3. Lipid derived mediators (prostaglandins)

4. Cytokines (peptide mediators)


How are mast cells activated ?

1. Pathogens

2. IgE (antibodies) (immunoglobins)

3. Complement Cascade (clotting system)

4. Physical damage


What do the terms Wheal and Flare mean? And what can this lead to?

1. Wheal- Swelling

2. Flare- Reddening

3. Leads to itch or pain- release of inflammatory mediators and activation of sensory nerves


Where is histamine released? And what does an injection of it cause?

1. Released by mast cells

2. Causes wheal and flare of the cells


How do anti-histmaines work?

They block the Histamine H1 receptors


How do drugs target lipid mediators?

1. Target the phospholipids from cell membranes which can stop inflammatory responses

2. Targeting one pathway can stop many other pathways

3. Example: Glucosteroids stops the production of Phospholipase A2 altogether which stops the inflammatory reaction altogether


How do NSAIDS work in targeting the lipid mediators?

They inhibit the cyclooxygenase (COX) enzyme and prevent prostaglandin formation


How does ibuprofen work in lipid mediators?

1. Inhibits the cyclooxygensae (COX) which converts arachidonic acid to prostaglandins

2. Prostaglandins work by mediating pain, inflammation and fever


How does Aspirin work in lipid mediators?

Non selective inhibition of COX1 and COX2 (anti-inflammatory effect) and the irreversible inhibition of COX1 (anti-platelet)


What side effects can NSAIDS cause and why?

1. Gastric problems- prostaglandins in gut wall involved in gastric mucosa (protects GI tract) reduction which can cause GI bleeding

2. Kidney problems- prostaglandins important in controlling blood flow to kidneys

3. Cardiovascular problems- imbalance in prostaglandins can lead to stroke

4. Contraindiction in ASTHMA (reducing prostaglandins)

This is mainly due to inhibition of COX 1


What can glucosteroids (corticosteroids) do to lipid mediators for inflammation? And how do they work?

1. Lipid mediators: They inhibit the induction of cycle-oxygenase which means it has a stronger effect than the NSAIDS

2. Alter expression of proteins involved in inflammation by altering DNA transcription

3. Promotes expression of anti-inflammatory proteins and suppresses expression of pro-inflammatory


What is the mechanism of action of glucocorticoid?

1. They normally circulate in the blood if they take are taken in orally or topically (based on the steroid of cortisol

2. They bind to the glucocorticoid receptors into the cytoplasm which go through the nucleus to bind to different genes

3. This affects the transcription of these different genes

4. The activated glucocorticoid receptor complex can interfere with cell signalling pathways

5. So doesn't have to get translocated into the nucleus


What does binding of the glucocorticoid do to the DNA binding dependent?

1. Increases expression of the genes



What does binding of the glucocorticoid do to the DNA binding independent?

1. Suppresses inflammation induced dependent gene transcription

2. It essentially blocks the intracellular signals which stimulate gene transcription and downstream of the receptors

3. This is stimulated by inflammatory mediators


Explain at a lipid mediator level (by corticosteroids) how you would induce a therapeutic effect of an anti-inflammatory?

1. Increase lipocortin-1 (annexin-1) synthesis

2. Block induction of COX-2


Explain at a lipid mediator level (by corticosteroids) how you would induce a therapeutic effect of immune suppression?

1. Decreases T and B cells

2. Inhibits cytokine production which are involved in recruiting and starting the immune response


Explain the indication of hydrocortisone and the mechanism of action?

1. Indication:
- Eye- local treatment of inflammation (short term)
- Skin- mild inflammatory disorders (eczema, nappy rash)
- Anaphylaxis- IV with adrenaline as emergency treatment

2. MoA:
- Glucocorticoid receptor agonist
- Binds to mineral corticoid receptors that regular blood pressure and volume
(can cause many side effects hence why preferred to be used topically)


Explain the indication of Dexamethasone and the mechanism of action?

1. Indication: nurmerous, where reducing inflammation or immune suppression is beneficial e.g. joint inflammation

2. MoA
- Glucocorticoid receptor agonist
- 40x more potent than hydrocortisone
- Doesn't bind to mineral corticoid receptors
- Has a longer half-life than hydrocortisone


What are some of the unwanted effects of glucosteroids being taken orally?

1. Suppress proliferation of skin cells- blocks scarring- can cause permanent scarring

2. Effects on skeleton- decreased bone density

3. Muscle- reduces it
- Reduce glucose uptake
- Stimulate protein breakdown
- Inhibit protein synthesis

4. Adrenal suppression
- atrophy of adrenal gland
- Abrupt withdrawal can lead to acute adrenal insufficiency hypotension or death


What can long term topical treatment of glucosteroids do?

1. Can induce a cutaneous side effect such as atrophy of the epidermis and the dermis (skin shrinking)

2. Disturbed wound healing


What can long term topical treatment of glucosteroids do?

1. Can induce a cutaneous side effect such as atrophy of the epidermis and the dermis (skin shrinking)

2. Disturbed wound healing


Which drugs target the sensory nerves?

1. Opiates directly block the nerve signals that cause pain- won't get rid of the information such as the inflammatory response

2. Prostaglandins can reduce pain signalling by sensing the nerve


Explain how pain occurs from the brain? And what does this cause?

1. Noxious stimuli causes a C fibre activity

2. This causes excitation of the transmission neuron which leads to pain

3. Inflammatory response is caused