College 7

What is the mechanism of NSAIDs

Goal; to block prostaglandins which is responsible for pain, fever, inflammation

• Mechanism: inhibit COX (cyclooxygenase) enzymes → ↓ prostaglandin synthesis

• COX converts arachidonic acid → PGH₂ → downstream prostaglandins

What are the three main receptor types of opioids?

• mu

• kappa

• delta

What is the MoA of opioids?

MoA; agonist for mu-opioid receptor (GPCRs on neuronal cells in the brain stem and thalamus

How does the mechanism of opioids work? pre and post synaptic side

On pre-synaptic side ↓ cAMP intracellular concentration and ↓ Ca2+ ion influx and ↓ release of excitatory neurotransmitters

Post-synaptic invoke hyperpolarization of the neuronal membrane → ↓ probability of action potential, ↓ neuronal excitability

Opioids side effects (not very important)

• Respiratory depression → μ receptors in brainstem respiratory centres → ↓ response to CO₂ → cause of overdose death

• Constipation → μ receptors in enteric nervous system → ↓ gut motility → tolerance does NOT develop

• Sedation → CNS depression

• Euphoria and addiction through activation of mesolimbic dopamine pathway → reward → dependence

• Etc → lots more things

What are immunosuppressants?

• drugs that reduce or suppress the activity of the immune system

• used when the immune system is overactive or misdirected

• Three main clinical settings;

  • transplantation to prevent organ rejection

  • autoimmune disease

  • inflammatory conditions

What are the 4 types of immunosuppressants?

• glycocorticosteroids

• antiproliferative agents

  • drugs acting on immunophilins

  • antimetabolites

  • alkylating agents

• lymphocyte depleting agents

• targeted therapies (JAK inhibitors, biologics)

Glycocorticosteroids

they simultaneously turn on anti-inflammatory genes and turn off pro-inflammatory genes

Antiproliferative agents in immunosuppression

• The immune response requires rapid multiplication of lymphocytes (T and B cells) to mount an attack

• Antiproliferative drugs interfere with this multiplication at different points (the signal, the building blocks, or the DNA itself)

• Fewer lymphocytes available → weaker immune response → less rejection or autoimmune damage

• These drugs are not lymphocyte-specific → they affect all rapidly dividing cells

Lymphocyte depleting agents

• do not block lymphocyte activation → physically remove them

• fewer lymphocytes in circulation → less immune activity

Biologics

• All previous classes suppress the immune system broadly, targeted therapies block one specific molecule or pathway

• Designed to be more precise → theoretically fewer side effects than broad immunosuppression

• Biologics are large protein molecules (antibodies or receptor decoys) that neutralise a specific cytokine or block a specific receptor

IV JAK inhibitors what are they and how do they work

• JAK inhibitors are small molecules that block the intracellular signalling pathway used by many cytokines simultaneously

• Rather than neutralising one cytokine outside the cell they block the common internal pathway many cytokines share

• One drug interrupts signals from IL-2, IL-6, IFN-γ and many others at once

• Despite being "targeted" still carry infection risk and other side effects because the pathways they target also have normal physiological roles

What do antihistamines block?

They block histamine receptors, primarily H1 receptors

How do antihistamines work?

• histamine is released from mast cells and basophils in response to allergens, injury or immune activation

• block histamine receptors, primarily H1 receptors

What is the nromal function of histamine

• H1 is a GPCR, specifically coupled to Gq protein

• When histamine binds H1 → activates Gq → activates phospholipase C (PLC)

• PLC cleaves PIP₂ into two second messengers:

  • (1) IP₃ (inositol trisphosphate) → releases Ca²⁺ from endoplasmic reticulum → ↑ intracellular Ca²⁺,

  • (2) DAG (diacylglycerol) → activates protein kinase C (PKC)

• ↑ intracellular Ca²⁺:

• Smooth muscle contraction (bronchoconstriction), oedema, itch and pain, runny nose (mucus), vasodilation (flushing and redness)

How do antihistamines work?

Antihistamines: competitive antagonists at H1 receptors (GPCRs)

• Block histamine binding → ↓ Gq signalling → ↓ IP₃ → ↓ intracellular Ca²⁺ → ↓ inflammatory effects

What are the four characteristics that distinguish them from normal cells;

• uncontrolled proliferation

• loss of fucntion becausse of lack of capacity to differentiate

• local invasiveness

• the abolity to metastasise

What are the five anti cancer drugs?

• cytotoxic drugs

• hormones and hormone antagonists

• protein kinase inhibitors

• monoclonal antibodies

• miscellaneous agents

What are the three general principles of chemotherapy?

• use drugs with different mechanisms to target multiple pathways

• use drugs with non-overlapping toxicities to avoid cumulative organ damage

• reduces development of drug resistance

cytotoxic drugs

• drugs that directly kill cells or prevent cell division

• target rapidly diving cells → both cancer cells and normal rapidly dividing cells

• often used in combination to target multiple mechanisms simultaneously

HOrmones and hormone antagonists

• some cancers are driven by hormones thus blocking hormonal signalling slows or stops growth

• examples; breast and prostate cancer

• generally better tolerated than cytotoxic drugs

• used as adjuvant therapy, after surgery, or as long-term maintancence

• resistance can develop over time as tumour can become more hormone-independent

Protein kinase inhibitors

• Cancer cells often have overactive kinases driving uncontrolled proliferation

• These drugs block specific kinases → ↓ growth factor receptor signalling → ↓ proliferation

• More selective than cytotoxic drugs → generally better tolerated

• Resistance develops frequently due to mutations in kinase domain

What are monoclonal antibodies?

large protein molecules targeting specific antigens on cancer cells or tumour vasculature

• more targeted than cytotoxic drugs because they act on specific surface markers

What are the three mechanisms of monoclonal antibodies?

• direct cell killing

• immune-mediated destruction

• blocking growth factor receptors or tumour vasculature

Future of chemotherapy (two main with some sub)

Living drugs and gene editing

• CAR-T cells → genetically modified T cells engineered to recognise and kill cancer cells

• Gene editing technology enables precise modification of T cells to enhance cancer killing ability

Personalised medicine

• tumour genotyping and immunological testing now routine in clinical practice

• identifies specific mutations and characteristics of individual tumour cells

• guides selection of optimal drug combination for each patient

• targeted individualised treatment

Facts about viruses

• accellular

• require a host cell to replicate

• have genetic material (a genome)

  • composed of single-stranded DNA

  • or single stranded or double stranded RNA

  • never both

• Resistance

• non motile

Facts protozoa

• unicellular eukaryotic microorganisms found in water, soil, and as parasites in hosts

• eukaryotic (has nucleus)

• DNA in nucleus

• No cell wall

• Motile; moves with cilia, flagella, pseudopodia

What are two types of medically important protozoa

• intestinal protozoa

• vloed and tissue protozoa

What are the six principles of antibiotic therapy

1. emipral therapy → local guidelines - antibiogram (resistance patterns) - patient history

2. targetted therapy - known causative organism

3. correct dose and route of administration

4. duration of therapy

5. adverse events

6. De-escalation