Pharmacology Test 2

Cyclophosphamide

Indication: Cancer

Class: Alkylating Agent (Cell Cycle Non Specific)

MOA: Binds to DNA in a number of ways and forms irreversible covalent bonds. This prevents cell replication, leading to apoptosis.

Adverse Effects:

• Toxicity to rapidly dividing cells causes hair loss, sterility and haematological issues.

Doxorubicin

Indication: Cancer

Class: Anthracyclines (Cell Cycle Non Specific)

MOA: Has 3 key mechanisms:

• Intercalation: Inserts itself between DNA bases, preventing DNA synthesis or repair, preventing cell division.

• Generation of Free Radicals: Causes DNA damage in cancerous cells.

• Inhibition of Topoisomerase II: inhibits the function of ensuring DNA integrity, allowing intercalation to occur.

Adverse Effects:

• Toxicity to rapidly dividing cells causes hair loss, sterility and haematological issues.

Methotrexate

Indication: Cancer

Class: Antimetabolites (Cell Cycle Specific)

MOA: Works in the S phase to prevent DNA synthesis. It inhibits dihydrofolate reductase, preventing purine and pyrimid synthesis, preventing formation of DNA bases and hence preventing DNA replication, preventing cell division.

Adverse Effects:

• Toxicity to rapidly dividing cells causes hair loss, sterility and haematological issues.

Paclitaxel

Indication: Cancer

Class: Taxane (Cell Cycle Specific)

MOA: Works in the M phase to prevent DNA synthesis. It stabilises microtubules, preventing microtubule disassembly and separation of chromosomes, preventing cell division.

Adverse Effects:

• Toxicity to rapidly dividing cells causes hair loss, sterility and haematological issues.

Tamoxifen

Indication: ER+ Breast Cancer

Class: Selective Estrogen Receptor Modulator (SERM)

MOA: Antagonises estrogen receptors in breast tissue. They prevent oestrogen binding to the cells, hence slowing growth of cancer cells.

• It also increases bone mineral density, and is cardioprotective.

Adverse Effects:

• Increased risk of endometrial cancer

• Toxicity to rapidly dividing cells causes hair loss, sterility and haematological issues.

Trastuzumab

Indication: HER+ Breast Cancer

Class: Monoclonal Antibody

MOA: Binds extracellularly to HER2 receptors and prevents dimerisation, and down regulates HER2 receptors. This prevents signal transduction, preventing cellular proliferation.

Adverse Effects:

• Toxicity to rapidly dividing cells causes hair loss, sterility and haematological issues.

Lapatinib

Indication: HER+ Cancer

Class: Tyrosine Kinase Inhibitor

MOA: Binds to intracellular portion of HER2 receptor, preventing phosphorylation and activation. This prevents signal transduction, preventing cellular proliferation.

Adverse Effects:

• Toxicity to rapidly dividing cells causes hair loss, sterility and haematological issues.

Cortisone

Indication: Inflammation

Class: Corticosteroid (Glucocorticoid + Mineralocorticoid)

MOA:

• Enters the cell and binds to intracellular glucocorticoid receptors. It enters the nucleus and dimerises, having effects on gene transcription. From here it has many effects:

  • It enhances production of anti-inflammatory mediators and reduces production of pro-inflammatory mediators.

  • Inhibits phospholipase A2, preventing production of inflammatory mediators leukotrienes and prostaglandins.

  • Decreases mast cell, neutrophil and macrophage infiltration.

  • Reduces histamine and complement release.

Adverse Effects:

• Increasing cortisol levels can suppress the bodies ability to make cortisol.

• This can lead to dyslipidemia, delayed wound healing, muscle wasting and skin atrophy, hypertension, fracture and osteoporosis risk.

Hydrocortisone

Indication: Inflammation

Class: Corticosteroid (Glucocorticoid + Mineralocorticoid)

MOA:

• Enters the cell and binds to intracellular glucocorticoid receptors. It enters the nucleus and dimerises, having effects on gene transcription. From here it has many effects:

  • It enhances production of anti-inflammatory mediators and reduces production of pro-inflammatory mediators.

  • Inhibits phospholipase A2, preventing production of inflammatory mediators leukotrienes and prostaglandins.

  • Decreases mast cell, neutrophil and macrophage infiltration.

  • Reduces histamine and complement release.

Adverse Effects:

• Increasing cortisol levels can suppress the bodies ability to make cortisol.

• This can lead to dyslipidemia, delayed wound healing, muscle wasting and skin atrophy, hypertension, fracture and osteoporosis risk.

Fludrocortisone

Indication: Inflammation

Class: Corticosteroid (Mainly Mineralocorticoid)

MOA:

• Enters the cell and binds to intracellular glucocorticoid receptors. It enters the nucleus and dimerises, having effects on gene transcription. From here it has many effects:

  • It enhances production of anti-inflammatory mediators and reduces production of pro-inflammatory mediators.

  • Inhibits phospholipase A2, preventing production of inflammatory mediators leukotrienes and prostaglandins.

  • Decreases mast cell, neutrophil and macrophage infiltration.

  • Reduces histamine and complement release.

Adverse Effects:

• Increasing cortisol levels can suppress the bodies ability to make cortisol.

• This can lead to dyslipidemia, delayed wound healing, muscle wasting and skin atrophy, hypertension, fracture and osteoporosis risk.

Prednisolone

Indication: Inflammation

Class: Corticosteroid (Mainly Glucocorticoid)

MOA:

• Enters the cell and binds to intracellular glucocorticoid receptors. It enters the nucleus and dimerises, having effects on gene transcription. From here it has many effects:

  • It enhances production of anti-inflammatory mediators and reduces production of pro-inflammatory mediators.

  • Inhibits phospholipase A2, preventing production of inflammatory mediators leukotrienes and prostaglandins.

  • Decreases mast cell, neutrophil and macrophage infiltration.

  • Reduces histamine and complement release.

Adverse Effects:

• Increasing cortisol levels can suppress the bodies ability to make cortisol.

• This can lead to dyslipidemia, delayed wound healing, muscle wasting and skin atrophy, hypertension, fracture and osteoporosis risk.

Methylprednisolone

Indication: Inflammation

Class: Corticosteroid (Mainly Glucocorticoid)

MOA:

• Enters the cell and binds to intracellular glucocorticoid receptors. It enters the nucleus and dimerises, having effects on gene transcription. From here it has many effects:

  • It enhances production of anti-inflammatory mediators and reduces production of pro-inflammatory mediators.

  • Inhibits phospholipase A2, preventing production of inflammatory mediators leukotrienes and prostaglandins.

  • Decreases mast cell, neutrophil and macrophage infiltration.

  • Reduces histamine and complement release.

Adverse Effects:

• Increasing cortisol levels can suppress the bodies ability to make cortisol.

• This can lead to dyslipidemia, delayed wound healing, muscle wasting and skin atrophy, hypertension, fracture and osteoporosis risk.

Dexamethasone

Indication: Inflammation

Class: Corticosteroid (Mainly Glucocorticoid)

MOA:

• Enters the cell and binds to intracellular glucocorticoid receptors. It enters the nucleus and dimerises, having effects on gene transcription. From here it has many effects:

  • It enhances production of anti-inflammatory mediators and reduces production of pro-inflammatory mediators.

  • Inhibits phospholipase A2, preventing production of inflammatory mediators leukotrienes and prostaglandins.

  • Decreases mast cell, neutrophil and macrophage infiltration.

  • Reduces histamine and complement release.

Adverse Effects:

• Increasing cortisol levels can suppress the bodies ability to make cortisol.

• This can lead to dyslipidemia, delayed wound healing, muscle wasting and skin atrophy, hypertension, fracture and osteoporosis risk.

Ibuprofen

Indication: Nociceptive Pain and Inflammation

Class: NSAID (COX 1 + COX 2)

MOA: Inhibits COX enzymes, preventing the conversion of archidonic acid into eicosanoids: prostaglandins and thromboxanes. Reductions to prostaglandin concentration prevents binding to specific G-protein coupled receptors, reducing pain sensation, inflammation (by reducing vasodilation), and fever. Reductions to thromboxane reduce blood clotting.

Adverse Effects:

• Gastrointestinal (ulcers, gastritis, bleeding)

• Bleeding risk

• Nephrotoxicity

Diclofenac

Indication: Nociceptive Pain and Inflammation

Class: NSAID (COX 1 + COX 2)

MOA: Inhibits COX enzymes, preventing the conversion of archidonic acid into eicosanoids: prostaglandins and thromboxanes. Reductions to prostaglandin concentration prevents binding to specific G-protein coupled receptors, reducing pain sensation, inflammation (by reducing vasodilation), and fever. Reductions to thromboxane reduce blood clotting.

Adverse Effects:

• Gastrointestinal (ulcers, gastritis, bleeding)

• Bleeding risk

• Nephrotoxicity

Aspirin

Indication: Nociceptive Pain and Inflammation

Class: NSAID (COX 1 + COX 2)

MOA: Inhibits COX enzymes, preventing the conversion of archidonic acid into eicosanoids: prostaglandins and thromboxanes. Reductions to prostaglandin concentration prevents binding to specific G-protein coupled receptors, reducing pain sensation, inflammation (by reducing vasodilation), and fever. Reductions to thromboxane reduce blood clotting.

Adverse Effects:

• Gastrointestinal (ulcers, gastritis, bleeding)

• Bleeding risk

• Nephrotoxicity

Naproxen

Indication: Nociceptive Pain and Inflammation

Class: NSAID (COX 1 + COX 2)

MOA: Inhibits COX enzymes, preventing the conversion of archidonic acid into eicosanoids: prostaglandins and thromboxanes. Reductions to prostaglandin concentration prevents binding to specific G-protein coupled receptors, reducing pain sensation, inflammation (by reducing vasodilation), and fever. Reductions to thromboxane reduce blood clotting.

Adverse Effects:

• Gastrointestinal (ulcers, gastritis, bleeding)

• Bleeding risk

• Nephrotoxicity

Mefenamic Acid

Indication: Nociceptive Pain and Inflammation

Class: NSAID (COX 1 + COX 2)

MOA: Inhibits COX enzymes, preventing the conversion of archidonic acid into eicosanoids: prostaglandins and thromboxanes. Reductions to prostaglandin concentration prevents binding to specific G-protein coupled receptors, reducing pain sensation, inflammation (by reducing vasodilation), and fever. Reductions to thromboxane reduce blood clotting.

Adverse Effects:

• Gastrointestinal (ulcers, gastritis, bleeding)

• Bleeding risk

• Nephrotoxicity

Celecoxib

Indication: Nociceptive Pain and Inflammation

Class: NSAID (COX 2 specific)

MOA: Inhibits COX enzymes, preventing the conversion of archidonic acid into eicosanoids: prostaglandins and thromboxanes. Reductions to prostaglandin concentration prevents binding to specific G-protein coupled receptors, reducing pain sensation, inflammation (by reducing vasodilation), and fever. Reductions to thromboxane reduce blood clotting.

Adverse Effects:

• Cardiovascular risk (heart attack or stroke)

• Nephrotoxicity

• Asthma

Paracetamol

Indication: Nociceptive Pain + Fever

MOA: Unsure, but likely reduces central prostaglandin synthesis.

Adverse Effects:

• At therapeutic doses, effects are uncommon.

• High doses can lead to hepatotoxicity.

Gabapentin

Indication: Neuropathic Pain

Class: Adjuvant (Gabapentinoid)

MOA: Modulates central sensitisation by binding to the α2δ subunit on voltage-gated calcium channels reducing calcium influx, hence reducing excessive neurotransmitter release. This prevents hyper excitability, and transmission of pain impulses.

Adverse Effects:

• Sedation

• Respiratory depression

• Prone to misuse and dependance.

Pregabalin

Indication: Neuropathic Pain

Class: Adjuvant (Gabapentinoid)

MOA: Modulates central sensitisation by binding to the α2δ subunit on voltage-gated calcium channels reducing calcium influx, hence reducing excessive neurotransmitter release. This prevents hyper excitability, and transmission of pain impulses.

Adverse Effects:

• Sedation

• Respiratory depression

• Prone to misuse and dependance.

Amitriptyline

Indication: Neuropathic and Nociplastic Pain

Class: Tricyclic Antidepressant

MOA: Inhibits the re-uptake of serotonin and noradrenaline, increasing their concentration in the synapse. This enhances descending pain modulating pathways and reduces nociceptive signal transmission, reducing pain sensations.

Adverse Effects:

• Anti-cholinergic: dry mouth, blurry vision, urinary retention.

• Sedation

• Serotonin Toxicity

Duloxetine

Indication:Neuropathic and Nociplastic Pain

Class: Serotonin and Noradrenaline Reuptake Inhibitor (SNRI)

MOA: Blocks serotonin and noradrenaline reuptake transporters, causing their concentration to increase in the synapse. This enhances descending pain modulating pathways and reduces nociceptive signal transmission, reducing pain sensations.

Adverse Effects:

• Gastrointestinal

• Serotonin Toxicity

Morphine

Indication: Pain

Class: Strong Opioid Agonist

MOA: Binds to and agonise mu-opioid receptors, producing analgesia by modulating descending inhibitory pathways and inhibiting neurotransmitter release from primary afferent terminals in the CNS.

Adverse Effects:

• Seizure risk in those with epilepsy.

• Respiratory depression in those with asthma

• Impaired renal function

Oxycodone

Indication: Pain

Class: Strong Opioid Agonist

MOA: Binds to and agonise mu-opioid receptors, producing analgesia by modulating descending inhibitory pathways and inhibiting neurotransmitter release from primary afferent terminals in the CNS.

Adverse Effects:

• Seizure risk in those with epilepsy.

• Respiratory depression in those with asthma

• Impaired renal function

Methadone

Indication: Pain (also commonly used for withdrawal treatment)

Class: Strong Opioid Agonist

MOA: Binds to and agonise mu-opioid receptors, producing analgesia by modulating descending inhibitory pathways and inhibiting neurotransmitter release from primary afferent terminals in the CNS.

Adverse Effects:

• Seizure risk in those with epilepsy.

• Respiratory depression in those with asthma

• Impaired renal function

Fentanyl

Indication: Pain

Class: Strong Opioid Agonist

MOA: Binds to and agonise mu-opioid receptors, producing analgesia by modulating descending inhibitory pathways and inhibiting neurotransmitter release from primary afferent terminals in the CNS.

Adverse Effects:

• Seizure risk in those with epilepsy.

• Respiratory depression in those with asthma

• Impaired renal function

Tapentadol

Indication: Pain

Class: Strong Opioid Agonist

MOA: Binds to and agonise mu-opioid receptors, producing analgesia by modulating descending inhibitory pathways and inhibiting neurotransmitter release from primary afferent terminals in the CNS.

Adverse Effects:

• Seizure risk in those with epilepsy.

• Respiratory depression in those with asthma

• Impaired renal function

Codeine

Indication: Pain

Class: Weak Opioid Agonist

MOA: Binds to and agonise mu-opioid receptors, producing analgesia by modulating descending inhibitory pathways and inhibiting neurotransmitter release from primary afferent terminals in the CNS.

Adverse Effects:

• Seizure risk in those with epilepsy.

• Respiratory depression in those with asthma

• Impaired renal function

Tramadol

Indication: Pain

Class: Weak Opioid Agonist

MOA: The metabolite binds to and agonises mu-opioid receptors, producing analgesia by modulating descending inhibitory pathways and inhibiting neurotransmitter release from primary afferent terminals in the CNS. The parent drug inhibits reuptake of serotonin and noradrenaline.

Adverse Effects:

• Serotonin Toxicity

• Seizure risk in those with epilepsy.

• Respiratory depression in those with asthma

• Impaired renal function

Buprenorphine

Indication: Pain

Class: Partial Opioid Agonist (has threshold value)

MOA: The metabolite binds to and agonises mu-opioid receptors, producing analgesia by modulating descending inhibitory pathways and inhibiting neurotransmitter release from primary afferent terminals in the CNS. The parent drug inhibits reuptake of serotonin and noradrenaline.

Adverse Effects:

• Seizure risk in those with epilepsy.

• Respiratory depression in those with asthma

• Impaired renal function

Diphenoxylate

Indication: Diarrhoea

Class: Peripheral Acting Opioid Agonist

MOA: Binds to and activates opioid receptors in the gut wall. This reduces bowl motility and increases fluid reabsorption, preventing diarrhoea

Adverse Effects:

• Abdominal pain and bloating

• Nausea and vomiting

• Constipation

• Drowsiness / Dizziness

Loperamide

Indication: Diarrhoea

Class: Peripheral Acting Opioid Agonist

MOA: Binds to and activates opioid receptors in the gut wall. This reduces bowl motility and increases fluid reabsorption, preventing diarrhoea

Adverse Effects:

• Abdominal pain and bloating

• Nausea and vomiting

• Constipation

• Drowsiness / Dizziness

Naloxone

Indication: Opioid Overdose

Class: Opioid Antagonist (short acting)

MOA: Competitively antagonises mu-opioid receptors in the CNS, rapidly reversing the effects of opioids.

Adverse Effects:

• Acute withdrawal (if opioid dependant)

• Anxiety

• Agitation

• Tachycardia

• Confusion

Naltrexone

Indication: Opioid abstinence

Class: Opioid Antagonist (long acting)

MOA: Reversibly blocks opioid receptors for 24 - 72 hours, used to reduce the pleasurable affects associated with opioids.

Adverse Effects:

• Anxiety

• Agitation

• Tachycardia

• Confusion

Methylnaltrexone

Indication: Constipation (caused by opioids)

Class: Peripheral Opioid Antagonist

MOA: Prevents activation of opioid receptors in the gut wall. This enhanced bowl motility and reduces fluid reabsorption, preventing constipation

Adverse Effects:

Tetrahydrocannabinol (THC)

Indication: Pain

Class: Cannabinoid

MOA: Acts as a partial agonist at cannabinoid 1 and 2 receptors, reducing symptoms of pain, muscle spasticity, vomiting and nausea, as well as improving sleep and appetite.

Adverse Effects:

• Fatigue / Sedation

• Dizziness / Confusion

• Nausea / vomiting

Cannabinol (CBD)

Indication: Pain

Class: Cannabinoid

MOA: Acts as an antagonist at cannabinoid 1 and 2 receptors. Used to reduce side effects of THC, and appears useful in the management of seizures, pain, and reducing anxiety.

Adverse Effects:

• Fatigue / Sedation

• Dizziness / Confusion

• Nausea / vomiting