BIOM Pharmacodynamics 4 Types of Antagonism

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2 BIOM Pharmacodynamics 4 Types of Antagonism 1. Chemical Antagonism 2. Pharmacokinetic Antagonism 3. Physiological Antagonism 4. Pharmacological Antagonism Where two drugs bind to each other, so that one drug inactivates the action of the second drug - meaning the properties of the active drug is lost. When Drug A acts as an antagonist by reducing the concentration of Drug B at its site of action (Note: can't increase concentration) Drug A can increase or decrease GIT or liver absorption therefore [Drug B] different at site of action. When two drugs interact whose opposing actions in the body tend to cancel each other out. Drug A binds to Receptor A --> Response A Drug B binds to Receptor B--> Response B But Response B is opposite to Response A. Also called 'receptor-block' antagonism - it involves two major mechanisms: Reversible competitive antagonism Irreversible competitive antagonism Note: see next page Note: convulsion = sudden, violent, irregular movement of body caused by involuntary contractions of muscles Note: coagulant = change into solid or semi-solid state therefore, anticoagulant = make watery

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6 BIOM2009 Pain + Inflammation Module Succinct Lecture Note Summaries Lectures 1-5 Tiffany Lim s BIOM2009 Pain + Inflammation Succinct Lecture Note Summaries Page 1 of 9

7 BIOM2009 Pain + Infla Lecture Note Summary Week 9.2 Pain + Infla 5 Rheumatology Objectives: To distinguish between rheumatoid arthritis and osteoarthritis and their causes Understand how DMARDs, methotrexate and other drugs work to threat these conditions Understand what gout is and how it can be treated Lecture outline and main concepts: Arthritis is caused by the inflammation of the joints. 1. Rheumatoid Arthritis: An autoimmune disease (more common in women and older adults) in which the immune system directs an aggressive and destructive attack on its own tissues, primarily those associated with synovial joints, resulting in painful deformity and immobility, especially in the fingers, wrists, feet and ankles. The inflammation is chronic and irreversible tissue remodelling occurs in the long term First, the immune cells attack the synovial membrane that encloses the joint. Then, the membrane thickens and becomes inflamed. Secondly, pro-inflammatory mediators (prostaglandins, kinins, cytokines, interleukins and TNF-alpha) play a key role in promoting the reaction and causing damage (inflammation occurs inside the synovial fluid). 2. Osteoarthritis: Incidence rises sharply with age, osteoarthritis is caused by the physical wearing down of the joint leading to the breakdown of cartilage, causing unprotected bones to rub against each other resulting in pain. Wear and tear is associated with being overweight or a previous injury to the major joints (eg. Knee/hip) or overuse of joints eg. Repetitive manual labour eg. require heavy lifting grinding down of protective barrier pressure promotes osteoarthritis Drugs to treat arthritic disorders (inflammatory drugs): NSAIDs can treat the symptoms of arthritis, but will not stop the progression of the disease SAIDs are rarely used as chronic treatment of corticosteroids will change appearance and many side effects (Cushing s syndrome) and even cause osteoporosis! However, it can be injected directly into the synovial fluid between the synovial membranes as a last resort (in severe inflammation during acute flare-ups). NB Corticosteroids reduce the expression of COX enzymes instead of blocking them. DMARDS (disease-modifying anti-rheumatic drugs) are most commonly used for initial therapy. These aim to halt or even reverse the underlying disease itself, rather than drugs like NSAIDs which are used purely to relieve symptoms instead of treating the underlying symptoms. They will: 1. reduce the number of swollen joints 2. reduce pain 3. reduce the quantity of acute phase rheumatoid-associated proteins 4. improve x-ray appearances (less inflammation, can see clearer). The patient may still have arthritis, but is manageable and not severe. Methotrexate (DMARD) widely used in RA and also anticancer drug common 1 st line drug and has a higher efficacy and better tolerated compared to other DMARDs. However it is a folic acid antagonist. Folate is needed to synthesis DNA and RNA. Folate is derived from food and folic acid is man-made. Methotrexate is structurally similar (a bit bulkier antagonist) and compete with folic acid for the enzyme dihydrofolate reductase involved in the nucleic acid synthesis. This slows down the production of purines (DNA) and hence rapidly dividing cells (cancer, skin cells, hair, fingernails) can t reproduce at the desired rate for inflammation. Tiffany Lim s BIOM2009 Pain + Inflammation Succinct Lecture Note Summaries Page 8 of 9

8 BIOM2009 Central Nervous System (CNS) Module Succinct Lecture Note Summaries CNS Lectures 1-6 Tiffany Lim s BIOM2009 Succinct CNS Lecture Note Summaries Page 1 of 7

9 BIOM2009 CNS Lecture Note Summary Week11.2 CNS 3 Anxiety Objectives: To understand the basic symptoms of anxiety and associated disorders To understand the mechanisms of action of drug classes used to treat anxiety (anxiolytics and mild sedatives) and to assist in sleep (hypnotics) To be aware of the possible hazardous combinations when taking these drugs Lecture outline and main concepts: Anxiety often has an early onset teens to early 20s, peaking at 35-44, with a 2:1 female ratio Anxiety is the umbrella term with many subjects listed beneath it (eg. GAD, OCD, phobic etc) In an anxiety disorder, there is a shift in the balance of CNS neurotransmitters resulting in OVEREXCITATION. TO counter this effect, we need to DECREASE the neuronal and synaptic activity of the nervous system. Inhibition via GABA is mediated by ionotropic GABA A receptors (influx of Cl- results in hyperpolarisation = no AP). Benzodiazepines don t have any effect on the GABA A receptors themselves, but allosterically enhance the affinity of the receptors for its OWN GABA the natural endogenous compound. Barbiturates are not commonly used for anxiety anymore due to their very narrow therapeutic window. 4x dose of getting hypnosis = DEATH BIOM2009 CNS Lecture Note Summary Week12.1 CNS 4 Schizophrenia Objectives: To understand the basic symptoms of psychoses with prominence in schizophrenia To understand the mechanisms of action of typical and atypical antipsychotic medications, with mechanisms of their potential side effects Lecture outline and main concepts: Schizophrenia is a long-term mental disorder of a type involving a breakdown in the relation between thought, emotion and behaviour leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion and a sense of mental fragmentation. It affects people in their youths and ranks among the top 10 causes of disability in developed countries. There is strong evidence that schizophrenia is genetic. Dopamine, glutamate and serotonin level imbalances may play a role in schizophrenia. Anti-psychotic drugs are not a cure, but helps control the disease people must be treated with meds indefinitely as the disease is lifelong. There are older typical drugs modelled on the D 2 receptor antagonism but high extra pyramidal symptoms (EPS). Examples: chlorpromazine, haloperidol The newer atypical drugs are modelled on the 5-HT 2 /D 2 receptor antagonism Hit and Run Antagonism - but associated with weight gain, sedation and diabetes increase example clozapine, resperidone The cause of the illness (other than genetic component) is still unknown and there is no explanation for why some patients recover, why some don t and why some have recurring illness. Page 4 of 7 Tiffany Lim s BIOM2009 Succinct CNS Lecture Note Summaries