5: Pharmacology of Major Drug Classes Flashcards
What is Chemotherapy?
- The use of chemicals to destroy pathogens which have invaded the body
- It includes the use of chemicals to destroy our own cells which have become malignant
Enemy Bacteria: Cell Wall Synthesis
Our cells don’t have cell walls, but they are vital to the survival of bacteria and fungi. Disruption of the ability to make or maintain the cell wall will therefore destroy the bacteria but not affect our cells (penicillin)
Enemy Bacteria: Protein Synthesis
Bacteria synthesise proteins like our cells do, but their ribosomes are different. Here again, is a point that could be disrupted without harming our cells
Enemy Bacteria: Cell Membrane
Our cells have a cell membrane of course, and the bacterial cell membrane is similar to ours (phospholipid bilayer), but in bacteria it is much more readily disrupted by detergents than ours
Enemy Bacteria: Metabolic Pathways
The best example is the synthesis of folic acid. Folic acid is vital for all cells – it is involved in the process of DNA synthesis. However, we have to absorb and use folic acid from our food, as we cannot synthesise it, whereas bacteria and fungi have to make theirs, as they cannot absorb it. Blocking the production of folic acid will therefore prevent the bacteria from synthesising DNA and therefore replicating. Drugs that act in this way are known as bacteriostatic. Successful use of these drugs does depend on an effective immune system in the patient, though
Enemy Bacteria: RNA or DNA Synthesis
All cells have to do this, but in bacteria, different enzymes are used at some stages. Again, this can be exploited to prevent the cells from reproducing
Enemy Bacteria: Recognising or Attaching Host Cells
The ability to recognise or attach to a host cell impact on the ability of the invaders to spread from cell to cell and therefore take over. Reducing this ability can give the immune system time to deal with the pathogens before it is overwhelmed by their rapid proliferation
Enemy Fungi
- Most prominent lipid in fungi cell membranes is ergosterol
- Different lipid, therefore different enzymes to make it. A point of attack that will disrupt the fungal cell membrane but not harm ours
- Cell wall enzymes or components can be attacked (we don’t have so it won’t affect us)
Enemy Viruses
- The virus is essentially a bundle of RNA inside a protective coat
- In order to reproduce and spread successfully, it has to hijack our own cell’s machinery
- The points of attack for viruses therefore, tend to be in the way they interact with the host cells
Tumour Cells
- Difficult to differentiate cancer cells from healthy ones
- No structural or metabolic differences to exploit
- Cytotoxic effects on both cancer cells and healthy cells
Cytotoxic Drugs
- Cell death by apoptosis
- Damage the cell’s DNA or disrupt the separation of chromatids during mitosis
Treatment of Mania
- Most commonly seen as a component of bipolar disorder
- Lithium is a mood stabiliser, which “evens out” moods, and limits the occurrence of manic episodes and also of depressive episodes:
> Narrow therapeutic index (margin of safety) and so blood levels need to be monitored
> Toxic doses can result in confusion, seizures and coma
> Side effects include fine muscle tremor, nausea, vomiting, diarrhoea, polydipsia
Lithium: Mechanism of Action
Reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission
Autonomic Drugs
- Potential to be used for many conditions, since these can manipulate autonomic effects in organs and glands
- In practice, use is limited, as side effects are often a problem
Autonomic Neurotransmitters: Sympathetic Division (Fight or Flight)
- Noradrenaline
- Adrenaline
Autonomic Neurotransmitters: Parasympathetic Division
Acetylcholine
Receptors for Acetylcholine: Cholinergic Receptors
- Nicotinic – found on skeletal muscle, produce contraction
- Muscarinic – found in brain and on organs and glands, produce parasympathetic response
Clinical Uses for Autonomic Drugs
- Treatment of hypertension
- Reduction of risk of cardiac arrhythmia after an M.I.
- Treatment of asthma
- Treatment of glaucoma
- Treatment of nasal congestion
- Treatment of diarrhoea, motion sickness
- Emergency resuscitation (cardiac arrest)
- Treatment of anaphylaxis
Analgesics: NSAIDs
- Reduce inflammation
- The NSAIDs operate by reducing the stimulation of nociceptors by reducing the production of inflammatory mediators in response to tissue damage
Analgesics: Opioids
- Act more centrally
- The opioids act at the site of tissue damage, in the spinal cord and also in the brain, to reduce the pain signals. In doing this, opioid drugs are simply mimicking the effects of our natural endogenous opioids on their own pain modulation system
Pain
- Nociceptors signal pain to brain via spinal cord
- Perceived in the cerebral cortex
- Activates the limbic structures of the brain, responsible for emotions
Inflammation Cardinal Signs
- Heat
- Redness
- Swelling
- Pain
- Loss of function
Inflammation: Prostaglandins and Histamine
- P stimulate pain receptors
- Histamine causes blood vessels to dilate and also increase their permeability
How do NSAIDs Have Their Effects?
- Act by inhibiting the enzyme cyclooxygenase (COX)
- This enzyme is required for the production of prostaglandins
- NSAIDs are analgesic, anti-inflammatory, and anti-pyretic
