L36 Pharmacodynamics Flashcards
(35 cards)
what are the 3 properties of drugs?
affinity - The chemical forces that cause the drug to bind the receptor site
efficacy - The extent of functional change imparted to a receptor upon binding of a drug
potency - Dose of drug needed to produce a biological effect
what are receptors?
macromolecules involved in chemical signalling between and within cells
Cell activity changes once stimulated
Receptor must recognise the molecule and action has to happen
what is an agonist?
Drug that binds to receptors and initiates a cellular response
It has high affinity and efficacy
what is a partial and inverse agonist?
Partial Agonists – act on the same receptor but do not produce the same maximal response
Inverse Agonist – acts on the same receptor but produces an opposite effect
what is an antagonist?
Drug that binds to receptors but does not initiate a cellular response
It has affinity but no efficacy
what is a competitive and non-competitive antagonist?
Competitive Antagonist - binds to the same site as the agonist but does not activate it
Non-competitive Antagonist - binds to an allosteric site to prevent activation of the receptor
what are the 4 receptor families?
ligand-gated ion channels
g-protein coupled receptor
enzyme-linked receptors
intracellular receptors
what are ligand-gated ion channels?
A group of transmembrane ion channel proteins which open to allow ions to pass through the membrane in response to the binding of a ligand such as a neurotransmitter.
E.g. Glutamate, Serotonin, Dopmaine, Acetylcholine
what is a g-protein-coupled receptor?
These receptors are linked to their responses by regulatory Guanosine Triphosphate (GTP)-binding proteins or G proteins
This complex induces conformational change in the G protein
how does the g-protein-coupled receptor work?
signal binds to GPCR, causing shape change and interaction with G protein, GDP is displaced by GTP
active g protein binds to enzyme causing cellular response
gtp is hydrolysed into gdp causing enzyme to release the g protein and reaction stops
what are second messengers?
Allow signals conduction to be amplifies
Enzymes that produce second messengers include:
adenyl cylase – involved in activation of protein kinase
Phospholipase C – involved in production of inositol triphosphate (IPS3) and diacyglycerol (DAG)
explain lock and key theory concept using histamine H2 receptor antagonists as an example
Gastric acid secretion is stimulated by histamine, acetylcholine and gastrin
Activation of H2 receptors potentiates gastrin-induced acid secretion and enhances cAMP (second messenger)
H2 receptor antagonist block H2 receptor therefore inhibiting action of histamine. This reduces cAMP formation and acid secretion
what are receptor kinases?
Activate cascades of intracellular signals
Most are receptor tyrosine-kinases and are activated by growth factors
E.g. Insulin, growth factors
what are nuclear receptors?
The receptor is entirely intracellular
Ligand must be lipid soluble
Primary targets are transcription factors
E.g. steroid hormones
hormone binds to receptor in cytoplasm and the complex enters nucleus, where it binds to receptor sites on chromatin, activating mRNA transcription
what are neurotransmitters and synapses?
Nerve impulses are transmitted are along neurone.
Impulses are conducted across the space by neurotransmitters
Neurones that conduct to the synapse are presynaptic neurones
Those that conduct the impulse away from the synapse are post synaptic neurones
what are the functions and the problems caused by imbalances in the following neurotransmitters:
acetylcholine noradrenaline dopamine GABA serotonin
acetylchoine - enables muscle action, learning and memory. low levels = alzheimer’s
noradrenaline - Helps control alertness, mood. Increases heart rate. low = depression. high = insomnia
dopamine - Influences movement, attention and emotion. low = parkinsons. high = schizophrenia
GABA - major inhibitory neurotransmitter. low = anxiety
serotonin - Affects sleep, mood, hunger and arousal. low = depression
what do NSAIDs that inhibit enzymes do?
tissue injury –> arachidonic acid
arachidonic acid + COX1 (constitutional) --> Cytoprotective prostaglandins: - Protect gastric mucosa - Protect renal perfusion r Thromboxanes: - Aid platelet aggregation (adhesion)
arachidonic acid + COX2 (inducible) –>
Inflammatory prostaglandins:
- Recruit inflammatory cells (inflammation, vasodilation)
- Sensitise skin pain receptors (pain)
summarise the renin-angiotensinogen aldosterone system (RAAS) when there is low bp
dec bp –> kidneys –> renin turns angiotensinogen from liver into angiotensin 1. angiotensin-converting enzyme in lung capillaries turns this into angiotensin 2 –> causes vasoconstriction to inc bp and in adrenal cortex rels aldosterone which inc water reabsorption and decs urine volume to inc bp
what do calcium channel blockers do?
Bind to calcium channels on smooth muscles, blocking the influx of calcium causes smooth muscle relaxation and decreased heart rate
what are the 3 classes of calcium channel blockers?
Dihydropyridines (amlopdipine, felodpine) – most smooth muscle selective
Phenylalkylamine (verapamil) – selective to myocardium and less effective as a vasodilator
Benzothiazepine (diltiazem) – has both cardiac depressant and vasodilator actions
what do local anaesthetics do?
Produce a transient and reversible loss of sensation in restricted area of the body without loss consciousness
Causes depression of excitation in nerve endings or inhibition of the conduction process in peripheral nerves
what is the structure of local anaesthetics?
Local anaesthetics generally have a lipid-soluble hydrophobic aromatic group and a charged, hydrophilic amine group.
The bond between these two groups determines the class of the drug, and may be amide or ester
LAs are weak bases
how are local anesthetics classified?
Esters
Rapidly hydrolysed and the breakdown product PABA (para amino benzoic acid) is associated with allergic and hypersensitive reactions
e.g. cocaine and amethocaine
Amides
Relatively stable and hypersensitivity reactions are rare
e.g. lignocaine, bupivacaine and prilocaine
why are amide local anaesthetics used more commonly than ester local anaesthetics?
The ester linkage is more easily broken than the amide bond so the ester drugs are less stable in solution and cannot be stored for as long as amides
