What are some sites that antagonists can affect?
The binding of an agonist to its receptor The response of a receptor to an agonist The activation caused by a receptor, or the pathway leading to an effect Countering the overall effect by activating an opposing pathway (eg SNS vs PNS)
Describe allosteric modulation
Allosteric modulation refers to altering the activity of a receptor by a molecule binding to an area of the receptor that is not the usual ligand binding site. This allosteric binding can alter properties of the receptor such as the ligand affinity, ligand efficacy and receptor activation level.
Describe allosteric modulation
Allosteric modulation refers to altering the activity of a receptor by a molecule binding to an area of the receptor that is not the usual ligand binding site. This allosteric binding can alter properties of the receptor such as the ligand affinity, ligand efficacy and receptor activation level.
What steps are involved in getting a drug to and then from its site of action?
Administration, Absorption, Distribution, Elimination (Metabolism and Excretion)
What are factors to consider in administration
Convenience, cost, bioavailability st site of action, whether a local or systemic effect is desired
How can the extent of absorption of a drug affect the broadness of its effect?
A poorly absorbed drug will have limited access to tissues. For it to have a systemic effect, it either must be well absorbedm or it must be delivered intravenously
How can the extent of absorption of a drug affect the broadness of its effect?
A poorly absorbed drug will have limited access to tissues. For it to have a systemic effect, it either must be well absorbed or it must be delivered intravenously
What factors can affect drug distribution in the body?
Molecular size and thus ability to cross vascular endothelium Extent of binding to blood proteins Lipid solubility (affecting ability to cross cell membranes, sequestration in certain tissues, and ability to cross blood/brain barrier)
What are drug reservoirs?
Areas in a body in with drug can accumulate
How is volume of distribution calculated, and what does it indicate?
volume of distribution=volume of drug in body/concentration in plasma It is an indication of how widely a drug is distributed in the body. If it is high, it is mainly distributed in tissue. If it is low, it is mostly bound to plasma proteins
What are the components of renal clearance?
Glomerular filtration, active tubular secretion and passive tubular reabsorption
What are the phases of drug metabolism?
Phase I adds a functional group to the drug. Phase II adds a water soluble molecule to the functional group
What are the usual products of drug metabolism?
Less active, more water soluble molecules
How are neurotransmitters introduced to and removed from the synapse?
How is ACh synthesised?
How is NA synthesised?
How is adrenaline synthesised?
How is ACh inactivated once it has completed its function in the synapse?
It is degraded by acetylcholine esterase on the post-junctional membrane
How is NA inactivated once it has completed its function in the synapse?
Reuptake. The neuronal cell has a high affinity transporter. Once the NA is taken up, it is either repackaged, or degraded by monoamine oxidase (MAO). There are also extraneuronal transporters that contribute in part to reuptake, but these transporters have a low affinity
What are the main neurotransmittors and receptors for the different components of the peripheral nervous system?
How does butulinum toxin affect ACh?
Prevent ACh release.
Taken up by cholinergic neurons, activates, cleaves SNARE proteins, synaptic complex unable to form without SNARE proteins, neurotransmitter unable to be released
How does anticholinesterase affect ACh?
Prevents the degradation of ACh by blocking the action of acetylcholinesterase. Reduced degradation increases the effects of ACh
How are nicotinic receptor antagonists used?
Prevent contraction of muscles, and are used presurgery
How are muscarinic repector agonists used?
They cause salivation, lacrimation, urination and defecation. Clinically, they are used to treat glaucoma by increasing the draining of the eye
What methods can be used to increase the action of noradrenaline in the synapse?
Block reuptake by direct action on the transporter (cocaine)
Block intracellular degradation by inhibiting monoamine oxidase (MAO)
Indirectly acting aympathomimetics taking the place of NA molecules within the synaptic vesicle - contraindicated by MAO inhibitors
Which adrenoceptors are localised to with tissues?
b1 - heart
b2 - smooth muscle
a1 - vasculature
What are H1 receptor antagonists used for?