week 2

Question 1

what determines binding?

Answer 1

1. receptor and ligand concentration
2. the likelihood of ligand to bind to receptor (affinity)
3. the likelihood of ligand to activate receptor (efficacy)

Question 2

What is affinity, how is it quantified?

Answer 2

affinity is a measure of the attraction of a ligand for a biological target. quantified by equilibrium dissociation constant, Ka. Ka = ligand concentration at which half of the receptors are occupied with drug at equilibrium. drugs with lower Ka have a higher affinity.

Question 3

what are the properties of a high affinity ligand?

Answer 3

high affinity ligands bind to its target rapidly, bind for longer at the target, and there are many bound targets at lower concentrations.

Question 4

what efficacy and how is it quantified?

Answer 4

efficacy is the strength of the agonst-receptor complex in evoking a response of the tissue. quantified by Emax, the maximal response/effect that a drug can produce. partal agonists have lower Emax compared to full agonists.

Question 5

What is potency and how is it quantified?

Answer 5

the drug concentration required to elicit a given effect. quantified by EC50, the concentration that elicits a 50% response. drugs with lower EC50 have higher potency.

Question 6

What is Receptor Reserve?

Answer 6

receptor reserve, refers to a phenomenon where not all available receptors need to be occupied by an agonist to produce Emax. This explains why some drugs can produce strong effects at lower doses.

Question 7

What is desensitisation (tachyphylaxis) and diminished tolerance and what are the causes?

Answer 7

the effect of a drug can gradually diminish upon continuous administration either minutes or less (tachphylaxis) or hours/days/weeks (tolerance). change in receptor expression, exhastion od mediators, physiological adaption.

Question 8

Define antagonist

Answer 8

A molecule that interferes with the interaction of an agonist and a receptor protein or a molecule that blocks the constitutive elevated basal response of a physiological system.

Question 9

What are competitive antagonists (reversible)

Answer 9

most common type of antagonist due to high potency and selectivity. the drug binds to agonist binding site (orthosteric site), and does not activate the receptor. It prevents the agonist from binding, and dissociates and rebounds continuously.

It shifts the curve to the right, reducing the potency of the agonist. The effects of the antagonist can be overcome by increasing concentration of agonist (competing for same site).

Question 10

how are reversible competitive antagonists quantified?

Answer 10

Kb is the equilibrium dissociation constant of competitive antagonists, a measure of affinity.

IC50 is the concentration of antagonist required to reduce a response to a fixed concentrstion of agonist by 50%.

IC50 is dependent on the concentration of agonist: more agonist requires more antagonist for the same amount of inhibition.

Question 11

What are competitive antagonists (irreversible)

Answer 11

binds to the agonist binding site covalently (or dissociates very slowly), termed the orthosteric site, without activating the receptor. prevents agonist from binding to that site.

At high enough concentration, irreversible competitive antagonists cannot be outcompeted = insurmountable inhibition.

both potency and Emax decrease, however, it may not show reduced Emax if there are spare receptors.

Question 12

What are non-competitive antagonists?

Answer 12

binds to an allosteric site (binds to the receptor at a different place to the agonist). upon binding, changes the conformational shape of the receptor, decreasing the affinity and efficacy of agonist to orthosteric site.

Question 13

what is a chemical antagonist?

Answer 13

A molecule which directly binds to or destroys the ligand/agonist, preventing it from binding to it’s receptor.

Question 14

What are functional (physiological) antagonists.

Answer 14

oppose the biological effects of an agonist by acting at a different receptor (as an agonist).

Question 15

What are the major parts of the central nervous system?

Answer 15

1. cerebrum
2. diencephalon (hypothalamus, thalamus, pineal gland)
3. Brainstem (midbrain, pons, medulla oblongata)
4. cerebellum
5. spinal cord

Question 16

What is the longitudinal fissure?

Answer 16

the longitudinal fissure divides the left and right hemisphere.

Question 17

What is structure of the meninges of the brain?

Answer 17

the skull is protected by a layer of periosteum and skin. below the skull is the meninges.
1. dura mater (subdural space)
2. arachnoid mater (subarachnoid space)
3. pia mater

Arachnoid villus: arachnoid mater that has protruded through the dura mater, allowing for the reabsorption of cerebrospinal fluid.

Question 18

define the location of the falx cerebri, the tentorium cerebelli and the falx cerebelli.

Answer 18

falx cerebri is a dura fold along the longitudinal fissure between the right and left cerebral hemispheres.

the tentorium cerebelli is a dura fold which sits between the cerebellum and the cereberum.

the falx cerebelli is a dura fold which sits between the left and right hemispheres of the cerebellum.

Question 19

What is the function of ventricles and the choroid plexus in the brain?

Answer 19

the choroid plexus filters blood. Plasma filters across into the ventricles and forms cerebrospinal fluid. This enters the subarachnoid space and baths the brain.

Question 20

What is the difference between white and grey matter?

Answer 20

white matter is myelinated axons whilst grey matter are neuronal cell bodies and non-myelinated dendrites.

Question 21

What are the four sections of the spinal cord? How is the spinal cord protected?

Answer 21

1. cervical cord (thicker - upper limbs)
2. thoracic cord
3. lumbar cord (thicker - lower limbs) -
4. sacral cord

the meninges, and the CSF in the subarachnoid space protects the spinal cord.

Question 22

What is the conus medullaris?

Answer 22

the spinal cord ends at L2 at a structure called the conus medullaris. A bundle of nerves (cauda equina) extend into the sacral cord, until your left with one single fibre (filum terminale) that goes into the coccyx.

Question 23

what is the structure of a nerve?

Answer 23

a nerve refers to axons in the periphery which cluster together to form nerves.
collections of thousands of individual axons within a common external connective tissue (epineurium). within the nerve, axons are sub grouped into fascicles, surrounded by a perineurial sheath. a single nerve fibre is surrounded by a endoneurium sheath.

Question 24

What are efferent and afferent signals and how do they travel through the CNS?

Answer 24

efferent signals carry signals from the CNS to muscles (motor).

afferent signals carry signals to the CNS (sensory).

efferent and afferent axons segregate at the point just before contact to the spinal cord. sensory axons joins via the dorsal (posterior) root whilst motor axons join at the ventral (anterior) root.

dorsal root ganglia (swelling from sensory neuronal cell bodies).