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PHAR0007 With Complete Solutions Latest Update
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PHAR0007 With Complete Solutions LatestUpdate
What is selective toxicity? - correct answers The ability of a drug to act at target
sites possessed only by or more essential to the survival of the pathogen than the
host.
What is the proprietary name of a drug? - correct answers The brand name given
by the manufacturer.
What is the TI? - correct answers Therapeutic index = TD50/ED50 (TD50 = dose
that is toxic to 50% of the population, ED50 = dose that produces therapeutic
effects in 50% of the population).
What value of TI is preferable? High or low? - correct answers High since that
means that the TD50 is much higher (so less likely to be reached accidentally) than
the ED50.
What is the variation of the TI used in animal studies? - correct answers
LD50/ED50 where LD50 = the dose which is lethal in 50% of the population.
What is Popper's law? - correct answers Statements can never be shown to be
true, only falsifiable.
What is Carson's consolation? - correct answers No experiment is ever useless, it
can always be used as a bad example.
,What is pharmacodynamics? - correct answers The study of biochemical and
physiological effects of a drug on a living organism and its method of action.
What is pharmacokinetics? - correct answers The study of the drug concentrations
throughout a living organism over time, including the studies of metabolites and
the mathematical interpretation of the data.
What are the 4 broad categories of receptors? - correct answers Ligand-gated ion
channels, GPCRs, kinase-linked and related receptors and intracellular/nuclear
receptors
What is an oligomeric protein? - correct answers A protein which consists of
multiple subunits.
What are the three subfamilies of ligand-gated ion channels? - correct answers
Cys-loop receptors (ie nAChR), glutamate receptors and P2X receptors (ATP)
What is the difference in the effect of opening a cationic ion channel vs anionic? -
correct answers The opening of a cationic ion channel (ie Na+), will lead to
depolarisation of the membrane whereas opening of an anionic ion channel (ie
Cl-) will lead to hyperpolarisation of the membrane.
Out of Cys-loop receptors, glutamate receptors and P2X receptors, which is
pentameric, which is tetrameric and which is trimeric? - correct answers Cys-loop
receptors = pentameric
Glutamate receptors = tetrameric
P2X receptors = trimeric
,Describe the general structure of a LGIC. - correct answers A LGIC consists of
between 3-5 subunits and forms a ring structure with a central pore, with each
subunit capable of ligand binding. Each subunit has 2-4 transmembrane domains.
What is the difference between a homomeric LGIC and a heteromeric? - correct
answers A homomeric LGIC is composed of only a single type of subunit whereas a
heteromeric LGIC consists of two or more different types of subunit.
Describe the general structure of a GPCR. - correct answers A GPCR has an
extracellular N-terminus and intracellular C-terminus with 7 transmembrane
domains.
Explain the activation process of a GPCR. - correct answers When a ligand binds to
the extracellular N-terminal domain it induces a conformational change in the
GPCR causing its affinity for G-proteins to increase. This leads to interaction
between the GPCR and the Gα subunit of the G-protein in which the GPCR acts as
a GEF and causes a bound molecule of GDP to be exchanged for GTP. This causes a
conformational change in the G-protein and so dissociation of the Gα-GTP and the
βγ complex from one another and from the GPCR. The Gα-GTP and βγ complexes
are now able to diffuse laterally through the membrane and activate ion channels
or secondary effectors such as adenylyl cyclase. After a period of time,
spontaneous intrinsic GTPase activity of the Gα subunit leads to GTP hydrolysis
which causes a conformational change and for the Gα and βγ complexes to re-
associate ready for activation by another GPCR.
Explain the function of Gs proteins. - correct answers Stimulate adenyl cyclase to
convert ATP to cAMP which activates protein kinase A, going onto phosphorylate
other proteins.
, Explain the function of Gi proteins. - correct answers Inhibit adenyl cyclase and so
restrict phosphorylation of certain proteins.
Explain the function of Gq proteins. - correct answers Activates phospholipase C
which hydrolyses PIP2 into DAG (remains associated to the PM and activates
protein kinase C) and IP3 (releases Ca2+ from intracellular stores).
Explain the function of Go proteins. - correct answers Closes certain types of
voltage-gated Ca2+ channels so causing inhibition.
Give an example of a GPCR which forms dimers? - correct answers GABAB-Rs.
Which loop of a GPCR is crucial for proper interaction with a G-protein? - correct
answers The third intracellular loop.
How many transmembrane domains do kinase-linked and related receptors have?
- correct answers 1.
Describe the activation mechanism of RTKs and the downstream signalling. -
correct answers Ligand binding to the extracellular domain will cause dimerisation
with the association of the two intracellular kinase domains leading to mutual
autophosphorylation of intracellular domain tyrosine residues. These pY residues
then act as high-affinity docking sites for intracellular proteins with SH2 domains.
This interaction of proteins with the kinase domain leads to a kinase cascade
which results in modulation of gene expression.
What are intracellular/nuclear receptors? - correct answers Soluble receptors
which regulate transcription.
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