Drug Receptor Interactions Flashcards

Question

Give some examples of drugs that target transport systems

Answer 1

Tricyclic Anti-depressants (TCAs). | Cardiac glycosides.

Answer 2

its own specific transporter system | e.g NA uptake 1 only found in NA nerve terminals

Answer 3

Interfere with the function of NA uptake 1 protein In clinical depression, the NA transport system is not functioning optimally in the CNS TCAs slow down the uptake system of NA- so more remains in the synaptic cleft for longer enhancing NA. Also enhances the activity of 5-HT- aiding in reducing the effects of depression.

Answer 4

Glycosides e.g digoxin have a central effect, stimulating the vagus nerve and increasing parasympathetic stimulation, thus slowing heart rate. It simultaneously exerts its positive inotropic effect by inhibition of Na+/K+ ATPase. Inhibiting Na+/K+ ATPase increases the intracellular Na+, which increases I.C Ca2+- improving contractility.

Answer 5

catalytic proteins that increase rate of reaction.

Answer 6

Drug interactions:- i) enzyme inhibitors e. g. anticholinesterases (neostigmine) ii) false substrates e. g. methyldopa iii) prodrugs e. g. chloral hydrate  trichloroethanol

Answer 7

sympathetic nerve terminals make NA. one of the steps in the biosynthesis of NA is the conversion of dopa to dopamine using DOPA decarboxylase when methyldopa is used- methyl noradrenaline is released instead which has less potent effects compared to noradrenaline therefore you reduce the vasoconstrictive effects of NA and get more vasodilation- reducing BP

Answer 8

chloral hydrate- hypnotic- used to treat insomnia converted to trichloroethanol by enzymes in the liver- trichloroethanol is the hypnotic drug (i.e the active ingredient).

Answer 9

If you take too much paracetamol, the enzyme system that metabolises paracetamol in the liver becomes saturate. this results in paracetamol being metabolised by a different set of enzymes which results in the production of toxic products- which can damage the liver and kidney.

Answer 10

Intravenous acetylcysteine or methionine - boosts the glutathione system- which mops up these reactive intermediates.

Answer 11

The drug isn’t specific to a receptor etc. Physiochemical properties : antacids osmotic purgatives

Answer 12

o Antacids – simple addition of a base to the acidic environment which evens acid-base balance- makes salt increasing pH- reducing symptoms of dyspepsia (usually magnesium or aluminium salts) o Osmotic purgatives (laxatives) – draws water into the gut to decrease viscosity- softens the stool

Answer 13

indigestion

Answer 14

Drugs bind to albumin- leading to a reservoir of inactive drugs No physiological response- not a drug target- more to do with pharmacokinetics as no response is mediated

Answer 15

N.B. Some drugs bind very strongly to plasma proteins and so can provide a dangerous and untapped reservoir of the drug (e.g. warfarin).

Answer 16

Agonist (ACh; nicotine)

Answer 17

Antagonist (atropine; hexamethonium) | Hexamethonium is a nicotinic antagonist

Answer 18

It was formerly used to treat disorders, such as chronic hypertension, of the peripheral nervous system, which is innervated only by the sympathetic nervous system. The non-specificity of this treatment led to discontinuing its use. Blocks autonomic ganglia

Answer 19

‘Potency’ of a drug depends on: i) Affinity ii) Efficacy (‘intrinsic activity’)  conformational change of receptor

Answer 20

o Affinity – Strength-of-binding/Avidity of the drug to the receptor.

Answer 21

o Drugs can also have FULL or PARTIAL agonistic effects. o PARTIAL agonists can lead to some antagonist activity. partial agonists never generate the full response- have antagonist activity when co-administered with full agonists.

Answer 22

Selectivity – we don’t use the word specific as a drug may not be specific to the same receptors at a higher concentration (may bind to other receptors).

Answer 23

Can begin to have actions on other drug targets- leading to the onset of side effects

Answer 24

Structure-activity relationship  ‘lock and key’  agonists  antagonists  pharmacokinetics small changes in the structure of a drug can completely change its activity- potentially turning an agonist into an antagonist. changes in structure can also slow down its metabolism- leading to pharmacokinetic changes.

Answer 25

long range forces- bring drug to its target

Answer 26

the transducer system- enzymes its linked to- opening an ion channel etc.

Answer 27

when tissue response against conc- rectangular hyperbola when tissue response against log of the conc-- sigmoid

Answer 28

Can see max response more easily- can be analysed mathematically due to long straight section of the graph.

Answer 29

Affinity but no efficacy

Answer 30

Competitive and irreversible

Answer 31

1. Competitive  same site as agonist  surmountable  shifts D-R curve to right

Answer 32

atropine | : propranolol

Answer 33

2. Irreversible  binds tightly or at different site (may bind to cation channel- agonist won't be able to compete)  insurmountable

Answer 34

A competitive Ach muscarinic receptor antagonist

Answer 35

In the presence of a competitive antagonist, the agonist occupancy (i.e proportion of receptors to which the agonist is bound) at a given agonist concentration is reduced, because the receptor can only accommodate one molecule at a time.

Answer 36

A simple theoretical analysis predicts that in the presence of a fixed concentration of the antagonist, the log concentration-effect curve for the agonist will shift parallel to the right, without any change in slope or maximum.

Answer 37

As a dose ratio (the ratio by which the agonist concentration has to be increased in the presence of the antagonist in order to restore a given level of response). Theory predicts that the dose ration linearly increases with the concentration of the antagonist.

Answer 38

Shift of the agonist log concentration-effect curve to the right, without change of slope or maximum (i.e antagonism can be overcome by increasing the concentration of the agonist) linear relationship between agonist dose ratio and antagonist concentration evidence of competition from binding studies.

Answer 39

They reflect the fact that agonist and competitive antagonist molecules do not stay bound to the receptor but dissociate and rebind continuously. The rate of dissociation of the antagonist molecules is sufficiently high that a new equilibrium is rapidly established on addition of the agonist. In effect, agonist molecules are able to replace the antagonist molecules on the receptors when the antagonist unbinds, although they cannot of course, evict bound antagonist molecules.

Answer 40

Displacement occurs because, by occupying a proportion of the vacant receptors, the agonist effectively reduces the rate of association of the antagonist molecules; consequently, the rate of dissociation temporarily exceeds that of association, and the overall antagonist occupancy falls.

Answer 41

The antagonist binds to the same site on the receptor as the agonist but dissociates very slowly, or not at all, from the receptors, with the result that no change in the antagonist occupancy takes place when the agonist is applied. Can also change the conformation of the active site.

Answer 42

Due to the phenomenon of spare receptors; if the agonist occupancy required to produce a maximal response is very small (say 1% of the total receptor pool), then it is possible to block irreversibly 99% of the receptors without reducing the maximal response. The effect of a lesser degree of antagonist occupancy will be to produce a parallel shift of the log concentration-effect curve that is indistinguishable from competitive antagonism Only when the antagonist occupancy exceeds 99% will the maximum response be reduced.

Answer 43

In drugs that possess reactive groups that form covalent bonds with the receptor

Answer 44

Transport protein

Answer 45

The curve will shift to the right and fall. | Can't achieve max response- response blocked.