Specific And Non Specific Targets

Question 1

What is drug action?

Answer 1

(Most drugs) =Specific action on recognition sites. (some drugs) = non specific action

Question 2

Targets of drug action on specific macromolecules:

Answer 2

Known as proteins and they can be divided into
Receptors, carrier proteins, ion channels, enzymes, DNA

Question 3

Specific action of drugs on receptors:

Answer 3

Most common site of drug action
Located in the cell membrane
Receptors for steroids is located inside the cell

(Receptors are transducers capable of converting the energy of environmental stimulus into nerve impulses)

Question 4

Receptor structure and functions (classification):

Answer 4

1.) Selective agonists= bind to receptor and becomes activated
2.) Selective antagonists= blocks the receptor causing no effect
3.) Ligand binding studies= can track the drug in the body, can also calculate association and dissociation constants
4.) Transduction pathways= further info for receptors under investigation, mechanism and action of drugs done before drugs are sent into clinical trials.
5.) Molecular structure

Question 5

Examples of drugs acting on receptors:

Answer 5

Histamine receptors:
H1 receptors-blockade by antihistamines results in treating allergic or inflammatory response
H2 receptors- blockhead by antihistamines results in treating peptic ulcers

Question 6

Specific drug action on ion channels:

Answer 6

-There’s a pore in the cell membrane which opens and closes and allows or prevents passage of ions down a concentration gradient
-Opening and closing of channels, depends on the structure of the macromolecule protein which forms the pore
-Drugs may bind onto different sites of this macromolecule which affects the opening and closing of the channel

Question 7

Examples of drugs acting on ion channels:

Answer 7

-benzodiazepines use as an anxiety, hypnotic and anti-convulsant agents = increases conductance of chloride ions by increasing the frequency of chloride channel
-Extending the opening time of the channel, making the inside of the cell more negative than the outside, which means it’s less likely for the cell to get excited
-Calcium blockers= stops calcium from going into the cardiac and vascular cells= contractions of the heart is reduced
-local anaesthetic = blocks sodium channels= no sodium is entering the cell; no positive charge so prevents cells from becoming excited —-> leads to it becoming numb.

Question 8

Specific drug action on carrier proteins:

Answer 8

Located in the cell membrane or intracellular organelles
Transfer materials against concentration gradient by using energy

Question 9

Example of drugs acting on carrier proteins:

Answer 9

-sodium pump = pumps Na+ out and K+ into the cells using ATP
The action of the pump is inhibited by cardiac glycolide, for example, Digoxin in patients with heart failure
-NaCl Transporters in kidney inhibited by thiazide diuretics, for example, chlorothiazide and loop, diuretics, or another example is frusemide. They are both used to treat heart failure.

Question 10

Specific Drug action on enzymes:

Answer 10

Enzymes are macromolecular proteins, they catalyse and speed up the rate of chemical reactions.
Drugs can bind to enzymes and inhibit or interfere with action

Question 11

Examples of drugs acting on enzymes:

Answer 11

-Aspirin inhibit cyclic-oxygenase leading to inhibition of formation of prostaglandins (local meditator)
-Some diuretics inhibit carbonic anhydrase leading to an increase in urine output
-Some antibiotics with the synthesis of DNA of bacteria
-Nitrates, which is used in patients with angina, activate the granulate cyclase enzyme in blood vessels, resulting in an increase formation of cyclic GMP lead to relaxation of the wall of blood vessels which means more blood flow to supply the heart muscles.

Question 12

Drugs action on DNA:

Answer 12

Drugs may bind to DNA and modify the replication in the cell division process. An example of this is anticancer, drugs, or cisplatin.

Question 13

Non specific action of drugs:

Answer 13

-Show poor structural relationship
-Required in high concentrations

Question 14

Non specific action of drug examples:

Answer 14

-General anaesthetics work by diminishing the activity of the excitable tissues by dissolving in membrane
-The potency correlates well with a degree of line lipophilicity
-Brain areas with consciousness are very sensitive, -Some laxatives and diuretics bulking effects, methylcellulose, branmannitol diuretics and faecal lubricants

Question 15

Drugs effects:

Answer 15

-Beneficial or therapeutic effect, results from binding of a drug to sites with high affinity. I.e. drugs that show high affinity for a specific site.
-Adverse effect, results when drugs bind to sites that are not desired, may be seen in some individuals depending on genetic factors

Question 16

Drug effects: beneficial and adverse effects might be:
Mediated by the same mechanisms

Answer 16

E.g. hypoglycaemia induced by insulin; anticoagulant induced bleeding

In different tissues e.g. cancer drugs kills both cancer and healthy tissues; corticosteroids reduce inflammation but induce adverse effects by modifying metabolisms.

Question 17

Drug effects : beneficial and adverse effects might be:
Mediated by different mechanisms

Answer 17

E.g. anti-allergic action but also has anti-muscarinic effects: paracetamol as a pain killer but also damages liver; ibuprofen as a painkiller also damages the kidney

Question 18

High or low therapeutic index:

Answer 18

A high therapeutic index is preferable to a low one, this corresponds to a situation in which one would have to take a much higher amount of a drug to do harm than the amount taken to do good, the narrower the margin the more likely it is that the drug will produce unwanted effects.
Generally a drug narrow therapeutic range (i.e. with little differences between toxic and therapeutic doses) may have it’s dosage adjusted according to measurements of the blood levels achieved in the person taking it
CAN BE ACHIEVED THROUGH THERAPEUTIC DRUG MONITORING (TDM) protocols

Question 19

What is therapeutic index:

Answer 19

Therapeutic index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxic effects

Question 20

Therapeutic ratio:

Answer 20

Therapeutic ratio = TD50/ED50

(It is the ratio given by the toxic dose divided by the therapeutic dose. A commonly used measure of therapeutic index is the toxic dose of a drug for 50% of the population (TD50) divided by the minimum effective dose for 50% of the population (ED50))

Question 21

Examples of drugs with a narrow therapeutic range:

Answer 21

They may require drug monitoring both to achieve therapeutic levels and minimize toxicity include:
Digoxin
Dimercaprol
Theopphylline
Lithium carbonate

Question 22

Drug selectivity rather than specificity:

Answer 22

A single drug doesn’t cause a single specific effect because no drug binds to a single site or activates a single mechanism
-so drug actions are selective rather than specific