Mechanism Of Drug Action

Question 1

Pharmacodynamics is Derived from two Greek words:

Answer 1

•Pharmakon =drug
•Dynamikos =force or power

Question 2

Pharmacodynamics involves

Answer 2

Receptor binding (including receptor sensitivity)
Post receptor effects
Chemical interactions

Question 3

is the study of biochemical and physiological effects of drug and their mechanism of action at _________ & _______level

Answer 3

Organ
Cell

Question 4

What biological structures do drugs interact with

Answer 4

Enzyme
Receptors
Transporter - carrier molecules
Ion channels

Question 5

How does penicillin kill bacteria?

Answer 5

Penicillin molecule binds to a bacterial enzyme transpeptidase and prevents “cross links” in the bacterial cell wall

•Thus, inability of the bacteria to create strong cell walls kill bacteria.

•Large amounts of penicillin completely blocks the enzyme and in the presence of small amounts, the enzyme resumes its normal function.

Question 6

drug’s pharmacodynamics can be affected by physiologic changes due to disorders which can ?

Answer 6

change receptor binding
alter the level of binding proteins
decrease receptor sensitivity
genetic mutations
malnutrition
thyrotoxicosis.

•Other factors are aging as well as the effects of other drugs

Question 7

The 3 principles of drug action are

Answer 7

Drugs
-Do NOT impart new functions on any system, organ or cell.
-Only alter the PACE of ongoing activity.

Question 8

The exception to the principles of drug action is

Answer 8

Gene based drugs

Question 9

The 5 basic types of drug action are

Answer 9

Stimulation
Depression
Irritation
Replacement
Cytotoxic action

Question 10

Stimulation involves?

With examples

Answer 10

selective enhancement of the level of activity of specialized cells,

e.g adrenaline on the heart,
pilocarpine on salivary glands. (Used to treat dey mouth

Question 11

Depression involves?

With examples

Answer 11

selective diminution of activity of specialized cells

e.g. barbiturates on the CNS
quinidine on the heart (anti arrhythmic agent)
omeprazole on gastric secretion. (Decreases amount of stomach acid)
Lisinopril as anti hypertensive works on blood pressure

Question 12

Irritation is particularly applied to?

Answer 12

non-specialized cells (epithelium, connective tissue),

Question 13

Strong irritation leads to?
Examples

Answer 13

a non-selective and often noxious effect. Strong irritation results in
inflammation,
corrosion
necrosis
and consequently, loss of function

E.g. bitters on salivary and gastric secretions.
Methylsalycylate for joint and muscle pain

Question 14

Replacement is

Examples

Answer 14

Use of natural metabolites, hormones or their congeners in deficiency states.

E.g levodopa in Parkinson’s disease,
insulin in diabetes mellitus.

Question 15

Cytotoxic action is

With examples

Answer 15

: selective cytotoxic action on cancer cells or invading organisms, attenuating them without significantly affecting the host cells.

E.g. cyclophosphamide chemotherapy

zidovudine antiretroviral

penicillin for infection

Question 16

Mechanism of drug action can be divided into

3.
2 is here. Give examples

Answer 16

Physical when the drug does not produce any chemical reaction or change in the cells of the body and the effect is only physical.
-Activated charcoal binds with poisons in the stomach.
-Mannitol as an osmotic diuretic, freely filtered but not reabsorbed.
-laxatives e.g. ispaghula. For constipation through osmosis

Chemical drugs act by producing chemical reactions in the body:
-NaHCO3 as an antacid.
-Dimercaprol, penicillamine, desferrioxamine as chelating agents.
-Pralidoxime as a choline esterase reactivator.
-Cholestyramine for sequestration of bile acids and cholesterol in the gut.

Question 17

Biochemical mechanism : RICE
E
Drug-enzyme interactions may take place as enzyme activation or enzyme inhibition.
Enzyme inhibition could either be competitive or non competitive.
Examples of competitive inhibition?

Answer 17

1.Angiotensin converting enzyme inhibitors e.g. captopril/ enalapril/ lisonopril for hypertension

2.Reversible anticholinesterases e.g. neostigmine, physostigmine

3.Allopurinol used in gout since it inhibits xanthine oxidase, the enzyme which converts xanthine and hypoxanthine to Uric acid

Question 18

C
Non-competitive inhibition (effects are prolonged

Examples are

Answer 18

1.Irreversible anticholinesterases e.g. organophosphorus compounds (insectisides and war gases)

2.Aspirin inhibits cyclooxygenase enzyme and therefore prostaglandin synthesis.

3.Monoamine oxidase inhibitors used to treat depression e.g. imipramine.

4.Proton pump inhibitors: e.g. omeprazole inhibit the H+/K+ ATPase in parietal cells of stomach.

Question 19

I
Ion Channels drugs are

Answer 19

Drug interfere with the flow of ions through the channels that are specific for these ions. These are Na+, K+, Ca++ and Cl- channels.

Question 20

I
Sodium channel drugs:

Answer 20

quinidine
procainamide

local anaesthetics block the channels, thus depolarization does not take place and there is no nerve conduction in that localized area. They are used respectively in cardiac arrhythmias and as local anaesthetic

Question 21

I
Calcium channel drugs

Answer 21

nifedipine
verapamil
diltiazem
Block the voltage gated calcium channels; useful in hypertension and arrhythmias.

Question 22

I Potassium channel drugs

Answer 22

amiodarone,
sulfonylureas

Amiodarone is used in arrhythmias, blockade of the channels leads to a prolonged refractory period

Question 23

I
Chloride channel drugs

Answer 23

upon activation, the GABA A receptor selectively conducts Cl- through its pore, resulting in hyperpolarization of the neuron, which causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring.

e.g. benzodiazepines chloride channel activator

Question 24

C
Drugs that inhibit carrier molecules 5

Answer 24

Inhibition of choline carrier by hemicholinium.

Inhibition of noradrenaline vesicular uptake by reserpine

-Inhibition of neuronal reuptake of noradrenaline by desipramine.

-Inhibition of neuronal reuptake of serotonin by fluoxetine.

-Inhibition of weak acid (e.g. uric acid) carrier by drugs (e.g. probenecid, which prevents uric acid tubular reabsorption, thus enhancing its excretion).

Question 25

Receptor

Agonists are an agent which activates a receptor to produce an effect similar to that of the physiological signal molecule. e.g

Answer 25

acetylcholine
adrenaline
noradrenaline
Benzodiazepine Gaba agonist

Question 26

R
Antagonists: An agent which prevents the action of an agonist on a receptor, but does not have any effect of its own. e.g.

Answer 26

atropine
scopolamine
phenoxybenzamine.
Flumazenil GABA antagonist

Question 27

Partial agonists

Answer 27

: An agent which activates a receptor to produce submaximal effect, but antagonizes the effect of a full agonist.

Question 28

Inverse agonist

Answer 28

agent which activates a receptor to produce an effect in the opposite direction to that of the agonist. e.g. Beta carbolines.

Question 29

What are ligands

Answer 29

Any molecule which attaches selectively to particular receptors or sites. e.g. endogenous substances, molecules or compounds like Ach, adrenaline, noradrenaline, glutamate, aspartate and GABA.

Question 30

Affinity: the “tenacity” by which a ligand binds to its receptor.
•Intrinsic activity (IA): Capacity to induce functional change in the receptor in a way that produces an effect; some drugs possess affinity but NOT efficacy.
If explained in terms of affinity and IA:
•Agonist:
•Antagonist:
•Partial agonist:
•Inverse agonist:

Answer 30

Affinity + IA = 1

Affinity + IA = 0

Affinity + IA between 0 and 1.

Affinity + IA between 0 and -1.

Question 31

2essential functions of receptors

2 domains of receptors

Answer 31

• Recognition of specific ligand molecule
• Transduction of signal into response

Two Domains:
- Ligand binding domain
- Effectors Domain: undergoes functional
conformational change

Question 32

Biochemical Mechanism of Drug Action involves RICE

Give one example each

Answer 32

Receptors : Albuterol for Asthma

Ion channels: Lidocaine for local anesthesia

Carrier proteins: Omeprazole for peptic ulcer disease

Enzymes: captopril for hypertension

Question 33

Drug action vs drug effect

Answer 33

Drug action mechanism by which a drug causes an effect
is what the drug causes in the body but can’t be seen eg sildenafil dilated blood vessels in penis

Drug effect physiological change brought about by drug on the body
is what we can see ERECTIONNNNNNNNNN

Question 34

Receptors have 2 domains?

Which are linked by?

Answer 34

Ligand domain

Effector domain

Transduction or coupling path way

Question 35

Receptor are classified based on 5 with case study acetylcholine

Answer 35

1. Pharmacological criteria : cholinergic receptor (acetylcholine)
2. Ligand binding: Muscarinic & nicotinic
3. Transducer pathway: muscarinic: G protein (metabotropic)
   Nicotinic: ligand gated ion
4. Tissue distribution: N: muscle, nerve
   M: m1-m5
5. Molecular cloning: the protein that makes it up