Mechanism Of Drug Action Flashcards
Pharmacodynamics is Derived from two Greek words:
•Pharmakon =drug
•Dynamikos =force or power
Pharmacodynamics involves
Receptor binding (including receptor sensitivity)
Post receptor effects
Chemical interactions
is the study of biochemical and physiological effects of drug and their mechanism of action at _________ & _______level
Organ
Cell
What biological structures do drugs interact with
Enzyme
Receptors
Transporter - carrier molecules
Ion channels
How does penicillin kill bacteria?
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.
drug’s pharmacodynamics can be affected by physiologic changes due to disorders which can ?
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
The 3 principles of drug action are
Drugs
-Do NOT impart new functions on any system, organ or cell.
-Only alter the PACE of ongoing activity.
The exception to the principles of drug action is
Gene based drugs
The 5 basic types of drug action are
Stimulation
Depression
Irritation
Replacement
Cytotoxic action
Stimulation involves?
With examples
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
Depression involves?
With examples
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
Irritation is particularly applied to?
non-specialized cells (epithelium, connective tissue),
Strong irritation leads to?
Examples
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
Replacement is
Examples
Use of natural metabolites, hormones or their congeners in deficiency states.
E.g levodopa in Parkinson’s disease,
insulin in diabetes mellitus.
Cytotoxic action is
With examples
: 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
Mechanism of drug action can be divided into
3.
2 is here. Give examples
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.
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?
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
C
Non-competitive inhibition (effects are prolonged
Examples are
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.
I
Ion Channels drugs are
Drug interfere with the flow of ions through the channels that are specific for these ions. These are Na+, K+, Ca++ and Cl- channels.
I
Sodium channel drugs:
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
I
Calcium channel drugs
nifedipine
verapamil
diltiazem
Block the voltage gated calcium channels; useful in hypertension and arrhythmias.
I Potassium channel drugs
amiodarone,
sulfonylureas
Amiodarone is used in arrhythmias, blockade of the channels leads to a prolonged refractory period
I
Chloride channel drugs
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
C
Drugs that inhibit carrier molecules 5
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).
Receptor
Agonists are an agent which activates a receptor to produce an effect similar to that of the physiological signal molecule. e.g
acetylcholine
adrenaline
noradrenaline
Benzodiazepine Gaba agonist
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.
atropine
scopolamine
phenoxybenzamine.
Flumazenil GABA antagonist
Partial agonists
: An agent which activates a receptor to produce submaximal effect, but antagonizes the effect of a full agonist.
Inverse agonist
agent which activates a receptor to produce an effect in the opposite direction to that of the agonist. e.g. Beta carbolines.
What are ligands
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.
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:
Affinity + IA = 1
Affinity + IA = 0
Affinity + IA between 0 and 1.
Affinity + IA between 0 and -1.
2essential functions of receptors
2 domains of receptors
- Recognition of specific ligand molecule
- Transduction of signal into response
Two Domains:
- Ligand binding domain
- Effectors Domain: undergoes functional
conformational change
Biochemical Mechanism of Drug Action involves RICE
Give one example each
Receptors : Albuterol for Asthma
Ion channels: Lidocaine for local anesthesia
Carrier proteins: Omeprazole for peptic ulcer disease
Enzymes: captopril for hypertension
Drug action vs drug effect
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
Receptors have 2 domains?
Which are linked by?
Ligand domain
Effector domain
Transduction or coupling path way
Receptor are classified based on 5 with case study acetylcholine
- Pharmacological criteria : cholinergic receptor (acetylcholine)
- Ligand binding: Muscarinic & nicotinic
- Transducer pathway: muscarinic: G protein (metabotropic)
Nicotinic: ligand gated ion - Tissue distribution: N: muscle, nerve
M: m1-m5 - Molecular cloning: the protein that makes it up
