Pharmacology tutorials : Pharmacodynamics [Part 3]

The previous two parts : One , Two and this is the third.

Pharmacodynamics : in simple words it means what the drug does to your body, pharmacodynamics explain the drug mechanism of action, the biochemical and physiological changes to the body by the drug , the drug receptor relationship and the effect (action) of the drug on the target organ or system.

Receptors : are proteins or glycoproteins on the cell surface or within the cell , these proteins permit molecules to bind to them “ligands” and then modify the response which may increased , decreased or completely altered !

When the ligand “exogenous like drugs when administered ” binds to its receptor one of these action may occur :

• Ion channel opened or closed.
• biological messengers released. (endogenous ligands)
• Change biological response of this molecule.

Key-lock relationship :

The relation between the ligand and the receptor is like a key with its lock , it means every ligand (drug) should have a specific design to bind with its lock ( receptor ) effectively regardless the response exerted!

Drug response relationship :

The response of the drug on its target receptor depends on two factors ( Affinity & Efficacy ).  Affinity represents how strong the bonds between the drug and  its target, is the bond reversible ? irreversible ? strong enough ? weak ? .. etc

The drug affinity for the receptor is measured by dissociation constant , which is the concentration of the drug required to achieve 50% occupancy of the target receptors.

So , when the drug has affinity to bind with the receptor , the drug may be :

1. Agonist : drug binds to the receptor and produce a response , this response called agonistic activity or intrinsic activity.
   

2. Antagonist : drugs that binds to the receptors and prevent the agonist ligands from binding with these receptors . Antagonism has two subtypes :
   

• Competitive antagonist : competes with agonist for the same site , this type of bonds are reversible and agonist can overcome this at higher concentration.
•  Non Competitive antagonist : the bond is irreversible , so higher concentrations of agonist don’t overcome the antagonism.
  3. Partial agonist : drugs that fail to produce the maximum response even of all the target receptors are occupied and a maximum dose was given.
  

Drug efficacy : A degree in which the drug is able to produce the maximum desired effect.

Effective dose (ED50) : the dose of the drug required to induce desired action in 50% of all who use the drug.

Toxic dose (TD50) : the dose of the drug required to induce toxic action in 50% of all who use the drug.

Lethal dose ( LD50) : the dose of the drug which results in death of 50% of all who use the drug.

Therapeutic index : Ration between LD50 and ED50 (LD50/ED50), so a higher (wide) therapeutic index is desirable while narrow therapeutic index is an indicator of the lethality of the drug.

Difference between potency and efficacy ( Potent drug VS Effective drug ) :

Efficacy is used to compare drugs with different mechanism of action for example Opoid analgesics are more effective in controlling post operative pain more than NSAID analgesics.

Potency is used to compare drugs share the same chemical class, chemical properties or mechanism of action. it depends on the amount, drug A and drug B are statins , both drugs reduce blood cholesterol by inhibiting HMG-CoA reductase but only 5 mg needed from drug A compared to 10 mg of drug B , so drug A is more potent than drug B.

Drugs interactions :

Two or more drugs can interact with each other at the biological system , there 4 types of these interactions :

1. Addition : the response produced by the drugs is equal to the summation of responses of all the individual drugs  ->    1+1+1=3
2. Synergism : the response produced is greater than the responses of all individual drugs -> 1+1+1=7
3.  Potential effect : drug with no response enhances the effect of another drug -> 0+1 =2
4. Antagonism : the drugs inhibit the response of each other -> 1+1=0

Drug Patient Response :

People are different , so patient’s response to drugs may be different , there are factors considered like :

• Gender.
• Age.
• Medical conditions.
• Family history.
• Hepatic functions.
• Renal functions.
• Infections.
• Sensitivity to the drug or any component.

and many other factors.

Drug tolerance : The need to increase the dose of the drug to produce the same effect of lower previous dose.

Drug dependency : The need of the drug to produce or enhance a function the dependency may be physical like the need of laxatives to enhance the movement of the bowel or may be psychological dependency like drinking coffee every morning.

Drug Idiosyncrasy : Unexpected or predicted action of the drug , this is specific for individual patient.

Summary :

• Drug can produce a several effects at the same time , the drug “ligand” interact with the receptor producing desirable or undesirable effect.
• There is a selectivity between the ligand and the receptor , clarified as key-lock principle.
• Agonist produces response while antagonist blocks the response.
• The safety margin of the drug measured by its therapeutic index.
• Drugs interactions include , addition , potential, synergism and antagonism.
• Antagonism may be competitive or may be noncompetitive.