Translational Medicine
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Short Note on Pharmacodynamics

Harry Dolstra^{* *}Correspondence: Harry Dolstra, Department of Center for Internal Medicine, University Hospital, Ulm, Germany, Email:

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Description

The study of a drug's molecular, biochemical, and physiologic effects or actions is known as pharmacodynamics. It is derived from the Greek terms "pharmakon" and "dynamikos," which mean "drug" and "power," respectively. All medications work by interacting with biological structures or targets on a molecular level to modify how the target molecule operates in relation to subsequent intermolecular interactions. Receptor binding, postreceptor effects and chemical interactions are examples of these interactions. Medications that bind to an enzyme's active site, pharmaceuticals that engage with cell surface signalling proteins to impair downstream signalling, and drugs that function by binding substances like tumour necrosis factor are all examples of these types of interactions (TNF).

Effects are elicited as a result of the drug-target interaction downstream, which can be assessed biochemically or clinically. The inhibition of platelet aggregation after taking aspirin, the reduction of blood pressure after taking ACE inhibitors, and the blood-glucose-lowering impact of insulin are all examples of this.

While these examples may seem self-evident, practitioners should keep in mind that these drugs are administered to reduce the risks of cerebrovascular accident, myocardial infarction, renal and eye complications through the drug's pharmacodynamics effects, rather than to inhibit platelet aggregation, lower blood pressure, or lower blood glucose. It's critical for healthcare providers to remember that they're treating the patient, not the symptom or the lab result.

Pharmacodynamics and pharmacokinetics are two disciplines of pharmacology, with pharmacodynamics focusing on the drug's action on the body and pharmacokinetics on the drug's effect on the body.

Pharmacodynamics actions include:

• Stimulating activity by blocking a receptor and its downstream effects directly.

• Direct receptor inhibition and its downstream effects depress activity.

• Antagonistic means it binds to a receptor but does not activate it.

• Stabilizing effect, in which the medicine appears to be neither an agonist nor an antagonist.

Chemical reactions that are carried out directly (beneficially in therapy and also as an adverse event)

Any of these elements has the potential to be both therapeutic and cause an adverse event.

Pharmacodynamics concepts

In the discussion of pharmacodynamics, a few essential concepts and terminology are employed to explain the magnitude and duration of a drug's impact.

.• Emax refers to a drug's maximum effect on a parameter being measured. This might be, for example, an ex-vivo test of platelet inhibition or the maximal blood pressure reduction.

• The EC50 is the drug's steady-state concentration that delivers half of the greatest effect.

• The slope of the relationship between drug concentration and drug effect is known as the Hill coefficient. Hill coefficient values above 2 suggest a steep relationship (small changes in concentration cause large changes in effect), while hill coefficient values above 3 indicate an almost immediate "all or none" effect.

Other pharmacodynamics concepts include

Kd: The pharmacologic response is determined by the drug's ability to bind to its target as well as the drug's concentration at the receptor site. Kd is a metric that indicates how firmly a medication binds to its receptor. The ratio of rate constants for drug attachment (kon) and dissociation (koff) to and from receptors is known as Kd. The rate of creation of the receptordrug complex is equal to the rate of dissociation into its constituent’s receptor + drug at equilibrium. The equilibrium or affinity constant (1/Kd) can be defined by measuring the reaction rate constants. The lower the Kd value, the stronger the antibody's affinity for its target.

Receptor occupancy: The larger the pharmacodynamics response, according to the law of mass action, the more receptors that are occupied by the drug, but all receptors do not need to be occupied in order to produce a maximal response. Spare receptors, which include muscarinic and nicotinic acetylcholine receptors, steroid receptors, and catecholamine receptors, are examples of this principle. Signal amplification achieves maximum effects by using less than maximal receptor occupancy.

Receptor up- and down regulation: Chronic exposure to an antagonist causes up regulation, or a rise in the number of receptors, whereas chronic exposure to an agonist causes down regulation, or a reduction in the number of receptors. Up-or down modulation without changing the amount of receptors on the cell membrane may be accomplished by other processes involving changes in downstream receptor signalling. Chronic insulin exposure causes the insulin receptor to be down regulated. Insulin surface receptors are increasingly depleted as a result of receptor internalisation and degradation caused by increased hormone binding. The nicotine receptor is an exception to the rule, as it shows increase in receptor numbers with prolonged exposure to nicotine, despite the fact that nicotine is an agonist, which explains some of its addictive features.