Pharmacokinetics and pharmacodynamics

Role of chemical structure

Chemical structure is a fundamental factor that determines the entire pharmacological profile of a drug. The physicochemical properties of the substance, required dosages or concentrations, as well as the specifics of its fate in the body (pharmacokinetics) and the nature of the effects produced (pharmacodynamics), all depend on the molecular structure.

Substances belonging to the same chemical group and sharing a similar structure exhibit group specificity. This means they produce identical pharmacological effects. A classic example of this phenomenon is benzodiazepines, which demonstrate a similar spectrum of action due to their structural affinity.

The interaction within the “substance — biological target” (e.g., receptor) system is strictly determined by chemistry. For a drug molecule to successfully bind to a receptor, it must possess three characteristics:

• The presence of specific functionally active groups.
• Specific spatial orientation.
• Appropriate molecular size.

Pharmacodynamics using phentolamine as an example

Phentolamine serves as a key prototype drug for understanding receptor interactions. Its mechanism of action involves the blockade of postsynaptic $\alpha_1$-adrenergic receptors, as well as all types of $\alpha_2$-adrenergic receptors: postsynaptic, extrasynaptic, and, most importantly, presynaptic.

Blockade of $\alpha$-receptors in blood vessels leads to pronounced vasodilation. The hemodynamic result of this vascular effect is a decrease in both arterial and venous pressure.

However, the drug causes tachycardia, the mechanism of which is dual in nature:

1. Reflex tachycardia: occurs as a baroreceptor response to a sharp drop in blood pressure.
2. Direct tachycardia: caused by the blockade of presynaptic $\alpha_2$-receptors. Normally, they provide negative feedback. When they are blocked, this mechanism is disrupted, and an excessive amount of noradrenaline is released from sympathetic nerve terminals into the synaptic cleft. This neurotransmitter directly stimulates cardiac $\beta_1$-receptors.

Metabolic and physiological consequences of such changes include an increase in myocardial oxygen demand (due to rapid heart rate) and enhanced renin secretion.

The pharmacokinetics of phentolamine is characterized by a short duration: upon intravenous administration, the effect lasts only 10–15 minutes. The reason lies in the mechanism of action itself: excess noradrenaline released due to the presynaptic block begins to competitively displace phentolamine from its binding to postsynaptic $\alpha_1$-receptors. As soon as this happens, vasodilation ceases.

Features of analgesic action (nalbuphine)

Nalbuphine demonstrates a complex pharmacodynamic profile: it acts as a $\kappa$-receptor agonist and simultaneously as a $\mu$-receptor antagonist. In its analgesic activity, the drug is close to morphine, but it has a higher safety profile since it causes less respiratory depression compared to pure agonists.

Its most important distinguishing feature is its effect on hemodynamics. Unlike analogues such as pentazocine and butorphanol, nalbuphine does not affect hemodynamics. Due to this property, its main indication is severe pain syndromes, including the need for analgesia in myocardial infarction. Pharmacokinetically, the drug provides a duration of action of up to 6 hours.

Mechanisms of action of laxatives

Laxatives are classified by their mechanism of action and site of effect, which directly determines their pharmacokinetics and indications.

• Agents acting throughout the intestine: their mechanism is based on irritation of the mucous membrane receptors along the entire GI tract. The pharmacodynamic effect occurs in 4–6 hours. It is important to remember that they are strictly contraindicated in acute poisonings with fat-soluble poisons, as they can promote the absorption of toxins into the bloodstream.
• Bulk-forming agents: this group includes kelp (Laminaria) and methylcellulose. They act predominantly in the large intestine. The mechanism consists of irritating receptors by increasing the volume of intestinal contents. The main indication is chronic atonic constipation.
• Emollient agents (oils): representatives of the group are liquid paraffin and almond oil. Their pharmacokinetic feature is that they are not absorbed when taken orally. The mechanism of action comes down to the mechanical softening of feces and creating a “lubricating” effect. Classified as mild laxatives.

Class and exam questions

What else to study on this topic

• Specificity of benzodiazepine receptor binding
• Negative feedback mechanisms in synapses
• Comparative characteristics of pentazocine and butorphanol
• Pharmacokinetics of methylcellulose and kelp preparations

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.