Drug Action Targets

Frequently asked questions

Which enzymes are targets for drug action?

Targets for drug action include human bodily enzymes as well as enzymes of pathogens. Sources list the following target enzymes:

• Monoamine oxidase (MAO) — responsible for the oxidative deamination of catecholamines; MAO inhibitors disrupt metabolism and cause the accumulation of norepinephrine, dopamine, and serotonin in the CNS.
• Cyclooxygenase (COX) — target of NSAIDs; inhibition reduces prostaglandin biosynthesis.
• Acetylcholinesterase — target of anticholinesterase agents; blockade of acetylcholine hydrolysis increases its concentration in the synaptic cleft.
• Phosphodiesterase-III (PDE-III) — target of milrinone; selective inhibition in cardiomyocytes leads to intracellular cAMP accumulation.
• Angiotensin-converting enzyme (ACE) — participates in angiotensin II formation within the vascular bed; ACE inhibition also prevents bradykinin degradation.
• Catechol-O-methyltransferase (COMT) — an enzyme whose inhibitors are used to increase levodopa efficacy.
• Dihydrofolate reductase — target of methotrexate; overexpression of this enzyme is a resistance mechanism.
• $H^+/K^+$-ATPase — the proton pump of gastric parietal cells.
• $Na^+$-$K^+$-ATPase — the sodium-potassium pump of cardiomyocytes, blocked by cardiac glycosides.
• Reverse transcriptase, integrase, and protease — viral enzymes whose inhibition is the target of antiviral therapy.

Which drugs act via direct extracellular chemical reactions?

Sources describe the following agents and substances acting via direct chemical reactions or extracellular chemical interactions:

• Antacids — neutralize hydrochloric acid in the stomach chemically.
• Antidotes in chemical antagonism — undergo chemical reactions to form inactive compounds:
• Sodium thiosulfate forms non-toxic sulfites in heavy metal poisoning;
• Digibind binds cardiac glycosides into inactive complexes;
• Protamine sulfate binds to heparin and neutralizes its anticoagulant effect.
• Protamine sulfate — forms an insoluble complex with heparin during severe hemorrhage associated with heparin, causing chemical neutralization.
• Potassium permanganate — causes chemical oxidation of morphine during gastric lavage for acute morphine poisoning.
• Components of the "Carisolv" kit for chemomechanical caries removal: gel No. 1 dissolves degraded mineral components of carious dentin, and gel No. 2 with sodium hypochlorite dissolves exposed collagen fibers.

Which transport systems serve as targets for drugs?

Targets for drugs include carrier proteins and ion pumps, the disruption of which alters transmembrane transport. Sources list the following transport systems:

• Presynaptic membrane transport proteins — blocked by tricyclic antidepressants; this disrupts neuronal reuptake of norepinephrine and serotonin and increases their concentration in the synapse.
• Cardiomyocyte $Na^+$-$K^+$-ATPase — blocked by cardiac glycosides; disrupts $Na^+$ transport out of the cell in exchange for $K^+$.
• NKCC2 — sodium-potassium-chloride cotransporter of the apical membrane of epithelial cells in the thick ascending limb of the loop of Henle; selective blockade inhibits this carrier protein's function.
• NCC — sodium-chloride cotransporter of the distal convoluted tubule; its blockade impairs sodium and chloride ion reabsorption.
• P-glycoprotein — a transporter protein whose activity can be altered by drugs or dietary components, changing the plasma concentrations of its substrates.

Which receptors are coupled to G proteins?

G protein-coupled receptors (metabotropic receptors) are the most common type of receptors in the human body. Key representatives of this group include:

• Dopamine receptors.
• Serotonin receptors (certain subtypes).
• Opioid receptors.
• Histamine receptors.
• Receptors for most peptide hormones.
• $\beta_1$-adrenergic receptors — coupled to the $G_s$ protein, which activates adenylate cyclase.

What types of ion channels exist based on their opening mechanism?

Sources do not provide a complete classification of ion channels by opening mechanism, but mention the following types:

• Voltage-gated channels — e.g., voltage-gated $Ca^{2+}$ channels, which open upon membrane depolarization; also describes voltage-gated $Ca^{2+}$ channel opening in $\beta$-cells.
• ATP-sensitive channels — e.g., ATP-sensitive $K^+$ channels of $\beta$-cells, whose closure is linked to rising ATP concentration.
• Receptors directly coupled to ion channels, or ionotropic receptors — one type of membrane receptor.
• $GABA_A$ receptor complex — linked to chloride channels; sodium thiopental leads to prolonged activation of chloride channels and chloride influx into the cell.
• Test sources also mention ligand-gated calcium channels.

How do drugs without specific targets work?

Their action is driven exclusively by physicochemical properties. For example, the diuretic mannitol simply increases osmotic pressure in the kidneys, retaining water and increasing urine output without receptor binding.

What is the mechanism of action of nonsteroidal anti-inflammatory drugs?

NSAIDs inhibit the enzyme cyclooxygenase (COX). This leads to decreased biosynthesis of prostaglandins, ultimately providing an anti-inflammatory effect.

How do potassium channel activators work?

They open channels, promoting the efflux of potassium ions out of the cell. This causes cell membrane hyperpolarization, reduced vascular smooth muscle tone, and a drop in blood pressure.