Abstract: This paper investigates the Penning ionization (PI) processes in cold gas media of alkali atoms. The PI autoionization widths of atomic pairs show a drastic dependence (by orders of magnitude) on the orbital quantum numbers of Rydberg atoms involved in a long-range dipole-dipole interaction. The nontrivial dependence of the PI efficiency on the size of colliding particles was considered, with a particular accent to the applications in the research of cold matter created in the experiments with magneto-optical traps. We have analytically described the optimal, highly asymmetric configurations of atomic Rydberg pairs, which lead to an explosive intensification (by several orders of magnitude) of a free-electron escaping due to PI. The excited states of atoms in the optimal pairs turn out to have a strong difference in atomic shell sizes. The optimal pairs’ properties may be favorable for the generation of primary (seeding) charged particles when a cold Rydberg medium evolves into a cold plasma. Within the framework of the semiclassical approach, we have obtained universal analytical formulas containing two adjustable parameters and present here their values in tabulated form, which allows estimating the PI rate constants for various pairs of alkali metal atoms. Graphical abstract: [Figure not available: see fulltext.]