Na+ channel and K⁺ channel blocking drugs have both anti- and pro-arrhythmic effects. Their effects during fibrillation, however, remain poorly understood. We used computer simulation of two-dimensional (2D) structurally normal tissue model with phase I of the Luo and Rudy action potential model to study the effects of Na+ and K⁺ channel blockade on vulnerability to and termination of reentry in simulated multiple wavelet and mother rotor fibrillation. The main findings are: 1) Na+ channel blockade decreased, while K⁺ channel blockade increased, the vulnerable window of reentry in heterogeneous 2D tissue, due to their opposing effects on dynamical wave instability. 2) Na⁺ channel blockade increased the cycle length of reentry more than it increased refractoriness. In multiple wavelet fibrillation, Na⁺ channel blockade first increased and then decreased the average duration or transient time <T_s> of fibrillation. In mother rotor fibrillation, Na⁺ channel blockade caused peripheral fibrillatory conduction block to resolve and the mother rotor to drift, leading either to self-termination or sustained tachycardia. 3) K⁺ channel blockade increased dynamical instability by steepening action potential duration restitution. In multiple wavelet fibrillation, this effect shortened <T_s> due to enhanced wave instability. In mother rotor fibrillation, this effect converted mother rotor fibrillation into multiple wavelet fibrillation, which then could self-terminate. Our findings help to illuminate, from a theoretical perspective, the possible underlying mechanisms of termination of different types of fibrillation by antiarrhythmic drugs.