I would say that the effects you describe probably point to too high doses, and/or too frequent dosing. I don't have too much insight into the neurochemistry and dopamine specifically as it relates to irritability, but from my laypersons understanding it's probably something to do with the interaction between dopamine and serotonin. Many dopaminergic stimulants have seronergic activity as well, and (excuse the broscience I am about to spew here) the serotonin system is notoriously a little more "fragile" than the dopamine system, more prone to damage, and takes longer to recover.
Low serotonin is often linked to irritability (complicating factors with other neurotransmitter systems obviously play a part also here but I won't go into this for simplicity, and also as I just don't have enough knowledge) so I would suspect that with sustained or higher doses the serotonin system starts to burn out, so to speak, before the dopamine system does, and this disrupted neurotransmitter balance contributes to the less desirable effects.
Other hormones probably play a part also such as cortisol, as too much stimulation is hard on the body and likely triggers the release of these "stress hormones", leading after a while to increased feelings of stress, irritability and mental fatigue which are all somewhat linked, and eventually are not counterbalanced by the overactivation of the brain's "reward" pathways.
I was thinking I read something before that suggested methylphenidate had a lower incidence of these side effects compared to amphetamine, and methylphenidate has less serotonergic activity so this would seem to be in support of my broscience hypothesis - but this might not actually be accurate so please don't take me at my word for this.
Just found this study which is somewhat interesting and related:
Changes in behavior as side effects in methylphenidate treatment: review of the literature
In a study of seven healthy adult humans, a dose of 0.25 mg/kg body weight or higher resulted in the inhibition of more than 50% of dopamine transporters. Long-term treatment with methylphenidate in humans led to significantly increased activity in the caudate and putamen regions. Wang et al suggested that the increased activity of dopamine transporters compensates for their pharmacological inhibition, resulting in increased inattention and the need for an increase in the dose administered.
This study was actually inconclusive, and obviously it is not discussion an amphetamine, but the quoted section above specifically relating to long term treatment and incidence of negative side effects seems to imply that changes induced in dopamine transporters are the cause of these side effects. I initially interpreted this to mean that the increased dopamine activity is an effort to compensate for changes going on in other neurotransmitter systems which initially hold up but eventually can't keep up and the positive effects of increased dopamine start to be negated by the changes in other neurological systems... but actually maybe not, maybe this just implies that it's changes in the dopamine system alone that over time just make these substances more likely to induce undesirable effects.
Again, please excuse my prolific butchering of the science and please, someone correct me here if I'm way off. I maybe shouldn't be posting as I am on a cathinone right now and thus have a desire to research and communicate, but my judgement is probably impaired, including my judgement of the accuracy of my judgement, but this is a topic that interests me also so thought I'd give my 2c...
One final point - I believe there are recent studies suggesting that prescribed amphetamines in reasonable doses actually do not generally cause lasting maladaptive changes to reinforcement/reward pathways as it was once thought (and as some stimulants, ie, cocaine, most definitely
do), so again, dosage and pattern of use is obviously important here.
Of course, as you mentioned, there is probably also a psychological aspect which is no doubt translated to a neurochemical explanation although I don't know how to do so - amphetamines speed up your thinking, so it's probably easier just to get frustrated when the world or your actions in it can't keep up - hence irritation.
Not so sure about methamphetamine. Obviously this is heavily serotonergic, but it is also prescribed in low doses very rarely and I believe there is a threshold dose where neurotoxicity is not apparent (am I correct here? Someone please tell me, as I type this I am not so sure). In my very limited experience with both amphetamine and methamphetamine I actually found the former to be MORE prone to inducing irritability on the comedown - which would support the idea that serotonin/dopamine balance is a factor - but I just don't have enough experience or knowledge again to say if this is the norm.
Hopefully someone with a solid understanding of amphetamine neuropharmacology can chime in!