Mechanism of action moment

Focus on alpha-2-delta calcium channel blockade

Two antiepileptic/antineuropathic pain medications utilize this unique mechanism of action

• – Gabapentin (Neurontin)

• – Pregabalin (Lyrica)

Blockade of neuronal calcium channels has the net effect of dampening neuronal firing

If this occurs in

• – Peripheral pain neurons, then pain lessens

• – Cortical neurons, then synchronous epileptiform waves diminish

• – Sleep-promoting center neurons, then delta wave sleep increases

• – The limbic system, then anxiety symptoms diminish and alcohol use may diminish

If the neuron experiences minor excitatory depolarization from synaptic input, sodium channels open, allowing further neuronal depolarization

This secondary depolarization allows calcium channels (called N and P/Q presynaptic channels) to undergo a conformational change, which opens a calcium channel and calcium ion influx further excites the neuron toward an actional potential and firing

In cortical neurons, this excitation might initiate a seizure, and in peripheral pain or central thalamic neurons, may create sensitization whereby excessive pain signaling is created

Theoretically, excitation elsewhere in the brain may create anxiety, insomnia, or the drive to drink alcohol

Gabapentin (Neurontin), used in the current case, and its counterpart pregabalin (Lyrica), are both alpha-2-delta binding drugs

• – When either drug is introduced and binds to the alpha-2-delta subunit of voltage-sensitive calcium channels depicted in Figure 26.1, they close the channels because the protein structure of the channel changes, helping to narrow or close the channel passageway or central pore. Calcium ions cannot gain entry into the neuron

• – This pharmacodynamic activity diminishes excessive neuronal activity and theoretically lowers psychiatric symptoms as well as neurological symptoms

• – Although these drugs are structurally related to GABA, they are not true analogs and do not have direct actions on GABA-A receptors

Figure 26.1. Sodium and calcium ion influx channels of a neuron.

Two-minute tutorial

pharmacologic strategies for alcohol cessation for use in a busy, office-based practice

Psychopharmacologists seem to put off treating addiction symptoms while performing standard psychopharmacological outpatient practice

Psychopharmacologists seem willing to become amateur neurologists when they treat EPS

Psychopharmacologists seem willing to become amateur urologists when they treat sexual dysfunction caused by SSRIs

Some psychopharmacologists seem willing to become amateur PCPs when they treat antipsychotic-induced weight gain, diabetes, or hyperlipidemia

It is interesting in that psychopharmacologists are willing to go the distance, become educated about non-psychiatric medications and their application for use in off-label manners, but we often seem scared to use alcohol cessation medications that are clearly well studied and FDA approved and are de facto psychiatric in nature

It is also interesting that, in a similar fashion, psychopharmacologists likely underutilize the smoking cessation medications of nicotine replacement therapy, bupropion-XL (Zyban) and varenicline (Chantix)

Compared to other DSM-5 disorders, nicotine use disorder and AUD likely have the largest impact on population health (morbidity, mortality, accidents), and we often minimally address these in the general adult psychiatric practice

Consider learning about the following three approved AUD treatments and possibly employing them in day-to-day office-based psychiatric practice