6.2.4. Sympatholytic drugs

← PREVIOUS: [[6.2.3. Vasoconstrictor drugs]] | NEXT: [[6.3. Psychological support and coping strategies]] → -------- ##### Summary >[!Summary] >- central sympatholytic drugs can also be used to decrease sympathetic tone in patients with prominent hyperadrenergic features, but might produce drowsiness and worsening of the mental clouding[[#^1]] > >**Clonidine** >- α-2 adrenergic receptor agonist that can decrease sympathetic nerve traffic centrally, and norepinephrine release from peripheral sympathetic neurons[[#^4]] >- net effect is to decreasing sympathetic overactivity[[#^4]] >- can be taken as 0.1 to 0.2 mg 2 to 3 times daily or as a long acting transdermal patch[[#^4]] >- has narrow therapeutic range, and it is important to start with lower dose [[#^3]] >- long-term treatment with clonidine decreased catecholamine levels and symptoms in POTS patients who did not respond to β-blockers[[#^4]] >- main challenge to clonidine is tolerability, as it is a central nervous system depressant. It can cause profound fatigue. The short-acting tablets can lead to on/off phenomenon with surges and then troughs in sympathetic nerve traffic, with matching symptoms[[#^4]] > >**Methyldopa** >- inhibits the enzyme DOPA decarboxylase to inhibit conversion of LDOPA to dopamine, which is a precursor of norepinephrine and epinephrine[[#^5]] >- gets converted to alpha-methyl-norepinephrine, which can inhibit central alpha-2 receptors (like clonidine) and decrease central sympathetic nervous system traffic[[#^5]] >- net effect of both actions is to blunt central sympathetic tone[[#^5]] >- one advantage of methyldopa over clonidine is that it has a longer half-life, and so does not have the peaks & troughs of actions that can be seen with clonidine[[#^5]] >- start methyldopa at a dose of 125 mg just at bedtime. if it is tolerated, increase it to 125 mg twice daily, and up to 250 mg twice daily[[#^5]] >- can worsen fatigue and brain fog but may be useful in patients with particularly high sympathetic nervous system activity who have not responded well to other treatments[[#^5]] -------- >*“Central sympatholytics (e.g. clonidine and methyldopa) can also be used to decrease sympathetic tone in patients *([p. 9](zotero://open-pdf/library/items/CAWTWYLR?page=9&annotation=345ST2Z9)) with prominent hyperadrenergic features, but might produce drowsiness and worsening of the mental clouding” *([[Garland-2015]], [p. 10](zotero://open-pdf/library/items/CAWTWYLR?page=10&annotation=6L646KTW))^1 >*“Central sympatholytic drugs can be useful in patients with increased sympathetic activity or hyperadrenergic POTS (Sheldon et al., 2015).”* ([[Miller-2018]], [p. 5](zotero://open-pdf/library/items/A3CIPE3G?page=5&annotation=PX92AP57))^2 >*“Central sympatholytic drugs can be useful in patients with increased sympathetic activity or hyperadrenergic features. Clonidine and methyldopa are both antihypertensive medications that can decrease central sympathetic nerve traffic and norepinephrine release from peripheral sympathetic neurons. Both medications have narrow therapeutic ranges, and it is important to start with lower doses.”* ([[Raj-2022]], [p. 6](zotero://open-pdf/library/items/YN8BG2FZ?page=6&annotation=F8SCG4QR))^3 ##### 1. Clonidine >*“Clonidine is an α-2 adrenergic receptor agonist that can decrease sympathetic nerve traffic centrally, and norepinephrine release from peripheral sympathetic neurons. The net effect is to decreasing sympathetic overactivity. Clonidine can be taken as 0.1 to 0.2 mg 2 to 3 times daily or as a long acting transdermal patch. One study found that long-term treatment with clonidine decreased catecholamine levels and symptoms in POTS patients who did not respond to β-blockers (Gaffney et al., 1983). The main challenge to clonidine is tolerability, as it is a central nervous system depressant. It can cause profound fatigue. The short-acting tablets can lead to on/off phenomenon with surges and then troughs in sympathetic nerve traffic, with matching symptoms.”* ([[Miller-2018]], [p. 5](zotero://open-pdf/library/items/A3CIPE3G?page=5&annotation=32DLEKXF))^4 ##### 2. Methyldopa >*“Methyldopa likely has 2 synergistic mechanisms of action. First, it inhibits the enzyme DOPA decarboxylase to inhibit conversion of LDOPA to dopamine, which is a precursor of norepinephrine and epinephrine. Second, methyldopa gets converted to alpha-methyl-norepinephrine, which can inhibit central alpha-2 receptors (like clonidine) and decrease central sympathetic nervous system traffic. The net effect of both actions is to blunt central sympathetic tone. One advantage of methyldopa over clonidine is that it has a longer half-life, and so does not have the peaks & troughs of actions that can be seen with clonidine. We start methyldopa at a dose of 125 mg just at bedtime. If it is tolerated, we will then increase it to 125 mg twice daily, and up to 250 mg twice daily. We have never gotten a POTS patient beyond this dose. Both clonidine and methyldopa can worsen fatigue and brain fog but may be useful in patients with particularly high sympathetic nervous system activity who have not responded well to other treatments.”* ([[Miller-2018]], [p. 5](zotero://open-pdf/library/items/A3CIPE3G?page=5&annotation=EN8DQ2QI))^5