Miscellaneous Drugs for HTN Flashcards
Alpha2 agonists
Clonidine, Guanabenz, Guanfacine, Methyldopa (prodrug)
NE Storage depletors
Reserpine and Metyrosine
Effects of long term stimulation of alpha2 receptors
G-protein signaling becomes desensitized to alpha2 activation leading to endocytosis of the receptor and loss of function
Alpha2 effect on autoreceptors
limit release of NE from sympathetic nerves and E from adrenal chromatin cells at rest
Alpha2 effect on heteroreceptors
bradycardia, hypotension through vagal activation; analgesia, sedation, hypothermia, and anesthetic-sparing effect
Affects of alpha2 agonists
in vasculature causes vasoconstriction, but only seen when given locally, usually obscured by central inhibition of sympathetic tone and decreased BP
Alpha 2 agonists that do not penetrate BBB and do not effectively lower BP
Clincal effects of alpha2 agonists
Withdrawal of SNS tone leading to fall in PVR and SBP/DBP
HR may reduce, but no reflex tachy occur
decreased plasma renin activity, regression of LV hypertrophy, salt and water retention
Reasons to use
no effect on blood glucose or lung function so good for diabetics and asthmatics
Usually given adjectively to block reflex tachycardia
Routes of administration
Clonidine transdermal or IV; methyldopa IV; others orally only
Methyldope has shortest half life, guanfacine has longest
Methyldopa
must be metabolized to become active; shorter half life can be given IV; dose adjustment need in renal failure; chelated by concurrent iron supplement so separate dosing is needed.
interferes with catcholamine quantitation, contra in pheochromocytoma
SE of alpha2 agonists
SOMNOLENCE and dry mouth
Less likely: ab pain, constipation, hypotension, brady, decreased libido and impotence
First line therapy for HTN during pregnancy
Methyldopa - because has most data without bad results, i.e. everyone uses it
Labetalol can also be used
ACEi contraindicated
Reserpine
Binds tightly (long lasting) to adrenergic storage vesicles of adrenergic neurons inhibiting VMAT2 the catecholamine transporter, making the neuron lose its capacity to concentrate and store NE and dopamine; takes days to weeks to recover stores after stopping treatment
Acts centrally and peripherally
Completely metabolized to inactive products
Reserpine toxicity
CNS: sedation and inability to concentrate of perform complex tasks, depression, increased suicide ideation
Contra: in PUD or ulcerative colitis since it can exacerbate
Avoid in pregnancy and breast feeding
Aliskiren
Direct renin inhibitor; causes vasodilation and natriuresis
SE: 1st dose hypotension, hyperkalemia, angioedema, fetotoxicity
Drug interactions due to p-glyoprotein inhibition characteristic of this drug; avoid with other p-glycoprotein inhibitors (erythromycin, amiodarone, etc)
