Antihypertensives I Flashcards
What are the qualitative ways of measuring blood pressure goals?
- ) Reduced incidence of heart failure
- ) Reduced stroke incidence
- ) Reduced overall cardiovascular mortality
What are the six types of antihypertensive drug types?
- ) Centrally acting agents
- ) Peripheral anti-adrenergics
- ) Beta-adrenergic receptor antagonists
- ) Peripheral vasodilators
- ) RAS altering drugs
- ) Diuretics
What receptors can centrally acting agents stimulate?
- ) Stimulate imidazoline-1 receptors
2. ) Stimulate alpha-2 receptors
Where are imidazoline-1 receptors found?
Rostral ventral lateral medulla
Where are alpha-2 receptors found?
Nucleus tractus solitaris (NTS)
What does stimulation of imidazoline-1 receptors cause?
Decreased sympathetic tone
What does stimulation of alpha-2 receptors cause?
Increased parasympathetic tone
Decreased sympathetic tone
What centrally acting drugs cause sedation?
Drugs that stimulate the alpha-2 receptors
What are the selective alpha-2 receptor stimulants?
Guanabenz
Alpha-methyldopa
Guanfacine
What is a combined imidazoline-alpha-2 receptor stimulant?
Clonidine
What is the most used centrally acting agent and why?
Clonidine because it has much less sedation than selective alpha-2 stimulants and imidazoline-1 is a stronger antihypertensive
What is the net effect of centrally acting drugs?
Decreased sympathetic outflow to heart
Decreased sympathetic outflow to peripheral vasculature
Increased parasympathetic outflow to heart
What innervates peripheral vasculature?
Sympathetic but not parasympathetic
Why do centrally acting drugs typically need a diuretic used with them?
Because in essential hypertension when you decrease PVR the baroreceptors think you are hypotensive (even though you are normotensive) and increase the RAS (also CO/HR)
What is alpha-methyldopa?
A prodrug converted to alpha-methylnorepinephrine (false transmitter) in the brain (alpha-2 selective)
What blocks alpha-methyldopa action?
Neuronal uptake inhibitors
Side effects of centrally acting agents?
Sedation
Dry mouth
What occurs if you quit cold turkey antihypertensives? Why?
Rebound hypertension; increased adrenergic receptors and increased affinity
What are the peripheral adrenergic neuronal inhibitors?
Guanethidine
How is guanethidine uptaken?
Transported into adrenergic nerves by neuronal amine transport (NAT)
How does guanethidine work?
It is uptaken by vesicular monoamine transport (MAO) releasing NE from vesicles and depleting NE stores
What does guanethidine ultimately cause?
Prevention of NE release with nerve stimulation
What happens after administration of guanethidine?
Hypertension from NE release then hypotension from NE depletion
Net effect of guanethidine?
Decreased CO
Decreased PVR
Severe salt/water retention
