Chapter 2 Peripheral nervous system drugs - presynaptic adrenergic nerve blockers

Question 1

clonidine (catapres);

• guanabenz (tenex)
• guanfacine (tenex)

central anti-adrenergics

Answer 1

• potent a2 agonist
• DECREASE preganglionic sympathic outflow from brain l/t decreased BP

undesirable effects:
* orthostatic hypotension
* sedation
* rebound HTN (Rebound hypertension occurs when blood pressure rises after you stop taking or lower the dose of a drug (typically a medicine to lower high blood pressure). This is common for medicines that block the sympathetic nervous system like beta blockers and clonidine)

CLINICAL USE – HTN

Question 2

central anti-andrenergics

Answer 2

• commonly used to tx HTN
• clonidine and guanabenz suppress sympathetic outflow from brain by binding to a2 adrenergic receptors
• a-methyl norepineprhine — metabolized and released from presynaptic terminal => a-methylnorepinephrine acts as a potent a2 agonist
• a2 receptors are found on presynaptic nerve terminals where they inhibit NE release
• extent of their effects unknown

Question 3

methyldopa (aldomet)

central anti-adrenergics

Answer 3

• decarboxylated to a-methyldopamine then b-hydroxylated to a-methylnorepinephrine
• a potent a2 agonist
• causing decreased sympathetic outflow from CNS (particularly preganglionic sympathetic output)
• BP RAPIDLY loweres but sympathetic system can respond w/ cardiac stimulation

undesirable effects:
* sedation
* mild orthostatic hypotension
* coombs positive RBC (An abnormal (positive) direct Coombs test means you have antibodies that act against your red blood cells)
* salt and water retention
* rebound HTN

CLINICAL use - HTN

Question 4

guanethidine (ismelin)

guanadrel (hylorel)
bretylium (bretylol)

peripheral presynaptic anti-adrenergics

Answer 4

• unknown initial effect
• greater decrease in NE release
• l/t decreased norepinephrine concentration in nerve terminals
• chronically sensitive to sympathomimetics

actions
* rapid IV infusion — decreased BP, then transient HTN => decreased arterial pressure if pt is standing afterwards // INCREASED GI MOTILITY and fluid retention
* orally — hypotension

• guanethidine — used for severe HTN and renal HTN (SELDOM USED….)
• guanadrel — used for HTN
• EXCEPTION for bretylium — prolongs myocardial action potential // used for arrhythmias

Question 5

peripheral presynaptic anti-adrenergics

Answer 5

• inhibit NE release from presynaptic terminal via
  1) guanadrel and reserpine deplete NE uptake into presynaptic vesicles (in gaunadrel’s case – initially release NE from terminal causing transient inc)
  2) while resperine is long acting, which cause post synaptic neurons to the lack of NE by increasing # of receptors on postsynaptic membrane [as a result supersensitive to direct sympathomimetics]
  3) consequently, monoamine oxidase inhibitors (which prevent destruction of NE and Epinephrine] and direct sympathomimetics should be avoid in patients with resperine

Question 6

reserpine

peripheral presynaptic anti-adrenergics

Answer 6

• depletes catecholamines and serotonin in brain, adrenal, and brain
• inhibits uptake of NE into presynaptic vesicles
• chronically sensitizes pateint to sympathomimetics

actions:
1) gradual decrease in mean arterial pressure w/ bradycardia
2) antihypertensive effects d/t cardiac output
3) tranqulization, sedation

unwanted effects
* nightmares, depression
* diarrhea, cramps, peptic ulcers
* inc risk of breast cancer
* parasympathetic predominance

clinical use – HTN
* somtimes used for noncomplinat patients d/t long half life
* no rebound effect d/t long lasting effects