review autonomics
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- Alpha 2 agonists: reduce IOP (reduce synthesis of aqueous
humor)
Effects on Vascular system
Alpha 1 agonist
(ex.
Phenylephrine)
Constrict skin and splanchnic blood vessels
Inc PVR and BP
Evoke compensatory reflex bradycardia
Alpha 2 agonists
(ex. Clonidine)
IV/ topical: vasoconstriction
PO: acculumate in CNS, reduce sympathetic
outflow and BP
Beta 1 agonists Little effect on blood vessel
Beta 2 agonists Reduce PVR and BP
Dopamine Vasodilation in splachnic and renal vascular
beds (D1)
High doses – activate B receptors
Higher doses- activate alpha
- Sympathomimetics with both alpha and beta1 effects (ex.
NE) have a reflex increase in vagal outflow (evoke
baroreceptor reflex)
o Inc BP with bradycardia
o If reflex is blocked (ganglion blocker), inc BP with
tachycardia
- - Pure alpha agonist (phenylephrine): bradycardia due to
baroreceptor reflex
- Pure B agonist (isoproterenol): tachycardia
- Beta 1 agonists: increase renin secretion
- Beta 2 agonists: increase insulin secretion and liver
glycogenolysis
Clinical Uses
Phenylephrine Mydriasis
No effect on accommodation/cycloplegia
Reduce conjunctival itching and congestion
glaucoma
Terbutaline Tocolysis
Relax uterus
Epinephrine Immediate treatment of anaphylactic shock
glaucoma
B2 selective
antagonists
Acute asthmatic bronchoconstriction
Salmeterol Prophylaxis of bronchoconstriction
Alpha 1 agonists Spinal shock (not for septic shock or MI)
Often mixed with local anesthetics : to
reduce loss of anesthetic into circulation
Ephedrine or
Midodrine (a1)
Chronic orthostatic hypotension
B2 agonists
(Terbutaline,
Ritodrine)
Suppress premature labor
Ephedrine Urinary incontinence in children (enuresis)
Adrenoceptor Blockers
Alpha blocking drugs
Irreversible long acting Phenoxybenzamine
Reversible, shorter acting Phentolamine
Reversible Alpha 1 selective Prazosin
Alpha 2 selective Yohimbine and Rauwolscine
- Phentolamine – rarely given orally
- Phenoxybenzamine – short elimination t ½ but long
duration of action (48h)
MOA: Phenoxybenzamine binds covalently to alpha receptor
Effects of Alpha blocking drugs
Nonselective Blockers
- Reduction in vascular tone
- Reduction of both arterial and venous pressures
- No significant direct cardiac effects
- Baroreceptor reflex tachycardia
Epinephrine reversal
- Large doses of epinephrine with alpha blocker
- Pressor response (alpha) to depressor response (B2)
Clinical Uses
Phenoxybenzamine Pheochromocytoma- preparatory
Phentolamine Pheochromocytoma- during sx
Phentolamine Prevent tissue damage
Phentolamine Rebound hypertension
Phentolamine/
Yohimbine
Erectile dysfunction
Prazosin
Doxazosin
Terazosin
Hypertension
Prazosin
Doxazosin
Terazosin
Tamsulosin
Urinary hesitancy and prevention of
urinary retention in patients with
BPH
- Sudden cessation of clonidine therapy leads to rebound
hypertension
Toxicity
- Orthostatic hypotension
- Nonselective alpha: marked reflex tachycardia
Beta Blockers
- Competitive pharmacologic antagonists
- Prototype: propranolol
Nonselective B1 Selective Combined a/B
Nadolol
Propranolol
Timolol
Acebutolol
Atenolol
Esmolol
Metoprolol
Labetalol
Carvedilol
Partial Agonist Activity (ISA) Full Antagonist
Can cause bronchodilation Cause severe bronchospasm
Pindolol
Acebutolol
Propranolol (not for patients
with airway disease)
Esmolol: short acting, only used parenterally
Nadolol: longest acting B blocker
Toxicity
- Bradycardia, AV block, heart failure
- Severe asthma attacks in patient with airway disease