SYMPATHOTROPIC DRUGS
SYMPATHOLYTICS


Indications:
•hypertension (mild and moderate)
•antimigraine drugs
•disorders of peripheral vascularity
•benign prostatic hyperplasia
•urinary obstruction – postoperative atonia
•pheochromocytoma
Sympatholycs (direct and indirect)

Direct sympatholytics
α
               α-lytics                –   reversible
                                      –  irreversible
α1 lytics   α2-lytics
non-selective α-lytics
drugs with combined effect

•ergot alkaloids (ergotamine, ergometrine, ergotoxine, methylergometrine, dihydroergotamine,
dihydroergotoxine, dihydroergocristine)
Direct sympatholytics
 α non-selective

•in Secale cornutum, product of Claviceps purpurea, fungus that infects cereal crops
•derivatives of lysergic acid
•effects:
 - CNS (halucinations, ↓ prolactine secretion)
 - smooth muscle of blood vessel (effects mimetic or lytic)
 - uterine muscle →  contractions
Ergot alkaloids and their derivatives ➙ reversible α-lytics
Direct sympatholytics
 α non-selective

•ergotamine, ergometrine
   - parcial α-agonistic effects
    - uterotonic effect, amplified by methylation of derivatives (methylergometrine)
•ergotoxine
     - mixture of alkaloids, mainly ergocristine, ergocriptine and
       ergocornine - especially α-lytic effects
• α-lytic effects are increased in dihydro-derivatives  (dihydroergotamine, dihydroergotoxine,
dihydroergocristine)
!
Direct sympatholytics
 α non-selective
Ergot alkaloids

• methylergometrine
uterotonic effect

• therapy and prevention of uterine bleeding after childbirth (in hypotony and atony of myometrium)
•
Direct sympatholytics
 α non-selective
Ergot alkaloids

α1sympatholytics
Overview of drugs, use
•terazosin, doxazosin, alfuzosin, tamsulosin…
•prazosin (in Czech Rep. non registered)
•Use:
- hypertension (relaxation of arterial and venous smooth muscle)
- benign prostatic hyperplasia
- urinary obstruction
Direct sympatholytics
 α1 selective

•urapidil
•
•combined central and peripheral action, blocks α1 receptors, in CNS blocks H1 receptors, activates
5-HT1A receptors
•Use:
   -  hypertension (hypertension crisis, severe, respectively, very severe forms of hypertension
and hypertension resistant to standard therapy)
Direct sympatholytics with combined effect

α2 sympatholytics
•yohimbine (in Czech Rep. non registered)
•vasodilation in the pelvic area, afrodisiac effect
•it is contained in some dietary supplements
Direct sympatholytics
 α2 selective

•competitive antagonists (intrinsic aktivity = 0) or partial agonists
    (ISA - intrinsic sympathomimetic activity) = dualists
•nonselective or cardioselective (selectively block í β1 receptors)
•sufficient solubility in fats → penetration across HEB
Direct sympatholytics
β-blockers, β-sympatholytics

Organ effects
cardiovascular system: negatively chronotropic and inotropic effect → ↓ BP and HR
     - inhibition of vasodilation by β2-receptor blockade  → peripheral vascular resistence
increase
     - renine secretion reduction
bronchi: bronchoconstriction
eye: intraocular pressure decrease
metabolic effects: glycogenolysis reduction, lipolysis inhibition
Direct sympatholytics
β-blockers, β-sympatholytics

NONSELECTIVE (1 + 2)
  propranolol, metipranolol

(CARDIO)SELECTIVE (1)
atenolol, metoprolol
NONSELECTIVE (1 + 2) WITH ISA
 pindolol,
 bopindolol (in  Czech Rep. non registered)
(CARDIO)SELECTIVE (1) WITH ISA
acebutolol
WITH COMBINED EFFECTS  + 
labetalol
carvedilol
Direct sympatholytics
β-blockers, β-sympatholytics

Use, indications:
•hypertension
•Ischemic heart disease, non-stabil angina pectoris, status after acute myocardial infarction
•arrhytmia
•glaucoma
•hyperthyreosis
•anxiety (moderate effect)

Direct sympatholytics
β-blockers, β-sympatholytics

Side effects:
•asthma bronchiale, dyspnoea
•heart insufficiency
•bradycardia, blockade of heart impuls conduction
•masking of hypoglycemia symptoms
•disorders of peripheral blood circulation
•sleep disorders, depression (lipophilic drugs)
•rash, fever and other allergic symptoms (rarely)
•abrupt discontinuation of therapy – „rebound phenomena“
Direct sympatholytics
β-blockers, β-sympatholytics

decreases catecholamine concentration in the synaptic cleft by:

• inhibition of NT synthesis
• inhibition of NT storage
• inhibicí of NT release
• false precursors

Nondirect sympatholytics