parasympathetic and sympathetic nervous system Flashcards
M1 , M2, M3: where do they work?
- side effects
- M 1 ,M 3 stomach and glands, bronchial smooth
muscle, eye ciliary muscle excitation –, vascular
endothelium (NO) inhibition - M 2 heart inhibition
- Side effects: bradycardia bronchoconstrictio miosis salivation vomiting, diaorrhea urination
Muscarinic ACh receptors:
- response to ACh binding =
G protein cascade is activated
Indirect parasympathomimetics
- how they work
ACh esterase enzyme inhibition —> ACh
degradation is reduced
Carbachol
non specific to M ACh receptors: several side effects
excellent activity, nowadays: exclusively locally
1. applied in the uterus in the case of metritis (intrauterine)
- Bethanechol
2. Methacholine
used in human medicine mostly
- M- ACh specific
induction of intestinal peristalsis after operations
urinary bladder atony ! (veterinary field)
M ACh specific
cardiovascular system —> atrial fibrillation
pronounced peripherial vasodilatation —> ergot toxicosis
Pilocarpine
- use
- side effects
natural alkaloid ( Pilocarpus jaborandi)
earlier: important role in ophtalmology
1. GLAUCOMA therapy (miosis can be seen after approx. 15 mins)
2. KCS (Keratoconjunctivitis sicca): effect is ambiguous
side effect: mild after local administration
Direct parasympathomimetics
Acetylcholine (ACh) Carbachol Bethanechol Methacholine Pilocarpine
Receptors for indirect parasympathomimetics:
primarily on nicotinic ACh receptors
furthermore on muscarinic ACh receptors
on ACh receptors in the CNS
Physostigmine
- characteristics
- use
- contains tertiary nitrogen –> lipophilic –> kinetics!
- very small therapeutic index systemically (atropine poisoning)
- eye drop : glaucoma treatment
Neostigmine
- Characteristics
- use
•quaternary nitrogen —> less lipophilic –> kinetics!
•eye drop : treatment of glaucoma
•given systemically it is safer
- Given IV or IM
- myasthenia gravis treatment
suspending the action of non depolarizing muscle relaxants - increasing intestinal motility
- inducing emesis
Pyridostigmine
- Characteristics
- admin
- use
- quaternary nitrogen –> less lipophilic –> kinetics!
•given systemically it is safer
•orally this has the best bioavailability (F=3 8% only)
Use:
myasthenia gravis treatment
increasing intestinal motility
Edrophonium
- Characteristics
- effect, use
•competitive inhibition in the neuromuscular junction —> action is suspended by diffusion
•short effect: 5-15 minutes
- myasthenia gravis diagnosis = Tensilon test
Organophosphates
- Characteristics
- use
- antidote
- irreversible
- inhibitors of AChE
- ectoparasiticides (e.g. diazinon)
- in humans treatment of glaucoma (e.g. echothiophate)
antidote: atropine, pralidoxime
Indirect parasympathomimetics
Organophosphates Edrophonium Pyridostigmine Neostigmine Physostigmine
Atropine
Dose (mg/kg) Symptoms
Dose (mg/kg) Symptoms
0,5 :Mouth dryness, decreased perspiration
1: tachycardia, mydriasis
2: +accomodation, disturbances
5: +constipation
10: +ataxia, excitation, hallucination, delirium, coma
Drugs used in:
- diagnostic examination of the eye
- in uveitis the prevention of synechiae
- tropicamide,homatropine (short acting)
2. atropine (long acting)
atropine was used earlier for
premedication which drug is most used now?
glycopyrrolate
Drug used in treatment of horse RAO, COPD and human
(feline) asthma :
ipratropium
decreases secretion and motility (used
in ruminants)
benzethimide
decreases smooth muscle function –> antispasmodic
effect in the intestine –> very effective in horse colic
esp. butyl scopolamine
Which animal is relatively resistant to atropine! (liver atropinase)
Rabbit
Atropine toxicosis symptoms:
Symptoms: dry mouth, tachycardia, mydriasis, constipation, convulsions, coma, death
α1 receptor effects:
smooth muscle contraction
*increased sphincter constriction
vasoconstriction
mydriasis
α2 receptor effects:
inhibition of neurotransmitter release (NA!)
GI relaxation
inhibition of insulin release
β receptors effects:
- β1 receptor cardiac effects (positive inotropic, chronotropic)
- β2 receptor
vasodilatation
bronchodilatation
uterus relaxation - (β 3 receptor
lipolysis in fat tissue)
Nonspecific sympathomimetics
Adrenalin
Noradrenalin
Dopamine
Adrenaline
- receptors
- effects
- indications
- noncspecific: mainly β 1 and β 2 receptors
* α-receptors in higher dosage
cardiac effect
arrhytmogenic!
blood pressure increases
indications:
- cardiac stop
- severe bronchoconstriction
- anaphylaxia
- local vasoconstriction (haemorrhages)
- increase in duration of local anaesthetics
Noradrenaline
- receptors
- effects
- indications
- nonspecific (mainly β 1 and α 1 receptors)
cardiac effect
blood pressure is significantly increased!
indications (rare):
-hypotension
Dopamine
- receptors
- low dose D 1 receptors (kidney!)
- medium dose β 1 receptors (heart!)
- high dose α 1 receptors (pressor)
Specific sympathomimetics
Dobutamine
Isoproterenol
Beta agonists: (mainly B2, higher doses B1) clenbuterole salbutamole terbutaline salmeterole isoxsuprine
Dobutamine
- receptors
- effects
- indication
- mainly β 1 receptors
cardiac effect
indications:
-cardiogenic shock (IV. infusion)
Isoproterenol
only β receptors ( β 1 and β 2)
- heart+bronchi+muscle vessels
Which Beta 2 agonist is leaat lightly to cause cardiac effect?
clenbuterole 4:1
salbutamole 650:1
salmeterole 50000:1
β2 agonists indications:
horse RAO feline asthma bronchitis, bronchopneumonia tracheal hypoplasia tracheal collapse
Phenylephrine
- receptors
- uses
α adrenoceptor agonists mainly α 1 receptors --> vasoconstriction - use: rarely local and systemic usage Allergy, cold \+ Hypotension, shock (?)?)
Xylometazoline, oxymetazoline, naphazoline, tetryzoline are:
mainly α 1 receptors –> vasoconstriction
local usage
Phenylpropanolamine
mainly α 1 receptors —> urinary bladder sphincter
constriction!
per os usage (empty stomach)
side effects
α adrenoceptor agonists: 8stk
α2 agonists: 4stk
Phenylephrine Xylometazoline, oxymetazoline, naphazoline, tetryzoline Phenylpropanolamine Ephedrine Amphetamine
α 2 agonists (sedato hypnotics)
xylazine, detomidine, medetomidine, romifidine
Ephedrine
- receptors
- use
nonspecific, direct and indirect effects - uses: tachyphylaxis CNS allergy, incontinence (p.o.)
Nonspecific α antagonists
- drugs
- Phenoxybenzamine (urethra sphincter relaxation)
long duration of action - Phentolamine
- Tolazoline
α1 antagonists
prazosine, doxasozine (urethra sphincter relaxation)
α2 antagonists
atipamezole, yohimbine
Nonspecific β antagonists
Propranolole
Timolole
SIDE EFFECTS
Specific β 1 antagonists
Metoprolole
Atenolole
