Pharmacologie: Partie 2: Pharmacologie du système nerveux autonome, Sympathomimétiques /Sympatholytiques Flashcards
What does stimulation of alpha-1 post-synaptic receptors do in the SNS?
Vasoconstriction, mydriase, contraction of GI and bladder sphincters
What does stimulation of alpha-2 post-synaptic receptors do?
SNS: agrégation plaquettaire, inhibit insulin release, stimulate GH release, inhibit ADH release
CNS: analgesia, sedation, depression of CV system
What does stimulation of alpha-2 pre-synaptic receptors do?
Sympathetic (AR)
Inhibit noradrenaline release
Parasympathetic (HR)
Inhibit acetylcholine release
What does stimulation of beta-1 post-synaptic receptors do?
Sympathetic
Increase HR, increase cardiac automaticity and contractility, lipolysis
What does stimulation of beta-2 post-synaptic receptors do?
Sympathetic
vasodilation, bronchodilation, relaxation of GI tract, uterus and bladder, glycogenolysis, secretion of insulin
What does stimulation of beta-2 pre-synaptic receptors do?
Sympathetic (AR)
Increase NA secretion
Parasympathetic (HR)
Increase ACh secretion
What is a sympathomimétique?
Medication that reproduce the effects of a stimulation from the sympathetic nervous system
What are the two kinds of sympathomimétiques?
SYMAD: à action directe
- directly stimulates the receptor
SYMAID: à action indirecte
What is the effect of a sympathomimétique on alpha-1 receptors? SYMAD
NA released by post-ganglionnaire nerve…
Where are these receptors located?
blood vessels, intestines (sphincters), radial iris muscles, sphincter of the prostate
NO ALPHA-1 RECEPTORS ON THE HEART
-
Blood vessels:
- increase arterial pressure and vascular resistance (VASOCONSTRICTION)
-
Eyes:
- Contraction of muscle dilatateur radial de la pupille —> mydriase (opening of pupil)
-
Bladder:
- Contraction of sphincter
What are the clinical uses of sympathomimétiques in terms of alpha-1 agonists?
Reduce nasal congestion (vasoconstriction) —> DO NOT USE IN GLAUCOMA PTS
treatment of hypotension but be careful of bradycardia reflex in response to constriction
What is the effect of a sympathomimétique on alpha-2 receptors? SYMAD
Périphériques:
- not as important and not really prescribed for these effects but
- agrégation plaquettaire, inhibition of insulin/ADH release and stimulation of growth hormone
Central:
- analgesia, sedation, depression of CV system
Pre-synaptic:
- decrease in sympathetic tonus (inhibit NA release) and parasympathetic (inhibit ACh release)
- Auto and heteroreceptors on post-ganglionic nerve endings
What are the main clinical uses of sympathomimétiques in terms of alpha-2 agonists?
Clonidine: used often in chronic pain (per os)
Clonidine is an α-2 adrenergic receptor agonist with central and peripheral action. CNS effects are mediated in the ‘anxiety centre’ whilst the peripheral effects in the GI tract are via decreasing acetylcholine release, thereby reducing the strength and frequency of colonic motor contractions.
Dexmedetomidine: sedative w/o respiratory distress (IV)
short-term sedative and analgesic
What is the effect of a sympathomimétique on beta-1 receptors? SYMAD
ALL ABOUT THE HEART! —> increases ionotropy and HR and renin secretion (SRAA) but not as important as the heart
What is the effect of a sympathomimétique on beta-2 receptors? SYMAD
SNS: Vasodilation, bronchodilation, relaxation of GI/bladder, glycogenolysis, insulin secretion, increase of potassium capture by skeletal muscles, relaxation of cilliary muscle to accommodate for seeing far
pre-synaptic: auto/heteroreceptor… increase ACh and NA release
What is the impact of sympathomimétiques on insulin secretion? SYMAD
Alpha-1 —> lower secretion
Beta-2 —> increase secretion
What are the different types of SYMADs most used in clinical settings?
They can either be:
- selective for a subtype of receptor
- non-selective
This selectivity varies according to the molecule used and the dose
What are some examples of selective SYMADs?
phenylephrine —> alpha-1
isoproterol —> beta-1 > beta-2… NO ALPHA
clonidine —> alpha-1… VERY little alpha-1 stim
How do SYMAIDs work?
MOST NA MOLECULES ARE RECAPTURED (80%)
- Block recapture of NA in adrenergic nerve endings —> NA accumulation which decreases the NA reserves
- Inhibition of enzyme that degrades NA (inhibiteur de la monoamine oxydase)
- Increase NA secretion
Specifics of SYMAIDs… use 1:
Block recapture of NA in adrenergic nerve endings —> NA accumulation which decreases the NA reserves
examples?
cocaine and some anti-depressants
Specifics of SYMAIDs… use 2:
inhibition of enzyme that degrades NA (inhibiteur de la monoamine oxydase)
examples?
certain anti-depressants
Specifics of SYMAIDs… use 3:
increase NA secretion
example?
EPHEDRINE
What are the main clinical uses of sympathomimétiques? (SYMADs and SYMAIDs) –> 5
- Vasopressors
- Inotropic agents
- Epinephrine/adrenaline
- Treatment of bradyarrhythmia
- Clonidine
What are vasopressors?
Molecule used to increase BP via action on alpha-1 receptors
What are some examples of vasopressors?
phenylephrine (PURE)
- vasoconstriction but has bradycardia reflex via baroreceptors
norepinephrine/noradrenaline, epinephrine/adrenaline
ephedrine (indirect)
What are ionotropic agents?
Molecules used to increase force of contraction of the heart via action on beta-1 receptors
What are some examples of ionotropic agents?
norepinephrine/noradrenaline, epinephrine/adrenaline (wont dim. BP)
ephedrine
dobutamine, isoproterol —> also have beta-2 effect
What is epinephrine/adrenaline?
molecules used for reanimation and treatment of anaphylactic shock, used to promote hemostasis and increase the duration of action of local anesthetics
What SYMADs and SYMAIDs are used in the treatment of bradyarrythmia?
Epinepherine, dopamine and isoproterol (not really used cause it also decreases BP)
What is clonidine used for?
used to treat HTA because its effect on alpha-2 receptors —> dim. sympathetic
What conditions are counter indications for using sympathomimétiques?
Cardiovascular: insuffisance, arythmie, angor, HTA
Insomnia
Prostatic hyperplasia
How does cocaine work?
SYMAID
blocks neuronal recapture of NA and dopamine
What are alpha blockers?
Competitive antagonists for adrenergic alpha receptors
What are the different kinds of alpha blockers?
non-selective
ex: phentolamine (alpha-1 and alpha-2)
selective
ex: alpha-1 prazosine, alpha-2 yohimbine
Do alpha blockers impact beta receptors?
Sorta… indirectly by making NT more available
What are the principal effects of alpha-1 blockers?
relaxation of smooth vascular muscles —> hypotension, tachycardia reflex, postural hypotension
nasal congestion
myosis
relaxation of bladder sphincter —> easier to urinate
relaxation of prostate, vas deferens, seminal vesicles
What are the principal effects of alpha-2 blockers?
Increase NA liberation by adrenergic nerve endings (autoreceptor)
Increase ACh liberation by cholinergic nerve endings (heteroreceptor)
What are some clinical uses of alpha blockers?
Hypertensive emergencies:
- phentolamine (alpha-1 and 2)
Treat accidental sub-cutaneous infiltration for a sympathomimétique
- phenoxybenzamine (alpha-1 and 2) —> non-competitive antagonist
- MUST USE FAST OTHERWISE POSSIBLE NECROSIS OF TISSUE
Raynaud’s
- Phenoxybenzamine (alpha-1 and 2), prazosine (alpha-1)
Increase NA release —> pre-synaptic effects:
- Yohimbine (alpha-2)
- Treatment of idiopathic orthostatic hypotension
- Erectile dysfunction
Benign hypertrophy of the prostate:
- Tamsulosin (alpha-1a) VERY LOCAL AND SPECIFIC EFFECT BECAUSE OF TARGETED RECEPTOR
What conditions are counter indications for using alpha blockers?
Orthostatic hypotension (alpha-1) —> dim. of sympathetic vasoconstriction reflexes
Arrhythmia (tachycardia reflex)
Nasal congestion
Headaches
What are beta blockers?
Competitive antagonists for beta adrenergic receptors
What are the different kinds of beta blockers?
non selective
propranolol
selective
beta-1: metoprolol (cardioselective)
beta-2: butoxamine NO REAL CLINICAL USES
Do beta blockers impact alpha receptors?
No DIRECT effect BUT alpha effects are amplified due to a increased availability of NT
What are the principal effects of beta-1 blockers? (5)
dim. HR and contractility of heart
dim. speed of AV conduction
dim. débit cardiaque (short term)
dim. vascular resistance (long term)
dim. renin secretion and BP
What are the principal effects of beta-2 blockers?
Increase vascular resistance (short term)
Bronchoconstriction —> asthma = counterindication
dim. glycogenolysis and insulin secretion
dim. entry of potassium into muscle cells
dim. NA and ACh release (auto/heteroreceptors)
What are the main effects of alpha and beta blockers on the heart and blood vessels?
BLOQ beta-1: dim. HR, contractility, and débit –> dim. BP
BLOQ beta-2: constriction –> increases vascular resistance
BLOQ alpha-1: dilation –> dim. BP
What are some clinical uses of beta blockers? (beta-1 = lol)
HTA:
- propranolol (1 and 2), metoprolol (1), esmolol
Ischemia, arrhythmia, I.C:
- bisoprolol (1), metoprolol
Glaucoma:
- diminish the production of aqueous humour: timolol (1 and 2) —> drops
Other:
- Migraines and idiopathic tremors
What conditions are counter-indications for using beta blockers?
asthma, bradycardia and they can mask signs of hypoglycemia (shaking… so be careful if diabetic)
What are the important cholinomimétiques to know?
methacholine: used to induce bronchoconstriction
neostigmine: used to treat myasthenia gravis
organophosphates: sarin gaz
What are the important anticholinergiques to know?
atropine: used to treat the symptoms of low heart rate
glycopyrrolate: helps to control conditions such as peptic ulcers that involve excessive stomach acid production.
What are the important sympathomimétiques to know?
noradrenaline: used to treat people with very low blood pressure
- nonselective agonist of all adrenergic receptors
adrenaline: EpiPens
- alpha-1 receptors
phenylephrine: decongestant
- post-synaptic alpha-adrenergic receptor
isoproterenol: used for the treatment of bradycardia
- non-selective β adrenoceptor agonist
ephedrine:
- direct and indirect sympathomimetic. It binds directly to both alpha and beta receptors
clonidine:
- α-2 adrenergic receptor agonist
salbutamol: Ventolin (used to relieve symptoms of asthma and chronic obstructive pulmonary disease)
- selective beta-2 adrenergic receptor agonist
What are the important sympatholytiques to know?
phentolamine: alpha-adrenergic antagonist activity
metoprolol: beta1-selective (cardioselective) adrenergic receptor blocking agent
