lecture 7: Introduction to CNS medications Flashcards
The Neurotransmitter released from preganglionic parasympathetic to postganglionic parasympathetic is X and received by Y receptors
X: Ach
Y: Nicotinic (Nervous)
The adrenal gland receives the X neurotransmitter through its Y receptors
X: Ach
Y: Nicotinic
The Main neurotransmitter at a neuromuscular junction is X and received by Y receptors
X: Ach
Y: Nicotinic (Muscular)
Postganglionic sympathetic neurons release X which which is received by Y receptors
X: Norepinephrine
Y: Adrenergic receptors
the 4 types of Adrenergic receptors
α1 / α2 / β1 / β2
Muscarinic receptors are found on?
Effector organs Being parasympathetically innervated AND sweat glands (where Ach come from sympathetic neuronal release)
The Adrenal gland is sympathetically/parasympathetically innervated?
Sympathetically
The Adrenal gland is stimulated by X (category Y), received by Z receptors
X: Ach
Y: Sympathetic
Z: Nicotinic
Nicotinic and muscarinic are subtype of X innervation
Cholinergic
The 6 common types of neurotransmitters in the nervous system:
- Norepinephrine
- Ach
- Dopamine
- Serotonin
- Histamine
- Aminobutyric Acid
epinephrine is synonymous to…
Adrenaline
Nerve fibers secreting Epinephrine are called
Adrenergic
the Adenylyl cyclase pathway is activated by what type of G-protein?
Gs (has 3 subunits: α, β, γ)
The phospholipase C pathway is activated by which type of G-protein?
Gq (has 3 subunits: α, β, γ)
The 4 adrenergic receptor’s most common location?
α1 : Smooth muscle
α2 : GI
β1 : Cardiac tissue
β2: Smooth muscle
α1 receptors are X receptors, stimulated by Y and are excitatory/inhibitory in nature, acting through Gz protein pathway.
X: adrenergic
Y: norepinephrine
excitatory
Z: q
α2 receptors are X receptors which are excitatory/inhibitory in nature, acting through Gy protein pathway.
X: adrenergic
inhibitory (causing GI relaxation)
Y: i
β1 receptors are X receptors, stimulated by Y and are excitatory/inhibitory in nature, acting through Gz protein pathway.
X: adrenergic
Y: norepinephrine & epinephrine
excitatory
Z: s
β2 receptors are excitatory/inhibitory found on smooth muscles
inhibitory
Choline is taken into the neuron through what type of transport?
Cotransport with Na+ (energy required)
What blocks Choline Cotransport into the neuron?
hemicholinium
How do botulinum toxin and spider venom affect Ach vesicles?
Botulinum blocked vesicles releasing
Spider venom enhaces it (dramatically)
Nicotinic Ach receptors are mostly found?
In Ganglia & Neuro-muscular plate (& adrenal gland)
What category do nicotinic receptors belong to?
ligand-gated ion channel (requiring 2 Ach for conformational change)
the Major draw back of cholinergic agonists, limiting their clinical usefulness is?
They show little specificity (enhance Ach action EVERYWHERE).
Ach is therapeutically of no importance. why?
1- Multiplicity of Actions
2- Rapid inactivation by the cholinesterases
The major innervation system of the heart is Sympathetic/parasympathetic?
Parasympathetic
How does Ach lead to vasodilation?
Ach –> M3 receptors on smooth muscles –> production of NO –> stimulation of Protein Kinase G –> hyperpolarization & relaxation of vascular smooth muscles.
How does Atropine counteract Ach?
Atropine is a muscarinic receptor blocker
The main effects of Ach? (7)
- Decreased BP
- Vasodilation
- Increased salivary secretions
- Increased intestinal secretions and motility
- Enhanced bronchiolar secretions
- Increased tone of detrusor muscle, expulsion of urine
- Miosis (constriction of pupil)
- sweating (as part of glandular stimulation)
What type of activity does Betanechol have?
Muscarinic activity (on GI mainly ; ineffective on muscles and ganglia). This mean Betanechol doesn’t access the CNS
What’s the main therapeutic use of Betanechol?
used for non-obstructive urinary retention (she5 w 5ra).
Urination after anesthesia is the step that allows us to check the effect is over. Betanechol may be used to stimulate urination.
What type of activity does Carbachol have?
Both muscarinic & nicotinic actions (it reaches the CNS (its side-effect))
What are the main systems affected by Carbachol?
- Cardiovascular
- GI system
Because of ganglion-stimulating activity: It first enhances the systems through nicotinic activity then represses them through muscarininc activity.
How does Carbachol affect its systems? (long)
First its enhances them (GI & cardiac) through its nictotinic activity (causing postganglionic sympathetic to release Norepinephrine (also from adrenal glands)) then inhibits them (muscarinic activity acting on organs receptors (mimicing parasympathetic innervation)).
what’s the therapeutic usage of Carbachol?
treatment of glaucoma & increased intraoccular pressure.
Does Carbachol reach the CNS?
Yes, it has a ganglion-stimulating activity. Which is why its usage is limited to the eye (not absorbed there)
What type of activity does Carbachol have?
Both Nicotinic & Muscarinic activity (starts with nicotinic and ends with muscarinic)
What is Pilocarpine most therapeutically used for?
Drug of choice for emergency lowering of intraoccular pressure.
what’s the drug of choice for emergency lowering of intraoccular pressure.
Pilocarpine. By opening the trabecular meshwork around schlemm’s canal, increasing drainage of aqueous fluid.
What is Xerostomia/ how is it treated?
it’s intense dryness of the mouth due to lack of salivation. Pilocarpine is administered to induce salivation.
What are the main effects of Pilocarpine?
What are the side effects?
- Potent stimulator of secretions (sweat, saliva, tears)
- Myosis
The side effects is its ability to reach the CNS, causing disturbances (amnesia, etc..)
How do Anticholinesterases enhance Ach activity?
They inhibit Ach degradation, increase its stay thus its activity (can reach CNS).
Describe the activity of Physostigmine
Reversible binding to Acetylcholinesterase, causing potentiation of cholinergic activity in the body (nicotinic, muscarinic)
The main effects of Physostigmine?
Mainly used for treatment of overdoses of drugs with anticholinergic activity (such as Atropine (anti-muscarinic), phenothiazines & tricyclic antidepressants)
along with..
- increased intestinal & bladder motility
- Miosis, lowering of intraoccular pressure
Give 3 Anticholinergic drugs
Atropine, phenothiazines & tricyclic antidepressants
In the case of an anti-cholinergic drug abuse, what’s you treatment of choice?
Physostigmine (an anticholinesterase)
The main side effects of Physostigmine?
- Hypotension
- Bradychardia
What is Neostigmine usually used for? (2)
- Antidote for tubocurarine and other neuromuscular blocking agents.
- Treatment of Myasthemia gravis (auto-immunedegradation of nicotinic receptors at neuromuscular junction).
What is the drug most similar to neostigmine?
Physostigmine. Difference is that Neostigmine doesn’t reach CNS.
Describe the activity of Echothiophate
irreversible / covalent binding to the active site of acetylcholinesterase, making the enzyme permanently inactivated.
What is Pralydoxime?
It’s the only know reactivator of Anticholinesterases after being bound to Echothiophate. Still has a short period of action before completly losing the enzyme.
What kind of receptors do sweat glands have? What molecule binds it? Does this happen when sympathetically/parasympathetically innervated?
sweat glands have muscarinic receptors stimulated by Ach released from SYMPATHETIC neurons (called sympathetic cholinergic innervation).
