5. Autonomic Nervous System 2 Flashcards
What are the 2 things that mimic parasympathetic effects?
- Muscarinic receptor agonists (direct acting; carbachol, pilocarpine)
- Acetylcholinesterase inhibitors (indirect acting; these drugs delay the breakdown of ACh and prolong its action) neostigmine
What are the 2 things that block parasympathetic effects?
- Muscarinic receptor antagonists (atropine)
2 skeletal neuromuscular junction blockers (D-tubocurarine)
Why are the 4 uses of cholinergic agonists?
- Reduce intraocular pressure in wide angle glaucoma- also uses in narrow angle glaucoma (miosis)
- Increase the motility (peristalsis) of the gastrointestinal (GI) tract
- Increase motility of the urinary tract (bladder contractions)
- To increase salivary secretions-
What are cholinesterases?
Two types?
Acetylcholinesterase (AChE) present in synaptic cleft on the outer membrane of postjunctional cell
Hydrolyzes ACh and the enzyme becomes acetylated
Butyrylcholinesterase (BuChE)- located at non-neuronal sites, mainly in plasma and liver
Metabolizes certain drugs (some anaesthetics and succinylcholine muscle relaxant)
What are cholinesterase inhibitors?
Increase the duration of action of the released ACh and potentiate responses at muscarinic and skeletal neuromuscular nicotinic receptors
What are the 3 chemical reactions of cholinesterase inhibition and their clinical significance?
Compounds that bind to cholinesterase can produce one of 3 chemical reactions;
Acetylation- caused by ACh: acetylated enzyme-recovers rapidly
Carbamylation (reversible therapeutically used drugs)- carbamylated enzyme- recovers slowly
Phosphorylation (irreversible-poisons the enzyme ex: nerve gases)
Slide 46-48 autonomic nervous
What are the therapeutic uses of reversible ChE inhibitors?
Glaucoma- ups aqueous humor outflow down intraocular pressure (can cause cataracts with long term use)
CNS- treat memory loss of Alzheimer’s disease
Intestine- to stimulate peristalsis in post operative ileus, congenital megacolon
Urinary bladder- to treat urinary retention due to atony og smooth muscle
What is botulinum toxin?
Toxin released by the bacteria clostridium botulinum
Botulinum toxin blocks ACh release
It is used to paralyze skeletal muscle in cases of excessive involuntary skeletal muscle tone
Clinical uses: BOTOX to remove facial wrinkles
What are the uses of Muscarinic receptor antagonists for the; Heart Eyes GI tract Urinary bladder
Heart- to treat severe bradycardia
Eyes- cause pupil dilation (mydriasis) (for examination of retina)
GI tract- to treat excessive peristalsis (motility) of irritable bowel syndrome, cramping
Urinary bladder- treat 4 major symptoms of urinary incontinence: daytime urinary frequency, nocturia, urgency, and incontinence
What is the difference between scopolamine and atropine?
Scopolamine is well absorbed orally, and also reaches the brain more readily than atropine
Scopolamine is approx 10 times more potent at producing CND effects
Greater fraction of scopolamine is present in a unionized form at physiological pH than atropine - facilitates it’s absorption through skin
Scopolamine is used for motion sickness as transdermal patch
What are the 2 types of neuromuscular junction blockers?
Structure?
Competitive- competitively antagonize the actions of ACh at nicotinic acetylcholine receptors
Chemical structure different than that of ACh
Depolarizing agents- drug occupies and activates the nicotinic receptor (agonists) for a prolonged period of time, prevents repolarization and makes the muscle fibre refractory to further nerve impulses
Chemical structure resembles that of ACh
What is the competitive neuromuscular junction blockers sequence of muscle paralysis?
Produce motor weakness leads to flaccid paralysis when 90-95% receptors occupied
Small rapidly moving muscle paralyzed first- eyes, jaw, larynx
Muscles of the limbs, trunk
Intercostal muscles
Diaphragm- respiration stops
Recovery occurs in reverse
What do ChE inhibitors do?
Up in ACh
Used clinically to reverse neuromuscular block caused by competitive inhibitors
What are the 3 main side effects of competitive neuromuscular blockers?
Ganglionic blockade- fall in blood pressure, tachycardia
Block of vagal responses
Histamine release- bronchospasm, hypotension, up in bronchial and salivary secretions
What do depolarizing neuromuscular junction blockers do?
Bind to and activate muscle nicotinic receptors
Not metabolized by AChE
Causes persistent receptor stimulation
Succinylcholine- short duration of action
Rapid hydrolysis by plasma butyrylcholinesterase
Used in surgical anaesthetics to obtain relaxation of skeletal muscle, particularly in abdominal wall!!
What are the side effects of depolarizing neuromuscular junction blockers?
Depolarizing agents can release K+ rapidly from intracellular sites Cause hyperkalemia (dangerous in heart failure patients in diuretics) rhabdomyolysis and cardiac arrest
Malignant hyperthermia
Depolarization blockers should be avoided in patients with soft tissue trauma or burns
Not given to children under 8
What is malignant hyperthermia?
Seen after certain anaesthetics and neuromuscular blockers (succinylcholine)
Can be life threatening
Ups Ca2+ release from the sarcoplamsic reticulum of skeletal muscle
Contracture, rigidity, heat production from skeletal muscle, hyperthermia, accelerated muscle metabolism, metabolic acidosis, and tachycardia
What are the 4 things that mimic sympathetic effects?
- Adrenergic receptor agonists (direct acting)
- Norepinephrine uptake blockers (indirect acting)
- Monoamine oxidase and COMT inhibitors (these drugs delay the breakdown of NE and prolong its action)
- NE releasing agents (from nerve terminal, indirect acting) mean
What is the one thing that can block sympathetic effects?
Adrenergic receptor antagonists
How do you terminate norepinephrine action at the synapse?
Reuptake into nerve terminal
Released transmitter is taken up back into presynaptic nerve terminal
Uptake 1 can be blocked by several drugs including cocaine
Uptake 1 blockers will increase sympathetic activity
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What is the heart response in change of blood pressure?
Baroreceptor control of blood pressure and heart rate. SNS, sympathetic nervous system, PNS, parasympathetic decoys system
SLIDE 73 oct 3
What are adrenergic receptor agonists?
3 Types, what each type activates
Epinephrine- equipotent at α and β receptors
NE- can activate α and β1 receptors, has little activity at β2 receptors
(Is a little less potent than epinephrine at α receptors)
Dopamine too
What is epinephrine and norepinephrines effect on;
Heart rate?
Blood pressure?
Peripheral resistance?
Epinephrine:
Heart rate- raises it
Blood pressure- if high already it will raise it, if low already it will lower it
Peripheral resistance- drops it
Norepinephrine:
Heart rate- lowers it (reflex bradycardia)
Blood pressure- raises it
Peripheral resistance- raises it
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What are the 3 therapeutic uses of adrenergic drugs (agonists)?
Allergic reactions- anaphylactic shock (epinephrine EPIPEN) increases heart rate and contractility, constricts some and dilates some vessels to maintain BP
Bronchodilators (asthma)- albuterol, a β2 agonist
As pressor agents (hypotension)- Epi or NE (hypovolemic shock)
