Applied ANS Flashcards
Provide examples of the Indirecting Anticholinesterase agents that are reversible.
Neostigmine
Pyridostigmine
Indirect acting irreversible Anticholinesterase agents.
Organo Phosphorus Compounds.
What are the signs of too much ACh?
SLUDE
salivation, lacrimation, urination, diarrhoea, gastric
DUMBELS - diarrhoea, urination, miosis, bronchoconstriction, skeletal excitation, lacrimation and salivation/sweating.
Describe how organophosphate poisoning works.
Drug binds covalently to cholinesterase enzyme. New enzyme has to be synthesised to restore cholinesterase activity which takes several weeks.
Describe Myasthenia Gravis
an autoimmune disorder, is characterized by weakness and fatiguability of skeletal muscles. It is caused by autoantibody mediated dysfunction at the NMJ.
SIgns of Myasthenia Gravis.
Drooping eyelid
included diplopia, ptosis and dysarthria (oculobulbar form)
How can diagnose Myathenia Gravis?
Dx can be confirmed by using neostigmine (in South Africa) Edrophonium (short acting, reversible anticholinesterse).
What is the treatment of Myasthenia Gravis?
Pyridostigmine/neostigmine used in mild to moderate disease
How do you treat cholinergic side effects–> Cholinergic Toxidrome?
anticholinergic drug/cholinergic antagonist. (Such as glycopyrollate).
How does Clonidine (antihypertensive) work?
lowers BP by binding to presynaptic alpha 2 receptors with inhibition of the release of NA (which acts are vasoconstrictor).
Describe the effects of the inhibition of the release of ACh from vesicles.
Inhibition of sweating, giving symptoms of a dry, warm skin
Inhibition of salivation with symptoms of dry mouth
Pupillary dilatation
Provide examples of aminoglycosides that can inhibit the release of ACh on from the vesicles.
Streptomycin and neomycin
What are the sides effects of aminoglycosides and where is it contraindicated?
NMBlockade and respiratory paralysis, especially if given soon after anaesthesia or muscle relaxants.
In Myasthenia Gravis
How does Botox work?
blocks release of ACh at sweat glands (reduced sweating), and at NMJ (muscle paralysis)
What is the deadly triad of organophosphate poisoning?
BBB
Bronchorrhoea
Bronchoconstriction
Bradycardia
How does the inactivation of ACh occur?
cholinesterase
suxamethonium
Explain the effects Suxamethonium.
It is a muscle relaxant, that blocks the depolarization of the cells.
What is used to inactivate the suxamethonium?
Butyrylcholinesterase also called pseudocholinesterase found in liver, brain and GIT.
Describe Atropine.
Tertiary amine with competitive binding to muscarinic receptors
Treatment of organophosphate poisoning
Antispasmodic, antisecretory, mydriasis and cycloplegia
Describe glycopyrrolate.
Quaternary amine, preoperative medication
Ophthalmology to produce mydriasis and cycloplegia
Used in perioperative medicine to prevent secretions, bronchoconstriction and bradycardia
Describe Ipratropium Bromide.
cholinergic stimulation causes bronchospasm, therefore anticholinergic acts as bronchodilator
Describe Oxybutinin.
cholinergic stimulation of bladder leads to detrusor muscle contraction, therefore blocking cholinergic stimulation will have urinary antispasmodic effect.
What is the side effects of Imipramine (TCA)?
strong antimuscarinic action, reduced bladder contraction, reduces incontinence
Examples of drugs that are Antimuscuranic
M1-selective: Pirenzepine
Non-selelctive-atropine
Examples of drugs that are antinicotinic.
Ganglion blockers- hexamethonium
Neuromuscular blockers- tubocurarine
Example of the cholineterase regenerators.
Oximes-pralidoxime
Describe gluacoma.
Glaucoma refers to a group of eye disease causing loss of visual acuity from damage to the optic nerve, secondary to raised Intraocular pressure. (from obstructed/ineffective drainage of acqueos humor)
Describe acute closed angle glaucoma.
acute onset blockage to flow and drainage of acqueus humor is caused by the iris itself. Angle between cornea and iris is abnormally small, occasionally it closes completely
Describe the treatment of acute closed angle glaucoma.
Timolol a beta 2 receptor antagonist
it blocks B-2 receptors on the ciliary processes , binding to them causes vasoconstriction (blocks vasodilation) of the vessels supplying the ciliary process, with reduced ultrafiltration and acqueus formation
Describe the chronic open angle glaucoma.
gradual onset of blockage of drainage channels of eye, with a gradual increase in IOP.
Treatment centres around lowering intraocular pressure by improving drainage or decreasing aqueous secretion. . Management can be medical with topical agents, or if this fails surgical.
Describe Pilocarpine and its role in treating glaucomas
Direct acting cholinergic agonist.
direct acting cholinergic drug acting as agonist at muscarinic receptors in eye causing pupil constriction) reduce IOP by contracting the ciliary muscle. This pulls the sclera spur and result in the trabecular meshwork being stretched and separated. The fluid pathways are opened up and aqueous outflow is increased. Used in acute closed and chronic open angle glaucoma.
In which 3 ways does Sympathomimetics react?
Indirectly by enhancing release of NE/catecholamines from vesicles.
Direct acting. Directly activate the adrenoceptors mimicking the action of NA/A. This category includes catecholamine and non-catecholamines. Examples of non-catecholamines are alpha 1 and 2 agonist, beta agonists. Catecholamines can be endogenous (NE, E, Dopamine) or synthetic.
Mixed acting , acts both directly and indirectly.
Describe Ephedrine.
Mixed acting Adrenergic agonist.
Acts directly on alpha and beta receptors
Causes release of endogenous NE
Used in nasal decongestants
HPT, Arrythmias, Insomnia.
Describe adrenaline
Alpha 1 receptor activation - peripheral vasoconstriction
Beta 1 receptor activation - inotropic effect
Beta 2 receptor activation - Bronchodilation
Lower doses - predominantly Beta, higher doses - alpha effects.
Describe Noradrenaline.
Both alpha 1 and beta 1 receptors
Potent Vasoconstriction
Modest increase in C.O
Net effect = Increase BP; preferred vasopressor in septic shock.
Describe Dopamine.
Low doses - D receptors -renal, mesenteric, cerebral and coronary vasodilation
Mod. Doses - Beta-1 - inotropic effect
High Doses - Alpha 1 - vasoconstriction and increased SVR.
Describe the topical uses of epinephrine
Adjunvant of local anaesthesia
bleeding.
Describe the systematic uses of epinephrine.
Cardiac arrest
anaphylactic shock
acute bronchial asthma
Examples of indirect Adrenergic agonist.
Cocaine
Amphetamine
Tyramine
Adrenergic Antagonists.
α blocker
Doxazosin - selective α1
(hypertension, benign prostatic hyperplasia)
β blockers
Propranolol (Non-selective - B1 and B2)
Atenolol (β1 selective) – ischaemic heart disease and hypertension
Both α and β blockers
Carvedilol (hypertension, congestive heart failure)
Labetalol (hypertensive crisis)
Drug that (used to treat hypertension - mostly due to antiadrenergic effects) blocks to the VMAT2 with a slow rate of dissociation and prolonged duration of action. Leading to reduced uptake, and stores of NA, less adrenergic effect, so decreased BP.
Reserpine
Which adrenergic agonist is used for septic shock?
NE
Which adrenergic agonist is used for anaphylactic shock?
E
Arrange the effects of adrenaline on different adrenergic receptors.
A1-2
A2-1
B1-4
B2-3
Arrange the effects of noradrenaline on different adrenergic receptors.
a1-4
a2-1
b1-2
b2-1
Arrange the effects of phenlyphrine on different adrenergic receptors.
a1-4
a2-1
Arrange the effects of dobutamine on different adrenergic receptors.
a1-1
a2-0
b1-4
b2-2
oxymetazoline
stimulates alpha 1 receptors in nasal mucosa and eye, causing vasoconstriction for relief of nasal congestion and ocular erythema. Worth noting that many agents that are alpha 1 - agonist have at least some mixed alpha and beta-agonistic activity
Phenylephrine
PEP is selective for Alpha 1 receptors (virtually no Beta activity - no effect on cardiac inotropy or chronotropy) - causing peripheral vasoconstriction and raising BP. Also used in nasal decongestants
Clonidine
stimulates alpha 2 receptors in brain stem which has inhibitory effect on sympathetic outflow from CNS (responsible for negative feedback loop with resultant reduced NE release). Reduced sympathetic outflow leads to decrease in heart rate and blood pressure.
Methyldopa
similar to clonidine, centrally acting anti-hypertensive.
Dobutamine
Synthetic analogue of dopamine. used primarily for cardiogenic shock (when cause of shock related to pump failure). Primarily stimulates beta 1 receptors in myocardium resulting in increased contractility (inotropic) > heart rate (chronotropic), without any vasoconstriction.
salbutamol and salmeterol
used in treatment of asthma. Mechanism of action is bronchodilation via B2 receptor stimulation. Salbutamol also used in the prevention of preterm labour by reducing uterine contractions.
Amphetamine Synaptic mechanism
Slide 35
Tyramine mechanism
cheese effect- slide 36
Carvedilol
(hypertension, congestive heart failure)
Both beta and alpha
What is the problem with propanalol in asthmatic patients?
Non- selectivity of certain beta antagonist drugs is responsible for side effects - bronchospasm (when affecting B2 receptor in bronchial smooth muscle) - avoid in asthmatics.
Doxazosin.
alpha 1- are also used to treat hypertension.
Block alpha 1 receptor (normally causes vasoconstriction) leading to vasodilation.
How does Tamsulin overcome urinary retention in BNP?
Alpha 1-
Blockage of alpha receptors in prostate and bladder neck lead to muscle relaxation to overcome urinary retention related to BPH
Antenalol
β1 selective) – ischaemic heart disease and hypertension
Labetalol
Hypertensive crisis
Timolol in Glaucoma
a beta 2 receptor antagonist, it blocks B-2 receptors on the ciliary processes , binding to them causes vasoconstriction (blocks vasodilation) of the vessels supplying the ciliary process, with reduced ultrafiltration and acqueus formation. Used to manage open angle glaucoma (acute).
Pilocarpine in glaucoma.
(direct acting cholinergic drug acting as agonist at muscarinic receptors in eye causing pupil constriction) reduce IOP by contracting the ciliary muscle. This pulls the sclera spur and result in the trabecular meshwork being stretched and separated. The fluid pathways are opened up and aqueous outflow is increased. Used in acute closed and chronic open angle glaucoma.
imipramine
TCA with strong antimuscarinic action, reduced bladder contraction, reduces incontinence
