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PHA3112 - pharmacology > Autonomic Nervous System Drugs > Flashcards

Autonomic Nervous System Drugs Flashcards

Cholinergic and Adrenergic Drugs

1
Q

PNS Effects: SLUDGE

A

S - salivation
L - lacrimation
U - uresis (urination)
D - diaphoresis/ diarrhea
G - GI motility/ secretions
E - emesis

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2
Q

SLUDGE and the Killer Bs (+)

A

S - salivation
L - lacrimation
U - urination
D - diaphoresis/ diarrhea
G - GI motility/ secretions
E - Emesis

B - brady cardia
B - Bronchospasm (constriction)
B - Bronchorrhea - bronchi sec

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3
Q

Alpha Methyl Tyrosine

A

Adrenergic Synthesis Inhibitor
= dec sympathetic effects

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4
Q

Risperidone

A

Inhibition of adrenergic storage
= dec sympathetic effects

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5
Q

Amphetamines

A

Adrenergic displacement
= increased sympathetic action

Use: stimulation of CNS (improved mood, concentration)

Adverse Effects: insomnia, irritability, psychosis, anorexia, tachycardia, dependence, tolerance

Treatment of toxicity: acidification of urine

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6
Q

Guanethidine

A

Inhibits adrenergic release
= decreased sympathetic action

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7
Q

Dobutamine

A

Beta-1 adrenergic agonist
= increased sympathetic action

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8
Q

Metroprolol

A

Beta-1 adrenergic antagonist
= blocks sympathetic action (decreased)

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9
Q

Cocaine, Tricyclic Antidepressants

A

Adrenergic reuptake inhibitors
= increased sympathetic effects

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10
Q

Pargyline

A

Adrenergic MAO inhibitor –> sympathomimetic
= increased sympathetic effects

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11
Q

Muscarine

A

Muscarinic Receptor Agonist
(found in mushrooms - Amanita muscaria, Inocybe, Clitocybe)

effects: SLUDGE+
a. heart = bradycardia
b. exocrine glands = inc sweating, salivation, bronchial sec, sec of gastric acid
c. smooth muscle = contraction of bronchi, motility of GI smooth muscle, contraction (= defecation) of detrusor muscle of bladder + relaxation of trigone and sphincter (= urination), vasodilation (= dec BP)
–> overstimulation of muscles with ACh paralyzes them
d. eyes = miosis and accommodation

Treatment Atropine (Muscarinic receptor antagonist)

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12
Q

Treatment for Muscarine

A

Atropine

(antagonist blocks the agonist’s effects)

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13
Q

Neostigmine, Physotigmine, Edrophonium

A

AChE Inhibitors - temporarily inactivates AChE resulting in increased ACh levels in synapse
–> indirect cholinergic agonists (cause ACh levels to remain high = agonist-like effects)

Effects: SLUDGE +
–> overstimulation of muscles with ACh paralyzes them

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14
Q

Edrophonium

A

short-acting, reversible inhibitor of AChE
–> can be used to differentiate between a
cholinergic crisis and severe symptoms
of myasthenia gravis

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15
Q

If Edrophonium is administered and muscle paralysis/ weakness symptoms intensify, the crisis is _____

A

cholinergic (dose of Edrophonium is too high)

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16
Q

if Edrophonium is administered and the muscle paralysis/ weakness symptoms decrease, the crisis is _____

A

myasthenic (dose of Edrophonium is too low to have a therapeutic effect)

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17
Q

Echothiopate, insecticides, nerve gasses

A

long-acting, irreversible inhibitor of AChE –> permanently bound to the enzyme

Treatment: Pralidoxime

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18
Q

Pralidoxime

A

Treatment for long-acting, irreversible inhibitors of AChE
***can treat source of the AChE inhibitor, effectively inducing AChE breakdown and resolving associated SLUDGE symptoms, but CANNOT reverse paralysis of muscles resulting from receptor overstimulation
- oxygen used for diaphragm paralysis
- diazepam used for seizures

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19
Q

Clinical use of Edrophonium

A

Myasthenia Gravis - chronic autoimmune disease linked to Nm receptors
- muscles do not contract in response to normal levels of ACh release (muscle weakness)
- by inactivating AChE, more ACh is available to stimulate the receptors and encourage muscle contraction (inc muscle strength)

Paralysis induced by non-depolarizing neuromuscular blocks

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20
Q

Contraindications for Muscarinic Agonists/ AChE inhibitors

A

GI/ Urinary Obstructions - SLUDGE effects result in increase secretion and excretion (bad if there’s no route to exit)

Asthma - SLUDGE+ effect is bronchospasm (dangerous if bronchi are already constricted)

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21
Q

Cholinergic Crisis

A

characterized by excessive muscarinic stimulation and depolarizing neuromuscular blockage –> resulting in muscle weakness or frank paralysis
- SLUDGE+ symptoms - inc salivation, lacrimation, urination, diaphoresis, diarrhea, GI motility/ secretions, emesis, bronchospasm, bradycardia, bronchorrhea
- Nm overstimulation - muscle weakness, paralysis, twitching (risk of paralysis via apnea)

Risk of Myasthenia Gravis treatment with AChE inhibitors
–> overstimulation of muscular receptors can result in same muscle weakness/ paralysis effects (need to differentiate)

22
Q

Atropine

A

Muscarinic Antagonist
(derived from the plant Atropa belladonna)

Effects: OPPOSITE of SLUDGE+ (more SNS)
- increased HR and force of contraction = tachycardia
- decreased GI secretions and motility
- dilation of the bronchi
- mydriasis (pupil dilation
- cycloplegia (loss of accomodation)

23
Q

Muscarinic Antagonist Uses

A

purposes OPPOSITE of SLUDGE+
a. reduce urinary incontinence (relax bladder, contract sphincter
b. dec hypermobility of GI tract
c. pre-op/palliative care (reduce secretions)
d. eye exam/ surgery (dec lacrimation, mydriasis)
e. treatment of muscarinic poisoning (AChE inhibitors/ muscarinic agonists)
f. treatment of asthma (bronchodilator)

24
Q

Muscarinic Antagonist Adverse Effects

A

related to effects OPPOSITE of SLUDGE+
a. xerostomia (dry mouth d/t dec salivation)
b. Anhidrosis (lack of sweat)
c. urinary retention, constipation (bladder relaxation, sphincter contraction, dec GI mobility/ secretions)
d. burry vision, photophobia (mydriasis, cycloplegia)
e. psychosis, delirium (high doses excite CNS)

25
What plant is atropine derived from?
Atropa belladonna *** think atropine block's parasympathetic effect of miosis and accommodation, results in mydriasis associated with beauty (prob people couldn't see anymore)
26
Scopolamine
Muscarinic Antagonist --> specifically an antiemetic (reduces excessive secretions)
27
Neuromuscular Blockers
block nicotinic receptors on skeletal muscle (Nm) --> induces paralysis *** need to block minimum 70% of receptors to paralyze muscles (not all muscles have the same sensitivity) Uses: a. relaxation during surgery b. Endotracheal intubation, mechanical ventilation Adverse effects: a. excessive paralysis can result in cessation of breathing (if diaphragm is paralyzed) **AChE can reverse the effects of competitive antagonism (derivatives of curare) but will intensify the effects of succinylcholine
28
Types of Neuromuscular Blockers (2)
a. Non-depolarizing blockers (completive inhibitors) b. Depolarizing blockers (does not competitively block --> overstimulates)
29
Tubocurarine, Rocuronium, Citraturia
*derivatives of curare* compete with ACh for binding to muscle nicotinic (Nm) receptors - blockage of muscle contraction only occurs after more than 70% of receptors are blocked = paralysis - AChE inhibitors can reverse the effects of competative antagonism by increasing ACh levels (but will intensify the drugs that overstimulate Nm receptors - ie. Sux) ** fast twitch muscles are more sensitive than slow twitch muscles
30
Succinylcholine
"Sux" --> derivative of choline, acts like ACh - acts by overwhelming receptors until they become inactivated --> paralysis - short acting --> plasma cholinesterases break down Sux in the blood stream since its a choline derivative Adverse effects: can trigger Malignant Hyperthermia (MH)
31
Malignant Hyperthermia (MH)
potential risk of depolarizing blockers (Succinylcholine) - excessive muscle contractions general dangerous heat levels in the body - symptoms: high temp, rigid muscles/ spasms, rapid HR Treatment: Dantrolene
32
Dantrolene
Treatment for Malignant Hyperthermia - blocks calcium release from intracellular sarcoplasmic reticulum stores in skeletal muscles --> muscles cannot contract without calcium efflux (no contraction, no heat generated, heat decreases)
33
Catecholamines
- noradrenaline (NA) - norepinephrine (NE) - adrenaline (A) - epinephrine (E) - dopamine (DA)
34
Adrenaline/ Epinephrine
uses: - treatment of anaphylactic shock (combats broncospasm, vasodilation, leady bloodvessels and edema associated) - cardiac arrest (inc return of venous supply and inc HR) - controls bleeding of superficial cuts (vasoconstriction) - limits diffusion of meds injected into tissues (vasoconstriction) Caution: - arrythmias - inc HR, force of contraction - hypertension - inc vasoconstriction, inc contraction force - diabetes - inc blood glucose levels glycolysis + neogenesis
35
where does epinephrine/ adrenaline bind?
Alpha 1, Alpha 2, Beta 1, Beta 2 NOT dopamine
36
Where does norepinephrine/ noradrenaline bind?
Alpha 1, Alpha 2, Beta 1 NOT Beta 2
37
Phenylephrine
stimulates alpha 1 receptors (point and shoot - vasoconstriction and contraction) Uses: a. control superficial bleeding - vasoconstriction b. reduce congestion - vasoconstriction + reduced nasal secretions c. mydriasis - pupils dilate d. treat hypotensive emergencies - vasoconstriction Adverse Effects: excessive increase in BP if already high
38
Clonidine
stimulates alpha 2 receptors (negative feedback - reduced NA release = decreased SNS action) Uses: antihypertensive (vasodilation) Adverse Effects: hypotension (excessive vasodilation + already low BP = even lower BP), dry mouth (dec salivation), sedation
39
Dobutamine
stimulates beta 1 receptors (1 heart + kidneys) Uses: treatment of acute heart failure (increases HR and force of contraction) Adverse Effects: arrythmias, increased HR (tachycardia)
40
Salbutamol (Ventolin)
stimulates beta 2 receptors (2 lungs, relaxation and metabolic effects) Uses: relieves asthma by bronchospasm (bronchodilation) Adverse Effects: palpitations (increased HR + force of contraction), hyperglycemia (glycolysis, gluconeogenesis increases blood sugar), tremors
41
Mirabegron
stimulates beta 3 receptors (relaxation, metabolic effects) Uses: urinary urgency/ incontinence (relaxation of the bladder's detrusor muscle, prevents unnecessary contraction) Adverse Effects: tachycardia (inc HR + force of contraction), inc blood pressure (inc force of contraction)
42
Isoproterenol
can exert effects on beta 1 or 2 receptors --> effect depends on which tissues have which receptors
43
Ephedrine, Pseudoephedrine
indirectly acting sympathomimetics - displacement drug --> taken up by NA/NE reuptake transporter and stimulate the release of stored noradrenaline/norepinephrine from vesicles has displacer and agonist effects used for the treatment of nasal congestion
44
Prazosoin, Terazosin, Doxazosin
Alpha 1 antagonists (reduces vasoconstriction, contraction, point and shoot) Use: treatment of hypertension Adverse Effects: orthostatic hypertension with a reflex increase in HR
45
Yohimbine
alpha 2 antagonist (reduces negative feedback effect --> inc SNS effect) Use: erectile dysfunction, "fat burning" (lipolysis) Adverse Effects: tachycardia, hypertension, hyperglycemia
46
Phentolamine
non-specific alpha antagonist --> reversible Action: can either increase (A2) or decrease (A1) normal SNS action depending on the receptor it binds to Use: treatment of noradrenaline-secreting tumor
47
Phenoxygenzamine
non-specific alpha antagonist --> irreversible Action: can either increase (A2) or decrease (A1) normal SNS action depending on the receptor it binds to Use: treatment of noradrenaline-secreting tumor
48
name for noradrenaline-secreting tumor
pheochromocytoma
49
Metoprolol, Atenolol, Bisoprolol
beta 1 antagonist action: dec HR and cardiac contractility, dec secretion of renin, dec activation of renin-angiotensin-aldosterone system --> dec BP Use: angina, hypertension, heart failure, post MI, arrythmia, stage fright, anxiety, migraine prophylaxis Adverse Effects: bradycardia, heart failure, hypotension, sedation, lethargy, erectile dysfunction, nightmares
50
Beta 2 Antagonist Adverse Effects
bronchoconstriction, inhibition of hepatic glycogenolysis, inhibition of lipolysis, sedation, erectile dysfunction, nightmares
51
Propranolol
unwanted blockage of beta 2 receptors

PHA3112 - pharmacology (7 decks)

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