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Pharmacology > ANS cont'd > Flashcards

ANS cont'd Flashcards

1
Q

Phospholipase C system in heart

A
  1. Agonist activates alpha 1 and M3 receptors in smooth muscle
  2. Leads to activation of phospholipase C

3.Activates Ca release

  1. Activates Protein kinase
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2
Q

Adenylyl cyclase system in heart

A

1.Agonist activates either beta receptors OR alpha 2 and M2 receptors

  1. Leads to activation of adenylyl cyclase

3.Activates cAMP

  1. REsults in further activation of enzymes leading to increased contraction in heart (beta 1) and bronchodilation (beta 2)
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3
Q

What deactivates cAMP?

A

Phosphodiesterase (PDE3)
-will convert cAMP to AMP which is the inactive form

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4
Q

M3 of vascular endothelium

A
  1. Activated M3 on vascular endothelium, results in Ca Calmodolin release which acts on NO synthase to produce NO
  2. NO activates Guanylyl cyclase. Increasing cGMP causing relaxation

**deactivated by Phosphodiesterase converting cGMP into GMP

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5
Q

M3 of vascular smooth muscle activation

A

M3 receptor activation leads to Ca released in muscle, resulting in contraction

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6
Q

Viagra (sildenafil) as a phosphodiesterase inhibitor

A

-Works on vascular smooth muscle leading to the vasodilation of pulmonary arteries in pulmonary hypertension

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7
Q

Black widow spider venom

A

-Causes an increase in Ach release due to increased leakiness of vesicles into synapse

-will cause mild SLUD, and muscle twitching
*not usually deadly…usually from an allergy

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8
Q

Botulinum toxin

A

-Blocks exocytosis (release) of Ach vesicles= anticholinergic effect
**no systemic application! Many side effects!

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9
Q

Acetylcholinesterase

A

Acetylcholinesterase= OFF SIGNAL

-Cholinesterase inhibitors prevent off signal from occurring. Results in high levels of Ach present in the synapse= Cholinergic receptors are heavily acitivated

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10
Q

What occurs with high levels of Ach that cannot be removed due to acetylcholinesterase?

A
  1. SLUD
    salivation, lacrimation, urination, defecation
  2. Blue- extremely low heart rate
  3. Twitching
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11
Q

Cholinergic receptor agonists or antagonists

A

Either increase or decrease cholinergic receptors

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12
Q

Hemicholinium

A

-Inhibits Ach Synthesis from the broken down components of Ach (choline + acetate)

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13
Q

Adrenergic Neurotransmission

A

Associated with NE release into synapse which will bind to alpha and beta receptors

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14
Q

Metyrosine

A

Prevents the synthesis of NE

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15
Q

Amphetamine

A

Causes NE to leak out of nerve terminals

Results in excitation/stimulation (proadrenergic or indirect adrenergic agonist)

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16
Q

Bretylium

A

Prevents NE release

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17
Q

Cocaine

A

Blocks NE reuptake into the pre-synaptic neuron, resulting in accumulation of NE into the synaptic cleft

Increase HR, vasoconstriction, activated fight or flight response

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18
Q

Adrenergic receptor agonists or antagonists

A

-Either increase or decrease adrenergic alpha or beta receptors

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19
Q

Monoamine oxidase

A

Enzyme used to convert NE into metabolites
-antidepressants used to prevent it because increase serotonin production BUT will also result in higher levels of NE resulting in side effects

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20
Q

Neuromuscular junctions

A

Ach acts on Na channels
-Off signal=acetylcholinesterase

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21
Q

Acetylcholinesterase inhibitors

A
  1. Irreversible= insecticides

2.Reversible
- edrophonium

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22
Q

Tubocurarine or Pancuronium

A

Competitive antagonists for Ach at junction, preventing Ach effects on receptors
-Used when need flaccid paralysis (eg. orthopaedic procedures)

23
Q

Non selective (N=M) direct acting cholinergic

A

Acetylcholine
Carbachol

Non selective (equal at N and M receptors)

24
Q

Direct acting agonist nicotinic selective

A

Nicotine
-skeletal muscles and ganglion
-sympathetic and parasympathetic effects
-muscle twitching

25
Q

Direct acting agonists muscarinic selective

A

-muscarine (least used)
-bethanechol
-pilocarpine

Muscarinic selective
-used opthalmically or systemically for stimulating urination

26
Q

Non-selective cholinergic indirect acting agonists

A

Irreversible:
-organophosphate/carbamate insecticides

Reversible:
-edrophonium
-neostigmine

Equal between nicotinic and muscarinic
-accumulation of Ach; both parasympathetic and sympathetic stimulation
-SLUD

27
Q

Muscarinic selective cholinergic antagonists

A

-atropine
-ipratropium

-competes for Ach binding at muscarinic receptors. Used as preanesthetic drug to prevent secretions/drooling, treat insecticide poisoning

28
Q

Nicotinic blocker cholinergic antagonists

A

-hexamethonium
-trimethaphan

-block nicotinic neuronal more than nicotinic muscle receptors
-both parasympathetic and sympathetic systems.
-used in surgeries- cardiovascular for controlled hypotension
-cuts out baroreceptor keeping HR low

29
Q

Muscarinic blocker cholinergic antagonists

A

-tubocurarine
-pancuronium
-succinyl choline

-Selects for muscle nicotinic receptors over neural nicotinic receptors, and then muscarinic

30
Q

Amount of dose impact on various effects

A

At low dose:
-first see reduced salivation and low effect on urination inhibition

Moderate dose:
-higher effect resulting in decrease in salivation and urination
-increases HR
-Causes a decrease in eye accommodation (ability to see close)

High dose:
-max effect on decreased salivation, urination, and increased HR and accommodation

31
Q

Dose dependent effects of Ach SLIDE

A

Nicotinic receptors in autonomic ganglia

Low dose: not enough to cause much of an effect
High dose: effect on nicotinic autonomic ganglion

Muscarinic receptors in heart and GI
Low dose: Ach causes vasorelaxation, drop peripheral resistance, drop diastolic pressure. Will increase GI motility
High dose: Ach cannot antagonize effects from previously given atropine. Can see an increase in HR and BP showing sympathetic effects BECAUSE parasympathetic effects are being blocked by Atropine

**give atropine: long lasting. Antagonize muscarinic responses/parasympathetic effects

alpha and beta blockers: block alpha 1 in arterioles, beta in heart
-no effect on GI and autonomic ganglia nicotinic, but blocks muscarinic in heart

Hexamethonium- blocks nicotinic receptors so see decrease in autonomic ganglia

32
Q

Receptor selectivity of Epi

A

alpha1=alpha2
beta1=beta 2

33
Q

Receptor selectivity of NE

A

alpha 1=alpha 2

beta 1 more than beta 2

34
Q

receptor selectivity of Isopreterenol

A

beta1=beta2&raquo_space;alpha

35
Q

receptor selectivity of Dopamine

A

D1 (renal vasculature=dilation) > beta 1> beta 2> alpha

36
Q

receptor selectivity of Dobutamine

A

Beta1>beta 2> alpha

37
Q

receptor selectivity of Phenylephrine

A

alpha1 > alpha 2&raquo_space;beta

**predominantly vasoconstriction

38
Q

receptor selectivity of clonidine; xylazine

A

alpha2>alpha1&raquo_space;beta

39
Q

receptor selectivity of terbutaline

A

beta 2>beta 1&raquo_space;alpha

-predominantly bronchodilate= asthma

40
Q

receptor selectivity of Clenbuterol, salbutamol

A

beta 2 > beta 1» alpha

-predominantly bronchodilate= asthma

41
Q

receptor selectivity of Mirabegron

A

beta 3> beta 1&raquo_space;beta 2&raquo_space; alpha

**common in humans for overactive bladder treatment. Selective for detrusor muscle to relax body wall and make it harder to urinate
NOT efficient for animal use because beta 3 more equal to beta 1(side effects)

42
Q

Glaucoma

A

Condition of high intraocular pressure
-too much aqueous humour production
-impaired aqueous humour outflow

43
Q

Glaucoma Receptor involvement

A

-Muscarinic receptor stimulation increases aqueous humour outflow

-Beta adrenergic stimulation increases aqueous humour production

44
Q

Prazosin

A

-alpha antagonists
-alpha 1&raquo_space;»> alpha 2

45
Q

Phenoxybenzamine

A

-alpha antagonists
alpha 1 greater than alpha 2

46
Q

Phentolamine

A

-alpha antagonists
alpha 1=alpha 2

47
Q

Tolazoline, atipamezole

A

-alpha antagonists
alpha 2&raquo_space;alpha 1

-reversal agents

48
Q

Labetalol, carvedilol

A

-mixed antagonists
beta 1=beta 2 > alpha 1 > alpha 2

-used mostly in heart failure. Beta 1 antagonism to reduce heart issues. Alpha 1 receptor antagonism helps to reverse vasoconstriction

49
Q

Metoprolol, acebutolol, atenolol

A

beta antagonists

beta 1»> beta 2

-block effects in heart, and kidney (prevents renin release)

50
Q

Propranolol, timolol

A

-beta antagonists
beta 1=beta 2

-preferred beta blocker for controlling aqueous humour production, anti hypertension and anti arrhythmic

-Be careful!! Need beta 2 for asthmatics (need to prevent aggravation)

51
Q

NE on Heart

A

Peripheral Resistance:
-vasoconstriction
-large increase in peripheral resistance

Blood pressure:
-increase in diastolic pressure (due to increase in peripheral resistance)

Heart Rate:
Increase stretch from increase BP, increases baroreceptors: decrease sympathetic, increase vagal= total decrease in HR

52
Q

Epi on Heart

A

Peripheral Resistance:
-vasoconstriction, leading to increase in vasodilation to balance= decrease in peripheral resistance

BP:
-peripheral resistance decreased so diastolic decreases

HR:
Less stretch with baroreceptor=increase heart rate

53
Q

Isoproterenol on heart

A

Peripheral Resistance: vasodilation, leading to decreased resistance

BP:

HR:
-decreased baroreceptor stretch= increase sympathetic= increase in HR

54
Q

Dopamine on Heart

A

Peripheral Resistance: vasodilation leading to decreased resistance

BP: Increase systolic pressure, slight decrease in diastolic resistance

HR: decreased stretch=increase sympathetic= increase heart rate

Pharmacology (19 decks)

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