SNS agonists Flashcards
1
Q
what are directly acting SNS agonists/ sympathomimetics (DASA) ?
A
mimics the actions of NA/A by binding to and stimulating adrenoreceptors
2
Q
alpha 1
A
PLC, IP3, DAG
3
Q
alpha 2
A
decreased cAMP
NA release inhibition
selectively targeted by clonidine to reduce sympathetic tone
4
Q
beta 1
A
increased cAMP
5
Q
beta 2
A
increased cAMP
6
Q
what are the principle target sites for DASAs?
A
CVS
eyes
lungs
7
Q
alpha 1 locations
A
eye liver trigone and sphincter ureter genitalia male lacrimal glands salivary glands skin GI
8
Q
beta 2 locations
A
trachea and bronchioles liver detrusor salivary glands genitalia female skeletal muscle
9
Q
name some beta 1 locations
A
heart
adipose
kidney
salivary glands
10
Q
how does noradrenaline selectivity change for the adrenoreceptors?
A
a1/a2> b1/b2
11
Q
how does adrenaline selectivity change for the adrenoreceptors
A
b1/b2> a1/a2
12
Q
effect of NA binding to alpha 2 receptors?
A
negative feedback effect in NA exocytosis
13
Q
adrenaline (DASA)
A
non-selective b2- bronchodilator b1- tachycardia a1- peripheral vasodilation suppression of mediator release
14
Q
clinical scenarios to use adrenaline
A
- asthma, bronchospasm (COPD) for b2
- glaucoma a1
- cardiogenic shock b1
- spinal (maintain BP) and local anaesthesia ( prolong action on a1 to reduce blood flow and remove anaesthetic drug)
15
Q
how does adrenaline treat glaucoma?
A
the increased IOP is caused by the production of aqueous humour by the ciliary body. Vasoconstriction will reduce blood flow and there aq humour production to release IOP
16
Q
what are the unwanted effects of adrenaline (DASA)
A
- secretions are reduced and thickened
- CNS effect is minimal (BBB not crossed)
- tachycardia, palpitations, arrhythmia, hypertension
- cold extremities
- overdose leads to cerebral haemorrhage and pulmonary oedema
- GI effect is minimal
- tremor (beta receptors)
17
Q
phenylephrine (DASA)
A
- a1 selective (more than alpha 2, beta 1 and 2)
- structure similar to A
- however more resistant to COMT (not MAO) … longer lasting
18
Q
clinical uses of phenylephrine
A
- vasoconstriction (e.g. local anaesthetics’ hypotensive effects)
- mydriasis (dilation)
- nasal decongestant (vasoconstriction reduces fluid leakage in nasal sinus)
19
Q
clonidine (DASA)
A
- a2 selective more than a1, then beta
- acts on presynaptic a2 to inhibit NA release
20
Q
clinical uses of clonidine
A
- hypertension
- migraine
- reduce sympathetic tone
21
Q
isoprenaline (DASA)
A
- beta selective (over alpha)
- similar to A
- more resistant to MAO and uptake 1
- plasma half life of 2 hours ( fast)
22
Q
clinical uses of isoprenaline
A
- cardiogenic shock
- acute heart failure
- MI
however beta2 stimulation causes a drop in venous BP and therefore a reflex tachycardia due to BR stimulation
23
Q
dobutamine (DASA)
A
- beta 1 selective more than beta 2 (then alpha)
- rapidly metabolised by COMT
- administered by IV
- half life of 2 minutes
24
Q
clinical use of dobutamine
A
- cardiogenic shock (without the reflex tachycardia)
25
salbutamol [ventolin] (DASA)
- beta 2 selective more than beta 1 (then alpha)
- synthetic catecholamine derivative
- resistant to COMT and MAO
26
clinical uses of salbutamol
- asthma (relax smooth muscles b2, inhibit constriction substances)
- threatened premature labour (relax smooth muscles)
27
side effects of salbutamol
- reflex tachycardia
- tremor
- blood sugar dysregulation
28
indirecting acting SNS agonist examples
cocaine
| tyramine
29
Cocaine (IASA)
uptake 1 blocker
30
effects of cocaine on CNS
low dose- euphoria, excitement, increased motor activity
high dose- activation of CTZ (then vomiting), CNS depression, respiratory failure, convulsions and death
31
effects of cocaine on CVS
low dose- tachycardia, vasoconstriction, raised BP
32
tyramine (IASA)
- acts as false NT
- normally not a problem when MAO degradation mechanism is in place
- used to prescribe MAO inhibitors as anti-depressants
33
action of tyramine
1. Weak action at the receptors for NA.
2. Weak inhibitory effect on the uptake 1.
3. Displaces NA from the vesicles.
4. Competes for MAO breakdown so less breakdown of NA.
5. Leakage of NA out of the vesicles.
34
how can inhibition of MAO with tyramine administration lead to a hypertensive crisis?
tyramine competes with left over MAO with NA
| NA builds up
35
why is adrenaline used in anaphylactic shock?
mast cell degranulation and histamine release leads to bronchoconstriction and vasodilation
adrenaline will counteract these reactions
36
what is cardiogenic shock?
mediated by beta 1 (positive inotropic)
the sudden inability to pump sufficient oxygen-rich blood
when you have an MI
or cardiac arrest
37
why is adrenaline used in local anaethesia?
to keep the agent restricted to one area by having near by vessels constricted (prevent clearance)
via alpha 1 mediated vasoconstriction
38
why is adrenaline given in spinal anaesthesia?
the anaesthesia gets rid of sympathetic outflow so the peripheral vessels relax so BP is not maintained
adrenaline will constrict vessels to maintain the blood pressure
39
what mediated mydriasis?
radial muscles of the iris
they have alpha 1 adrenoceptors (use with phenylephrine)
contraction of these muscles--> dilation
40
how is phenylephrine used a nasal decongestant?
acts on alpha 1 (vasoconstriction)
this will reduce mucus production and swelling
41
where are alpha 2 uniquely located? what function does this enable?
pre-synaptically
| auto-inhibitory receptors to reduce the amount of NA released into the synaptic cleft
42
how does clonidine reduce sympathetic drive from the brain?
works on baroreceptors in the brainstem
43
how does clonidine treat hypertension and migraine?
- clonidine targets Alpha 2
- reduce NA levels in synaptic cleft
- reduce sympathetic tone
- reduced vascular tone
- decreased TPR
- decreased BP
clonidine also works on baroreceptors in the brainstem
44
how does isoprenaline differ to phenylephrine? what do they have in common
isoprenaline is more resistant to MAO degradation
- alpha 1 selective
phenylephrine is more resistant to COMT degradation
- beta selective
both are based on the structure of adrenaline
45
why is isoprenaline no longer used?
resulted in fatal reflex tachycardia or dysrhythmias due to action on beta 2 adrenoceptors
non selective Beta agonist
46
why is dobutamine better to use than isoprenaline?
dobutamine is selective for beta 1 (very little for beta 2)
isoprenaline is non-selective for beta
therefore dobutamine lacks the isoprenaline reflex tachycardia effect
47
how does dobutamine differ to isoprenaline is terms of metabolism?
very short half life (2min)
rapidly metabolised by COMT
isoprenaline is MAO degradation resistant
48
why does salbutamol have a longer doa than adrenaline and noradrenaline?
synthetic catecholamine derivative resistant to MAO and COMT degradation
49
how does salbutamol treat asthma?
- binds to beta 2--> bronchodilation
- bronchial smooth muscle relaxed
- inhibition of bronchoconstriction mediators from mast cells
50
how does salbutamol treat premature labour?
beta 2 mediated relaxation of uterine smooth muscle
51
what are some side effects of salbutamol? why must care be taken for some patients?
- reflex tachycardia
- tremor
- blood sugar dysregulation
take care in cardiac patients, hyperthyroidism, diabetics as beta 2 stimulated glycogenolysis
52
why must diabetics be careful with salbutamol?
- acts on beta 2
| - beta 2 mediated glycogenolysis
