Module 2 Sympathomimetics Flashcards
1
Q
The ultimate effects of sympathetic stimulation are mediated by release of what neurotransmitter?
A
Norepinephrine
2
Q
In responseto a variety of stimuli such as stress, the adrenal medulla releases this substance which is transported into the blood to target tissues
A
Epinephrine
3
Q
What do you call the drugs that mimics the actions of epinephrine or norepinephrine?
A
Sympathomimetic Drugs
4
Q
These drugs directly interact with and activate adrenoreceptors
A
Direct agonists
5
Q
These drugs’ actions are dependent on their ability to enhance the actions of endogenous cathecolamines
A
Indirect agonists
6
Q
2 mechanisms of Indirect Agonists
A
- They may displace stored catecholamines from the adrenergic nerve ending, or they may decrease clearance of released norepinephrine by:
2a. Inhibiting reuptake if catecholamines already released
2b. Preventing enzymatic metabolism of norepinephrine
7
Q
True or False: both types of sympathomimetics, both direct and indirect, ultimately cause inactivation of adrenoreceptors
A
False. Activation
8
Q
The pharmacologic effects of indirect sympathomimetics are greater under what conditions?
A
Increased sympathetic activity and norepinephrine storage and release
9
Q
The effects of catecholamines are mediated by what type of cell-surface receptors?
A
G protein-coupled receptors
10
Q
What are the G proteins that are of particular importance for adrenoreceptor function?
A
Gs, Gi, Go, Gq, G11
11
Q
What g protein stimulates adenylyl cyclase?
A
Gs
12
Q
This g protein inihibits adenylyl cyclase
A
Gi & Go
13
Q
These g proteins couple the alpha receptors to phospholipase c
A
Gq & G11
14
Q
Give the effectors of adrenoreceptor-activated alpha units
A
Adenylyl cyclase
cGMP phosphodiesterase
Phospholipase C
Ion channels
15
Q
To which substances are the alpha receptors potent to
A
Epinephrine>Norepinephrine»»»Isoprotenol
16
Q
To what substances are beta receptors potent to
A
Isoprotenol>epinephrine>norepinephrine
17
Q
Alpha receptors are coupled via g proteins in what family? To what are they coupled to?
A
Gq
Phospholipase C
18
Q
Phospholipase C hydrolizes polyphosphoinositides leading to formation of what?
A
Inositol 1,4,5-triphosphate (IP3)
Diacylglycerol (DAG)
19
Q
This promotes the release of sequestered Ca2+ from intracellular stores, which increase cytoplasmic free Ca2+ concentrations that activate various calcium-dependent protein kinases.
A
IP3
20
Q
This receptor activate signal transduction pathways that stimulate tyrosine kinases
A
Alpha 1 receptors
21
Q
These receptors are coupled to the inhibitory protein Gi that inhibiys adenylyl cyclase activity and cause intracellular cAMP levels to decrease
A
Alpha 2 receptors
22
Q
These agonists cause platelet aggregation and a decrease in platelet cAMP levels
A
Alpha 2 receptor agonists
23
Q
Activation of all three receptor subtypes of Beta receptors results in ______
A
Stimulation of adenylyl cyclase and increased cAMP
24
Q
In the liver, beta-receptor-activated cAMP synthesis leads to a cascade of events culminating in activation of what enzyme?
A
Glycogen Phosphorylase
25
In the heart, beta-receptor-activated cAMP synthesis leads to increase in what?
Increase the influx of Calcium
26
Beta receptor activation also promotes ____ of the smooth muscles
Relaxation
27
Which beta receptor is a low affinity receptor and is more resistantto desensitization
Beta 3
28
Beta 3 is expressed in the detrussor muscle of the bladder and induces its ______
Relaxation
29
What selective beta 3 agonist has been recently been approved as tx of symptoms of overactive bladder?
Mirabegron
30
This dopamine receptor is associated with stimulation of adenylyl cyclase
D1
31
D1-receptor-induced smooth muscle relaxation is due to what mechanism
cAMP accumulation in the smooth muscle
32
This dopamine receptor inhibits adenylyl cyclase activity, open patassium channels, and decrease calcium influx.
D2
33
This term means that a drug preferentially bind to one group of receptors at concentrations too low to interact intensivelywith another subgroup.
Selectivity
34
True or false: the effects of a given drug is independent of its selectivity to adrenoreceptor types and to the relative expression of receptor subtypes in a given tissue
False. Effects are DEPENDENT on these
35
After a cell or tissue has been exposed for a period of time to an agonist, that tissue often becomes less responsive to further stimulation by that agent.
What is this phenomenon called
Desensitization
36
Desensitization is significant because it may limit the therapeutic response to sympathomimetic agents. True or False
True
37
One of the two major categories of desensitization wherein the loss of responsiveness exclusively of receptors have been exposed to repeated or sustained activatoom by an agonist
Homologous desensitization
38
This ANS is an important regulator of virtuallyall organ systems
Sympathetic nervous system
39
This kind of sensitization refers to the process by which desensitization of one receptor by its agonist also results in desensitization of another receptor that has not been directly activated by the agonist in question
Heterologous Desensitization
40
These agonists selectively activate the arrestin-coupled signalling pathways
Biased agonists
41
The principal mechanism for removal of norepinephrine
Norepinephrine Transporter
42
In the heart, how much Norepinephrine is removed by NET?
90%
43
In the vasculature, how much norepinephrine is removed by NET?
60%
44
The remaining synaptic norepinephrine (not removed by NET) may escape into the extrasynaptic space and eneter the bloodstream or be taken up into extra neuronal cells and metabolized by what enzyme?
Catechol-O-methyltransferase (COMT) [sa heart]
45
Norepinephrine may reenter cells or undergo metablosim by what enzyme?
Monoamine Oxidase (MAO) [sa vasculature galing yung norepi]
46
The NET has equivalent affinity for _____ as for norepinephrine
Dopamine
47
This can sometimes clear dopamine in the brain areas where DATis low, like the cortex.
NET
48
What is the parent compound from which sympathomimetic drugs are derived?
Phenylethylamine
49
Alpha 1 receptors are widely expressed in vascular beds leading to arterial ________ and venous ______
Arterial and venous vasoconstriction
50
A pure alpha agonist increases....
Peripheral arterial resistance and decreases venous capacitance
51
True or false: any effect agents have on blood pressure is counteracted by compensatory autonomic baroreflex mechanisms aimed at restoring homeostasis.
True
52
Alpha 1 receptor stimulation leads to a rise in BP. However, this elicits a baroreceptor-mediated increase in....
Vagal tone + slowing of the heart
| But! CO is not diminished because increased VR may increase stroke volume
53
Skin vessels have predominantly _________ receptors and constrict in response to epinephrine and norepinephrine, as do the splanchic vessels.
Alpha receptors
54
This receptor is present in the vasculature and their activation leads to vasoconstriction. However, they should be given locally via IV or in very high oral doses for the effects to be observed.
Alpha 2
55
Alpha 2 agonists can be used as ______ in the tx of hypertension
Sympatholytics
56
Stimulation of this kind of receptor in the heart increases CO by increasing contractility and direct activation of the Sinus node to increase HR.
Beta receptors
57
Beta atonists also increase peripheral resistance by activating beta 1 receptors, leading to vasoconstriction in certain vascular beds.
True or false
False. Decrease peripheral resistance
| Vasodilation
58
What is the net effect of beta receptor activation?
Maintain or slightly increase sustolic pressure and to lower diastolic pressure so that the mean bp is decreased
59
Beta receptor activation results in increased calcium influx in cardiac cells. This leads to:
Sinoatrial Node and Purkinje fibers is increased: + Chronotropic effect
Atrioventricular node velocity is increased : + dromotropic effect
Intrinsic contractility is increased: + inotropic effect
60
Physiolic stimulation of the heart by catecholamines tends to...
Increase coronary blood flow
61
Intravenous administration of dopamine promotes _____ of renal, splanchic, coronary, cerebral, etc via activation of D1 receptors
Vasodilation
62
Effect of d1 receptor activation in renal vasculature
Natriuresis
63
The renal effects of dopamine have been used clinically to improve ______
Perfusion to the kidney in situations of oliguria
64
Dopamine also activates the _____ receptors in the heart. At low does, peripheral resistance may _______. At high doses, it activates alpha receptors leading to _____. High doses may mimic the actions of _______
Beta 1
Decrease
Vasoconstriction
Epinephrine
65
Beta 2 receptor activation in bronchial smooth muscles leads to....
Bronchodilation
Thus, very important in the tx of asthma
66
Radial pupillary dilator muscle of the iris contains ______ receptor; activation by phenylephrine causes mydriasis
Alpha receptors
67
Alpha ____ agonist increase the outflow of aqueous humor from the eye and can be used clinically to reduce IOP.
Alpha 2
68
Beta antagonists ______ production of aqueous humor
Decrease
| Therefore they are used in the tx of Glaucoma
69
The bladder base, urethral sphincter, and prostate contains this type of receptor. These mediate contraction and promote urinary continence
Alpha 1a
70
This receptor is found in the ductus deferens, seminal vesicle, and prostate, and plays a role in normal ejaculation
Alpha receptor
71
Detumescence of erectile tissue is brought about by what substance
Norepinephrine
72
Activation of beta adrenoreceptors in fat cells leads to...
Increased lipolysis with enhanced release of FFA and Glycerol into the blood
73
Human fat cells also contain alpha 2 receptors which....
Inhibit lipolysis by decreasing intracellular cAMP
74
Catecholamines in high concentration leads to...
Metabolic Acidosis
75
Insulin secretion is mediated by...
| And inhibited by...
Beta receptors
| Alpha 2 receptors
76
This is both an alpha and beta agonist. It is a potent vasoconstrictor and cardiac stimulant. It has + inotropic and chronotropic actions on the heart
Epinephrine
77
Epinephrine also activates beta 2 receptors in skel ms blood vessels leading to...
Dilation
78
Alpha 1 and alpha 2 agonist. Also activates beta 1. Increases tpr and both diastolic and systolic bp.
Norepinephrine
79
Immediate precursor of norepinephrine. Involved in the reward stimulus relevant to addiction. Its deficiency in the basal ganglia leads to Parkinson's disease
Dopamine
80
This is not a catechol derivative therefore it is not inactivated by COMt and has a longer duration of action. It is an effective mydriatic and decongestant and can be used to raise BP
Phenylephrine
81
This is a prodrug that is enzymatically hydrolyzed to desglymidodrine, a selective alpha 1 receptor agonist. This is used for the tx of orthostatic hypotension. But it may cause hypertension when subject is supine
Midodrine
82
Alpha 2 selective agonists _______ blood pressure thru actions in the CNS that _____ sympathetic tone.
Decrease
| Reduce
83
For sedation and intensive care setting before anesthesia. It reduces the requirements for opioids in pain control.
Dexmedetomidine
84
This is a centrally acting muscle relaxant
Tizanidine
85
Very potent beta receptor agonist. Has positive chronotropic and inotropic actions. Also a potent vasodilator. Leads to increased CO, fall in diastolic and MAP, and a lesser decrease in systolic pressure
Isoproterenol
86
Beta 1 selective agonist has these effects...
Increased CO
| Less reflex tachycardia
87
Has a positive inortropic actiom. Greater inotropic than chronotropic effect vs isoproterenol.
Dobutamine
88
First orally active sympathomimetic drug. Has high bioavailability and relatively long duration of action
Ephedrine
89
This is composed of a catechol nucleus + amine + sidechain
Catecholamines
90
What are the natural catecholamines?
Epinephrine, norepinephrine, dopamine
91
What are the synthetic catecholamines?
Dobutamine... Tska may isa pa huhu di ko sure basta Iso something
92
This kind of uptake is specific for norepi. This is found at the neuronal membrane and inhibited by Cocaine, TCAD, amphetamines.
This uptake is towards the terminal bulb
Uptake I
93
This kind of uptake is less specific and is towards the tissue. It is found on smooth and cardiac muscles. It has no pharmacologic importance.
Uptake II
94
This type of metabolism happens intracellularly (@ the mitochondrial membrane) and at the norepinephrine terminals at the liver & intestines.
Mono Amine Oxidase (MAO)
95
This metabolism inhibitor is used as antidepressants.
In depression, there is a decrease in catecholamines, so we use these drugs to increase this level.
MAO inhibitors
96
This enzyme is found on neuronal and non-neuronal tissue. This metabolizes catecholamines and their byproducts
COMT
97
These receptors decrease insulin secretion
Alpha 2
98
This receptor increases renin secretion
Beta 1
99
This receptor decreases renin secretion
Alpha 2
100
This is a potent vasoconstrictor and cardiac stimulant. But, this causes vasodilation in skeletal muscles to increase blood flow during exercise
Epinephrine
101
This acts on both alpha 1 and alpha 2 to increase total peripheral resistance and thus, increase systolic and diastolic BP
Norepinephrine
102
This is a pure alpha 1 agonist and is not inactivated by COMT thus it has a longer duration of action. It is also a mydriatic agent, decongestant, and it increases Bp
Phenylephrine
103
This is a prodrug that targets alpha 1 receptors. This is used as tx for orthostatic hypotension due to impaired ANS dysfunction.
Midodrine
104
This is like phenylephrine. This cause prolonged increase in BP and vagally mediated bradycardia.
Methoxamine
105
This drug if discontinued abruptly could cause rebound hypertension. This is an alpha 2 selective agonist
Clonidine
106
This is used for sedation of intubated pand mechanically ventilated patients
Dexmedetomidine
107
This is contraindicated for pre-eclampsia
Methyldopa
108
This is a beta agonist and has positive chronotropic and inotropic effects. This exclusively acts on beta receptors inducing vasodilation and thus increasing cardiac output
Isoproterenol
109
This is a beta 1 selective drug that has the same structure with dopamine. It has a positive inotropic effect
Dobutamine
110
This is the first orally active drug from the ma huang plant. It has high bioavailability and long duration of action. This is used for tx of asthma
Ephedrine
111
This is a mixed acting drug that is a common decongestant. This is a component of metamphetamine
Pseudoephrine
112
This is a mixed acting drug that is used as appetite suppressant and decongestant. This is associated with hemorrhagic stroke in females and can increase BP
Phenylpropanolamin
113
This is an indirect-acting sympathomimetic that stimulates the CNS. It is similar to ephedrine and increases mood & alertness while decreasing appetite. Its action is mediated via release of norepi
Amphetamines
114
This is used for children with ADHD. This has a paradoxic effect. This must be given before bedtime. Can cause cross stunting of growth
Methylphenidate
115
This increases the concentration of epinephrine, dopamine, serotonin, and glutamate while decreasing GABA levels. This improves wakefulness in narcolepsy. This can also increase BP and HR
Modafinili
116
This has high concentrations in fermented food. It is a byproduct of tyrosine metabolism and may cause increase in BP when taken with MAO inhibitors
Tyramine
117
This is a selective inhibitor of Norepinephrine reuptake and potentiate NE levels. This is also a tx for Pnoy este ADHD
Atomoxetine
118
This is the only FDA approved drug for the tx of obesity
Sibutramine
119
This is used as local anesthetics and inhibits dopamine reuptake. This can be smoked, snorted, or injected. This has an amphetamine-like effect tho shorter but more intense
Cocaine
120
This is used as tx for Parkinson's disease. Can readily pass the blood brain barrier.
Levodopa
121
This is a D1 agonist. It causes vasodilation and is used as tx for severe Hypertension
Fenoldepam
122
What drugs are used for acute hypotension?
Norepinephrine, phenylephrine, methoxanine
123
What drugs are used for CardiogenicShock and AHF. These aim to optimize perfusion not bp
Dopamine and dobutamine
124
These drugs are used for chronic orthostatic hypertension by increasing total peripheral resistance
Midodrine, ephedrine, phenylephrine
125
What are used for emergency management of complete heart block amd cardiac arrest?
Isoproterenol & epinephrine
Epinephrine redistribute blood to the brain and heart
126
These are used to induce local vasoconstriction. These are used during oral, facial, and nasopharyngeal surgery
Epinephrine and cocaine
127
What is the non selective drug for bronchial asthma?
Epinephrine
128
What is the beta selective drug for bronchial asthma?
Isoproterenol
129
These are beta-2 selective drug used for bronchial asthma
Albuterol, metaproterenol, terbutaline
130
This is used as initial tx for anaphylaxis
Epinephrine
131
These are used for tx of anaphylaxis
Glucocorticoids and antihistamine
132
What are the tx for narcolepsy
Amphetamine and modafinil
133
6.1 Which of the following is correct regarding adrenergic neurotransmission?
A. Epinephrine is the major neurotransmitter released from sympathetic nerve terminals.
B. Norepinephrine is mainly released from the adrenal glands.
C. Tricyclic antidepressants and cocaine prevent reuptake of norepinephrine into the nerve terminals.
D. Monoamine oxidase (MAO) converts dopamine to norepinephrine in the nerve terminal
C
134
All of the following are correct regarding adrenergic receptors, except:
A. α1 Receptors are primarily located on the postsynaptic membrane in the effector organs.
B. α2 Receptors are primarily located on the presynaptic sympathetic nerve terminals.
C. β1 Receptors are found mainly in the heart.
D. β2 Receptors are found mainly in adipose tissue
D
135
A hypertensive patient was accidentally given an α2 agonist instead of an α1 blocker. Which of the following is correct in this situation?
A. α2 Agonists can increase the release of norepinephrine from sympathetic nerve terminals.
B. α2 Agonists can reduce blood pressure in this patient.
C. α2 Agonists can increase blood pressure in this patient.
D. α2 Agonists will not affect blood pressure in this patient
B
