Adrenergic Pharmacology Flashcards
1
Q
The ionic composition of the blood and the interstitial fluid resembles ___ water.
A
sea
2
Q
The Na+ concentration outside of cells is ___ (low/high). K+ concentrations therefore are ___ (low/high).
A
high (remember that seawater is salty); low (opposite of Na+)
3
Q
Why is Cl- low inside the cell (cytoplasm)?
A
because it has been replaced by proteins. Proteins have a negative charge and this balances the other charges inside the cell (therefore no need for Cl-).
4
Q
The Na+ concentration inside the cell is ___ (low/high) and K+ is ___ (low/high).
A
low; high
5
Q
Cells have ___ channels that are working at rest and they provide membrane permeability at rest.
A
K+
The membrane is 100X more permeable to K+ than Na+ and therefore, the Na+K+ ATPase pump kicks out 3 Na+ and allows 2K+ in (with a net of 1Na+ going out) to maintain the electrochemical gradient.
6
Q
Because there is more K+ ___ the cell, there is a net flow to the ___ because of the concentration gradient. Therefore there is a little less K+ than ___ inside which creates an inside that is ___ compared to the outside.
A
inside; outside; Cl-; electronegative
7
Q
T/F. The net efflux of K+ continues until the chemical force leading K+ inside is balanced by the electrical force pushing it out.
A
False, The net efflux of K+ continues until the chemical force leading K+ OUTSIDE is balanced by the electrical force BRINGING IT BACK.
8
Q
What happens if a cell suddenly becomes permeable to Na+ at one location?
A
At the site, the Na+ current would counteract the K+ current, leading to depolarization.
Depolarization is the same as saying the cell becomes less electronegative or less polarized (or depolarized)
9
Q
T/F. Voltage-gated channels can be opened or closed based on the potential across the membrane.
A
True.
10
Q
T/F. The channels for K+ respond quicker to changes in voltage than the channels for Na+.
A
False, The channels for Na+ respond quicker to changes in voltage than the channels for K+.
11
Q
Place the following statements in order
- As hyperpolarization continues, the Na+ and K+ channels are closed and the cell is at its resting state.
- As the Na+ enters the cell, it spreads to neighboring regions thereby spreading the depolarization.
- Once the local depolarization reaches threshold, the voltage gated Na+ channels open.
- Continued depolarization will cause the K+ channels to open (slower) and hyperpolarization resumes. Now the Na+ channels begin to close.
- stimulus causes Na+ to enter the membrane and the cell begins to depolarize due to the Na+ current coming in.
A
5, 3, 2, 4, 1
12
Q
what cells are excitable?
A
nerve and skeletal muscle
13
Q
Action potentials in ___ tissue is much slower than in nerve or skeletal muscle.
A
cardiac
14
Q
Action potentials reach the nerve ___ and this causes ___ channels to open. ___ enters the cell and tells the vesicles to fuse with the presynaptic membrane to dumps its contents into the ___. The transmitter postsynaptic receptor proteins and open their ___ gates to let Na+ in, which starts local ___.
A
terminal; Ca2+; Ca2+; synapse; ion; depolarization
15
Q
Which division of the CNS projects from the CNS to targets in PNS and elicits an appropriate response?
A
efferent (motor) division
16
Q
The ___ division projects from PNS target to the CNS and provides information.
A
afferent (sensory)
17
Q
What nervous system provides motor innervation of all skeletal muscles?
A
somatic nervous system
18
Q
Define homeostasis.
A
the tendency of a higher animal, to maintain internal stability, owing to the coordinated response of its parts to any situation or stimulus that would tend to disturb its normal condition or function
19
Q
What two areas affect homeostasis?
A
- Autonomic nervous system
2. Endocrine system
20
Q
What does the autonomic nervous system regulate and coordinate?
A
- smooth muscle
- heart
- secretory glands (can self-regulate, but affected by the ANS)
21
Q
T/F. Many organs are affected by both the sympathetic and parasympathetic systems.
A
True.
22
Q
The parasympathetic innervation comes from the ___ region and the sympathetic innervation comes from the ___ region.
A
craniosacral; thoracolumbar
23
Q
T/F.The ganglia of the parasympathetic system are close to the spinal cord in a chain and the sympathetic ganglia are close to target organs.
A
False, The ganglia of the SYMPATHETIC systems are close to the spinal cord in a chain and the PARASYMPATHETIC ganglia are close to target organs.
24
Q
Match:
- Long postganglionic fibers
- Short postganglionic fibers
- Lots or postganglionic branching so that multiple organs can be mobilized at once
- Very little postganglionic branching
A. Sympathetic
B. Parasympathetic
A
1 - A
2 - B
3 - A
4 - B
25
T/F. There are ganglia located at the skeletal muscle.
False, there are no ganglia at these muscles.
26
What are the receptors used in the following systems at the EFFECTOR site- sympathetic innervation of adrenal medulla, sympathetic, parasympathetic, and somatic?
sympathetic innervation of adrenal medulla = adrenergic receptors
sympathetic = adrenergic receptor
parasympathetic = muscarinic receptor
somatic = nicotinic receptor
27
The preganglionic neurons of the sympathetic system release ___ which binds to the ___ receptor on the adrenal ___. The adrenal gland then releases ___ into the blood to bind to ___ receptors on effector organs (heart and vessels).
acetylcholine; nicotinic; medulla; epinephrine; adrenergic
28
Preganglionic sympathetic fibers release ___ which bind to ___ receptors on postganglionic fibers. These fibers release ___ to bind to ___ receptors on effector organs (heart and vessels).
acetylcholine; nicotinic; norephinephrine; adrenergic
29
Preganglionic parasympathetic fibers release ___ which bind to ___ receptors on postganglionic fibers. These fibers release ___ to bind to ___ receptors on effector organs (heart and vessels).
acetylcholine; nicotinic; acetylcholine; muscarinic
30
The ___ fibers release acetylcholine which binds to ___ on striated muscles.
somatic; nicotinic
31
Which receptors open postsynaptic membranes and let sodium in?
nicotinic receptors
32
Which receptors are GPCRs that transmit a signal inside the cell?
muscarinic
33
What is released from the postganglionic sympathetic fibers in renal vessels?
dopamine
34
T/F. When epi and norepi are released from the adrenal glands under sympathetic control into the blood they have widespread effects.
True.
35
What precursor amino acid is transported in adrenergic neurons into the nerve endings to synthesize catecholamine transmitters and store them in vesicles?
Tyrosine
36
Tyrosine → ___ → ___→ ___ → ___.
tyrosine → DOPA → dopamine → norepi → epi
37
How are adrenergic and cholinergic transmitters dealt with differently one inside the synaptic cleft?
adrenergic - transmitters are transported back into the presynaptic terminus (reuptake)
cholinergic - transmitter is hydrolyzed in the synapse (cholinesterases)
38
How many dopamine receptors are there? Where are they found?
5 (D1-D5)
| in CNS and periphery (kidneys, some smooth muscle)
39
What are the three major types of adrenergic receptors? What are the subtypes? What are the most important ones used in the PNS?
alpha-1, alpha-2, beta
alpha-1, alpha-2 (no drugs), beta-1, beta-2, beta-3 (not used)
alpha-1, beta-1 and beta-2
40
Alpha (1 and some 2) receptors on smooth muscle cells bind to G___, which increases IP3 and increase ___. This increases the activity of ___ ___ ___ ___ which phosphorylates myosin light chain and leads to increased muscle ___.
q; Ca2+; myosin light chain kinase; contractility
41
___-_ receptors are most important at the presynaptic termini where they inhibit ___ and ___ release.
Alpha-2; epinephrine; norepinephrine
42
___-_ receptors on smooth muscles increase PKA, which diminishes ___ and inhibits ___ ___ ___ ___. This leads to decreased muscle contractility.
Beta-2; Ca2+; myosin light chain kinase
43
PKA mediated-phosphorylation also activated ___ channels, which leads to ___ and the reduction of cellular Ca2+. This produces smooth muscle ___ because the activity of ___ is attenuated.
K+; hyperpolarization; relaxation; MLCK
44
Beta-1 receptors are located on what type of cells? What are the downstream events?
cardiac muscle cells (mainly B1 but also B2)
activate PKA, activate L-type Ca2+ channels, increase Ca2+ levels and increase muscle contractility
45
Drugs that active B1 receptors can improve contractility of the failing heart. What is a major concern of these drugs?
These drugs also increase heart rate and excess stimulation can result in arrhythmias. This is a major concern with drugs such as epi that can be absorbed systemically after injection.
46
B2 receptor activation leads to vascular and non-vascular smooth muscle ___ and A1 activation results in ___ (increased blood pressure). Which receptor type is more prevalent on vascular smooth muscles?
relaxation; constriction
A1
47
What receptors does Epi and NE activate?
Epi = A, B1, and B2
| NE does not activate B2
48
Local injection of Epi and NE produces ___ because alpha receptor activation predominates. What happens when the concentration of each is decreased?
vasoconstriction
Epi: alpha receptors are affected by this change in concentration so its stimulation is less and the B2 receptor activity dominates causing BP to decrease.
NE: same because NE does not bind to B2 receptors. Therefore, BP increases (this could lead to reflex bradycardia).
49
Alpha-1 antagonist act as a ___ and alpha-2 antagonist cause ___ that could produce cardiac complications.
vasodilator; vasoconstriction
50
T/F. When stimulated by Epi and NE, B2 receptors are GPCR that activate G-alpha-i and cause inhibition of PKA.
False, When stimulated by EPI ONLY, B2 receptors are GPCRs that activate G-ALPHA-S and cause activation of PKA.
51
What are the three effects that endogenous Epi and NE have on B receptors in cardiac tissue?
Mainly B1 but B2 contribute to Epi activity
1. increase the force of myocardial contraction
2. increase the rate of contraction
3. excess stimulation leads to arrhythmias
52
Relaxation of non-vascular smooth muscle is mediated by which receptor? What does this cause? What do Alpha receptors do?
B2
GI decreased motility, bronchodilation
Alpha receptors mediate sphincter contraction
53
What is the net effect of Epi and NE on salivary glands?
modest secretion with a high concentration of protein
mainly A1 and B1 with some B2
B1 stimulates protein secretion
54
T/F. Peripherally administered Epi and NE is able to cross the BBB.
False, Peripherally administered Epi and NE does NOT cross the BBB.
55
T/F. IV CNS effects cause feelings of anxiety, jitteriness, and apprehension due to indirect sensory input from the periphery.
True.
56
T/F. Endogenous dopamine is more important in the periphery than the CNS.
False, Endogenous dopamine is more important in the CNS, but not so much in the periphery.
57
What is a severe whole body response to allergen? What are some of the symptoms of this condition?
anaphylaxis
smooth muscle contraction
vasodilation (severe hypotension)
increased vascular permeability
58
How is Epi administered to treat anaphylaxis? What happens to each receptor it stimulates?
Intramuscular injection
Alpha receptor - increase blood pressure
Beta-1 receptor - positive cardiac effects
Beta-2 receptor - bronchodilation
59
What are these drugs examples of: methoxamine, phenylephrine, levonordefrin, midodrine, oxymetazoline, metaraminol?
Alpha-1 receptor agonist
These drugs act to produce contraction of vascular smooth muscle, resulting in an increase in blood pressure. Some are contained in commonly used oral or topical decongestants or in eye drops.
60
___ is sometimes used as a vasoconstrictor in conjunction with a local anesthetic. ___ is used to treat hypotension during surgery.
Levonordefrin (=corbadrine = alpha-methylnorepinephrine); Metaraminol
61
Why is epinephrine (common) and levonordefrin (less common) used in conjunction with local anesthetic?
1. prolong duration of nerve block and might improve likelihood of success of nerve block.
2. diminish systemic toxicity of the anesthetic
3. minimize blood loss during surgical procedure
62
If the concentration of epinephrine with lidocaine increases, how does this affect the effect of the anesthesia?
more epi causes longer lasting anesthesia
63
What are these drugs examples of: clonidine, guanfacine, guanoxabenz, guanethidine, xylazinel, tizanidine, medetomidine, methyldopa, fadolmidine, dexmedeomidine?
Alpha-2 receptor agonists
These drugs act in the CENTRAL NERVOUS SYSTEM by inhibiting EPI and NE release from presynaptic termini. Some agonists (clonidine, guanabenz, guanfacine, and methyldopa) are used to treat hypertension via autonomic regulation of the cardiovascular system. Others act as a muscle relaxant (tizanidine). Others are used to treat ADHD (clonidine) or as a sedative (dexmedetomidine).
64
What are B1 receptor agonists used for? Give examples.
These drugs are used primarily in the treatment of heart failure and cardiogenic shock via direct stimulation of B1 receptors.
Denopamine, Dobutamine, Xamoterol, isoprenaline (B1 and B2)
65
What is the function of B2 receptor agonists? Give examples.
These drugs produce smooth muscle relaxation. They are used primarily to treat respiratory disease (asthma) but can be used to produce vasodilation in muscle and liver and to produce relaxation of uterine tissue.
Albuterol, pirbuterol, isoprenaline (B1 and B2), formoterol, clenbuterol
66
What do dose related complication result from?
1. too large a dose
2. accidental intravascular injection
3. heightened sensitivity
4. patient with cardiovascular disease
67
What are the most serious results from cardiac disturbances?
myocardial ischemia, heart attack, and arrhythmias. Also hypertensive crises.
68
T/F. Alpha-1 adrenergic receptor antagonists inhibit vascular smooth muscle constriction and cause dilation. They are used to treat hypertension, pulmonary hypertension, hemodynamic shock (ineffective perfusion of organs), and Raynaud's disease (limited circulation of extremities).
True
69
T/F. Any inhibition by alpha-1 antagonist is good when dealing with conditions associated with increased sympathetic activity (pheochromocytoma).
True.
70
Do alpha-1 antagonist treat benign prostatic hypertrophy?
Yes, they antagonize bladder smooth muscle contraction
71
___ was the first alpha-1 selective antagonist. Non-selective alpha antagonist are not useful to treat ___ because of alpha-2 effects.
Prazosin; hypertension
72
___ and ___ are better absorbed and have tighter binding to plasma proteins leading to longer 1/2 life (12-20hrs).
Terazosin; doxazosin
73
What is a chief adverse effect of using prazosin, terazosin and doxazosin?
orthostatic hypotension (dizzyspell upon standing)
74
What alpha-1 antagonists acts primarily on the smooth muscle of the prostate (BPH drug)?
alfuzosin
75
How does tamulosin work?
specific for alpha-1A and -1D (not -1B)
selective for prostate
treatment for BPH
Does not increase blood pressure
76
___-___ alpha-2 antagonists block ___ mediated feedback loop and the transmitter limits transmitter release at the ___ terminus.
Non-selective; transmitter; presynaptic
77
What is phentolamine used to treat?
intravenous infusion to control acute episodes of hypertension during surgery of patients with pheochromocytoma.
78
What are the side effects of using phentolamine which limit its usefulness?
1. activities unrelated to adrenergic actions
| 2. reflex tachycardia due to alpha-2 blockage of feed back loop.
79
___ is used to reverse soft tissue numbness after administration of local anesthetics with vasoconstrictors. Injected after local anesthetic when pain relief is no longer needed.
Phentolamine counteracts the vasoconstriction and increases more blood to that site.
80
Which drug is used to treat pheochromocytoma but has limited utility because it irreversibly blocks alpha-1 and alpha-2 receptors?
phenoxybenzamine
81
Which receptor type has agonist that produce vasodilation, treat overactive bladder and stimulate lipolysis in rodents but has no clinical use for antagonist?
Beta-3
82
T/F. Blockage of beta-2 receptors on airway and vascular smooth muscle and endocrine cells is preferred.
False, Blockade of B2 adrenergic receptors is generally undesirable in airway and vascular smooth muscle and endocrine cells.
Hence, presently used Beta blockers are either non-selective (B1 and B2) or B1 selective (preferred).
83
What is the function of beta blockers?
decrease heart rate and force of contraction
84
How do beta blockers decrease blood pressure?
They diminish renin release from the kidney (decrease renin = decreased BP)
85
T/F. Some alpha-blockers have an activity known as intrinsic sympathomimetic activity or ISA whose consequence is that a low beta stimulation persists.
False, Some BETA-blockers have an activity known as intrinsic sympathomimetic activity or ISA (partial agonist) whose consequence is that a low beta stimulation persists.
86
Beta-blockers without ISA ___ resting heart rate; plasma ___ activity, and ___ output.
decrease; renin; cardiac
87
Beta-blockers with ISA do not depress ___ function or plasma ___ activity as well but do attenuate ___ driven increases.
cardiac; renin; agonist
88
List some therapeutic uses of beta-blockers
1. hypertension (renin system)
2. ischemic heart disease (reduce oxygen consumption by reducing cardiac output)
3. post-myocardial infarction (reduce oxygen consumption by reducing cardiac output)
4. congestive heart failure
5. arrhythmias
89
Which antagonists reduce vitreous humor production and are used in the treatment of glaucoma?
Beta blockers
90
Which antagonists get into the CNS and are used to treat migraines and tremors associated with anxiety?
Beta blockers
91
What two drugs are alpha receptor and beta receptor antagonists?
labetalol
| carvedilol
92
___ is 7x more potent as a beta blocker, ISA activity, used in long term management of hypertension.
Labetalol
93
___ has no ISA activity, is an effective treatment of CHF, and is an antioxidant activity.
Carvedilol
94
___ blockers can cause orthostatic hypotension.
Alpha
95
A patient taking a non-selective ___ blocker is more at risk of a hypertensive episode after receiving local anesthetic with a vasoconstrictor.
Beta
Why? because it doesn't get beta2 mediated vasodilation to counteract alpha mediated vasoconstriction.
96
___ causes xerostomia.
Clonidine
