Adrenergic Agonists Flashcards
(106 cards)
1
Q
What is the general term for NT/hormones in the sympathetic NS?
A
- catecholemines
2
Q
What are the major catecholamines?
A
- dopamine (DA)
- norepinephrine (NE)
- epinephrine (E)
3
Q
What are the categories of adrenergic receptors?
A
- alpha 1 (a1)
- alpha 2 (a2)
- beta (1, 2, 3)
- dopamine
4
Q
What type of receptors are adrenergic receptors?
A
- GPCRs
5
Q
What are the factors that can alter the degree to which any adrenergic receptor responds?
A
- selectivity
- regulation
- polymorphisms
- catacholamine metabolism
6
Q
What does receptor selectivity allow for?
A
- specific binding
- i.e. drug x only binds to a1 receptors but not a2 or b receptors
7
Q
What effects degree of drug binding?
A
- [drug]
8
Q
What does [low drug] allow for?
A
- selective binding
9
Q
What does [high drug] cause?
A
- non-selective binding
- i.e. larger [ ] flood receptors that usually do not bind the drug
10
Q
What is receptor regulation?
A
- increasing or decreasing the number of receptors based on the long term exposure
- i.e. up/down regulation
11
Q
What does receptor regulation result in?
A
- changes in the observed response to sympathomimetic drugs
12
Q
What is an example of receptor regulation?
A
- desensitization (aka: tolerance, refractoriness, tachyphylaxis)
13
Q
Describe desensitization
A
- decrease responsiveness of that cell/tissue to additional stimulation
14
Q
What are the mechanisms of desensitization?
A
- altered transcription/translation of DNA and/or RNA
- modifications of receptors via interactions with enzymes or other proteins
- long term exposure to an agonist
- interactions or messages from other receptors
15
Q
What is the desired therapeutic benefit of using desensitization?
A
- results in an increased response followed by the desired decreased physiological action
16
Q
Describe receptor polymorphism
A
- slight changes in a.a. sequences can occur in different people
- explains why some drugs work better in some people vs. others
17
Q
What are the mechanisms of NT termination?
A
- NE transporter (NET)
- diffusion
- metabolism by COMT or MAO
18
Q
What is the most important mechanism of NT termination?
A
- NET
19
Q
Describe the action of NET
A
- pre-synaptic pump to move NE out of synapse and back into neuron (reuptake)
20
Q
How does NET act as a therapeutic target?
A
- NET inhibition prolongs the presence of NE in the synaptic cleft leading to increased stimulation of adrenergic receptors
21
Q
What are drugs that are able to bind and inhibit NET action?
A
- atomoxetine (used in ADHD)
- cocaine
22
Q
What is the action of catechol-O-methyl transferase (COMT)?
A
- metabolizes all catecholemines
23
Q
What is a drug that inhibits COMT and what is its clinical use?
A
- entacapone
- Parkinson’s
24
Q
What is the action of monoamine oxidase (MAO)?
A
- metabolizes endogenous monoamines (i.e. linezolind)
25
Define sympathomimetic
- drug that mimics actions of NE, E, and DA
26
Define direct agonist sympathomimetics
- structure allows for binding to adrenergic receptors resulting in activation
27
Define indirect agonist sympathomimetics
- cause release of stored catecholamines
| - inhibits reuptake of catecholamines
28
What are the locations that changes can be made on sympathomimetic drugs?
- benzene ring
- beta C
- alpha C
- amino group
29
What is the major target of sympathomimetics?
- CV system
30
Where are a1 and b2 receptors in CV system?
- vascular
31
Where are b1 receptors in CV system?
- heart
32
What is the outcome of giving a drug dependent on?
- selectivity for a v. b receptors
- pharmacologic action at the receptors (agonist/antagonist)
- action of body's compensatory mechanisms to maintain homeostasis
33
Which receptors in the CV system cause vasoconstriction?
- a1
34
Which receptors in the CV system cause vasodilation?
- b2
35
What are the effects in the CV of a1 receptor activation?
- vasoconstriction leads to increased BP which causes reflex decrease on HR
36
What is an example of a CV system a1 agonist and when is it used?
- phenylephrine
| - nasal decongestion and maintaining BP
37
What is the effect of peripheral a2 agonists in the CV system?
- vasoconstriction, but only when given locally, IV push, or very high oral doses
- rare
38
What is the effect of central a2 agonists in the CV system?
- inhibits sympathetic vascular tone
| - lowers BP
39
What is an example of a CV system a2 agonist and when is it used?
- clonidine
| - HTN
40
What are the effects of a b1 receptor agonist in heart?
- increase contractility
- increase HR
- increase CO
41
What are the effects of a b2 receptor agonist in the vasculature?
- decrease resistance aka vasodilation
| - decreased BP
42
What is the effect of DA on d1 receptors in CV system?
- vasodilation
43
Where does DA bind in low doses?
- b2 receptors, specifically renal
44
Where does DA bind in medium doses?
- b1 receptors to increase HR and contractility
45
Where does DA bind in high doses?
- a1 receptors to increase BP
46
What receptors are activated by sympathomimetics in the lungs and what is the effect?
- b2
| - bronchodilation
47
What receptors are activated by sympathomimetics in the eye and what is the effect?
- a
| - mydriasis, increase outflow of aqueous humor, decreases IOP
48
What receptors are activated by sympathomimetics in the GU tract and what is the effect?
- a receptors
| - urine retention and mediate ejaculation
49
What receptors are activated by sympathomimetics in the salivary glands and what is the effect?
- b receptors
| - increase salivation
50
What is the effect of sympathomimetics on the apocrine sweat glands in the hands?
- increased sweat production in response to stress
51
What receptors are activated by sympathomimetics in metabolism and what is the effect?
- b receptors
| - increased glycogenolysis increases serum glucose which results in increased insulin
52
What are the effects of sympathomimetics on the CNS dependent on?
- ability to cross BBB
53
What are the endogenous catecholamines?
- NE
- E
- DA
54
At which receptors does E act as an agonist?
- a1 & 2
| - b1 & 2
55
What are the primary effects of E?
- vasoconstrictor
| - cardiac stimulant
56
What are the secondary effects of E?
- increased systolic BP due to a1 binding
- increased HR and CO due to b1 binding
- vasodilation due to b2 binding but only in skeletal m.
57
At which receptors does NE act as an agonist?
- a1 & 2
| - b1
58
What are the primary effects of NE?
- vasoconstrictor
| - cardiac stimulant
59
What are the secondary effects of NE?
- increased systolic BP due to a1 binding
- increased HR and CO due to b1 binding
*same as E*
60
What is a brand name for NE?
- Levophed (leave them dead)
61
What are the effects of DA in the CV system based on?
- doses
62
What is the effect of low does DA on the CV and where does it bind?
- vasodilation
| - b2
63
What is the effect of medium dose DA on the CV and where does it bind?
- increase HR and CO
| - b1
64
What is the effect of high dose DA on the CV and where does it bind?
- vasoconstriction
| - a1
65
What is an action of DA on the CNS?
- development of addiction based on reward stimuli
66
A deficiency of ______ can contribute to ______ disease.
- DA
| - Parkinson's
67
What type of receptors are targets for antipsychotic drugs?
- DA
68
What are the main effects of direct a1 agonists?
- vasoconstriction
| - increase BP
69
What are two examples of direct a1 agonists and what are their uses?
- phenylephrine (neosynephrine): decongestant and raise BP
| - midodrine (Amantine): increase BP and tx orthostatic HTN
70
What is the main effect of direct a2 agonists?
- decrease BP
71
What is the classic example of a direct a2 agonist and what is it used for?
- clonidine (Catapres): reduce BP and tx HTN (preeclampsia)
72
What are the effects of direct a1 AND a2?
- local vasoconstriction
73
What is an example of a direct a1 AND a2 drug and what is it used for?
- oxymetazoline (Afrin): decongestant
74
What is an example of a nonselective b agonist and what are the effects?
- isoproterenol (Isuprel): vasodilation via b2; decreased BP and MAP; increased HR and CO
75
What is the primary effect of b1 selective agonists?
- increase CO and HR
76
How does dobutamine produce its effects without changing BP?
- (+) isomer gives b1 action and a1 antagonism
- (-) isomer gives a1 agonism
* a1's cancel each others effects out*
77
What is the effect of b2 selective agonist?
- bronchodilation
| - relax uterine smooth m.
78
What are examples of b2 selective agonists for each of its effects and what are they used to treat?
- albuterol/salmeterol: asthma and COPD
| - ritodrine/terbulatine: premature labor
79
What effects are seen with mixed-acting sympathomimetics?
- both a and b, combo effects
| - i.e. vasoconstriction, decongestion, bronchodilation, appetite suppression, and CNS stimulation (fight or flight)
80
What are examples of mixed-acting sympathomimetic?
- ephedrine
| - pseudoephedrine
81
What are the indications and contraindications for psuedoephedrine?
- indications: congestion (decongestant)
| - contraindications: HTN
82
What are two mechanisms for indirect-acting sympathomimetics?
- displace stored catecholamines
| - inhibit reuptake of released NT by interfering with NET
83
What are examples of indirect-acting sympathomimetics?
- amphetamine/meth/phenmetrazine/methylphenidate (Ritalin)
- tyramine
- catecholamine reuptake inhibitors
84
What are the actions of indirect-acting sympathomimetics?
- release stored NE and DA
- increase mood and alertness
- decrease appetite
85
What is a therapeutic use for methyphenidate and how does it work?
- Ritalin
- tx: ADHD
- reduces uptake of NE, 'evens things out'
86
What is the action and therapeutic use of modafinil or armodafinil?
- indirect sympathomimetic
- inhibits NE and DA transporters in CNS
- increases wakefulness
- tx: nacolepsy, obstructive sleep apnea, and shift work disorders
87
What is the action of tyramine?
- releases stored catecholamines
88
What metabolizes tyramine?
- MAO
89
Who should avoid foods containing tyramine?
- patients on MAOIs
90
What are the therapeutic uses of catecholamine reuptake inhibitors?
- ADHD
- appetite suppressant
- antidepressant
91
What is the key feature of cocaine?
- inhibition of DA reuptake in pleasure center of brain leading to rapid addiction via stimulation of b1
92
What could be used to treat hypotension?
- a1 agonists to raise BP
| - i.e. NE, phenylephrine
93
What could be used to treat HTN?
- a2 agonists
| - i.e. clonidine
94
What could be used to treat orthostatic HTN?
- a1 agonist
| - i.e. midrodrine
95
What is used in emergency cardiac resuscitation?
- a1 and b2
| - E
96
What can be used to reduce blood loss at surgical site?
- a1 agonist
| - E or cocaine
97
What can be used to slow diffusion of anesthetics away from admin site?
- a1 agonist
| - lido + E, NE, phenyleprine
98
What can be used to treat sinus congestion?
- a1 agonist
| - oxymetazoline (Afrin)
99
What is a concern when taking an a1 agonist to treat sinus congestion?
- limit use to no more than 3 days due to risk of rebound effect
100
What can be used to treat asthma and COPD?
- b2 selective agonists
| - albuterol/salmeterol
101
How are anyphylactic reactions treated?
- a1, b1, b2 agonists
| - E (EpiPen) often in combo with steroid of antihistamine
102
What can be used to facilitate eye examinations?
- a1 agonists
103
What can reduce eye redness associated with allergies?
- a1 agonist
104
What can reduce IOP in patients with glaucoma?
- a2 agonist
| - apraclonidine (Lopidine) and brimonidine (Alphagan)
105
What can be used to prevent premature labor?
- b2 selective agonists
| - ritodrine, terbutaline
106
What can be used to improve patient comfort in the ICU?
- a2 agonists
