Lecture 6 Flashcards
1
Q
What are the two types of indirect-acting cholinomimetic drugs?
A
Carbamates
Phosphates
2
Q
What are 4 carbamates (cholinesterase inhibitors)?
A
Physostigmine
Neostigmine
Pyridostigmine
Edrophonium
3
Q
How do carbamates (cholinesterase inhibitors) work?
A
Bind AchE and block its active site
they are hydrolyzed within 2-8 hours
4
Q
Are carbamates (cholinesterase inhibitors) reversible?
A
Yes, they are water soluble and hydrolyzed
5
Q
WHat indirect-acting cholinomimetic drugs are irreversible?
A
Organophosphates (covalent binding, lipi-souble can cross BBB)
6
Q
What are 2 examples of organophosphates that are indirect-acting cholinomimetric drug that is used for the treatment of glaucoma? They amplify the effects of Ach.
A
Echothiophate
Isoflurophate
7
Q
What are some organophosphates that are volatile oils used in biologic warfare?
A
Tabun Sarin Soman Parathion Malathion
8
Q
This is a reversible water soluble cholinomimetic drug (indirect acting) that is used to treat glaucoma. It also increases intestinal and bladder motility; reverses CNS and cardiac effects of TCA and reverses CNS effects of atropine. It amplifies the effects of Ach.
A
Physostigmine
9
Q
This 3 drugs are used for myasthenia gravis and reversal of neuromuscular block. They amplify effects of Ach and increase muscle strength. They are carbamates (cholinesterase inhibitors).
A
Neostigmine, Pyridostigmine, Edrophonium
10
Q
What is a way to remember excessive acetylcholine effects?
A
DUMBELS Diarrhea Urination miosis Bronchoconstriction Excitation (CNS or skeletal muscle) Lacrimation Sweating and salivation
11
Q
What is a way to remember nicotinic manifestations of acetycholine effects?
A
M T W tH F Mydriasis, muscle twitching Tachycardia Weakness tH Hypertension, Hyperglycemia Fasiculations
12
Q
How do you treat posioning with organophosphate insecticides (ex- Sarin, soman) ?
A
Atropine (anti-muscarinic, reduces the effects of Ach at muscarinic sites)
Pralidoxime (cholinesterase reactivator, reaks down bond b/w drug and enzymes if drug hasnt’ aged)
13
Q
How long does it take for organophosphates (ex- sarin, soman) to age?
A
6-8 hours
14
Q
What areas are most sensitive to atropines effects?
A
Salivary
Bronchial
Sweat glands
Smooth muscles and heart are intermediate
15
Q
What are the effects of muscarinic blocking drugs
A
Basically opposite of Ach
ex- drowsiness, amnesia, mydriasis, slowed peristalsis, urinary retention, decrease of secretion
16
Q
What is a clinical application of the antimuscarinic drug Ipatropium?
A
Bronchdilate in asthma / COPD
17
Q
What is a clinical application of the antimuscarinic drug Benztropine?
A
Treat Parkinson’s disease and adverse effects of antipsychotics
18
Q
What is a clinical application of the antimuscarinic drug Scopolamine?
A
Prevent or reduce motion sickness
19
Q
What is the mnemoic that refers to the toxicity of antimuscarinic drugs?
A
Red as a beat Dry as a bone Blind as a bat mad as a hatter Hot as a hare
20
Q
What are other classes that cause anticholinergic toxicity?
A
H1 antagonists (antihistamines)-diphenhydramine
Tricyclic Antidepressants-amitryptyline
Atypical Antipsychotics-olanzapine
Neuroleptic Antipsychotics-chlorpromazine
21
Q
What type of receptor is a nicotinic receptor?
A
Ion-channel-linked receptor
Allows Na into the cell
22
Q
At the autonomic ganglia what response is ellicited by nicotinic receptors?
A
Depolarization
23
Q
At the adrenal medulla what response is mediated by nicotinic receptors?
A
Secretion of epinephrine
24
Q
At the NMJ what response is elicited by nicotinic receptors?
A
Depolarization of motor end-plate
25
What is the only drug available that activate nictonic receptors?
Nicotine (cigarettes, patches, gum)
26
What are the 2 types of nicotinic antagonists?
Neuromuscular blocking agents
| Ganglionic blocking agents
27
What do nicotinic antagonists that are ganglionic blockers do?
Interfere w/ postsynpatic trnamission of Ach
| Block actino of Ach on nicotinic receptors
28
Are ganglion-blocking drugs currently used?
No, once were for HTN but they have too many severe adverse effects
29
What are neuromuscular blocking drugs used for?
Induce skeletal muscle relaxation in surgery
30
Are non-depolarizing or depolarizing neuromuscular blocking agents competitive?
Non-depolarizing
31
How do depolarizing (non-competitive) neuromuscular blocking agents work?
Resistant to AChE so they persist in teh synpatic cleft and continually depolarizing the NMJ end-plate
32
What is an example of a depolarizing (non-competitive) neuromuscular blocking agent?
Succinylcholine
33
What are 2 long acting neuromuscular blocking agents?
Curare
| Pancuronium
34
What are 2 intermediate acting neuromuscular blocking agents?
Cisatracurium
Atacurium
** Elimination not dependent on hepatic or renal function
35
What are 2 short acting neuromuscular blocking agents?
Mivacurium
| Succinylcholine
36
Drugs that undergo ________ have a longer DOA.
Hepatic metabolism
37
Drugs that undergo __________ have a shorter DOA>
plasma cholinesterase or carboxylesterase metabolism
38
If Curare selective for NMJ?
No, it also effect ganglionic junction so it can lead to respiratory failure and death
39
What do nicotinic antagonists cause?
Tachycardia and hypotension
40
What do muscarinic antagonists induce?
Tachycardia
41
What does botulinum do?
Inhibits ach release thus interferes with nerve impulses
| Causes flaccid paralysis of muscles
42
What is the only depolarizing (non-competitive) neuromuscular blocking agent?
Succinylcholine
43
Which neuromuscular blocking agents are eliminated by the liver metabolism?
Rocuronium
| Vecuronium
44
What drug can cause malignant hyperthermia?
Succinylcholine
45
What are some clinical features of malignant hyperthermia?
Hyperthermia
metabolic acidosis
tachycardia
accelerated muscle metabolism and contractures
46
What drug can be used to stop the effects of malignant hyperthermia?
Dantrolene- blocks release from SR reducing heat production and muscular tone
47
is the sympathetic system considered essential for life?
No
48
Sympathetic innervation of the sweat glands is _______
cholinergic
49
Sympathetic innervation of renal vasculature is _______
dopaminergic
50
What must happen to DOPA to form dopamine?
be decarboxylated (occurs in cytoplams)
51
What blocks the transport of dopamine into synaptic vesicles by the amine transporter system?
Reserpine
52
What metabolizes both DOPA and dopamine to inactive metabolites?
monoamine oxidase (MAO)
53
What hydroxylates DA to norepinephrine (NE)?
dopamine B-hydroxylase within vesicles
54
Where is NE methylated into Epi?
adrenal medulla
55
Where is Epi stored?
choromaffin cells
56
What blocks the release of NE? (2 drugs)
Guanethidine and bretylium
57
What are the 3 mechanisms for for the reuptake and metabolism of catecholamines?
1. Reuptake by NET (norepinephrine transporter) or Uptake 1
2. Metabolism into an inactive metabolite by MAO or COMT
3. Diffusion of catecholamine away from the clef and enter systemic circulation
58
What inhibits tyrosine hydroxylase (first step in synthesis of catecholamines)?
alpha-methyltyrosine
59
What blocks VMAT, trransport of bioamines (NE, DA, 5-HT) from cytoplasm into storage vesicles?
Reserpine
60
What is a dietary amine that is usually metabolized by MAO in GI and liver. In patients with MAO inhibitors on board and large amount of this is absorbed and cause displacement of vesicular NE and non vesicular release --> hypertensive crisis.
Tyramine
61
What displaces NE in storage vesicles and leads to a gradual depletion of NE?
Guanethidine
62
This displaces endogenous NE, is a weak inhibitor of MAO, blocks reuptake by NET and DAT, and has little agonist action at alpha and beta receptors. Marked behavioral effects.
Amphetamine
63
This is a potent inhibitor of NET, and essentially eliminates catecholamine transport.
Cocaine
64
Name 2 drugs that are inhibitors of NET?
Imipramine, fluoxetine
65
What class of drugs blocks Na/K ATPase and blocks NET thereby increasing the DOA .
Tricyclic antidepressants
66
This drug inhibits MAO-A thereby increasing NE and 5-HT content.
Phenelzine
67
This drug inhibits MAO, increasing DA.
| Used in low doses for treatment of Parkinson's
Selegiline
68
What are the two families of adrenergic receptors?
Alpha
| Beta
69
What is the order from most to least of alpha affinity?
Epinephrine
Norepinephrine
Isoproteranol
70
What is the order from most to least for beta affinity?
Isoproteranol
Epinephrine
Norepinephrine
71
What are the 5 actions that occur when alpha 1 is activated?
```
Vasoconstriction
increase PVR
increase BP
mydriasis
increase the closure of internal bladder sphincter
```
72
What are the 2 actions that occur when alpha 2 is activated?
Inhibit norepinephrine release resulting in lower BP
| Inhibit insulin release
73
What are the 5 things that happen when Beta 1 is activated?
```
tachycardia
increased myocardial contractility
Results in increased cardiac output
Increased release of renin
Increased lipolysis (Beta 3)
```
74
What are the 7 things that happen when beta 2 is activated?
```
Vasodilation
decreased PVR
decreased DBP
bronchodilation
increased muscle and liver glycogenolysis
increased glucagon release
relax uterine smooth muscle
```
75
What is an adrenergic drug which acts directly on adrenergic receptor, activating it?
Symapthomimetic (aka adrenergic agonists)
76
What are 3 endogenous catecholamines?
Epinephrine
Norepinephrine
Dopamine (at supraphysiologic concentrations)
77
How do indirect acting adrenergic agonists work?
Work at the presynpatic terminals to cause release of NE.
| Do not bind the adrenergic receptors.
78
What are 2 drugs that are indirect andrenergic agoinsts?
Amphetamine
| Tyramine
79
What is a mixed (direct and in direct) adrenergic agonist?
Ephedrine
80
What receptors does epinephrine (endogenous) interact with?
alpha and beta
81
At low doses what receptor does epi interact with?
Beta (vasodilation)
82
At high doses what receptor does epi mostly interact with?
alpha (vasoconstriction)
83
Epi's affects at Beta 1 lead to what effects?
Increased cardiac output due to increased inotropic and chronotropic effects
84
What effects results from epi's activaiton of alpha?
Vasoconstricts arterioles
85
What effects result from epi's activation of beta 2?
Vasodilates vessels to liver and skeletal muscles
86
What is the net results of epi?
Increased SBP with slight decrease in diasotlic BP
87
What affects does epi have on the respiratory system (beta 2)?
Bronchodilation of smooth muscle
88
What effects does epi have on glucose?
Hyperglycemia
Decreased insulin release (alpha 2)
glycogenolysis, increase release of glucagon (beta 2)
89
Epi's activation of what receptor leads to lipolysis?
Beta 1
90
What are some therapeutic uses of epinephrine?
Emergent treatment of asthma
Glaucoma
anaphylaxis
prolongs duration of local anesthetics thur vasoconstriction (local)
91
How is epi administered?
Sub-Q
Inhalation
Endotracheal
Topically
92
What are some ADRs w/ epi?
Anxiety, fear, tension, HA tremor
hemorrhage from increased BP
arrhythmias
pulmonary edema
93
What happens if an individual with hyperthyroidism is given epi?
Exaggerated CV effects due to increased production of receptors
94
Epi plus what drug will lead to exaggerated CV effects due to prevention of reuptake?
cocaine
95
What receptors does norepinehprine affect?
Alpha 1 and Beta 1
96
What CV effects does norepinephrine have?
Increased vasoconstriction --> increased BP
| Increased baroreceptor reflex --> increased vagal activity causing bradycardia
97
Why can norepinehprine be used to treat shock?
through vascular resistance, increases BP
98
What receptors do low doses (<2 mcg/kg per minute) of dopamine act on?
D1 receptors in renal, mesenteric, and coronary vascular beds (vasocilation)
99
What receptor does higher doses (2-10 mcg/kg/min) of dopamine affect?
Beta 1, positive inotrope
100
What receptor do highes doses of dopamine (>10 mcg/kg/min) work on?
Alpha 1 leading to vasoconstriction
101
What conditions is dopamine useful in treating?
Low CO associated with compromised renal function such as severe CHF
102
What are three alpha-1 selective agonists?
Methoxamine
Phenylephrine
Oxymetazoline
103
What alpha-1 selective agonists is used in relief of nasal congestions and is used topically?
Phenylephrine
104
What alpha-1 selective agonist is used to constrict vascular smooth muscle in relief of opthalmic hyperemia?
Oxymetazoline
105
What are three alpha-2 agonists?
Clonidine
Alpha-methlydopa
Guanfacine
106
What alpha 2 agonist is used to decrease sympathetic outflow. Adverse effects include dry mouth, sedation.
Guanfacine
107
What alpha-2 agonists lowers BP by suppressing sympathetic outflow. Adverse effects include dry mouth, sedation.
Clonidine
108
What drug is a beta-nonselective agonist?
Isoproterenol
109
What drug is used clinically to stimulate the heart in emergencies? It have ionotropic and chronotropic effects (beta 1) and vasodilation of arterioles of skeletal muscle (beta 2) and bronchodilation (beta 2)?
Isoproterenol
110
What is a Beta 1 agonist?
Dobutamine
111
What is dobutamine used for?
Increase cardiac rate and output (more inotrope effects versus chronotrope effects)
112
What are 5 beta 2 selective agents?
```
Albuterol
pirbuterol
terbutaline
salmeterol
formoterol
```
113
Albuterol, pibuterol and terbutaline are all beta 2 _____ acting bronchodilator.
Short
114
Salmeterol and formoterol and beta 2 _____ acting bronchodilators.
long
115
What is a mixed-action drug that is used in nasals sparys for vasocontrictor activity and is used in urinary incontinence. Has a long DOA due to being a poor substrate for COMT and MAO.
Ephedrine
116
What are some conditions where adrenergic agonists are used?
Narcolepsy
Weight Reduction
ADHD
117
What is an adrenergic antagonist that is used to treat a pheochromocytoma to preclude HTN crisis. It is irreversible, nonselective and noncompetitive.
Phenoxybenzamine
118
What are 3 drugs that are selective alpha 1 blockers. Used to treat HTN, BPH, CHF by relaxing arterial and venous smooth muscles
Prazosin
Doxazosin
terazosin
119
What is a drug that is used to treat BPH by inhibiting alpha (1a) receptor on smooth tissue of the prostate.
Tamsulosin
120
What is a non-selective beta blocker that lowers BP, used to terat angina, cardiac arrhythmias, MI, glaucoma and prophylaxis for migraines.
Propranolol
121
What are 2 nonspecific beta-blockers used to treat glaucoma and HTN?
Timolol
| Nadolol
122
What are 4 drugs that preferentially block beta 1 receptors thereby eliminating unwanted bronchoconstriction and having little effect on CHO-meatbolism or PVR.
Acebutolol
Atenolol
Metoprolol
Esmolol
123
What class of drugs can cause or exacerbate HF in compensated HR, acute MI, cause life threatening increase in airway resistance and blunt recognition of hypoglycemia in patients with T1DM?
Beta blockers
124
What are 2 adrenergic antagonists with partial agonist acitivty?
PIndolol
| acebutolol
125
What is a drug that decreases lipid peroxdiation and vascular vall thickening and is an antagonists of alpha 1, beta 1 and 2?
Carvediol
126
What adrenergic antagonist works at alpha 1 and beta 1 and 2 and is used to rapidly lower BP as well as for HTN, CHF, PIH, HTN?
Labetolol
