Exam I cholinergics and adrenergics Flashcards
1
Q
What drugs are choline esters and what type of compound are they
A
acetylcholine, carbachol and bethanechol
quarternary ammonium
2
Q
why is bethanechol slower acting than carbachol and Ach
A
because it resists cholinesterases more
3
Q
choline esters and alkaloids act as agonists or antagonists on cholinergic R?
A
agonists
4
Q
what drugs are the alkaloids that act on chilinergic R
A
muscarine, nicotine and pilocarpine
5
Q
describe structures and modes of absoprtion for muscarine and nicotine
A
nictoine is tertiary amine so absorbed at most sites
muscarine is quaternary amine and highly toxin if ingested because can enter brain
6
Q
What Ach R are found in the nerves
A
M1 and the NN (dendrites) NM(NMJ)
7
Q
What Ach R are in the CNS
A
M4 M5 and NN
8
Q
What Ach R are in the Heart, and smooth m
A
M2
9
Q
What Ach R are in the glands, smooth m and endothelium
A
M3
10
Q
where are nACHR
A
skel muscle
11
Q
What happens in vasculature in the presence of high levels of Ach
A
constriction
12
Q
compare high doses Ach and low action on the heart
A
small cause vasodilation and dec in BP
large causes bradycardia and dec AV node conduction velocity and hypotension
13
Q
Differentiate smooth m contraction caused by M2 Ach R and M3
A
M2 directly activates contraction
M3 reduces cMP formation and reduces relaxation caused by adrenergic effects
14
Q
What Ach R predominate the brain and which ones the spinal cord
A
mACHR in brain and
spinal cord nACH R
15
Q
What are the ACH effects on the GI and GU tracts
A
nausea, vomiting, diarrhea, voiding of urine
16
Q
What are the side effects of too much muscarinic ACH
A
nausea, vomiting, diarrhea, urinary urgency, salivation, sweating, cutaneous vasodilation, bronchial constriction
17
Q
How do we block negative sideeffects of choline esters and ilocarpine
A
atropin, antimuscarinic compounds
18
Q
What are the major contraindications for mAchR agonists
A
asthma, hyperthyroidism, coronary insufficiency, acid-peptic disease
19
Q
What are signs of acute toxicity of direct acting cholinergics
A
convulsions, coma and respiratory arrest
depolarization blockads–> respiratory paralysis, HTN and cardiac arrythmias
20
Q
What is metacholine used for
A
to Dx hyperreactivity of broncial airway
21
Q
What is Bethanechol used for
A
to Tx urinary retention and heartburn
selective mAchR agonist
22
Q
What type of pharm agent is carbachol
A
nonspecific cholinergic agonist that is used for Tx of glaucoma
used to make miosis during surgery or ophthalmic examination
23
Q
What is cevimeline
A
oral tablet used to treat xerostomia (dry mouth)
metabolized via p450 and eliminated in urine
24
Q
What is pilocarpine used to treat
A
xerostomia, also head and neck cancer Tx related to xerostomia
miosis for opthalmic procedures and glaucoma
mAchR agonist
25
What is Varenicline used to Tx and how does it work
smoking cessation
partial agonists to a4b2 nAchR in brain
released dopamaine thought to curve craving
26
what are side effects of varenicline
nausea, neuropsychiatric symptoms like change in behavior, agitation, depressed mood, suicidal ideation
27
What are indirect acting cholinergic agonists
cholinesterase inhibitors
28
What are the chemical groups of Achesterase inhibitors
alcohol
carbamic acid esters
organophosphates
29
What is structure and mech of alcohol indirect-acting cholinergic agonists
alcohol group and quaternary ammonium group
| bind to AchE is non-covalent and reversible
30
What are types of organophosphate indirect acting cholinergic agonists
echthiophate, parathion, malation, sarin, soman and tabun
31
Describe the binding of organophosphates
bind to AchE covalent and irreversible
32
Describe pharmakinetics of quaternary and charged AchE inhibitors
relatively insoluble in lipids and absorption from conjunctiva, skin and lungs is poor
parenteral admin
no CNS involvement
duration of effect determined by stability of inhibitor-enzyme complexx
33
describe pharmacokinetics of teriaty and uncharged AchE inhibitors
well absorbed everywhere
CNS distribution
more toxic than polar quaternary carbamates
e.g. physotigmine, donepezil, tacrine, rivastrigmine, galantamine
34
describe pharmacokinetics of organophosphates
lipid-soluble and readibly absored making dangerous to humans
distributed everywhere
includes CNS toxicity
coavalent and irreversible so usually biotransformation pathways
35
describe AchE inhibitors activity of CV system
SAN and PAN ganglia
PAN dominates so CO decreases
modest bradycardia, dec contractility of atria
decrease in BP
36
What are the main therapeutic uses of agents that stimulate AchR
galucoma, GI and urinar tracts, NMJ (myasthenia gravis)
heart (rarely for certain atrial arrhythmias
alzheimer disease
37
What do we use to reverse NMJ blocking in anestheia
AchE inhibitors
38
how do AchE inhibitors help with glaucoma
reduce intraocular pressure by stimulating mAchR of ciliary body causing contraction allowing outflow of aqueous humor
39
What are symptoms of anticholinergic overdose
cutaneous vasodilation, anhidrosis, anhydrotic hyperthermia, nonreactive mydriasis, delirium, hallucinations, reduction or elimination of the desire to urinate
40
What is used to reverse overdose of anticholinergic effects
physostigmine because crosses bbb
41
what happens when you combine a nondepolarizing NMJ blocking agent with AchE inhibitor
diminsh the blockade
42
What happens with succinylcholine and AchE inhibitors
enhance phase 1 block and antagonize phase 2 block
43
What happens with cholinergic agonists(direct) and AcheE inhibitor
enhance effects of cholinergic agonists
44
what happens when you combine beta blocker and AchE inhibitor
enhance bradycaric effects
45
what happens when you combine systemic corticosteroids with AchE inhibiors
enhance muscle weakness seen in patients with myasthenia gravis
46
what are the dominant initial signs of acute AchE inhibitiro intoxication
miosis, salivation, sweating, bronchial constriction, vomiting, diarrhea
47
how do you Dx deliberate poisoning
AchE activity measurement in RBC and plasma
48
What are cholinesterase regenerators used for
they restore stimulation of motor nerve after organophosphorus dosage that blocks the stimulus
49
What is pyridostigmine
a prophylactic for AchE inhibitor poisoning,
| military use it if in area where might be exposed to nerve gas
50
what is the prototype antimuscarininc compound
atropine
51
where are tertiary amines of anticholinergic drugs targeted?
eye or central nervouse system
| atropine, tropicamide, benztropine
52
where are the quaternary amines of anticholinergic drugs targeted?
antimuscarinic effects in the periphery
| ipratropium and glycopyrrolate
53
what is the half life of atropine
2 hours
54
is atropine reversible
yes
55
what tissues are most sensitive to atropine
bronchial, sweat glands and salivary
56
lwhat mAchR does atropine work on
all 5
57
what drug is used to prevent motion sickness
scopolamine
58
describe mode of action of antimuscarinic agents on the eye
weaken ciliary muscle causing inability to focus on nearby vision
and reduce lacrimal secretions
59
describe atopine effects on respiratory system
smooth muscle and secretory glands of airway receive vagal innervations and contain mAchRs
case bronchodilation and reduce secretion
60
describe effects of atropine on GU tract
relax smooth muscle of ureters and bladder wall
| slow voiding
61
what cholinergic antagonists are used for parkinsons
benztropine, trihexyphenidyl and procyclidine
62
describe uses of atropine in anesthesia
paired with neostigmine to block parasympathetic effects during reversal of skel muscle relaxation
63
What are the NE reuptake blockers
cocaine, Imipramine, venlafaxine
64
What are the main catecholamines reuptake drugs that are NOT taken orally
epinephrine, norepinephrine
isoproterenol
dopamine
dobutamine
65
what is the main alpha agonist drg
phenylephrine
66
what are the beta 2 agonists
albuterol, salmeterol and formoterol
67
what are the effects of alpha adrenergic drugs
```
constriction of blood vessels(a1)
mydriasis (a1)
contraction of spleen and uterus (a1)
glycogenolysis of liver (a1)
ejaculation vas deferens (a1)
inhibit release of insulin (a2)
relaxation of intestinal smooth muscle (a2)
```
68
what are the effects of beta adrenergic drugs
positive inotropic and chronotropic effects on the heart (b1)
stimulates release of renin (b1)
relaxation of bronchioles and uterus (b2)
relaxation of vas smooth m in skel m coronaries (b2)
metabolif effects, glycogenolysis and lipolysis
stimulates release of insulin (b2)
relaxation of detrusor and intestinal smooth m (b2)
69
what are the cardiac effects of epinephrine
```
+ positive chronotropic effect
+ inotropic effect
increased conduction in atria,
increased oxygen consumption
increased work of the heart
```
70
what R does epinephrine have greatest affinity for
beta2
71
descirbe the effects of epinephrine on blood vessels
low doses- beta2 causing relaxation
| high doses- alpha 1, causing contraction
72
what are the effects of epi on renal circulation
vasoconstriction
| alpha 1
73
what aa are vasodilated with epi
coronaries (beta2)
74
how is epi used in asthma
bronchodilator (b2) vasoconstrictor (a1) and inhibitor of Ag-induced release of histamine (b2)
75
what is a bad side effect of epi if used concurrently with halogenated hydrocarbons
arrhythmias
76
what are the CNS side effects from epinephrine
fear, anxiety and headaches
77
what conditions are contraindicated in use of epinephrine
HTN, shock, Hyperthyroidism, angina pectoris, asthmatics with degenerative heart disease
78
What are the pharmacological effects of Norepi
agonist to a1 and 2 and b1
79
what are the effects of norepi on the heart
direct, positive inotropic and chronotropic effects
| indirectly causes a reflex of bradycardia
80
what is the bradycardic reflex from nor epi stimulated by
vasoconstriction
81
how to we prevent the reflex bradycardia seen after admin of norepi
atropine
82
what R in blood vessels are activated by norepi
a1
83
What is the net effect of Norepi on blood vessels
increased blood pressure
84
what are the metabolic effects of norepi
a1 causes weak glycogenolysis and beta3 causes lipolysis
85
what are the side effects of norepi on blood vessels
anxiety, slow forceful heart beat, headache
86
What R does isopoterenol target
agonist B1 B2 and B3
87
what are the effects of isoproterenol on heart
increased HR and force on contraction
88
what are the effects of isopoterenol on blood vessels
vasodilation of blood vessels in skel m
89
What is the net change in BP from isoproterenol
decreased in mean atrial BP
90
what are the effects of isoporterenol on smooth m
relaxes bronchial and uterine smooth m
91
what are the metabolic effects os isoporterenol
increased FFA because release insulin and opposes B2 glycogenolysis in liver
92
what is isoproterenol used for in th ehar
hear block, intracardial injection
cardiogenic shock after MI
increases CO and blood flow
93
what are the common sideeffects of isoproterenol
tachycardia, headache, flushing of skin
94
what are the serious side effects of isproterenol
arrhythmias, anginal pain.
95
what R does dopamine acticate
B1 and D1
| at high also a1
96
what are the effects of dopamine on the heart
mild positive inotropic and chronotropic effects compared to isopoterenol
97
what are the effects of dopamine on blood vessels
vasodilation of mesenteric and renal vascular beds (dopamine R)
98
how does dopamine help in schock
increase CO and enhance perfusion
99
How is dopamine effective in CHF
increases CO without increases TPR
100
What is Fenoldopam
synthetic dopamine D1 agonist
| used to Tx HTN
101
What is Bromocriptine
synthetic dopamine D2 agonist used to Tx parkinsons or prolactinemia
102
What R does Dobutamine act on
selective B1 agonist
| partial
103
How is dobutamine effective for AMI
smaller effects on HR and systolic pressure
| increases CO- lesser incidence of dopamine (especially for cardiogenic shock)
104
what is the main contraindication for dobutamine
idiopathic hypertrophic subaortic stenosis
105
What is different about metabolism of alpha adrenergic agonists "non-catecholamine" vs catecholamines
not metabolized as rapidly by COMT/MAO
106
What R does phenyleprhine act on
a1
107
What is phenylephrine used clinically for
nasal decongestant, infiltration with local anesthetics
pressor agent
paroxysmal atrial tachyardia inducing reflex bradycardia
glacoma
mydriasis(no effect on accomodation
108
What is Midodrine used for
orally for orthostatic hypotensions that is disabling
109
What are the main B2 agonists
albuterol, salmeterol, formoterol metaproterenol, terbutaline, ritodrine
110
what are side effects of albuterol
muscle tremors, tachycardia, headaches, hypoglycemia, hypokalemia
111
how do amphetamines work adrenergically
release NE from nerve endings and inhibit reuptake NE
112
What are examples of pharm amphetamines
adderall (benzedrine)
| dexedrine
113
What are the CNS effects of amphetamines
increased alertness, confidence, ability to concentrate and decreased sense fatigue
114
What are the CV effects of amphetamines
vasoconstriction, positive inotropic effect
115
what are the smooth mm effects of amphetamines
mild constriction of sphincter of bladder
116
what are the metabolic effects of amphetamines
last several hours
117
what do we use amphetamines for clinically
nacrolepsy, ADHD and obesity (Anorexic effects)
118
What are main side effects of amphetamines
CNS, insomnia delirium, anxiety
CV, arrhythmias anginal pain
GI: nausea vomiting
119
What are signs of acute and chronic amphetamine toxicity
acute: convulsions, coma, death
chronic: abnormal mental state, weight loss, psychotic reactions
120
How do we reverse amphetamines
are weak bases and therefore acidity-urine with ammonium chloride to prevent reabsorption
121
what R does ephedrine and pseudoephedrine act on
mixed
| B receptor and indirect actions (release NE)
122
why are ephedrine and pseudoephedrine so long acting
not hydrolyzed by COMT or MAO
123
What is ephedrine and pseudo ephedrine used for
pressor agent in spinal anesthesia, nasal decongestant, severe acture bronchospasm by parenteral admin
124
What are sideeffects of ephedrine
anxiety, insomnia, palpitations
125
What receptors do nasal decongestants act onact on
alpha 1 causing casoconstrictor
126
What nasal decongestant should not be used in patients with HTN
otricin which is xylometazoline
127
what nasal decongestant should not be used in children
tetrahydrozoline (tyzine and visine)
