Selective Alpha adrenergic Receptor Agonist Flashcards
1
Q
Selective alpha 1 antagonists
A
competivive
reversitbel, ALL 3 subtyps (Alpha1a, alpha 1b, alpha 1d)
NO ALPHA 2 ANTAGONIST
2
Q
Primary use of alpha 1 adrenergic
What is an alternative to Phenoxybenzamine?
A
Used for BPH
Prazosin as an ALTERNATIVE to phenoxybenxamine
3
Q
Seleactive Alpha adrenergic receptor CV
A
Greater vasodilation at veins and arteries
4
Q
Selective alpha 1 adrenergic found where?
A
found in bladder
5
Q
Adverse effects
A
Orthostatic hypotension, fluid retention, vertigo, syncope and nasal congestion
6
Q
The administration of usual doses of
A
an alpha 1 agonists such as phenylephrine may not produce the desired effect in patients , MAY HAVE TO GIVE SLIGHLY MORE MEDS
7
Q
Selective ALPHA 1 A receptor antagonists
A
Tamsulosin, Silodosin
Both selective, competitive post synaptic alpha 1 a antagonists
Alpha 1 a : BLADDER and PROSTATIC TISSUE
8
Q
Mechanism of action
A
Selectively inhbiti alpha 1a recepotrs found in smooth muscle in the bladder base, bladder necks, prostatic capsule
9
Q
Beta adrenergic Receptor Antagonists
A
Bind selectively, reversibly and competitively to beta adrenergic recepotrs and INHIBIT catecholamins, and other sympathomimetics –> Decreased adenylate cyclase which decreases the concertation of cAMP
10
Q
Beta adrenergic antagonist main pharm effect
A
Mechanism of INVERSE AGONIST
11
Q
More drugs to compete
A
ccompetitive reversible.
12
Q
Classification of Beta adrenergic
A
Receptor antagonized intrinsic sympathomimetic difference in lipid solubility Membrane stabilizing effects Differences in pharmacokinetic profile.
13
Q
Beta adrenergic receptor antagonists
A
Non selective beta or cardio selective
14
Q
Non selective beta adrenergic agonists
A
Beta 1 and beta 2
INhibit chrono, ino, and vasodilator responses
Propanolol, nadolol,, sotalol, timolol, carvedilol, labetalol, carteolol, pinolol
15
Q
Cardio selecte beta 1 ANTAGONISTS
A
Less likely to proDUCE BRONCHOSPASM
vASOCONSTRICITION
AND ALTER METABOLIC EFFECTS
16
Q
It is imnt to recognize that cardioselectily is dose dependent and beta 1 selectivity is lost whe
A
higher larger doses of these agents are administered and they can inhbiti beta 2 recepots
17
Q
It is important to recognize that cardioselectily is dose dependent and beta 1 selectivity is lost whe
A
higher larger doses of these agents are administered and they can inhbiti beta 2 recepots
18
Q
Intrisic Sympathomimetic Activity
A
Can actually have slight AGONIST effect even though it is an antagonists
19
Q
ISA means
But when endogenous NE is high
A
ISA means that the beta adrenergic antagonist demonstrates a PARTIAL AGONISTS effect at the beta receptor site and will partially activate the beta receptor If the concentration of endogenous NE is LOW, as in resting state.
But when endogenous NE is high, these agents will still be occupying beta receptors and the overall effect will be antagonism of NE effects
20
Q
ISA agents cause less direct myocardial depression and result in
A
less bradycardia than agents that do not have ISA
21
Q
Bottom line for the anesthesia providers: ISA
A
DONT USE THEM IN PATIENT UNLESS YOU HAVE TO
22
Q
Beta adrenergic antagonists that have ISA are to be used in
A
Extreme caution with HR diseases.
23
Q
Lipid solubility
A
Beta blocker high , mod, or high lipophilicity
High cross BB, decrease SNS outflow by antagonizing beta receptors.
24
Q
Post op propranolol
A
Lethargy
Vivid dreams
25
The highest lipid soluble beta blocker is
PROPANOLOL
26
MSA (not releveant at normal doses ONLY IN
TOXICITY
Membrane Stabilizing activity
Can inhibit fast Na channels in the heart
Quinidine 1a antiarrythymic agents
27
MSA meds
```
Propanolol
Acebutolol
Carvedilol
Metoproplol
Pindolol
Labetalol
Nebidolol
```
28
Elmination of esmolol
Esterases in Cytosol of RBCs
| Half life 9 minutes.
29
Know nonselective or CARDIOSELECTIve agents
BOLD : drugs, know ISA< MSA
30
Beta blocker uses : TAPIE
```
Essential HTN
ACS
Tachyarrythmia
Intra op HTN
Preventative to prevent negative outcomes
```
31
Anesthesia purpose use of Beta Blockers
Prevention of excessive SNS activity with
Direct laryngeal and tracheal intubation
Hypertrophic obstructive cardiomyopathies
Hyperthyroidism
Cyanotic
baroreceptor reflex
anxiety and panic attacks
32
*****PERIOPERATIVE USE OF Beta BLOCKERS
```
Patients are
Risk for Myocardia ischemia (or previous MI)
Known CAD
Diabetic
LVH
Positive PRE-OP stress test
At risk for MI, from a certain surgeries
```
The general goal is a resting HR between 65-80 per minute
Avoid using beta adrenergic receptor antagonist that POSSES INTRINCIS sympathomimetic activity for this indication.
33
Beta Blockers MOA on NODAL '
_______automaticity
_________Sinus rate
__________AV nodal conduction velocity
________ Refractory period of the AV node
_________ PR interval
________ chronotrope and dromotropic effects
_________SLOPE OF PHASE 4 SPONTANEOUS DEPOLARIZATION
Decrease automaticity
Decrease Sinus rate
Slows AV nodal conduction velocity
Increased Refractory period of the AV node
Lengthens PR interval
Negative chronotrope and dromotropic effects
DECREASE SLOPE OF PHASE 4 SPONTANEOUS DEPOLARIZATION
34
Beta blockers MOA on Myocytes
___________ phase 2 of the fast action potential
__________ force of contraction in cardiac muscle cells
________ inotrope effects
These agent reset the baroreceptors reflex ___________
Decreases phase 2 of the fast action potential
Decrease force of contraction in cardiac muscle cells
Negative inotrope effects
These agent reset the baroreceptors reflex DOWNWARD
35
Beta blockers on PVR and Afterload?
Decrease PVR which will decrease afterload
36
Cardiac effects of Beta blockers
| HR< FOC< CO, PVR, Diastolic filling, myocardial oxygen demand.
```
Decreased HR
Decreased FOC
Decreased CO
Decreased PVR
Increase DIASTOLIC FILLING time
Decrease myocardial oxygen demand
```
37
No beta blockers for patients with
AV blocks
38
Non selective beta adrenergic agonists inhibits
VASODILATION of the beta agonists such as ISOPROTERENOL
39
The cardio stimulating effects of
CALCIUM
GLUCAGON
DIGOXIN
are not effected by beta adrenergic antagonists.
40
Non selective beta adrenergic antagnostis enehcnaeg
the pressor response to epinephrine since non selective beta adrenergic antagnosits prevent the beta 2 vasodilating effects of epinephrine and leave UNOPPOSED alpha 1 mediated vasocontasticn which can lead to exaggerated HTN
41
Beta adredergic receptor antagonisms
should only be used after adequate alpha block
42
PORTAL BLOOD FLOW EFFECTS
Non selective antagonists, reduce by producing splanchnic vasoconstriction thereby reducing portal blood flow .
43
Portal HTN
Reduces the flow, decrease the pressure
44
Portal HTN beta blocks user
propranolol
Nadolol
Carvedilol
45
Non-cardiac effects of beta adrenergic
Beta 2 agonism can lead to bronchoconstriction and increased airway resistance
uSE BETA BLOCKERS WITH bronchospactic effects
46
Metabolims of
Modify the metabolism of carbohydrate and lipids
| Decreased with Glycogenolysis and pancreatic glucagon stimulation can occur, primarily via beta 2 blockadge.
47
Beta blockers and blood sugar
Type I diabetic patients : mask hypoglycemia
48
FOr anesthesia, patients with diabetes
ALWAYS give Beta 1 selective antagonists.
49
ALl beta blockers can interfere
with the counterregulartory effects of catecholamins that are secreted during hypogleycemina by blunting the pereception of tachycardia, tremor and nervousness.
50
Tachycardia is
an important warning sign fof HYPOGLYCMEIA is BLUNTED AND MASKED BY beta adrenergic antagnoists.
51
Beta blockers may mask
HYPOGLYCEMIA.
52
______Effects may occur between beta antagnoists and drugs used during anesthesia
Additive
53
Beta Blockers contraindications (ABSOLUTE)
```
Sinus bradycardia
2nd and 3rd degree HB
Cardiogenic shock
Decompensated HF
Sick Sinus syndrome.
Non selective beta blockers are contraidncated in bronchial asthma/bronchospatic disease.
```
54
Beta Blockers contraindications (ABSOLUTE)
```
Sinus bradycardia
2nd and 3rd degree HB
Cardiogenic shock
Decompensated HF
Sick Sinus syndrome.
```
Non selective beta blockers are contraindicated in bronchial asthma/bronchospatic disease.
Cardio-selective beta blockers may be use in asthma and are the preferred beta blockers in these patient should be used with caution.
55
Cardioselective
PVD, diabetes, used cardioselective
56
Myocardial depression produced by INHALED or INJECTED scould be
Additive, with depression caused by beta blockers is usually excessive.
57
******Additive cardiovascular effects with inhaled anesthetics when patients on beta blockers
***ENFLURANE, very high risk
INtermediatRISK e with HALOTHANE
ISOFLURANE< SEVOFLURANE< DESFLURANE low
58
Avoid ketamine always
stimulate the SNS and promotes an increase in SVR and afterload.
59
Non-dypyrimides beta blockers
CCB with Beta blockers, can be given with caution.
60
Clinical manifestation of poisoning are dependent on:
ISA,
MSA
degree of beta 1 and beta 2 agonistsm
61
Beta adrenergic antagonists with MSA may cause
QRS prolongation (quinidine like effects)
62
Treatment of Beta BLOCKERS
IV fluids
Glucagon 2-10mg IVP followed by 5mg/hr
ATropine (DOESN'T WORK)
Calcium chloride 1-2 gm
Catecholamines
63
Specific for ANESTHESIA
The elimination 1/2 is considered in the periop period when redosing intervals are being developed or when conversion to another beta receptor antagonists is planned
Propanolol, METOPROLOL< LABETALOL, ESMOLOL are particularly useful in anesthetic practice because they are widely available in IV formulation.
64
Propanolol
non selective beta blocker lacks ISA
Prototype drug
IV and oral (absorbed completely) 25 % reachest systemic circulation
65
There is a great inter-individual varation
Propanolol
66
Several CYP 450 enzymes metabolism
Hepatic metabolism of propanolol
67
Metaboism depenednet of PROPANOLOL
HEPATIC BLOOD FLOW
68
active metabolite of propanolol
4-hydroxypropanolol
69
Elimination t 1/propranolol
2-5 hours
70
Propanolol is
Highly protein bound
| No adjustments for renal dysfunction
71
Propanolol ONSET OF ACTION
IV 0.25- 5mg IV
72
Propanolol Anesthesia interaction
propranolol decreases the clearance of AMIDE local anesthetics by decreasing hepatic blood flow and inhibiting metabolism in the liver.
The toxicities of agens such as bupivacaine and lidocaine are increased by propranolol
73
Propanolol anesthesia interaction
Pulmonary first pass uptake of fentanyl is substantially decreased in patients chronically treated with propranolol, as a result 2-4 times as much fentanyl
74
Nadolol is a non
SHORT DISCUSSION
75
Timolol
Main Beta blocker in eye gtt
76
Timolol
Main Beta blocker in eye gtt
| Side effects: Bradycardia and hypotension
77
CARDIOSELECTIVE
Metoprolol
Selective inhibitor of beta 1 adrenergic recepotrs
LACKS ISA, and has MSA
78
CARDIOSELECTIVE
| Prototype
Metoprolol
Selective inhibitor of beta 1 adrenergic receptors, competitively block beta 1 and prevent inotropic and chronotropic responses
LACKS ISA, and has MSA (only at doses much greater than required for beta blocker)
79
Metoprolol is a
Beta 1 selectivity of metoprolol is dose related, such that beta 1 selectivity is lost at high doses
80
Metoprolol dosage form
IV , PO
Duration 5-8
peak IV effect : 20 minutes.
Typical IV dose of peri-operative area 1-5mg
81
Metoprolol dosage form:
```
IV , PO
Duration 5-8 (high variable)
peak IV effect : 20 minutes.
Typical IV dose of peri-operative area 1-5mg
LOW PROTEIN BINDING
```
82
Atenolol (TENORMIN)
comment on ISA, MSA, Lipophillix vs/ Hydrophillic
What does the administration of atenolol help?
Kidney dose adjustment?
TEST on boards
Cardioselective, no ISA< NO MSA, low lipophilicity, very hydrophilic.
Periop administration of atenolol in patients at risk for CAD decrease the incidence of post op MI
Prolonged effect --> only one dosing required.
Dose adjustment for kidney patients
83
With metoprolol, what remains intact?
Bronchodilator
Vasodilator
metabolic effects of beta 2 receptors remain intact since it's cardio selective
84
With beta blockers what is lost at higher doses?
Beta 1 selectivity of metoprolol is dose related and beta 1 selectivity is lost at high/large doses.
85
Esmolol
Rapid onset, short duration, no significant ISA or MSA at therapeutic dosages and is a low lipiphillic agent
86
*****know ESMOLOL doses (SVT doses)
0.5mg/kg IV over 1 min f/b 50mcg/kg/min for 4 minutes
87
If after initial 5 minute infusion your response is inadequate
give a 2nd 0.5mg/kg over 1 minu, then increase drip to 100mcg/kg/min max drip is 200mcg/kg/min
88
For esmolol give a maximum up to
3 loading doses
89
Loading dose always equals ______over ____min for esmolol
0.5/kg ; 1 min
90
Intra-OP POST OP tachycardia use of Esmolol for immediate control
For intraop tx of tachycardia and HTN
1mg/kg bolus dose over 30 seconds f/b 150mcg/kg/min
infusion, if necessary.
Adjust the infusion rate as required up to a max of 200mcg/kg/min for tachy tx and 300mcg/kg/min for HTN tx
91
Intra-OP POST OP tachycardia use of Esmolol for GRADUAL control
For post op tx of tachy or hypertension
500mcg/kg IV loading dose over 1 min f/b by a 4 minute infusion @ 50mcg/Kg/min
Reassess
92
Esmolol onset of action is _____
fast 2-5 minutes
93
Esmolol Duration of action
when infusion stop, within 10-30 minutes, effects of drugs are gone.
94
Esmolol; metabolism of action via
ESTERASES in the CYTOSOL of RBCs
(esmolol contains ester linkage is rapidly metabolized by hydrolysis of the ester linkage, chierfly by the esterases in the cytosol of RBCs)
95
Esmolol is lipid soluble?
NO
96
Esmolol can be associated with ________ when used in labor and delivery, use with caution
Fetal bradycardia; uncommon
97
Elimination half life of esmolol is
9 minutes
98
Excretion of esmolol
73-88 % appears in urine
99
Most common adverse effects of esmolol
Hypotension
Diaphoresis
RARERLY REPORTED WITH Esmolol: bradycardia.
100
In hypovolemic patient, esmolol can
attenuate reflex tachycardia and increase the risk of hypotension
101
Drug to drugs anesthesia Esmolol
a.Combining esmolol with succinylcholine, duration of succ induce neuromuscular blockade is PROLONGED
b.WIth mivacurium prolonged clinical duration and recovery index of mivacurium
ESMOLOL and propofl significant DECREASES the plasma concentration of Propofol.
102
Esmolol with catecholamines
ESMOLOL should NOT be used to control tachycardia in the presence of vasoconstrictive and positive inotropic agents such as dopamine, epi, NE, because the danger of reducing cardiac contractility in the presence of HIGH SVR
103
NEBIVOLOL (oral)
Highly CARDIOSLECTIVE beta 1 receptor antagonists that also have ENDOTHELIAL NO-MEDIATED VASODILATION Activity
NO ISA or MSA
104
Combined ALPHA and BETA ADRENERGIC ANTAGNOISTS
Both beta blockers and alpha 1 antagonists
105
Labetalol
competitive antagoistn, at alpha 1, beta 1 and beta 2
Partial agonists of B2 agonists (Vasodilation)
Affinity for 4 receptors,
106
Labetalol has _____isomers
4
107
The ration of B : Alpha 1 blocking potency is
3: 1 for oral
7: 1 for IV
108
Labetalol is 1/10th to 1/5th as potent as phentolamine at ________ AND 1/4th to 1/3rd as potent as propranolol at blocking Beta adrenergic receptors
ALPHA 2
109
MOA of labetalol (act on 4 receptors)
Alpha 1 antagonism--> relaxation of arterial SM and vasodilation causing decrease SVR and BP
Non-selective B2 blockade, decreased HR
B1 blockade decreased BP
it is a PARTIAL AGONIST at Beta 2 recepots, vasodilation
110
Labetalol CV effects
| CO, BP, onset, peak, Duration, can you give as continuous?
```
CO unchanged
Hypotensive action
Onset 2-5 mns
Peak 5-15 mns
Duration: 2-4 hours
May be given as continuous DONT DO IT
```
111
Labetalol: pharmacokinetics
Undergoas extensive HEPATIC METABOLIMS
t 1/2 prolonged in the liver
Decreased blood flow decrease metabolism
Increase liver blood flow increase metabolism
112
Main route of clearance is
Hepatic metabolism
113
Pregnancy induced HTN crisis treated with
Labetalol
114
Dose of labetalol for HTN emergencies
Labetalol 5-20 mg IV may be repeated EVERY 10-15 MINUTES UNTIL desired effect. GIve time to work .
115
Labetalol use for treatment of
Pheochromocytoma also
116
Adverse effects of labetalol
Hypotension
Orthostatic hypotension
Bronchospasm
CAUTION with CHF
117
Carvedilol is a
competitive antagonists at alpha 1, beta 1 and beta 2
118
Carvedilol
antioxidant
and anti-inflammatory
***FOR HF, HfREF
Has MSA< lacks ISA
119
Mnemonic for drugs with MSA and list
```
PAcMP BLCa
Propranolol
Acebutalol
Metoprolol
Pinodolol
Betaxolol
Labetalol
Carvedilol
```
120
Mnemonic for drugs with ISA and list
La Pin Ace
Labetolol
Pindolol
Acebutalol
121
Mnemonic for drugs with Low Lipophilicity and list
BetEsANadSotA
```
Betaxolol
Esmolol
Acebutalol
nadolol
sotalol
Atenolol
```
122
Mnemonic for drugs with mod lipophilicity and list
BisMetPinTiCarLa
```
Bisoprolol
metoprolol
pindolol
Timolol
Carvedilol
Labetalol
```
123
Mnemonic for drugs with High lipophilicity and list
Nebi - Pro
124
Drugs with clearance Hepatic 1 then Renal 2
BetAcePinTim -- Bis (Renal -> hepatic)
```
Betaxolol
Acebutalol
Pinodolol
Timolol
Bisoprolol
```
125
Hepatic only clearance drugs
```
MetNebProLa
metoprolol
Nebidolol
Propranolol
Labetalol
```
126
Renal only clearance
SoCartNaAt
127
Biliary 1 than hepatic only (think BH)
CARVEDILOL
128
What is not effected by Beta adrenergic antagonism?
the cardio stimulating effects of CDG
Calcium
Digoxin
Glucagon.
