Exam 2 Week 2 Cardiovascular Drugs Flashcards
1
Q
Central Nervous System NT
A
epinephrine norepinephrine dopamine serotonin gamma aminobutyric acid acetylcholine
2
Q
Natural Catecholamine Agonists
A
Epi
NE
dopamine
3
Q
Synthetic Catecholamine Agonist
A
isoproterenol
dobutamine
4
Q
Order of potency for alpha receptors
A
NE>E>Iso
5
Q
Order of Potency for Beta Receptors
A
Iso>E>NE
6
Q
Alpha 1 Receptor Physiology (location and effect)
A
Post-synaptically found in the vasculature, heart, glands and gut
Activation causes vasoconstriction and relaxation of the GI tract
7
Q
Alpha 2 Receptor Physiology (Location and Effect)
Pre
A
Pre-synaptic
- Found in peripheral vascular smooth muscle, coronaries and brain
- Activation causes inhibition of NE release and inhibition of sympathetic outflow leading to decrease BP and decrease HR
- inhibition of CNS activity
8
Q
Alpha 2 Receptor Physiology (Location and Effect)
Post
A
found in: coronaries, CNS
activation causes constriction and sedation and analgesia
9
Q
Beta 1 Receptor Physiology (Location and Effect)
A
found in: myocardium, SA node, ventricular conduction system, coronaries, kidney
Activations causes: increase in inotropy, chronotropy, myocardial conduction, velocity, coronary relaxation and renin release
10
Q
Beta 2 Receptor Physiology (Location and Effect)
A
Found in: Vascular, bronchial, and uterine smooth muscle, smooth muscle in the skin, myocardium, coronaries, kidneys, gi tract
Activation causes: vasodilation, bronchodilation, uterine relaxation, gluconeogensis, insulin release, potassium uptake by the cells
11
Q
Synthetic Non Catecholamines
A
Ephedrine (Direct and Indirect)
Phenylephrine (Direct)
12
Q
Pharmacologic Targets of HTN: Local regulators
A
endothelin antagonist
nitroprusside
ACEi
ARB
13
Q
Pharmacologic Targets of HTN: Circulating regulators
A
Alpha 1 antagonists
alpha 2 agoinst
ACEi
ARB
14
Q
Pharmacologic Targets of HTN: Na/H20 Retention
A
Diuretics
ACEi
ARB
15
Q
Pharmacologic Targets of HTN: Venous Tone
A
alpha 1 antagonist
ARB
ACEi
Nitroprusside
16
Q
Pharmacologic Targets of HTN: HR
A
Beta antagonist
CCB
17
Q
What are the effects of most anesthetics?
A
myocardial depressant and vasodilators
18
Q
Alpha 1 of most vascular smooth muscle (blood vessels, sphincters & bronchi) cause
A
contraction
19
Q
Alpha 1 receptors of Iris (radial muscle) causes
A
contraction (dilates pupils= mydriasis)
20
Q
Alpha 1 receptors of pilomotor smooth muscle causes
A
erect hair
21
Q
alpha 1 receptors of prostate and uterus causes
A
contraction
22
Q
alpha 1 receptors of the heart causes
A
increase force of contraction (B1 more impt)
23
Q
Alpha 2 receptors of platelets cause
A
aggregation
24
Q
Alpha 2 receptors of the adrenrgic & cholinergic nerve terminals (presynaptic)
A
inhibit transmitter release (decrease BP and decrease HR)
25
Alpha 2 receptors of vascular smooth muscle cause
contraction (post synaptic) OR dilation (pre-synaptic, CNS)
26
Alpha 2 receptors of the GI tract causes
relaxation (presynaptic)
27
Alpha 2 receptors of the CNS cause
sedation and analgesia via decrease SNS outflow from brain stem
28
Beta 1 receptors on kidney and heart cause
increase force and rate of contraction
chronotropy, inotropy
stimulation of renin release
29
Beta 2 receptors on respiratory, uterine, vascular, GI, GU (visceral smooth muscle) causes
promotes smooth muscle relaxation
30
Beta 2 receptors on mast cells cause
decrease histamine release
31
Beta 2 receptors on skeletal muscles
potassium uptake, dilation of vascular beds, tremor, increase speed contraction
32
Beta 2 receptors on liver, pancrease and adrenergic nerve terminals cause
glyconeolysis, increase insulin secretion, increase NE release
33
Beta 3 receptors on fat cells cause
activates lipolysis; thermogenesis
34
Dopamine 1 receptors located on smooth muscle cause
dilation of renal, mesenteric, coronary, cerebral blood vessels (post synaptic)
35
dopamine 2 receptors located on nerve endings cause
modulates transmitter release, nausea and vomitting (pre-synaptic)
36
Alpha adrenergic receptors
GPCR
| ligands include NE, E and DA
37
alpha 1 excitatory pathway is
increase in Ca leads to increase camodulin activiation, increases actin-myosin interaction causes smooth muscle contraction
38
Alpha 2 inhibitory pathway includes
decrease cAMP decrease NE release
39
Beta adrenergic receptors
B1-B3
GCPRs, G3s
activation of adenyl cyclase, increase cAMP, increase kinase activation and phosphorlyation
40
Classes of drugs that treat hypertension include
sympathetic nervous system
renin-angiotensin-aldosterone system
endothelium derived mediator and/or ion channel modulators
41
What is a normal BP?
less then 120/80
42
When should someone implement lifestyle modications
>120/80
43
Treatment Goals (age 18-59)
no comorbidites and 60 and older with diabetes and/or chronic kidney disease <140/90
44
Treatment Goals (age >60)
<150/90 with no diabetes or kidney disease
45
First line therapy for HTN
thiazide diuretic unless compelling indication (ie decompensation)
46
Hypertensive Urgency
diastolic BP >120 with evidence of progressive end organ damage
47
Goal of Hypertensive Urgency is
decrease DBP to 100-105 within 24 hours (clonidine)
48
Hypertensive Crisis
diastolic BP >120 with evidence of EOP
49
Goal of Hypertensive Crisis
decrease DBP 100-105 asap (nitroprusside, nitroglycerin, labetalol, fenoldapam)
50
Alpha antagonist
bind selectively to alpha receptors and interfere with the ability of catecholamines to cause a response
51
Competitive alpha antagonist
phentolamine, prazosin, yohimibine
52
Phenoxybenzamine
binds covalently and is tough to overcome
53
Alpha 1 antagonist effects
smooth muscle relaxation
decrease PVR
decrease BP
54
Alpha 1 antagonist clinical uses include
hypertension
| BPH
55
alpha 1>>>alpha 2
| Alpha antagonist
prazosin, terazosin, doxazosin
56
alpha 1>alpha 2
| Alpha antagonist
phenoxybenzamine
57
Alpha 2= alpha 1
| Alpha antagonist
phentolamine
58
Alpha 2>>>Alpha 1
yohimibine, tolazoline
59
Mixed alpha and beta antagonist
labetalol and carvedilol
| B1=B2 >/or equal to alpha 1 > alpha 2
60
B1>B2
| beta antagonist
metoprolol, atenolol, esmolol
61
B1=B2
| beta antagonist
propanolol, nadolol, timolol
62
B2> b1
| beta antagonist
butoxamine
63
cardiovascular effects of alpha 1 antagonism
decrease PVR and lower BP
| postural hypotension due to failure of venous vasoconstriction upon standing
64
Cardiovascular effects of alpha 2 antagonism
increases NE release from nerve terminals result in tachycardia due to stimulation of beta receptors in the heart
65
Alpha antagonist GU effects
blockade in prostate and bladder cause muscle relaxation and ease micturation
66
Additional alpha antagonist effects
miosis
| increase nasal congestion
67
Phenoxybenzamine
binds covalently
alpha 1>alpha 2
decrease SVR, vasodilation
nonselective alpha antagonist
less alpha 2 so less associated with tachycardia with decrease in SVR
PO medication for pre-operative control of blood pressure in patients with pheochromocytoma (0.5-1mg/kg)
68
Pharmacokinetics for Phenoxybenzamine
pro-drug with 1 hours onset time
long acting
e1/2 24 hours
used for patients with raynaud disease
69
Phentolamine
nonselective alpha antagonist
produces peripheral vasodilation and a decrease in SCR
causes reflex mediated and alpha 2 associated increase in HR and CO
70
Uses of phentolamine
intraoperative management of HTN crisis (30-70mcg/kg)
pheochromyocytoma manipulation
autonomic hyper-reflexia
extravascular administration of sympathomimetic agents (2.5-5mg)
71
Prazosin
selective alpha1 antagonist
less likely to cause tachycardia
dilates both arterioles and veins
72
Uses of prazosin
pre-op prep of patients with pheochromocytoma
(controls BP)
essential HTN (combined with thiazides)
decreasing afterload in patients with heart failure
raynaud phenomenon
73
Yohimibine
alpha 2 selective blocker
increases the release of NE from post synaptic neuronu
used with increase orthostatic hypotension, impotence
74
Terazosin and Tamsulosin
Taking for BPH
long acting selective alpha 1a particularly effective in prostatic smooth muscle relaxation
vary in elimination times
orthostatic hypotension is biggest concern
75
Beta Blocker in the heart cause
bradycardia, decreased contractility, decreased conduction velocity, improves O2 supply and demand balance
76
Beta Blocker in the Airway
bronchoconstriction can provoke bronchospasm in patietns with asthma or COPD
77
BB in the BV cause
vasoconstriction in skeletal muscles
| PVD symptoms increase
78
BB in the Juxtaglomerular cells cause
decrease renin release
| indirect way of decrease BP
79
BB in the pancreas
decrease stimulation of insulin release of epi/NE at B2 and then masked symptoms of hypoglycemia B1
80
MOA of beta adrengeric receptor antagonist
selective binding to beta receptors (influence inotropy, chronotropy)
competitive and reversible inhibition- large doses of agonist will completely overcome antagonism
chronic use of associated with increase in the # of receptors (up-regulation)
81
Nonselective BB
propanolol, nadalol, timolol, pindolol
82
Cardioselective BB
beta 1
metoprolol, atenolol, acebutolol, betaxolol, esmolol
large doses lose sensitivity
83
Clinical Uses of BB
treatment of HTN
management of Angina
decrease mortality in treatment of Post MI
used periop and preop for pts at risk for MI
suppression of tachyarrthmias
prevention of excessive sympathetic nervous system activity
84
Relative contraindications of BB
pre-existing AV heart block or cardiac failure
reactive airway disease
DM (W/O BS monitoring)
hypovolemia
85
Side effects of BB
decrease HR, contractility, BP
exacerbation of PVD (block of B2 vasodilation)
airway resistance
alter carb and fat metabolism, mask hypoglycemia
distribution of extracellular K
interaction of anesthetic (decrease MP with IA)
fatigue, lethergy
N/V/D
reduction in IOP
decreased concentrations of HDL
86
Propanolol Protype
nonselective beta blocker
decreases HR and contractility
undergoes extensive 1st pass effect
limited use in anesthesia
concerns with anesthesized pt w/ propanolol:
decrease clearance of amide local anesthestics, decrease pulmonary clearance of fentanyl
Administered with goal HR of 55-60bpm
87
Cardiac Effects of Propanolol
decreased HR, contractility, decreased CO
above effects are especially prominent during excerise and sympathetic outflow
blockade of B2 receptors increased PVR, increase Cop vascular resistance
however, due to decreased HR and CO oxygen demand in lowered opposing the above effects
reduction in renin
88
Pharmacokinetics of Propanolol
significant first pass effect
oral dose larger then IV dose
Protein bound (90-95%)
metabolized in liver
E1/2t of 2-3 hours (will be increase in low hepatic blood flow states)
decreases clearance of amide LAs due to a decrease in hepatic blood flow inhibiting metabolism in the liver- risk of systemic toxicity of amide local anesthetics
89
Metoprolol
```
Lopressor
Beta 1 selective (inotropic and chronotropic)
selectivity is dose related
about 60% thru first pass effect
metabolized in liver
E1/2t 3-4 hours
IV form
```
90
IV propanolol dose
0.05mg/kg IV
| 1-10mg (give slowly 1mg q5mins)
91
Metoprolol Dose
PO 50-400mg
| IV 1-15mg (max)
92
Atenolol
most selective beta 1 antagonist and thought to have the least CNS effects
E1/2t is 6-7 hours
not metabolized in liver, excreted via renal system
pts with renal dx, e1/2t increased
advantageous to pt who need beta 2 receptor activity
oral drug for HTN
long lasting antihypertensive effects
93
Esmolol
Breviblock
rapid onset and short duration on beta 1 selective blocker
IV only
metabolized by plasma esterase (less than 1% of drug is excreted unchanged in urine)
Poor lipid solubility dose not cross BBB or placenta
rapidly hydrolyzed by plasma esterase
no effect on succinylcholine metabolism or duration of action
94
Esmolol Onset of Action
60 seconds
95
Esmolol E1/2t
9 minutes
96
Esmolol DOA
30 minutes
97
Esmolol Treats
useful in treating HTN and tachycardia associated with laryngoscopy
Treats: phenochromocytoma, thyrotoxicosis, thyroid storm
98
Timolol
Brimonidine
nonselective beta blocker
used to treat glaucoma
decreases intraocular pressure by decrease produciton of aqeuous humor
eye drops can cause decrease BP, HR and increased airway resistance
99
Nadolol
nonselective BB
no significant metabolism (renal/biliay elim)
e1/2t of 20-40 hours take 1x daily
100
Betaxolol
cardioselective B1 blocker
E1/2 time is 11-22 hours
single dose daily for HTN
topical used for glaucoma, with less risk of bronchospasm as seen with timolol, so good alternative choice in asthmatics with glaucoma
101
Side effects of Timolol
xerostomia, dizziness, weakness
102
Timolol Potential interactions
```
alpha agonist
beta agonist
amiodarone
cardiac glycosides
CNS depressants
lidocaine
methacholine
MAOis/ SSRIs
quinidine
alcohol
```
103
Precautions with timolol
```
bronchospastic disease
DM
glaucoma, angle closure
MGravis
Thyrotoxicosis
hepatic/ renal impairment
pregnancy/ lactation
```
104
Contraindications of Timolol
Hypersensitivity to drug and/or its components
sinus bradycardia
cardiogenic shock
heart failure, uncompensated
heart black, 2nd or 3rd degree (except with pacemarker)
Severe COPD/asthma
MAO inhibitor use with or within 14 days
105
Labetalol
combined nonselective antagonist
IV beta to alpha blockade 7:1
PO beta to alpha blockade 3:1
metabolism with conjugation of glcuronic acid; < 5% receovered unchanged in urine
E1/2t of 5-8 hours, prolonged in liver disease not effected by renal dysfunction
maximum drop in BP 5-10 mins after IV administration
decreases systemic BP with attenuated reflex tachycardia (beta 2 blockade)
used to treat intraoperative HTN and hypertensive crisis
can be used in hypotensive technique without an increase in HR
can cause orthostatic hypotension, bronchospasm, heart block , CHF and bradycardia
106
Dose of Labetalol
0.1-0.5 mg/kg
| usually 5mg at a time for mild hypertension in the OR
107
Centrally acting BP agents MOA
reduce sympathetic outflow from vasomotor centers in the brain stem
centrally acting selective partial alpha2 adrenegric agonist
108
Centrally acting BP agents Site of action
CNS non adrenergic binding sites and alpha 2 receptor agonism
109
Clinical uses of Centrally acting BP agents
hypertension, induce sedation, decrease anesthetic requirements, improve peri-operative hemodynamics, analgesia
110
Clonidine
centrally acting agent
results in decreased BP from decreased CO to decrease HR and peripheral resistance
rebound HTN and abrupt cessation
111
Side effects of Clonidine
```
bradycardia
sedation
xerostomia (dry mouth)
impaired concentration
nightmares
depression
vertigo
EPS
lactation in men
```
112
Pharmacokinetics of Clonidine
available as PO or transdermal patch
| 50/50 hepatic metabolism and excretion
113
Withdrawal Syndrome of Centrally acting agents
occurs with doses >1.2mg/day
occurs 18 hours after acute discontinuation of drug
lasts 24-72 hours
treatment for rectal or transdermal clonidine
114
Sympathomimetics
```
ephedrine
phenylephrine
vasopressin
epinephrine
NE
dopamine
Dobutamine
```
