Stoelting: Chapter 19 Flashcards
(244 cards)
1
Q
What is Phentolamine?
A
- A substituted imidazoline derivative
- Cause transient nonselective α-adrenergic blockade.
2
Q
How is Phentolamine administered and what are its immediate effects?
A
- Administered intravenously
- It causes peripheral vasodilation
- Decreases blood pressure within 2 min
- Last 10-15 minutes.
3
Q
What cardiovascular effects does Phentolamine have?
A
- Increased heart rate.
- Increase cardiac output due to α1 and α2 receptor blockade.
4
Q
What are Phentolamine’s clinical uses?
A
- Used for acute hypertensive emergencies
- Intraoperative management of pheochromocytoma
5
Q
Describe Phentolamine’s metabolism.
A
- Principally metabolized in the liver.
- About 10% excreted unchanged in urine.
6
Q
What are some side effects of Phentolamine?
A
- Cardiac dysrhythmias
- Angina pectoris
- Hyperperistalsis
- Abdominal pain
- Diarrhea
7
Q
How is Phentolamine used for the extravascular administration of vasoconstrictors?
A
- A solution containing 5-15 mg in 10 mL of normal saline
- Is used for local infiltration.
8
Q
What are α-Adrenergic Receptor Antagonists?
A
- They selectively bind to α-adrenergic receptors
- Block the effects of catecholamines and sympathomimetics.
9
Q
What are the clinical effects of α-adrenergic blockade?
A
- It prevents catecholamine effects on the heart and vasculature
- Stops epinephrine’s action on insulin secretion.
10
Q
What are the common side effects of α-adrenergic antagonists?
A
- Orthostatic hypotension
- Reflex tachycardia
- Impotence.
11
Q
How do Phentolamine, Prazosin, and Yohimbine function as α-antagonists?
A
- They are competitive antagonists
- Reversibly binding to receptors.
12
Q
What is the mechanism of Phenoxybenzamine?
A
- It binds irreversibly to α-receptors
- Blocking them even against high levels of sympathomimetics.
13
Q
Difference between Phentolamine, Phenoxybenzamine, Prazosin, and Yohimbine.
A
- Phentolamine and Phenoxybenzamine are nonselective, acting on α1 and α2
- Prazosin targets α1.
- Yohimbine targets α2.
14
Q
What are α- and β-Adrenergic Receptor Antagonists?
A
- They block the interaction of neurotransmitters like norepinephrine with adrenergic receptors.
15
Q
How do α- and β-Adrenergic Antagonists affect the sympathetic nervous system?
A
- They attenuate sympathetic nervous system functions.
- Leading to predictable pharmacological responses.
16
Q
What is the role of α2 Receptors in adrenergic antagonism?
A
- Reduces sympathetic outflow
- Downregulating neurotransmitter release.
17
Q
What is Phenoxybenzamine?
A
- A haloalkylamine derivative
- A nonselective α-adrenergic antagonist.
18
Q
Phenoxybenzamine Pharmacokinetics:
A
- Incomplete GI absorption
- Peak effect takes up to 60 minutes post-IV
- Half-time about 24 hours.
19
Q
Cardiovascular Effects of Phenoxybenzamine:
A
- It causes orthostatic hypotension
- Does not significantly change systemic BP in normovolemic patients.
20
Q
Noncardiac Effects of Phenoxybenzamine:
A
- It prevents epinephrine’s action on insulin
- Causes miosis, sedation, and nasal stuffiness.
21
Q
Clinical Uses of Phenoxybenzamine:
A
- Treats hypertensive emergencies,
- Preoperative control in pheochromocytoma
- Raynaud disease.
22
Q
What is Yohimbine?
A
- Selective α2 receptor antagonist.
- Enhance norepinephrine release.
23
Q
Yohimbine’s Clinical Application:
A
- Treats idiopathic orthostatic hypotension.
- Erectile dysfunction.
24
Q
Neurological Impact of Yohimbine:
A
- Can cross the blood-brain barrier
- Potentially causing tremors and increased muscle activity.
25
Adverse Effects of Yohimbine:
* Tachycardia.
* Hypertension.
* Rhinorrhea.
* Paresthesias.
* Dissociative states.
26
Yohimbine and Anesthetic Interaction:
* Possible interaction with volatile anesthetics
* Due to its effects on CNS α2 receptors.
27
What is Doxazosin used for?
* Treats hypertension.
* Benign prostatic hypertrophy (BPH).
28
Doxazosin's Selectivity and Bioavailability:
* Selective α1-receptor antagonist.
* 65% bioavailable orally.
29
Doxazosin's Peak Levels and Effect:
* Peak levels 2-3 hours after oral intake.
* Relaxes prostatic and vascular smooth muscle.
30
Metabolism and Excretion of Doxazosin:
* Metabolized in the liver.
* Excreted in feces.
31
Doxazosin's Half-Life and Dosage Recommendation:
* Terminal half-life is 22 hours
* Recommended as a single daily morning dose.
32
What is Prazosin's receptor selectivity?
* Selective for postsynaptic α1-receptors.
* minimize reflex tachycardia.
33
Effects of Prazosin on Blood Vessels:
Dilates arterioles and veins.
34
Onset and Duration of Prazosin:
* Action starts about 30 minutes post oral intake
* Lasting 4-6 hours.
35
How is Prazosin eliminated from the body?
Mainly metabolized by the liver.
36
Terazosin's Function in Treating BPH:
* A long-acting α1-adrenergic antagonist.
* Effective in relaxing prostatic smooth muscle.
37
Mechanism of Terazosin in BPH Management:
* Targets α1-mediated innervation
* Controls prostate contraction and bladder outlet obstruction.
38
Administration Method of Terazosin:
Orally effective for benign prostatic hyperplasia treatment.
39
Tamsulosin's Role in BPH Treatment:
* An α1a-adrenergic antagonist.
* Used orally for treating benign prostatic hyperplasia (BPH) symptoms.
40
Common Side Effects of Tamsulosin:
* Orthostatic hypotension.
* Vertigo.
* Syncope.
* Possible sexual side effects like ejaculatory dysfunction.
41
Drug Interactions with Tamsulosin:
Clearance of Tamsulosin is decreased in the presence of **cimetidine.**
42
Alfuzosin's Therapeutic Use:
* Selective **α1a-adrenergic receptor inhibitor.**
* Primarily used in treating benign prostatic hyperplasia (BPH).
* Especially in younger populations.
43
Side Effects of Alfuzosin:
* Dizziness.
* Systemic hypotension.
* Reflex tachycardia.
* Sexual side effects are less common compared to similar drugs.
44
Metabolism and Excretion of Alfuzosin:
* Alfuzosin undergoes extensive liver metabolism into inactive metabolites.
* Excretion is mainly through bile (3:1 ratio)
* Only 11% remaining unchanged and excreted by the kidneys.
45
Silodosin's Selectivity and Use:
* Highly selective **α1a-adrenergic receptor antagonist.**
* Specifically targeting prostate with fewer systemic side effects.
* Used for treating benign prostatic hyperplasia (BPH).
46
Absorption and Bioavailability of Silodosin:
* Rapid oral absorption.
* Bioavailability of only 32%.
47
Metabolism and Excretion of Silodosin:
* Metabolized via two hepatic pathways.
* Its primary metabolite is active, possessing half the activity of the parent compound.
* The metabolites are excreted in a 3:2 ratio, **primarily hepatically.**
48
Tolazoline's Pharmacological Classification:
Competitive nonselective α-adrenergic receptor antagonist.
49
Tolazoline's Primary Clinical Use:
* Previously used for treating persistent pulmonary hypertension in newborns.
* Now largely replaced by nitric oxide.
50
Tolazoline's Side Effects:
* Systemic hypotension.
* Reflex tachycardia.
* Cardiac dysrhythmias.
* Potential for pulmonary and gastrointestinal hemorrhages.
51
Excretion of Tolazoline:
Mainly excreted unchanged through the kidneys.
52
Role of α2-Adrenergic Receptor Agonists
* Bind to presynaptic α2 receptors
* Decrease norepinephrine release
* Reduce sympathetic outflow
* Result in hypotension and bradycardia
53
α2 Receptor Locations and Effects
* Primarily in CNS, brainstem, & Locus ceruleus.
* Peripheral inhibition affects pancreas
* Can inhibit insulin and induce glucagon
* Clinical effects: hypotension, bradycardia, sedation
54
Mechanism of α2-Agonists
* Competitively bind to α2 receptors
* Can be displaced for CNS effect reversal
* Withdrawal can cause rebound hypertension
55
CNS Effects of α2-Agonists
* Central sedation and mild analgesia
* Can reverse CNS effects by displacing the drug
56
α2-Agonists Clinical Use and Side Effects
* Used for hypotension and central sedation.
* Side effects include rebound hypertension post-withdrawal.
57
α2-Agonists in Hypertension
* Reduce blood pressure comparably to α1 antagonists.
* Withdrawal needs careful monitoring
58
Clonidine Overview
* Treats resistant hypertension, tremors, opioid withdrawal
* Partial α2 receptor agonist, 400:1 α2-α1 preference
59
Clonidine Pharmacokinetics
* Metabolized in liver
* Mostly excreted unchanged in urine.
* Variable half-life with liver/kidney dysfunction
60
Clonidine Dosage Forms
* Available IV, oral, transdermal
* Dosing depends on the treatment purpose
61
Clonidine Effects
* Dose-dependent heart rate and blood pressure reduction.
* Clinical use for cardiovascular and withdrawal symptoms
62
Monitoring Clonidine Therapy
* Monitor for effects on heart rate and blood pressure.
* Watch for variability in patients with organ dysfunction
63
Clonidine and Organ Dysfunction
* Half-life can significantly vary
* Important to adjust dosing in liver/kidney impairment
64
Dexmedetomidine Profile
* Selective α2 agonist, 1600:1 α2 preference
* Used for sedation and analgesia in ICU/OR
65
Dexmedetomidine Administration
* IV infusion: 0.1 to 1.5 μg/kg/min
* Terminal half-life: 2 hours
66
Dexmedetomidine Pharmacokinetics
* Extensive liver biotransformation
* Excreted primarily in urine
67
Dexmedetomidine and Liver Impairment
* Liver impairment increases plasma levels/duration
* Requires careful monitoring and dose adjustment
68
Dexmedetomidine Dependence
* Can induce physical dependence.
* Withdrawal can cause tachycardia, hypertension, anxiety
69
Dexmedetomidine Bolus Effect
* Large IV bolus can cause paradoxical hypertension and bradycardia.
* Crossover α1 stimulation effects similar to phenylephrine
70
Beta-Adrenergic Receptor Antagonists - Overview
* Block effects of catecholamines on heart, airways, blood vessels
* Maintain during perioperative to avoid rebound effects
71
Beta-Adrenergic Antagonists - Mechanism
* Competitive inhibition at beta receptors
* Increases receptor numbers over time, may require dose adjustment
72
Beta-Adrenergic Receptors - Function
* G protein-coupled
* Activation increases cAMP
* **Effects: ↑ heart rate, contractility, conduction, ↓ relaxation time**
73
Beta Antagonists - Structure-Activity
* Derivatives of isoproterenol
* Levorotatory forms more potent than dextrorotatory forms
74
Beta Antagonists - Classification
* Nonselective: affect β1 and β2
* Cardioselective: prefer β1, better for asthma/patients with reactive airways
75
Beta Antagonists - Cardiovascular Effects
* Reduce heart rate, AV node conduction, inotropy
* Increase myocardial perfusion, reduce ischemia during exercise
76
Beta Antagonists - Risks and Side Effects
* Risk of bronchospasm in reactive airway disease
* May worsen peripheral vascular disease symptoms
77
What is the range of elimination half-time for β-adrenergic receptor antagonists?
* varies from brief (esmolol ~10 minutes) to several hours.
* Considered in the perioperative period for dosing intervals or drug conversion.
78
Which β-adrenergic receptor antagonists are highly protein-bound?
* Propranolol and Nebivolol.
* High volume of distribution.
* Rapid distribution post-IV administration.
79
How are β-adrenergic receptor antagonists eliminated?
* Through various pathways.
* Renal and hepatic functions influence elimination.
* Requires consideration in renal/hepatic dysfunction.
80
What causes interpatient variability in response to β-adrenergic receptor antagonists?
* Basal sympathetic nervous system tone differences.
* Flat dose-response curves.
* Impact of active metabolites.
* Genetic differences in β-adrenergic receptors.
81
What are the key effects of Propranolol on the heart?
* Decreases heart rate and myocardial contractility.
* Lowers cardiac output, especially during exercise or increased sympathetic activity.
* Increases peripheral vascular resistance, including coronary vascular resistance.
82
Describe the pharmacokinetics of Propranolol.
* Rapid and almost complete GI absorption
* Limited systemic availability due to hepatic first-pass metabolism.
* Variable metabolism leading to 20-fold differences in plasma concentrations.
* Not effective via intramuscular administration.
83
How does Propranolol interact with plasma proteins?
* Extensively bound (90%-95%) to plasma proteins.
* Plasma protein binding can be altered by factors like heparin-induced increases in free fatty acids.
84
How is Propranolol metabolized and eliminated?
* Primarily metabolized in the liver
* Active metabolite is 4-hydroxypropranolol.
* Elimination half-time is 2-3 hours.
* Clearance affected by hepatic blood flow and enzyme activity.
85
How does Propranolol affect the clearance of local anesthetics?
* Decreases clearance by reducing hepatic blood flow and metabolism.
* Alters systemic toxicity potential of local anesthetics like bupivacaine.
86
How does Propranolol influence opioid clearance?
* Reduces pulmonary first-pass uptake of opioids like fentanyl.
* Increases the amount of opioid entering systemic circulation post-injection.
87
What are the key pharmacokinetic properties of Nadolol?
* Slow and incomplete GI absorption (about 30%).
* Mostly excreted unchanged in urine; minimal metabolism.
* Long elimination half-time of 20-40 hours allows once daily dosing.
88
Describe Pindolol's pharmacokinetic characteristics.
* Elimination half-time of 3-4 hours.
* Extended half-time to over 11 hours in renal failure patients.
89
What is the primary use of Timolol and its systemic effects?
* Used as eyedrops for glaucoma to decrease intraocular pressure.
* Can cause systemic effects like bradycardia and increased airway resistance.
90
Timolol's Pharmacokinetics
* Rapid and almost complete oral absorption.
* Extensive first-pass hepatic metabolism limits systemic availability.
* Elimination half-time is about 4 hours.
91
Metoprolol: Classification
* Selective β1-adrenergic receptor antagonist
* Less likely to cause airway resistance or peripheral vascular disease effects
92
Pharmacokinetics of Metoprolol
* Oral absorption; first-pass hepatic metabolism
* Only about 40% reach systemic circulation
* Low protein binding (around 10%)
* Metabolites inactive; less than 10% excreted unchanged in urine
93
Metoprolol: Effects on the Cardiovascular System
* Decreases heart rate and myocardial contractility
* Reduces cardiac output, especially during exercise or increased sympathetic activity
* Increases coronary vascular resistance but overall reduces myocardial oxygen demand
94
Dosage Forms of Metoprolol
* Metoprolol tartrate: Shorter half-life (2-3 hours), requires frequent dosing
* Metoprolol succinate: Extended-release, allows once or twice daily dosing
95
Metoprolol: Clinical Use
* Treatment of hypertension, angina, heart failure, and some arrhythmias
* Reduces risk of myocardial infarction and death in patients with heart disease
96
Metoprolol: Side Effects
* Bradycardia, hypotension, fatigue, dizziness
* Can worsen symptoms in patients with asthma or COPD at high doses
97
Metoprolol: Drug Interactions
* Can interact with other blood pressure medications,
* Increasing risk of hypotension
* May enhance effects of other heart medications like digoxin
98
Metoprolol: Considerations in Pregnancy
* Category C: Risk cannot be ruled out
* Consult healthcare provider for risks and benefits
99
Metoprolol: Pediatric Dose
* Varies based on condition
* Typically starts low and adjusted based on response
100
Metoprolol: Mechanism of Action
* Blocks β1-adrenergic receptors
* Reduce sympathetic stimulation of the heart
101
Metoprolol: Elimination Half-time
* Varies based on formulation
* Important in determining dosing frequency
102
Why is **Atenolol** particularly valued in certain patients over nonselective β-adrenergic antagonists?
* Highly selective for β1 receptors
* Maintains β2 activity
* Beneficial for those with airway diseases
103
How does **Atenolol** benefit patients with coronary artery disease undergoing surgery?
* Reduces postoperative myocardial ischemia
* Lowers mortality and cardiovascular complications
104
What is the duration of **Atenolol's** antihypertensive effect and dosing frequency?
* Prolonged effect allows once-daily dosing
* Suitable for treating hypertension
105
Does atenolol significantly penetrate the central nervous system (CNS)?
* Minimal CNS entry
* May cause fatigue
* Mental depression
106
Can atenolol be used in diabetic patients with hypertension?
* Safe for diabetics
* Does not enhance insulin-induced hypoglycemia
107
What are the key pharmacokinetic properties of atenolol?
* 50% oral absorption rate
* Peak concentration in 1-2 hours
* Primarily renally excreted
108
What is the elimination half-life of atenolol and its implications in renal failure?
* 6-7 hours under normal conditions
* May exceed 24 hours in renal failure
109
What makes betaxolol suitable for patients with airway diseases?
* Cardioselective β1 antagonist
* Less bronchoconstriction risk compared to nonselective β blockers
110
What is betaxolol's absorption rate and how often should it be administered for hypertension?
* Nearly complete oral absorption
* Once daily dosing due to long action
111
What is the elimination half-life of betaxolol and its primary clearance method?
* 11-22 hours elimination half-life
* Mainly metabolized, less renal elimination
112
How is betaxolol used in the treatment of glaucoma?
* Topical form for chronic open-angle glaucoma
* Alternative to timolol with fewer airway risks
113
Why is **Bisoprolol** particularly effective for patients with heart conditions?
* Highly β1-selective
* Minimal intrinsic agonist activity
114
What is the elimination half-time of Bisoprolol and how is it excreted?
* Elimination half-time is 9-12 hours
* Equally by renal and nonrenal mechanisms
115
What conditions is bisoprolol commonly prescribed for?
* Essential hypertension
* Congestive heart failure, with noted survival improvement
116
Are the metabolites of bisoprolol pharmacologically active?
No, metabolites are inactive
117
What is the selectivity of Nebivolol?
Very potent, selective β1-antagonist.
118
How does Nebivolol's selectivity compare to Bisoprolol?
3.5 times more selective than Bisoprolol.
119
Does Nebivolol exhibit any β2 antagonism?
Yes, at doses above 10 mg or certain genetic profiles.
120
What is the elimination half-life of Nebivolol?
12 to 19 hours.
121
How often should Nebivolol be taken?
Once daily, with flexible dosing.
122
How is Nebivolol metabolized and excreted?
* Urine (unchanged)
* Feces (inactive metabolite).
123
What is Nebivolol currently approved to treat?
Essential hypertension.
124
What is Esmolol?
* Is a rapid-onset and short-acting selective β1-adrenergic receptor antagonist.
125
How is Esmolol administered?
Esmolol is administered only intravenously (IV).
126
What is the typical initial dose of Esmolol IV?
0.5 mg/kg IV over about 60 seconds.
127
When does the full therapeutic effect of Esmolol become evident?
Within 5 minutes after administration.
128
How long does the action of Esmolol last after administration is discontinued?
Ceases within 10 to 30 minutes after administration is discontinued.
129
When is Esmolol useful in clinical settings?
* Is useful for preventing or treating adverse systemic blood pressure.
* Heart rate increases that occur intraoperatively in response to noxious stimulation, such as during tracheal intubation.
130
How does Esmolol affect heart rate and systolic blood pressure during tracheal intubation?
* Protects against increases in both heart rate and systolic blood pressure.
131
What are alternative drugs for blunting the increase in systolic blood pressure associated with laryngoscopy and tracheal intubation?
* Lidocaine.
* Fentanyl.
| Both are effective alternatives
132
Does lidocaine or fentanyl influence heart rate during tracheal intubation?
No, heart rate is not influenced by lidocaine or fentanyl.
133
Besides tracheal intubation, in what other situations can Esmolol be used?
* In preventing perioperative tachycardia and hypertension, during electroconvulsive therapy,
Management of conditions like:
* Pheochromocytomas
* Thyrotoxicosis
* Pregnancy-induced hypertension, and more.
134
What adverse effects are associated with the use of **β-adrenergic receptor antagonists** for excessive sympathetic nervous system activity?
* Fulminant pulmonary edema
* Irreversible cardiovascular collapse may occur.
135
What is the β1 selectivity of Esmolol?
selective β1-adrenergic receptor antagonist.
136
How does Esmolol interact with patients chronically treated with β-adrenergic antagonists?
* It does not produce additional negative inotropic effects when administered to such patients.
137
How does Esmolol affect the plasma concentration of propofol required to prevent patient movement in response to a surgical skin incision?
* significantly decreases the plasma concentration of propofol required.
138
What is the mechanism of action of Esmolol?
* Is a β1-adrenergic receptor antagonist.
* It blocks the effects of epinephrine on β1 receptors.
139
In what form is Esmolol available for administration?
is available for IV (intravenous) administration only.
140
Besides Esmolol, which other β-adrenergic antagonists can be administered IV?
* **Propranolol and metoprolol** are the other β-adrenergic antagonists that may be administered IV.
141
What is the pH range of the commercial preparation of Esmolol?
pH 4.5 to 5.5.
142
Why may pain occur on injection of Esmolol?
* The pH range of Esmolol's commercial preparation (4.5 to 5.5) may be one of the factors responsible for pain on injection.
143
What is the elimination half-time of Esmolol?
About 9 minutes.
144
How is Esmolol metabolized and excreted in the body?
* Rapidly hydrolyzed in the blood by plasma esterases
* Independent of renal and hepatic function.
* Less than 1% of the drug is excreted unchanged in urine
* About 75% is recovered as an inactive acid metabolite.
145
Is methanol formed as a result of Esmolol's metabolism?
Yes, clinically insignificant amounts of methanol can occur from the hydrolysis of Esmolol.
146
How long does it take for the heart rate to return to predrug levels after discontinuing Esmolol?
Within 15 minutes after discontinuing Esmolol.
147
Why is Esmolol's transfer into the central nervous system (CNS) or across the placenta limited?
* Has poor lipid solubility
* Which limits its transfer into the CNS or across the placenta.
148
What are the common side effects associated with β-adrenergic antagonists?
* Cardiovascular effects.
* Altered airway resistance.
* Changes in carbohydrate and lipid metabolism.
* Shifts in extracellular ions.
149
Do β-adrenergic antagonists pose a risk of hypoglycemia?
Yes, β-adrenergic antagonists may cause hypoglycemia.
150
When β-adrenergic antagonists are used with anesthesia drugs, what additive effects may occur?
* Sedation
* Bradycardia
* Hypotension
| When β-adrenergic antagonists are combined with anesthesia drugs
151
Do many β-adrenergic antagonists penetrate the blood-brain barrier?
Yes, many β-adrenergic antagonists can cross the blood-brain barrier.
152
What gastrointestinal side effects may be associated with β-adrenergic antagonist use?
* Nausea.
* vomiting.
* Diarrhea.
153
List some other effects associated with chronic β-adrenergic antagonist treatment.
* Fever
* Rash
* Myopathy
* Alopecia
* Thrombocytopenia
* Also affect lipid levels by decreasing high-density lipoproteins
* Increase triglycerides and uric acid levels.
154
What is the principal contraindication for the administration of β-adrenergic antagonists?
* Preexisting atrioventricular heart block
* Acute cardiac failure not caused by tachycardia.
155
When should caution be exercised with β-adrenergic antagonist administration regarding hypotension?
* To hypovolemic patients with compensatory tachycardia.
* It may lead to profound and resistant hypotension.
156
Are nonselective β-adrenergic antagonists or high doses of selective β-adrenergic antagonists recommended for patients with reactive or obstructive airway disease?
* No, They are not recommended for patients with any diagnosis of reactive or obstructive airway disease.
157
What is the risk associated with β-adrenergic blockade in patients with diabetes mellitus?
* May mask the signs of hypo- or hyperglycemia.
* Potentially delaying clinical recognition.
158
What are the primary cardiovascular effects of β-adrenergic antagonists?
* Produce negative inotropic and chronotropic effects.
* Slow conduction through the atrioventricular node.
* Decrease spontaneous phase 4 depolarization.
159
How do β-adrenergic antagonists affect preexisting atrioventricular heart block?
* Likely to be accentuated by β-adrenergic antagonists.
160
What is the mechanism behind the cardiovascular effects of β-adrenergic blockade?
* Effects result from the removal of sympathetic nervous system innervation to the heart (β1-blockade).
* Nonselective β-blockade may also impede left ventricular ejection due to α-adrenergic receptor-mediated peripheral vasoconstriction.
161
How do β-adrenergic antagonists affect heart rate during exercise?
* The tachycardia of exercise is consistently attenuated by β-adrenergic antagonists.
* Age-adjusted maximal heart rate should be further adjusted down by 10 beats per minute.
162
Do patients with peripheral vascular disease tolerate β2-receptor blockade well?
* Patients may develop cold hands and feet as a common side effect of nonselective β-adrenergic antagonists.
163
What is the principal antidysrhythmic effect of β-adrenergic blockade?
* Prevents the dysrhythmogenic effect of endogenous or exogenous catecholamines or sympathomimetics
| By decreasing sympathetic nervous system activity.
164
How should excessive myocardial depression due to β-adrenergic blockade be initially treated?
Atropine in incremental IV doses of 7 μg/kg. (initially)
165
What are some alternative treatments for myocardial depression caused by β-adrenergic antagonists?
* Continuous infusion of isoproterenol (for pure β-blockade)
* Dobutamine (for β1-adrenergic effects)
* Glucagon
* Calcium chloride.
166
How does glucagon reverse myocardial depression caused by β-adrenergic antagonists?
* Stimulates adenylate cyclase
* Increases intracellular cAMP concentrations independent of β-adrenergic receptors
| Making it effective in reversing myocardial depression.
167
When should hemodialysis be considered in the treatment of β-adrenergic antagonist overdose?
* Hemodialysis should be reserved for patients refractory to pharmacologic therapy
* Is used to remove minimally protein-bound, renally excreted β-adrenergic antagonists.
168
What effect do nonselective β-adrenergic antagonists like propranolol have on airway resistance and why?
* Increase airway resistance via bronchoconstriction.
* Due to β2 receptor blockade.
* Effects exaggerated in obstructive airway disease.
169
How do selective β1-adrenergic antagonists compare to nonselective ones regarding airway resistance?
* Less likely to increase airway resistance.
* Examples: bisoprolol, metoprolol, esmolol.
* Do not block β2 receptors responsible for bronchodilation.
170
How do β-adrenergic antagonists affect carbohydrate and fat metabolism?
* Interfere with glycogenolysis during hypoglycemia.
* Blunt tachycardia response to hypoglycemia.
* Altered fat metabolism; reduced free fatty acid release.
171
Why are nonselective β-adrenergic antagonists not recommended for diabetic patients on insulin or oral hypoglycemics?
* Increase hypoglycemia risk due to glycogenolysis interference.
* Mask hypoglycemia warning signs like tachycardia.
172
How does β-adrenergic blockade affect extracellular potassium distribution?
* Inhibits potassium uptake in skeletal muscles.
* Can increase plasma potassium concentration.
* Selective β1 antagonists less likely to impair potassium uptake.
173
What is the interaction between β-adrenergic antagonists and anesthetics?
* Potential additive myocardial depression.
* Clinical experience shows it's not excessive.
* **Safe to continue β-antagonists perioperatively.**
174
How do β-adrenergic antagonists impact the nervous system?
* Can cross blood-brain barrier.
* Side effects: fatigue, lethargy, vivid dreams.
* Rarely cause psychotic reactions or memory loss.
175
What are the fetal risks associated with β-adrenergic antagonists?
* Can cause fetal bradycardia, hypotension, hypoglycemia.
* Effects vary by drug lipophilicity and protein binding.
* Some β-antagonists safe for use in pregnancy and breastfeeding.
176
What happens with acute discontinuation of β-adrenergic antagonist therapy?
* Excess sympathetic activity within 24-48 hours.
* Due to upregulation of β-adrenergic receptors.
* Continuous infusion can maintain therapeutic levels.
177
What are the clinical uses of β-adrenergic antagonists in the perioperative period?
* Multiple therapeutic effects.
* Recommended to continue uninterrupted perioperatively.
* Beneficial for high-risk myocardial ischemia patients during surgery.
178
How do β-adrenergic antagonists treat essential hypertension?
* Gradual systemic blood pressure decrease.
* Lowers cardiac output and heart rate.
* Often combined with vasodilators to balance effects.
179
What is the role of β-adrenergic antagonists in managing angina pectoris?
* Decrease likelihood of myocardial ischemia.
* Lower myocardial oxygen requirements.
* Effective dose reduces resting heart rate to <60 bpm.
180
Discuss β-adrenergic antagonists in acute coronary syndrome treatment.
* Recommended post-myocardial infarction.
* Contraindicated in severe bradycardia, left ventricular failure, AV block.
* Caution in asthma, depression, fatigue, peripheral vascular disease.
181
What are the contraindications and considerations for β-adrenergic antagonists in acute coronary syndrome?
* Not recommended within first 8 hours of ST elevation myocardial infarction.
* Risk of cardiogenic shock.
* Decreases incidence of nonfatal reinfarction.
182
What is the cardioprotective mechanism of β-adrenergic antagonists?
* Antidysrhythmic actions.
* Nonselective β-antagonists prevent epinephrine-induced potassium decrease.
* Useful in reducing ventricular dysrhythmias.
183
What is the role of β-adrenergic receptor blockade in perioperative care?
* Recommended for at-risk patients during high-risk surgery.
* Aim for resting heart rate between 65-80 bpm.
* Reduces perioperative myocardial ischemia and mortality.
184
How should β-adrenergic receptor blockade be managed preoperatively?
* Oral atenolol, bisoprolol, or metoprolol.
* IV atenolol or metoprolol if initiated on surgery day.
* Esmolol for intraoperative and ICU care.
185
What are the concerns with starting β-blockers in the acute preoperative setting?
* Risk of increased all-cause mortality.
* Potential cerebrovascular events.
* Low-dose regimens recommended for preoperative initiation.
186
How are β-adrenergic receptor blockers used in treating intraoperative myocardial ischemia?
* Titrate to achieve heart rate around 60 bpm.
* Options: esmolol, metoprolol, atenolol, propranolol.
* **Esmolol** preferred for heart rate titration.
187
What is the role of β-adrenergic receptor blockers in suppressing cardiac dysrhythmias?
* Control ventricular response in atrial fibrillation/flutter.
* Effective post-cardiac surgery for atrial dysrhythmias.
* Propranolol for torsades de pointes in prolonged QTc.
188
How do β-adrenergic antagonists manage congestive heart failure?
* Improve ejection fraction and survival.
* Examples: metoprolol, carvedilol, bisoprolol.
* Start with minimal doses, gradually increase.
189
Describe the use of β-adrenergic blockers for preventing excessive sympathetic nervous system activity.
* Attenuate heart rate/blood pressure changes during intubation.
* Treat hypertrophic obstructive cardiomyopathy, pheochromocytoma, hyperthyroidism.
* Reduce cyanotic episodes in tetralogy of Fallot.
190
How is propranolol used in preoperative preparation of hyperthyroid patients?
* IV or oral administration.
* Rapid suppression of sympathetic nervous system activity.
* Avoids need for iodine or antithyroid drugs.
191
What are the **characteristics** and effects of **Labetalol**?
* Selective α1 and nonselective β1/β2 antagonist.
* Spares presynaptic α2 receptors.
* Lower potency compared to phentolamine (α-blocker) and propranolol (β-blocker).
192
Describe the pharmacokinetics of Labetalol.
* Metabolized by glucuronic acid conjugation.
* 5% excreted unchanged in urine.
* Elimination half-time: 5-8 hours; prolonged in liver disease.
193
What are the **cardiovascular effects of Labetalol**?
* Lowers blood pressure by decreasing vascular resistance (α1-blockade).
* Prevents reflex tachycardia (β-blockade).
* Cardiac output remains unchanged.
194
Discuss the clinical uses of labetalol.
* Treats hypertensive emergencies.
* Controls hypertension in epinephrine overdose.
* Used in angina pectoris treatment.
195
How is labetalol administered in surgical settings?
* IV doses of 0.1-0.5 mg/kg to attenuate heart rate and blood pressure.
* Can be used for controlled hypotension.
* Effects may be accentuated by anesthetic drugs.
196
What are the **side effects** of **Labetalol** therapy?
* Common: Orthostatic hypotension.
* Possible bronchospasm in susceptible patients.
* Less severe congestive heart failure, bradycardia, heart block risks.
197
What are the key features and uses of carvedilol?
* Nonselective β-adrenergic antagonist with α1-blocking activity.
* No intrinsic β-adrenergic agonist effect.
* Used for mild to moderate congestive heart failure and essential hypertension.
198
Describe the pharmacokinetics of carvedilol.
* Extensively metabolized post-oral administration.
* Elimination half-time: 7-10 hours.
* High protein binding.
199
What is the mechanism of action of calcium channel blockers?
* Interfere with calcium ion movement across cardiac and vascular smooth muscle cells.
* Bind to L, N, and T type calcium channels, maintaining them in a closed state.
* Reduce calcium influx, leading to reduced intracellular calcium.
200
How are calcium channel blockers classified and what are their effects?
* Classified as phenylalkylamines, dihydropyridines, benzothiazepines.
* **Phenylalkylamines and benzothiazepines**: selective for AV node.
* **Dihydropyridines**: selective for arteriolar beds.
* **Common effects**: slow heart rate, reduce myocardial contractility, relax vascular smooth muscle.
201
What are the common side effects of calcium channel blockers?
* Systemic hypotension.
* Peripheral edema.
* Flushing.
* Headache.
202
Describe the role of calcium in cardiac and vascular smooth muscle cells.
* Key in electrical excitation.
* Involved in excitation/contraction coupling.
* Calcium influx through L-type channels is critical for cardiac action potential phase 2.
203
What are the pharmacologic effects of calcium channel blockers?
* Decrease myocardial contractility.
* Decrease heart rate and sinoatrial node activity.
* Slow conduction through atrioventricular node.
* Cause vascular smooth muscle relaxation and vasodilation.
* Reduce systemic blood pressure.
204
How do calcium channel blockers help in treating coronary artery spasm and angina pectoris?
* Increase coronary blood flow by decreasing vascular smooth muscle contractility.
* Reduce systemic vascular resistance and blood pressure.
* Effective in chronic stable angina and unstable angina pectoris.
* Complement nitrates in coronary artery spasm treatment.
205
Which calcium channel blockers have the most significant negative inotropic effects?
* Verapamil and diltiazem.
* Exert strong negative effects on myocardial contractility.
## Footnote
**Negative inotropic effect**: This decreases the strength of the heart's contractions. Imagine the heart pumping with less force, like turning down the power on a pump.
206
Describe the binding mechanism and action of phenylalkylamines like verapamil on calcium channels.
* Bind to intracellular part of L-type channel α1 subunit in an open state.
* Verapamil: synthetic papaverine derivative, affects slow calcium channels.
* Dextroisomer acts on fast sodium channels; levoisomer specific for slow calcium channels.
207
Side effects and contraindications of **Verapamil**?
* Major depressant effect on atrioventricular node.
* Negative chronotropic effect on sinoatrial node.
* Negative inotropic effect on cardiac muscle.
* Not advised for heart failure, severe bradycardia, sinus node dysfunction, AV nodal block.
208
What are the clinical uses of verapamil?
* Treats supraventricular tachydysrhythmias, vasospastic angina, essential hypertension.
* Mild vasodilator, less active on vascular smooth muscle than Nifedipine.
* Useful in hypertrophic cardiomyopathy treatment.
209
Describe the pharmacokinetics of verapamil.
* Oral bioavailability: 10-20% due to hepatic first-pass metabolism.
* Oral dose ~10 times IV dose.
* Peaks in 30-45 mins orally, 15 mins IV.
* Elimination half-time: 6-12 hours, prolonged in liver disease.
* Highly protein-bound (90%).
210
What is the action mechanism of dihydropyridines like nifedipine?
* Prevent calcium entry into vascular smooth cells via extracellular modulation of L-type calcium channels.
* Focus on peripheral arterioles, minimal effect on venous vessels.
* Can cause reflex tachycardia due to sympathetic activity or baroreceptor reflexes.
211
Describe the clinical uses and pharmacokinetics of **Nifedipine.**
* Treats angina pectoris, especially coronary artery vasospasm.
* Oral dose: 10-30 mg, effect in 20 mins, peaks in 60-90 mins.
* Absorption ~90%, highly protein-bound.
* Hepatic metabolism, elimination half-time: 3-7 hours.
212
What are the **side effects of Nifedipine**?
* Common: Flushing, vertigo, headache.
* Less common: Peripheral edema, hypotension, paresthesias, muscle weakness.
* Rare: Glucose intolerance, hepatic dysfunction.
* Abrupt discontinuation may cause coronary artery vasospasm.
213
What is the impact of Nicardipine on the sinoatrial and atrioventricular nodes, and its overall effect on the heart?
* No effect on sinoatrial and atrioventricular nodes.
* Minimal myocardial depressant effects.
* Prominent coronary artery vasodilation.
214
How is Nicardipine used in combination therapy for angina?
* Combined with β-adrenergic antagonists.
* Does not significantly depress the sinoatrial node.
* Helps manage residual hypertension and angina.
215
Describe the pharmacokinetics of Nicardipine.
* High lipophilicity; nearly complete GI absorption.
* Bioavailability ~35% due to first-pass metabolism.
* IV half-lives: α – 2.7 min, β – 44.8 min, γ – 14.4 hours.
216
What are the side effects of Nicardipine?
* Similar to Nifedipine.
* Includes vasodilation-related effects like headache and flushing.
217
What are the clinical uses of Nicardipine?
* Previously used as a tocolytic.
* Administered for electroconvulsive therapy to blunt acute hemodynamic responses.
* Treats angina and hypertension.
218
What is the recommended dosage and administration method for Nicardipine in different clinical settings?
* IV administration: 40 μg/kg for electroconvulsive therapy.
* Oral and IV forms available.
* IV functional vasodilation lasts 9-15 minutes; adjust oral doses every 72 hours.
* Dosage adjustments necessary for liver metabolism and high protein binding.
219
What are the key characteristics and uses of **Clevidipine**?
* Third-generation dihydropyridine; extremely lipophilic, ultrashort acting.
* FDA approved for acute, severe hypertension.
* Administered intravenously.
220
Describe the pharmacokinetics of Clevidipine.
* Metabolized by plasma esterases; half-life ~1 minute.
* Clearance unaffected by liver or kidney function.
* Pseudocholinesterase deficiency significantly delays metabolism.
221
How is Clevidipine dosed?
* Starts at 1-2 mg/hour; doubled every 90 seconds until BP nears goal.
* Median range: 4-8 mg/hour; up to 32 mg/hour possible.
* Requires nutritional adjustments at higher doses.
222
What are the side effects and cautions associated with Clevidipine?
* Common side effects: Hypotension, tachycardia.
* Not recommended in hyperlipidemic states, pancreatitis, heart failure with reduced ejection fraction.
* Higher doses may cause negative inotropic effects.
223
What are the properties and clinical uses of Nimodipine?
* Lipid-soluble analogue of nifedipine.
* Enters CNS, blocks calcium ion influx in cerebral arteries.
* Used in subarachnoid hemorrhage treatment.
224
How does Nimodipine work in treating cerebral vasospasm?
* Dilates cerebral arteries, preventing/attenuating vasospasm after subarachnoid hemorrhage.
* Oral dose: 0.7 mg/kg initially, then 0.35 mg/kg every 4 hours for 21 days.
* Can be administered via nasogastric tube if necessary.
225
What is the role of Nimodipine in cerebral protection?
* Evaluated for cerebral protection after global ischemia, like cardiac arrest.
* Improves neurologic outcomes in subarachnoid hemorrhage.
* IV dose: 10 μg/kg followed by 1 μg/kg per minute.
226
What are the side effects and administration considerations for Nimodipine?
* Side effects: Peripheral vasodilation, systemic hypotension.
* Possible increase in intracranial pressure due to cerebral vasodilation.
* Effective even with decreases in blood pressure.
227
What are the key properties and clinical applications of Amlodipine?
* Dihydropyridine derivative, oral administration.
* Used for acute coronary syndrome treatment.
* Can be combined with β-blockers for myocardial ischemia.
228
Describe the pharmacokinetics of Amlodipine.
* Oral dose: 5-10 mg.
* Peak plasma concentration: 6-12 hours.
* Elimination half-time: 30-40 hours.
* 90% hepatically metabolized to inactive products.
229
What are the effects of Amlodipine on myocardial contractility?
* Minimal detrimental effects on myocardial contractility.
* Provides anti-ischemic effects similar to β-blockers.
230
What are the properties and actions of Benzothiazepines like Diltiazem?
* Act at L-type calcium channels, blocking calcium entry.
* Additional actions: affect sodium-potassium pump, inhibit calcium-calmodulin binding.
* Intermediate effects between Verapamil and dihydropyridines.
231
What are the clinical uses of Diltiazem?
* First-line medication for supraventricular tachydysrhythmias.
* Chronic control of essential hypertension.
* IV administration for angina pectoris.
232
Describe the pharmacokinetics and recommended dosing of Diltiazem.
* Excellent oral absorption; onset in 15 mins, peak in 30 mins.
* IV dose: 0.25-0.35 mg/kg over 2 minutes, repeatable in 15 mins.
* Continuous infusion: 10 mg/hour for up to 24 hours.
* 70-80% protein bound; excreted in bile and urine.
* Elimination half-time: 4-6 hours (parent drug), 20 hours (metabolites).
233
What are the drug interactions and considerations for Diltiazem?
* May enhance atrioventricular heart block with β-blockers or digoxin.
* Interactions with volatile anesthetics may exaggerate myocardial depression, peripheral vasodilation.
* Continue use until surgery; watch for preexisting heart conditions.
234
What are the considerations for using calcium channel blockers with anesthetic drugs?
* Vasodilators and myocardial depressants.
* Caution needed in patients with left ventricular dysfunction or hypovolemia.
* Interact with volatile anesthetics, inhibiting calcium channels.
235
How do calcium channel blockers affect anesthetized patients with cardiac issues?
* Can lead to myocardial depression, decreased cardiac output.
* Further decrease in ventricular function with verapamil or diltiazem during surgery.
* Cardiac protection related to calcium overload prevention.
236
What are the effects of calcium channel blockers on cardiac dysrhythmias and conduction in anesthetized patients?
* Transient decreases in systemic blood pressure.
* Infrequent P-R interval prolongation.
* Use cautiously with digitalis or β-adrenergic blocking drugs.
237
How do β-adrenergic agonists interact with calcium channel blockers in the context of anesthesia?
* Increase the number of functioning slow calcium channels in myocardial cells.
* Counter the effects of calcium channel blockers.
* No increased anesthesia risk for patients treated with calcium channel blockers.
238
How do calcium channel blockers interact with neuromuscular blocking drugs?
* Do not produce skeletal muscle relaxant effect alone.
* Potentiate effects of both depolarizing and nondepolarizing neuromuscular blockers.
* Similar to potentiation by mycin antibiotics.
239
What is the role of local anesthetic effects in the potentiation of neuromuscular blocking drugs?
* Verapamil and diltiazem inhibit sodium ion flux, contributing to potentiation.
* May affect patients with compromised neuromuscular transmission.
* No evidence of inhibition of physical function in frail elderly.
240
How do calcium channel blockers affect potassium levels and potassium-containing solution administration?
* Slow inward movement of potassium ions.
* May cause hyperkalemia with lower doses of exogenous potassium.
* Does not affect plasma potassium increases from succinylcholine in animals.
241
What is the interaction between calcium channel blockers and platelet function?
* May interfere with calcium-mediated platelet function.
* Interaction with clopidogrel via P450 enzyme 3A4 metabolism.
* Reduced conversion of clopidogrel, increasing risk of cardiac events.
242
How do calcium channel blockers affect the plasma concentration of digoxin?
* Increase plasma concentration of digoxin.
* Decrease plasma clearance of digoxin.
243
What is the interaction between calcium channel blockers and H2 antagonists?
* Cimetidine and ranitidine may increase plasma concentrations of calcium channel blockers.
* Alters hepatic enzyme activity and/or hepatic blood flow.
244
What is the role of calcium channel blockers in cytoprotection?
* Protect against ischemic reperfusion injury.
* Decrease calcium ion entry, limiting oxygen free radical accumulation.
* May attenuate renal injury from nephrotoxic drugs.
* Increase renal blood flow and glomerular filtration rate, favoring natriuresis.
