ANS Pharmacology Flashcards
Study on shuffle
Identify the class to which the drugs belong: epinephrine, norepinephrine, dopamine
Adrenergic agonists
Identify the class to which the drugs belong: isoproterenol, dobutamine
Synthetic catecholamine
Identify the class to which the drugs belong: ephedrine, phenylephrine
Synthetic noncatecholamine
Identify the class to which the drugs belong: albuterol, salmeterol
Selective beta-adrenergic agonists
Identify the class to which the drugs belong: clonidine, dexmedtomidine
Selective alpha 2 agonists
Identify the class to which the drugs belong: propanolol, esmolol
Beta 1 and 2 antagonists
Identify the class to which the drugs belong: labetalol, carvedilol
Mixed function alpha and beta antagonists
Identify the class to which the drugs belong: nicotine, bethanechol, physostigmine
Cholinergic agonists
Identify the class to which the drugs belong: atropine, scopolamine, glycopyrrolate
Antimuscarinics
Identify the class to which the drugs belong: verapamil, diltiazem
Calcium channel blockers
Identify the class to which the drugs belong: milrinone, slidenafil
Phosphodiesterase inhibitors
Identify the class to which the drugs belong: vasopressin
Arginine vasopressin
Identify the class to which the drugs belong: nitroprusside, nitroglycerin, hydralazine
Direct vasodilators/ nitrodilators
Identify the class to which the drugs belong: lisinopril, captopril, enalopril
ACE inhibitors
Identify the class to which the drugs belong: valsartan, olmesartan, losartan
ARBs
Identify the class to which the drugs belong: volatile agent, propofol, local anesthetics
Anesthetic agents
Three alpha-selective drugs
Phenylephrine (alpha 1)
Clonidine (alpha 2)
Dexmedetomidine (alpha 2)
Phenylephrine metabolism
MAO
Phenylephrine dosing
0.15-0.75 mcg/kg/min
Clonidine metabolism
50% liver
50% renal unchanged
Clonidine PO dosing
0.1-0.6 mg/day
Clonidine primary uses
HTN
Clonidine adverse effects
Rebound HTN with abrupt cessation
May cause sedation
Dexmedetomidine metabolism
CYP liver
Dexmedetomidine dosing
1 mcg/kg over 10 min (bolus)
0.2-0.8 mcg/kg/hr
Dexmedetomidine uses
Sedation
Analgesia without respiratory depression
Why are beta blockers contraindicated for phenylephrine overdose?
May induce pulmonary edema and irreversible cardiac collapse
Location of postsynaptic alpha 2 receptors
Smooth muscles
Several organs
Location of nonsynaptic alpha 2 receptors
Platelets
Alpha-2 stimulation in: medulla
Decrease SNS tone
Alpha-2 stimulation in: vagus nerve
Increase PNS tone
Alpha-2 stimulation in: locus coeruleus
Sedation, hypnosis
Alpha-2 stimulation in: dorsal horn of spinal cord
Analgesia
Alpha-2 stimulation in: vasculature
Vasoconstriction
Alpha-2 stimulation in: renal tubules
Inhibits ADH
Alpha-2 stimulation in: pancreas
Decrease insulin release
Alpha-2 stimulation in: platelets
Increase platelet aggregation
Alpha-2 stimulation in: salivary glands
Dry mouth
Alpha-2 stimulation in: GI tract
Decrease gut motility
Clonidine or Dexmedetomidine: 1600: 1 affinity for Alpha 2: Alpha 1
Dexmedetomidine
Clonidine or Dexmedetomidine: Partial alpha-2 agonist
Clonidine
Clonidine or Dexmedetomidine: Mild reduction in volatile and IV anesthetic requirement
Clonidine
Clonidine or Dexmedetomidine: 50% protein binding
Clonidine
Clonidine or Dexmedetomidine: 94% protein binding
Dexmedetomidine
Clonidine or Dexmedetomidine: 2 hour elimination half life
Dexmedetomidine
Clonidine or Dexmedetomidine: no respiratory depression
Both
Clonidine or Dexmedetomidine: 8 hour elimination half life
Clonidine
Clonidine or Dexmedetomidine: near total hepatic transformation to inactive metabolites
Dexmedetomidine
Clonidine or Dexmedetomidine: distribution half life >10 minutes
Clonidine
Clonidine or Dexmedetomidine: ~50% excreted unchanged, inactive metabolites
Clonidine
Clonidine or Dexmedetomidine: distribution half life 5-6 minutes
Dexmedetomidine
Epinephrine: effect on renal blood flow
Decreases
Epinephrine: effect on MAP
Moderately increases
Epinephrine: Airway resistance
Decreases
Epinephrine: metabolism
Reuptake
MAO and COMT
Epinephrine: receptor
B1> B2, A1
Epinephrine: infusion dose
0.01-0.2 mcg/kg/min
Epinephrine: primary uses
Shock
Anaphylaxis
ACLS
Norepinephrine: renal blood flow
Significantly decreases
Norepinephrine: MAP
Significantly increases
Norepinephrine: airway resistance
No change
Norepinephrine: metabolism
Reuptake
MAO and COMT
Norepinephrine: receptor agonism
A1, B1 > B2
Norepinephrine: infusion dosing
0.01-0.2 mcg/kg/min
Norepinephrine: primary uses
Shock
Vasoplegia
Dopamine: renal blood flow
Significantly increases
Dopamine: MAP
Moderately increases
Dopamine: airway resistance
No effect
Dopamine: metabolism
Reuptake
MAO and COMT
Dopamine: adrenergic receptor agonism
B1> B2, A1
Dopamine: infusion dosing
2-20 mcg/kg/min
Dopamine: primary uses
Shock
Isoproterenol: renal blood flow
Moderately decreases
Isoproterenol: MAP
Moderately increases
Isoproterenol: airway resistance
Significantly decreases
Isoproterenol: metabolism
COMT
Isoproterenol: adrenergic receptor agonism
B1>B2
Isoproterenol: infusion dosing
0.015-0.15 mcg/kg/min
Isoproterenol: primary uses
Drug pacing
Dobutamine: renal blood flow
Increases
Dobutamine: MAP
Moderately increases
Dobutamine: airway resistance
No effect
Dobutamine: metabolism
COMT
Dobutamine: adrenergic receptor agonism
B1 > B2 > A1
Dobutamine: infusion dosing
2-20 mcg/kg/min
Dobutamine: primary use
Cardiogenic shock
Stress testing
Ephedrine: renal blood flow
Decreases
Ephedrine: MAP
Increases
Ephedrine: airway resistance
Decreases
Ephedrine: metabolism
Liver
Most renal- unchanged
Ephedrine: adrenergic receptor agonism
A, B, indirect
Ephedrine: bolus dosing
5-25 mg IV
Up to 50 mg IV
Ephedrine: primary uses
Hypotension
Low dose epinephrine effects vs high dose effects
Low doses favor beta stimulation (increased HR, CO, inotropy, and pulse pressure, and a decrease in SVR)
High doses favor alpha effect (increased SVR and decreased CO)
Epinephrine effects on local anesthestics
Prolongs duration
Dopamine <3 mcg/kg/min effects
D1 stimulation –> vasodilation and increased renal and splanchnic blood flow
Dopamine 3-8 mcg/kg/min effects
A1 and B1 stimulation (heart and periphery) –> increased contractility and BP
Dopamine >10 mcg/kg/min effects
Pure A1 agonist –> increased BP
Post synaptic D1 receptor stimulation
Vasodilation of renal, GI coronary, and cerebral vessels
Presynaptic D2 stimulation
Inhibit norepinephrine release = vasodilation
Location of D2 receptors
Pituitary gland
Emetic center
Kidney
Isoproterenol potency vs epinephrine
2-3x more potent than epinephrine
Indirect action of ephedrine
Endocytosis of ephedrine into adrenergic presynaptic terminal > NE is displaced from secretory vesicles >NE activates target A1 and B1
Beta-2 agonists with black box warning
Salmeterol
Formoterol
Noncompetitive alpha antagonist that block the alpha- mediated activity of NE and epinephrine
Phenoxybenzamine
How is the effect of phenoxybenzamine terminated?
The synthesis of new receptors; its bond is permanent
Phenoxybenzamine indication
Preoperative management of pheochromocytoma
Common complication of phenoxybenzamine administraton
Orthostatic hypotension
Best treatment for hypotension in patients who have been taking phenoxybenzamine
Vasopressin
Fluids
Competitive nonselective alpha receptor antagonist
Phentolamine
Half-life of phentolamine
< 10 minutes
(much shorter than phenoxybenzamine)
In what patients should phentolamine be used cautiously?
Pts with flow-limited coronary artery disease (d/t rapid vasodilation resulting in reflex tachycardia)
Used to treat infiltration of epinephrine or norepinephrine
Phentolamine
Used to treat refractory hypertension d/t abrupt discontinuation of clonidine
Phentolamine
Alpha antagonist that has an affinity for 5-HT receptors = stimulates stomach acid secretion and induces mast cell degranulation
Phentolamine
Highly selective A1 receptor antagonist with 1000:1 A1:A2 affinity
Prazosin
Side effects of prazosin
Orthostatic hypotension
Prazosin analogs
Terazosin
Doxazosin
Tamsulosin
Beta blocker indications
Hypertension
Supraventricular tachycardia
Atrial fibrillation
Blunting an acute hemodynamic response
CHF and ischemic heart disease
Reducing myocardial O2 consumption and improving perfusion
What is membrane stabilizing activity?
Inhibits or abolishes action potential propagation across the cell membrane
Nonselective B-adrenergic antagonist prototype
Propranolol
Class of drugs that competes with B1 and B2 to prevent the action of epinephrine, norepinephrine, dopamine, dobutamine, and isoproterenol
Nonselective beta adrenergic antagonists
List nonselective beta adrenergic antagonists
Carvedilol
Pindolol
Propranolol
Sotalol
Timolol
Nadolol
Longest half-life of nonselective beta adrenergic antagonists
Nadolol
Nonselective beta adrenergic antagonist that has some weak B-agonist effects (ISA) and is associated with less HR slowing and less impact on BP
Pindolol
Selective beta adrenergic antagonist that has some weak B-agonist effects (ISA) and is associated with less HR slowing and less impact on BP
Acebutolol
Cardioselective B-adrenergic antagonists (list)
Metoprolol
Atenolol
Acebutolol
Esmolol
Bisoprolol
Relationship between dose of medication and beta selectivity
Inverse correlation: as dose increases, selectivity decreases
Beta blocker that is metabolized in the bloodstream
Esmolol
Beta blocker that is metabolized in the kidneys
Atenolol
Site of metabolism for most beta blockers
Liver
Metoprolol indications
Angina
Heart failure
MI
A fib
HTN
Beta blocker that is metabolized in the kidneys
Atenolol
Metoprolol IV dosing
2.5- 5mg increments to a maximum of 15mg
First line drug for rapid and perioperative control of HR and BP
Esmolol
Esmolol duration of action
<15 minutes
Bolus dose of esmolol
10-80 mg
Infusion dose of esmolol
50-300 mcg/kg/min
Name the drug
Propanolol
Name the drug
Esmolol
Atenolol indications
HTN
Chronic angina
Follow-up post MI
Name the drug
Labetalol
Labetalol primary indication
Acute HTN
Beta blocker with antioxidant and anti-inflammatory properties
Carvedilol
Carvedilol indications
Heart failure
Left ventricular dysfunction
HTN
Acute MI
Carvedilol dosing
12.5- 50mg PO in two doses
Carvedilol adverse effects
Orthostatic hypotension
Name the drug
Ephedrine
Name the drug
Phenylephrine
Used to identify reactive airway disease in pts who do not have clinically significant asthma
Methacholine
Receptor that methacholine activates
M3
Antimuscarinic that does not cross the BBB
Glycopyrrolate
Antimuscarinics’ effect on HR in descending order
Atropine > Glycopyrrolate > Scopolamine
Antimuscarinics’ effect as antisialagogue in descending order
Scopolamine > glyco > atropine
Antimuscarinics’ effect as sedative in descending order
Scopolamine > atropine > glyco (no effect)
Antimuscarinics’ mydriasis effect in descending order
Scopolamine > atropine > glyco (no effect)
Antimuscarinics’ effect on motion sickness in descending order
Scopolamine > atropine > glyco (no effect)
Effect of low dose atropine (<0.1 mg)
Worsening bradycardia d/t blocking M1 receptors on preganglionic parasympathetic fibers
Scopolamine and atropine toxicity symptoms
Increased HR
Dry mouth
Anhidrosis
Thirst
Palpitations
Mydriasis
Cycloplegia
Restlessness
Confusion
Hot, flushed skin
Fever
Hallucinations
Coma
Death
Treatment for scopolamine or atropine toxicity
Physostigmine 1-2mg IV (may need to be repeated)
Type of Ca++ channels that CCB block?
Long (L) type Ca++ channels
Three classes of CCB
- Dihydropyridines
- Benzothiazipines
- Phenylalkylamines
Dihydropyridines (list)
Nifedipine
Nimodipine
Nicardipine
Clevidipine
Benzothiazipines
Diltiazem
Phenylalkylamines
Verapamil
Best CCBs for HR control
Verapamil
Diltiazem
Rank CCB from highest to lowest impact on contractility reduction
Verapamil > nifedipine > diltiazem > nicardipine
Best CCB for treatment of HTN from elevated SVR
Nifedipine
Nicardipine
CCB used as a coronary antispasmodic
Nicardipine
The only CCB proven to reduce morbidity and mortality from cerebral vasospasm
Nimodipine
CCB have a greater impact on arterial or venous smooth muscle?
Arterial
Verapamil effect on cardiac conductivity
Reduces SA node discharge and decreases AV node conduction, prolonging PR interval
Verapamil dose
2.5-10 mg over 2 minutes
Diltiazem dose
0.25mg/ kg over 2 minutes
Clevidipine half life
~2 minutes
CCB that is useful in treating acute HTN, even in setting of pheo and intracerebral hemorrhage
Clevidipine
Clevidipine dose
1-2 mg/hr
Most lipophilic CCB
Nimodipine
CCB that fosters cerebral vasodilation
Nimodipine
CCB with baroreceptor-mediated increases in HR
Nifedipine
CCB that may worsen mortality in those with MI
Nifedipine
CCB often prescribed for pt with Raynaud’s
Nifedipine
Nifedipine dose
0.5 mg/hr
CCB that dilates coronary arteries with little effect on inotropy
Nicardipine
Nicardipine dose
5 mg/hr
Direct vasodilators (list)
Nitroglycerin
Nitroprusside
Hydralazine
Nitroglycerine primary action
Venodilator with reduced preload
Nitroprusside primary action
Reduces afterload and preload
Hydralazine primary action
Arterial smooth muscle dilator
Nitroglycerin dosing
5-100 mcg/min
Nitroglycerin onset
2-5 min
Nitroglycerin duration
5-10 min
Nitroglycerin site of artery dilation (possibly)
Coronary arteries
Nitroprusside dosing
0.3- 10 mcg/ kg/ min
Nitroprusside onset
Seconds
Nitroprusside duration
<5 minutes
Nitroprusside adverse effect
Potential for cyanide toxicity
Hydralazine dosing
2.5- 20 mg
Hydralazine onset
2- 20 min
Hydralazine duration
Up to 12 hours
NTG mechanism of action
Liberates nitric oxide = dilation
Why is nitroprusside not used in MI
It will induce coronary steal, taking blood flow away from ischemic tissue
PDE 5 inhibitors (list)
Slidenafil
Tadalafil
Vardenafil
PDE 5 inhibitors mechanism of action
Increase levels of cGMP by inhibiting its breakdown –> increase cGMP targets lungs and penis
PDE 5 inhibitors’ effects
Pulmonary vasodilation
Decrease PAP
PDE 4 inhibitors (list)
Roflumilast
Apremilast
Ibudilast
PDE 4 inhibitors MOA
Increase levels of cAMP targeting the airways, skin, and immune system
PDE 4 inhibitors uses
Airway smooth muscles relaxation
Inflammatory disorders of the skin, bowel, and joints
PDE 3 inhibitors (list)
Milrinone
Cilostazol
PDE 3 inhibitors MOA
Increase levels of cAMP and cGMP
PDE 3 inhibitors uses
Cardiovascular disease
Intermittent claudication
Prevent platelet aggregation for thrombosis prophylaxis
CPBP weaning
Milrinone dosing
25-50 mcg/kg over 10 min
0.375 -0.75 mcg/kg/min infusion
Nonspecific PDE inhibitors (list)
Theophylline
Methylxanthine
Vasopressin effect on healthy, conscious person
Little effect on BP d/t reflex mediation
Vasopressin effect on pt with SNS or renin-angiotensin- aldosterone axis dysfunction
Activates V1 to restore BP
Vasopressin indications
Distributive shock, pulmonary HTN, anaphylaxis, ACLS
Vasopressin dose
1-2 unit bolus
0.01- 0.1 unit/ minute infusion
Side effects of ACEi
Dry cough
Hyperkalemia
Fatigue
Renal dysfunction
Angioedema
Treatment for ACEi hypotension
Vasopressin may be necessary d/t refractory hypotension