Pharm Flashcards
Describe “context-sensitive half time”
Context-sensitive half-time often cannot be predicted by the elimination half-life when a drug is continuously infused (vs administered via single bolus).
Distribution of the drug and accumulation in tissues results in a longer half-life of drugs administered via continuous infusion.
With these drugs, it is important to occasionally rouse patient to assess CNS function.
What are examples of drugs that are more severely affected by context-sensitive half times, and an example of a drug that is not? What does this mean?
Fentanyl and benzodiazepines are significantly affected by their context-sensitive half-time; their half-lives are increased dramatically, and it is especially important to monitor patients’ CNS function during continuous infusion.
Propofol is not especially affected by its context-sensitive half-time; with both bolus and continuous infusions, patients wake quickly (half-life is not dramatically extended during continuous infusion).
Name some sedative/anesthetic drugs that work via GABA receptors
Barbituates
Propofol
Etomidate
Benzodiazepines
Name a sedative/anesthetic that works via glutamate receptors
Ketamine
Describe the MOA of and indications for benzodiazepines
Benzos work via modulation of GABA receptors. They do NOT directly bind GABA receptor sites - they bind allosterically to potentiate GABA’s effect. More Cl- flows through channels and GABA’s inhibitory effect is increased.
These are used perioperatively (for anterograde amnesia, anxiolysis, and induction), sedation/hypnosis, seizure control, and ICU sedation
Describe the MOA of and indications for barbituates
Effect GABA receptors (not emphasized in lecture)
Barbituates are potent anticonvulsants. These are used for induction, but are largely being replaced by propofol. They provide no analgesia.
Describe the MOA of and indications for propofol
Propofol acts on the GABA receptor to increase its binding affinity, increasing GABA-mediated inhibition.
It is indicated for use as a sedative/anxiolytic agent; can be used as an antipruritic, and as an antiemetic agent as subanesthetic doses. It is used in induction.
Describe the MOA of and indications for etomidate
Etomidate enhances the effects of GABA by binding a subunit and opening more Cl- channels, increasing inhibitory effects.
It is a short-acting hypnotic, indicated for use in induction (in conjunction with BZs), and used in cases of CV risk or neurosurgery. It does not provide analgesia.
Name a sedative/anesthetic that works on a-adrenergic receptors
Dexmedetomidine
Describe the MOA of and indications for ketamine
Ketamine inhibits the NDMA receptor complex at the glutamate receptor
It is indicated for analgesia at subanesthetic doses; as an anesthetic, it provides analgesia, amnesia, and unconsciousness
Often used in conjuction with BZs in emergent/trauma situations, and used in induction
Describe the MOA of and indications for dexmedetomidine
Dexmedetomidine is an a2-adrenergic agonist (2a and 2b, specifically)
It is indicated for analgesia and sedation (especially in ICU) but does not provide amnesia
What drug is used to block the effects of benzos? What’s an important characteristic of this drug?
Flumazenil - competitive antagonist to benzos.
Important to remember that flumazenil does not increase elimination of benzos and it has a shorter half life; if flumazenil is administered because benzos have caused respiratory distress/arrest, it’s important to intubate/be ready for respiratory depression as the flumazenil is redistributed.
Describe the administration of benzodiazepines
Midazolam is the MC used: can be used PO, IV for induction or IM (peak effect 30-90 minutes)
Diazepam is available PO (also available as lollipop/syrup for pediatrics)
Lorazepam can be used PO or IM
Describe the onset of benzoidazepines
In general, benzos have a slower onset than most other agents
Of the benzos, IV midazolam has the fastest onset (~3 minutes)
What is significant about the duration of action and metabolism of benzos?
They are the shortest of the drugs we discussed: 3-10 minutes. They undergo rapid redistribution to the tissues.
Midazolam and diazepam undergo hepatic metabolism to produce active metabolites –> renal elimination, which may be a consideration in patients with low GFR.
Lorazepam does not produce active metabolites.
Describe the effects and drawbacks of benzos.
Provide sedation and amnesia, incld ICU sedation
\+ Minimal CV effects \+ Minimal respiratory depression \+ Produce retrograde amnesia \+ Reduce anxiety \+ Anti-convulsant \+ Can minimize fasciculations
- Does NOT provide analgesia
Rarely used alone (short duration and lack of analgesia) but can be used to balance the CV/respiratory impact of other drugs
Which anesthetic class has the shortest duration of action?
Benzodiazepines (3-10 minutes)
Name the barbituate drugs we discussed
Methohexital (MC) and thiopental (not used)
What are important characteristics of proprofol that impact its administration?
Propofol is not water soluble, so it is delivered as a 10% lipid emulsion. The egg component of the emulsion can promote bacterial growth, so preservatives are needed and it is imperative that sterile technique and use within proper time frame is observed.
Long-term use is not appropriate for this reason.
Describe the effects and drawbacks of propofol.
Anesthetic and anticonvulsant
- REDUCES BP
- Dose-related RESPIRATORY DEPRESSION
Other effects: \+ Anti-convulsant \+ Anti-pruritus \+ Anxiolytic \+ Anti-emetic \+ Safe in pregnancy \+ Rapid awakening
- No muscle relaxation
- Hypertriglyceridemia –> pancreatitis when used >48 hours
- Pain with injection
Describe the effects and drawbacks of etomidate
Management of delirium
+ MINIMAL decline in SVR (good for high-risk CV pts)
- Suppresses synthesis of cortisol = DO NOT USE for ICU sedation (inhibits 11-B-hydroxylase)
- Fasciculations/hypertonus/myoclonus
- N/V
- No analgesia
Describe the effects and drawbacks of ketamine
Dissociative anesthesia
+ Minimal respiratory depression
+ Can act as bronchodilator
+ Analgesia (instant, lasts ~40 min)
+ Amnesia (instant, lasts ~40 min)
- INCREASES HR, BP, CO via inhibition of NE re-uptake
- Emergence reactions: delirium, excitation, confusion, euphoria, fear, hallucinations (minimize with benzos)
- Increased salivary/trachiobronchial secretions
- Increased muscle tone (spec uterine muscle contraction)
What is the indication for use of fospropofol?
Moderate IV sedation (monitored anesthesia care)
Describe the onset and duration of ketamine
Onset: 15-30 seconds
Dissociative anesthetic effects last ~10-15 minutes
Analgesia/amnesia effects last ~40 minutes
Describe the effects and drawbacks of dexmedetomidine
Sedation
+ Analgesia
+ Little respiratory depression
+ Immediate rouse to consciousness
+ Can be used for ICU sedation
- No amnesia
- CV effects: hypotension, bradycardia
- Withdrawal effects when used >24 hours
What was the emphasized recommendation for pharmacologic sedation?
Use propofol or dexmedetomidine for sedation instead of benzos
What was the emphasized recommendation for prevention/treatment of delirium?
Don’t use haloperidol or atypical antipsychotics to prevent or treat delirium
(dexmedetomidine can be used in certain patients)
What is the general MOA and the AEs of the first drug that would be used in a symptomatic, bradycardic patient?
Atropine would be used in a symptomatic, bradycardic patient
Atropine is an antimuscarinic that decreases vagal tone
AEs include tachycardia, blurred vision, photophobia, and anti-SLUD effects (decreased salivation, lacrimation, urination, defecation)
In a symptomatic patient who is not responding to atropine or transcutaneous pacing, which drugs would be indicated? What are their general MOAs and what are some AEs?
Epinephrine or dopamine could be used in this patient
- These are a1/B1 agonists
- AEs include HTN and potential for arrhythmias
Name the H’s and T’s
Hypoxia Hypovolemia Hypo/hyper K+ Hypothermia H+ (acidosis)
Toxins
Tamponade
Tension pneumo
Thrombosis (pulmonary or coronary)
Categorize the common tachyarrhythmias by rate (regular vs irregular) and QRS complex width
Arrhythmias with a normal/narrow QRS complex originate above the ventricles.
- If there is a regular rate, this might be sinus tachycardia or a supraventricular tachycardia (AVNRT; atrial tachycardia) - If there is an irregular rate, this might be A-flutter
Arrhythmias with wide QRS complexes originate in the ventricles.
- If there is a regular rate, consider V-tach (80% of wide complex tachycardias) or SVT with aberrancy (such as BBB) - If there is an irregular rate, consider A-fib + preexcitation (BBB, WPW, etc). If the rhythm is polymorphic, consider Torsade's.
What is the first line treatment for a symptomatic but stable patient with a regular, narrow-QRS complex tachycardia?
Valsalva maneuvers to increase vagal tone. This converts ~25% of patients.
If vagal maneuvers fail to convert a patient who is symptomatic but stable with a regular, narrow-QRS complex tachycardia, what is the first pharmacological intervention indicated? What is it’s MOA?
(Sinus tach or SVT/AVNRT)
Adenosine:
- Activates K+ channels in the SA/AV nodes, causing hyperpolarization and decreased Ca2++ channel activity. This results in a transient AV node block, allowing the SA node to resume pacing.
If adenosine fails in a symptomatic but stable patient with a regular, narrow-QRS complex tachycardia, what should be considered?
We assume patients with regular, narrow-QRS complex tachycardias are in a re-entry tachycardia. If adenosine fails, it is likely that they are NOT in one of these rhythms, and instead they are in a-flutter. We would continue to treat these patients as if they have a-flutter (which follows the treatment for A-fib, emphasizing rate control).
What is the first-line pharmacological treatment for a patient with an irregular, narrow QRS complex tachycardia? What is/are the MOA(s)?
We assume these patients to be in A-fib.
Pharmacological intervention emphasizes rate control (rather than rhythm control).
First line are either class II or class IV antiarrhythmics:
- Class II = B-blockers: MOA: reduces effects of catecholamines, leading to decreased HR, BP, and AV node conduction. - Class IV = CCBs: MOA: directly blocks Ca2++ channels, thereby slowing conduction through the AV node and increasing refractory time.
(Digoxin may also be used)
What is the action of and indication for digoxin in an ACLS setting?
Digoxin can be used for a patient in suspected a-fib (irregular, narrow-complex tachycardia).
It does the following:
- Increases PNS tone
- Positive inotrope (increases force of contraction)
- Negative chronotrope (decreases HR)
In patients who cannot tolerate more B-blockers or CCBs, or patients with reduced EF HF, digoxin may be beneficial
What is the first line pharmacologic treatment for a stable, symptomatic patient with a regular, wide-complex tachycardia?
We assume regular wide-complex tachycardias are V-tach (80%) or SVT+abberancy
**According to Norgard:
Start with adenosine:
- Will NOT terminate V-tach
- If it is an SVT reliant on AV node re-entry, adenosine will terminate the arrhythmia
- May "reveal" underlying a-flutter
***In practice (/if it’s a Ms. Hirst question):
Assume it’s V-tach and go straight to amiodarone
Your patient is stable but symptomatic with a regular, monomorphic, wide-complex tachycardia. You administered adenosine with no response. What is the next pharmacologic intervention? What is its MOA and AEs?
Because the adenosine did not have an effect, we can feel more confident that this is V-tach and not SVT with abberancy.
Amiodarone should be used next (150 mg over ~10 minutes)
MOA: blocks K+ channels resulting in longer action potentials and longer QT intervals
Also blocks Na+ and Ca2++ channels and B-receptors
AEs: LOTS. Affects about every organ system except renal. Remember that it may cause vasodilation when delivered IV (not from drug itself but a component in the emulsion).
You have administered amiodarone and adenosine to a symptomatic but stable patient with a regular, monomorphic, wide-complex tachycardia. They have not responded to treatment. What is/are second line treatments, CIx’s and AEs?
Lidocaine: This is slightly less effective than procainamide (below) but used more often because the CIx are fewer. AEs include tremor/seizure, hallucinations, hypotension, asystole (umm), coma, and N/V.
Procainamide: CIx for patients with prolonged QT or CHF. Can cause arrhythmia, N/V/anorexia, rash, lupus-like reactions, and granulocytosis.
What is the first line pharmacological treatment for a patient with an irregular, polymorphic, wide-complex tachycardia?
(Torsade’s)
Mg2++ and correction of electrolyte imbalances
What is the first line pharmacological treatment for a patient with suspected A-fib + pre-excitation? What is an important consideration when this arrhythmia is suspected, and how would it present on EKG?
This would present as an irregular, monomorphic, wide-complex tachycardia.
In this rhythm, fibrillation of the atria would normally cause a rate of 400-600 bpm, but fortunately the AV node is blocking many of those beats.
If we block the AV node (ex: with adenosine), we risk exacerbating the tachycardia, potentially causing v-fib and collapse.
We should treat with:
- Ibutilide - prolongs the AV node refractory period
or
- Procainamide - decreases excitability/conduction without inducing AV node block
Describe the presentation of a “cold & wet” hypotensive patient and the treatment for these patients
A “cold & wet” hypotensive patient could possibly present with any of the following: congestion at rest, JVD, ascites, edema, rales, orthopnea, cool extremities, low sodium, decreased pulse pressure, or decreased urinary output
Dopamine, dobutamine, or milrinone are appropriate inotropic therapies
If the patient is significantly hypotensive (ie: in septic shock), consider pressors such as high-dose dopamine or norepinephrine
What is the MOA of dopamine, and what are its actions/indications?
Dopamine is an inotropic agent. It is a B adrenergic agonist that increases the activity of adenylate cyclase, resulting in increased [cAMP] –> increased Ca2+ –> increased contractility.
At low doses, it acts only on the DA receptor and mediates vasodilation.
At moderate doses (used in hypotensive patients), it acts on both DA and B1 receptors, causing vasodilation and the desired increased contractility. Moderate doses are indicated for hypotension.
At high doses, it acts on DA, B1, and a1 receptors, mitigating any vasodilatory effects. High doses are indicated for severe hypotension.
What is the MOA of dobutamine? What are its actions/indications?
Dobutamine is an inotropic agent that works similarly to dopamine (B adrenergic agonist that increases the activity of adenylate cyclase, resulting in increased [cAMP] –> increased Ca2+ –> increased contractility). It is indicated for use in hypotension increase force of contraction.
At low/moderate doses it causes vasodilation and decreased SVR.
At high doses it has a stronger a1 effect, mitigating the SVR change.
What is the MOA of milrinone? What are its actions/indications?
Milrinone inhibits PDE3, thereby limiting breakdown of cAMP = increased Ca2+ and increased contractility. It can cause a decrease in SVR and PVR.
It is indicated for use in hypotension to increase force of contractility.
Which inotropic drug(s), used in the treatment of a symptomatically hypotensive patient, has the greatest likelihood of decreasing SVR?
Low doses of dobutamine (2.5-5 mcg/kg/min)
or
Milrinone (0.125-0.75 mcg/kg/min)
Which intropic drug, used in the treatment of a symptomatically hypotensive patient, has the greatest likelihood of increasing SVR?
Moderate doses of dopamine (10-15 mcg/kg/min)
Which inotropic drug, used in the treatment of a symptomatically hypotensive patient, has the greatest likelihood of decreasing peripheral vascular resistance?
Milrinone (0.125 - 0.75 mcg/kg/min)
Which drugs are indicated for use in severe hypotension (ex: septic shock)?
Pressors:
High dose dopamine (10-15 mcg/kg/min)
or
Norepinephrine (0.01 - 3 mcg/kg/min)
These both help preserve end-organ perfusion but increase SVR (afterload) which isn’t awesome.
Describe how intra-aortic balloon pumps assist cardiac function
Inflates during diastole and deflates during systole, helping to increase CO in cases of cardiogenic shock.
Describe an LVAD
Mechanical support used as a temporary intervention; assists movement of blood out of the left ventricle.
Describe ECMO and when it is used
Take the blood out, oxygenate it, and put it back in.
Helpful in the setting of pulmonary edema.
A patient presents with aortic dissection and severe hypertension. What are your goals of pharmacological treatment?
Reduce systolic blood pressure to <120 in first hour
Your patient presents with severe hypertension secondary to preeclampsia. What are your goals of pharmacologic BP management?
Reduce systolic blood pressure to <140 in first hour
Why do we reserve rapid BP reduction only for certain conditions? Which conditions are those?
Chronic HTN resets the autoregulatory “set point” – fast changes could lead to cerebral ischemia/relative hypotension/end-organ hypoperfusion as the body tries to maintain that set point in the face of rapid BP reduction.
Conditions that merit rapid BP reduction:
- Aortic dissection
- Pre-/eclampsia
- Pheochromocytoma
A patient presents with severe hypertension, SOB, vision changes, headache, and crackles. What is the goal of pharmacologic treatment of her BP?
Measured decrease in BP:
- Reduce by 25% in 1st hour
- Reduce to 160/100 in next 2-6 hours
- Reduce to normal within 24-48 hours
Describe the MOA of and indication for nicardipine and clevidipine.
Nicardipine and clevidipine are dihydropyridine Ca2+ channel blockers.
They are used in the treatment of hypertension. They have fast onset, are easy to titrate, and are generally well-tolerated.
Describe the class and indication for sodium nitroprusside. What is another commonly used drug in the same class? What are important things to monitor when using these drugs?
Sodium nitroprusside and nitroglycerin are NO-dependent vasodilators.
Intra-arterial pressures must be monitored when using to avoid overshooting BP reduction. These are used in ACS and/or pulmonary edema, but should NOT be used in volume-depleted patients.
Describe the class and indication for hydralazine.
Hydralazine is a direct vasodilator. It is used in hypertensive patients, but it is slow, unpredictable, and has a high risk of rebound tachycardia and angina.
To what class does esmolol belong? What is it’s indication and CIx’s?
Esmolol is a B1-selective B-blocker used in management of hypertensive patients.
It is contraindicated for use in:
- Bradycardia
- Current B-blocker use
- Decompensated HF
- Reactive airways
To what class does labetalol belong? What are it’s CIx’s?
Labetalol is a B-blocker, less selective than esmolol.
It is CIx in patients with reactive airways or COPD.
To what class does phentolamine belong? What is its indication?
Phentolamine is an adrenergic blocker, useful in patients with hypertension secondary to pheochromocytoma, cocaine use, or clonidine withdrawal.
To what class does fenoldopam belong? What are its indications and CIx’s?
Fenoldopam is a DE-1 agonist and causes vasodilation, used in management of hypertensive patients. It is CIx in patients with glaucoma or increased ICP.
To what class does enalaprilat belong? What is it used for and what are its CIx’s?
Enalaprilat is an ACE-inhibitor used in management of hypertensive patients. It is contraindicated in pregnancy, in the setting of acute MI, and in patients with bilateral renal artery stenosis.
What is Norgard’s preferred drug/drugs for treatment of an acutely, urgently hypertensive patient?
Dihydropyridine CCBs such as nicardipine or clevidipine.
What is the preferred treatment for a patient presenting with urgent hypertension secondary to cocaine use?
Phentolamine
Which sedative increases HR?
Ketamine
Which sedatives also provides analgesia?
Ketamine and dexmedetomidine
