Pharmacology Flashcards
4 sites of drug metabolism
Lungs
Liver
Kidneys
Cells
4 sites of drug excretion
Kidneys
Lungs
Bowels
Skin
Contraindications for Succinylcholine
- Hyperkalemia
- Rhabdomyolysis (burns/crush > 72hrs) due to up regulation of ACh receptors
- History of malignant hyperthermia
- Neuromuscular disease (safe in mysthenia gravis)
- Spinal cord injury
- Stroke, over 72 hours old
- Unable to BVM
- Pseudoactylcholinestrase deficiency
Succinylcholine administration cautions
- Can affect muscarinic receptors in myocardium and cause bradycardia (or the hyperkalemia can).
- Can increase ICP so avoid in TBI/CVA patients.
- Masseter spasm (*rarely associated with malignant hyperthermia)
- Will temporarily increase serum potassium levels by 0.5-1.0 mmol.
Rocuronium administration cautions
- Difficult BVM
- Anaphylaxis (can occur hours after administration)
MOI of most Pressors/Inotropes
- Modifies intracellular cyclic adenosine monophosphate (cAMP) levels
- Increases release of Ca++ from sarcoplasmic reticulum
- Increases sensitivity of troponin to Ca++
Effects of pH on SNS receptors
Mutates alpha and beta receptor sites and inhibits their binding with catecholamines. This often occurs with pH < 7.12. Consider NaHCO3 if vasopressors are ineffective.
Succinylcholine induction dose:
- 5mg/kg (actual body weight)
* Larger doses can potentially spill over and cause muscarinic activation –> bradycardia
Rocuronium induction dose:
0.6 to 1.2mg/kg (ideal body weight)
Rocuronium pharmacokinetics
Onset: 60-90 seconds
Duration: 30-45 minutes
Succinylcholine pharmacokinetics
Onset: <60 seconds (look for fasiculations)
Duration: 4-10 minutes
Ketamine doses
Induction: 0.5-4mg/kg
Maintenance: 0.5-4mg/kg/hr
IVP: 0.01 to 0.03mg/kg or just 5-20mg
*Going over won’t ‘dissociate’ the patient deeper, it will just prolong the effect of dissociation. It may, however, cause respiratory arrest!
Ketamine pharmacodynamics
- Antagonizes NMDA receptors and reduces catecholamine reuptake.
- Interrupts pathways between limbic system (emotions/memories) and the cortex (higher functions, wakefulness, perception) causing dissociation.
- Increases HR, BP and cardiac output.
- Can cause bronchodilation.
- Is associated with significant oropharyngeal secretions (can be dried with 0.2mg atropine).
Propofol doses
Induction: 2 to 4mg/kg (Will cause hypotension!!)
Maintenance: 5-100mcg/kg/min
IVP: 10-30mg
Propofol infusion syndrome can occur at doses of 80mcg/kg/min over 24 hours. Severe, refractory bradycardia leading to asystole. Crank up the milliamps and pace!
Propofol pharmacodynamics
- Works on GABA and NMDA receptors and modulates hypothalamic sleep pathways. Also, upregulates Mu receptors to make opioids more responsive.
- Amnesic, anxiolytic, anti-convulsant, anti-emetic, bronchodilatory effects, and muscle relaxing effects. No analgesia!
- Will sequester itself into adipose tissue to delay clearance. Elimination is not affected by renal/liver dysfunction.
Fentanyl doses
Induction: 50-100mcg (less for patients > 65)
Maintenance: 1-3mcg/kg/hr (50-200mcg/hr)
IVP: 20-50mcg
*Large doses of opioids for induction can cause “frozen chest wall.” The only treatment is paralytics or naloxone.
Ketamine pharmacokinetics
Onset: 1 minute
Duration: 15-20 minutes
Fentanyl pharmacokinetics
Onset: Immediate
Duration: 30-60 minutes
Is midazolam safe for pregnant patients?
No. All benzodiazepines are recognized as class D. Evidence shows strong risk to the fetus.
Choose another agent to treat eclampsia (MgSO4, phenytoin etc.)
Midazolam pharmacokinetics
Onset: 2-5 minutes
Duration: <2 hours
*Benzodiazepines can alter higher cognitive function in older adults for up to 6 months after administration!
Midazolam doses
Induction: 5-10mg
Maintenance: 5-10mg/hr
- Cut in half for anybody >65.
- Will have significant duration for anybody with renal/hepatic dysfunction since both drug and metabolite are active!
Low dose epinephrine receptor activation
Alpha: +
Beta 1: +++
Beta 2: ++
*Increases CO, decreases SVR
High dose epinephrine receptor activation
Alpha 1: +++
Beta 1: +++
Beta 2: +
Increases CO and increases SVR
Low dose (1-2mcg/kg) dopamine receptor activation
Alpha: -
Beta 1: +
Beta 2: -
Dopaminergic: ++ (causes selective vasodilation of renal, coronary, mesenteric and cerebral vessels)
Medium dose (5-10mcg/kg) dopamine receptor activation
Alpha: +
Beta 1: ++
Beta 2: -
Dopaminergic: ++
High dose (10-20mcg/kg) dopamine receptor activation
Alpha 1: ++ Beta 1: ++ Beta 2: - Dopaminergic: ++ *Be wary of dysrhythmias!
Dobutamine receptor activation
Alpha 1: - Beta 1: +++ Beta 2: ++ Dopaminergic: - *lower doses cause more inotropy while higher doses cause more vasodilation!
Vasopressin properties
- Works like anti-diuretic hormone (ADH) and exclusively works on V1 receptors.
- Increases water reabsorption in the kidney’s collecting ducts. Pulls more water than sodium so can cause relative hyponatremia. This is good for diabetes insipidus but bad for cerebral edema.
- Causes vasoconstriction, particularly in the splanchnic vessels so can be useful for esophageal varices.
- Unlike levophed, will constrict efferent renal arterioles, thus increasing glomerular flow.
- Considered second line agent for sepsis refractory to levophed or anaphylaxis refractory to sepsis
- Dose: 0.01 to 0.04 units/min. Doses higher than 0.03u/min are associated with mesenteric and coronary ischemia and increased pulmonary artery pressures.
- Particulalry useful in septic shock since there is possible reduced endogenous ADH in this shock state.
Levophed receptor activation
Alpha 1: +++
Beta 1: ++
Beta 2: -
Phenylephrine receptor activation
Alpha 1: +++
Beta 1: -
Beta 2: -
Milrinone properties
- Phosphodietrase-3 inhibitor
- Increases intracellular Ca++ levels
- Causes inotropy and vasodilation similar to dobutamine, but fewer dysrhythmias
- Consider as a secondary agent for refractory cardiogenic shock, or if cardiogenic patient is tachycardic or arrhythmogenic.
- Dose: 0.125 to 0.1mcg/kg/min
Dobutamine preparation
Dose: 2.5 -20mcg/kg/min
Prep: 250mg in 250mL
Levophed preparation
Dose: 1-20mcg/min
Regular strength prep: 4.0mg in 250mL (16mcg/mL)
Quad strength prep: 16.0mg in 250mL (64mcg/mL)
Phenylephrine preparation
Draw up 1mL (10mg) from vial and dilute in 100mL of N/S, making concentration of 100mcg/mL.
Dose: 50-100mcg IVP
*Consider reflexive bradycardia when correcting acute hypotension.
Fentanyl infusion preparation
Prep: 500mcg in 250mL of N/S
or 500mcg in 50mL of N/S
Ketamine infusion preparation
Prep: 500mg in 500mL of N/S
Dose: 0.5-4mg/kg/hr
Midazolam infusion preparation
Prep: 50mg in 50mL or 250mg in 250mL
Morphine infusion preparation
Prep: 50mg in 50mL of N/S
Three fundamental concepts of vasopressor and inotrope use
- One drug, many receptors
- Dose-response curve. A drug’s receptor affinity will change depending on dose.
- Direct vs reflex action. A drug’s direct action may be cancelled out due to reflexive physiology.
What is tachyphlaxis?
Responsiveness to a drug decreases after continuous or repeat doses.
How do you run vasopressin into a patient using a flight pump?
Dose: 0.01 - 0.04 units/min.
Med Calc off, standard infusion only.
10 units in 100mL of N/S = 0.01 units/mL. It’s run in in mL/hr so you have to multiply by 60, therefore, your infusion rate for 0.01 units/min is 0.6mL/hr. If you want 0.04units/min, run it at 2.4mL/hr
Composition of 0.9% Normal Saline
Sodium 154mEq/l
Chloride 154mEq/l
pH 5.5
*Chloride is a potent renal vasoconstricter and too much NaCl can worsen kidney outcomes/ICU length of stays.
Composition of Lactated Ringers
Sodium 130 mEq/l Chloride 109 mEq/l Potassium 4 mEq/l Calcium 3 mEq/l Lactate 28 mEq/l
pH 6.5
Composition of Plasmalyte
Sodium 140 mEq/l Chloride 98 mEq/l Potassium 5 mEq/l Magnesium 3 mEq/l Gluconate 23mEq/l
pH 7.4
Pros and Cons of Fentanyl
P: Immediate onset, less hypotension, metabolizes hepatically, no N/V.
C: Lipophillic and accumulates in adipose, chest wall stiffness can occur in high doses.
Pros and cons of morphine sulfate.
P: Non-CYP metabolized so fewer drug-drug interactions, longer acting.
C: Accumulates with hepatic/renal dysfunction and prolong effects, histamine release and vagally mediated venodilation, hypotension and bradycardia can be significant. N/V.
Pros and cons of propofol:
P: Anti-convulsant, anti-emetic, reduces ICP, reduces cerebral metabolism, muscle relaxant, rapid on/off, non-affected by renal/hepatic dysfunction. Has bronchodilatory effects so it’s good for inducing asthmatics.
C: Hypotension when bolused (vasodilation and myocardial depression), refractory bradycardia with prolonged use, negative inotrope, respiratory depression, increased caloric intake and CO2 production, longer context specific half-life due to lipophilicity.
Pros and cons of ketamine:
P: Potent sedative with analgesic properties, maintains or improves blood pressure, does not blunt reflexes, less respiratory depression, bronchodilator.
C: Oral secretions, hallucinations, N/V, and can cause myocardial/respiratory depression in rare cases. Sometimes arrhythmogenesic.
Pros and cons of midazolam:
P: Amnestic, anticonvulsant and anxiolytic, immediate onset and short duration.
C: Respiratory and myocardial depression, CYP metabolized into active metabolites that can cause prolonged sedation if delivered long term or if patient is renally impaired, requires hepatic/renal dysfunction dosing, many drug-drug interactions especially with ABx.
Considerations for emergence:
- Have enough analgesia in the patient that they wake up calm and not in pain.
- NODESAT the patient for 2-3 minutes before emergence just in case you need to snow them again and re-intubate.
What is context specific half-life?
The longer the duration of an infusion designed to deliver constant plasma levels of drug, the longer the emergence phase will be.
Does midazolam have antegrade or retrograde amnesic properties?
Angegrade. The patient won’t remember anything moving forward from the time of drug administration.
Lidocaine infusions… Discuss.
- Makes patients drowsy and augments other analgesics.
- Significant context specific half-life
- Can cause lidocaine toxicity. Treat with shitloads of propofol (the lipid make up soaks up the Na+ receptor blocker). NaHCO3- can also be helpful.
Haloperidol cautions
- Depresses ALL the CNS.
- Prolongs QTc and potentially causes Torsades de Pointes.
- Extrapyramidal dystopias (treat with diphenhydramine).
- Neuroleptic malignant syndrome.
- Parkinsonism.
You have 7 infusions and 6 channels. How to problem solve?
- Best to put analgesics/sedatives together. M and M is a handy one since it’s a 1:1 ratio. That drops you to 6 infusions.
- Another option is to give IVP of analgesia/sedation.
By which mechanism is propofol considered a neuro-protective agent?
Assists with auto regulation of blood flow during cerebral insult. Acts on more cerebral receptors to cause more global cerebral depression and reduced metabolism.
Maintains blood flow to the areas of the brain that are working and need it while shunting it away from areas that don’t (flow-metabolism coupling).
Talk to me Goose…
Tell me about Furosemide’s effects on ADHF. How does it work? What electrolytes are commonly lost?
- Reduces circulating volume (diuresis) and provides dilation of peripheral capacitance vessels (venodilation).
- Inhibits reabsorption of Na and Cl in ascending loop.
- Causes increased excretion of water, Na, Cl, Mg and Ca.
List me some inotropes:
- Dopamine (a +/++, b1 +/++, b2 -, d++)
- Dobutamine (a - , b1 +++, b2 ++, d -)
- Milrinone (a -, b1 -, b2 -, d -, PDE3, +)
- LD Epinephrine (a +/++, b1 +++, b2 ++)
How ‘bout dem vasopressors?
- Phenylephrine (a +++, b1 -, b2 -, v -)
- Norepinephrine (a +++, b1 ++, b2 -, v -)
- Vasopressin (a -, b1 -, b2 -, v1 ++)
- HD Epinephrine (a +++, b1 +++, b2 +, v -)
Concerns when administering vasopressin
- Pulls more water than salt from the kidneys so can potentially create/worsen hyponatremia. A particular concern with any form of cerebral edema.
- Causes splanchnic vasoconstriction which can worsen hepatorenal syndrome.
The inotropes, and when to use them:
- Milrinone: cool peripherally with tachycardia
- Dobutamine: cool peripherally with relative bradycardia
- Epinephrine: warm peripherally, bradycardia, shitty heart
- Dopamine: warm peripherally, relative bradycardia, no CVC
Early in critical disease coma, the brain is rich with _________ receptors. Later, these same receptors down regulate themselves and leave more ________ receptors available.
- GABA
- NMDA
Hence why midazolam/propofol are good initial maintenance drugs, but then ketamine infusions start to make more sense.
List the key features of Propofol infusion syndrome:
- Approx 80mcg/kg/min for 12-24 hours
- Mitochondrial dysfunction leads to increased CK, increased lactate, hypotension and refractory bradycardia.
Patient getting swamped out in ketamine induced oral secretions? Suction, but what else can you do?
0.2mg of atropine will dry that shit right up!
Labetalol dosing…
Either 5mg bolus, doubled every 5 minutes to a max single dose of 80mg or a total dose of 300mg.
Or…
Infusion starting of 0.2-10mg/min and increasing.
What type of blocker is Labetalol?
Alpha-1, Beta-1 and Beta-2
IV, it has a 7:1 ratio of beta to alpha effects.
Hydralazine dosing…
5-10mg every 5 min to a max of 40mg
Pantaloc dosing…
80mg bolus, then 8mg/hr
Amiodarone dosing…
150mg bolus
1mg/min for 8 hours
0.5mg/min for the next 16 hours
TXA dosing…
1g over 10 minutes, then 1g over the next 8 hours (1g in 1000cc at 125ml/hr)
What are some benefits of Haldol?
What is a normal dose?
Anti-psychotic
Anti-emetic
Analgesic (can be potent if combined with ketamine)
Dose: 5mg IV, 10mg IM
