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Pharmacokinetics: Half-Life, Volume of Distribution, and Clearance

Sources: Goodman & Gilman's The Pharmacological Basis of Therapeutics, Barash Clinical Anesthesia 9e, Katzung's Basic and Clinical Pharmacology 16e

The Four Core Pharmacokinetic Parameters

These govern everything about how a drug behaves in the body:

Parameter	Symbol	What It Measures	Units
Bioavailability	F	Fraction of dose reaching systemic circulation	% or 0–1
Volume of Distribution	V_d	Apparent space drug occupies in body	Litres (L) or L/kg
Clearance	CL	Rate of drug removal from circulation	mL/min or L/h
Half-Life	t½	Time for plasma concentration to fall by 50%	Hours, minutes

1. Clearance (CL)

Definition

Clearance is the volume of biological fluid completely cleared of drug per unit time. It is the single most important parameter for designing long-term dosing regimens.

$$CL = \frac{\text{Rate of Elimination}}{C}$$

Because most drugs follow first-order kinetics (enzymes not saturated), a constant fraction — not amount — is eliminated per unit time. This means clearance remains constant across typical clinical concentrations.

Key principle for dosing:

$$\text{Dosing Rate} = CL \times C_{ss}$$

To hit a target steady-state concentration, you simply scale the dose rate by clearance. If clearance is halved (e.g., renal failure), the dosing rate must be halved to avoid toxicity.

Organ contributions — clearances are additive:

$$CL_{\text{total}} = CL_{\text{renal}} + CL_{\text{hepatic}} + CL_{\text{other}}$$

Hepatic Clearance

$$CL_{\text{hepatic}} = Q_H \cdot E_H$$

Where Q_H = hepatic blood flow (~1,500 mL/min) and E_H = hepatic extraction ratio.

High extraction drugs (E_H > 0.7): CL limited by blood flow (e.g., lidocaine, propranolol, morphine). Liver disease → reduced flow → reduced CL.
Low extraction drugs (E_H < 0.3): CL limited by intrinsic metabolic capacity (e.g., warfarin, diazepam). Enzyme induction/inhibition matters most.

Renal Clearance

$$CL_{\text{renal}} = \frac{\text{Rate of excretion in urine}}{C_{\text{plasma}}}$$

Creatinine clearance serves as a practical surrogate for estimating renal drug clearance.

2. Volume of Distribution (V_d)

Definition

The apparent volume of distribution relates the total amount of drug in the body to the plasma concentration:

$$V_d = \frac{\text{Amount of drug in body}}{C_{\text{plasma}}}$$

It is called "apparent" because it is a mathematical construct — not a real anatomical volume. Many drugs have V_d values far exceeding total body volume (42 L in a 70 kg adult).

What determines V_d?

Factor	Effect on V_d
High tissue binding (lipophilic drugs)	↑↑ V_d (drug leaves plasma)
High plasma protein binding	↓ V_d (drug stays in plasma)
Lipophilicity	↑ V_d
Hydrophilicity	↓ V_d
Obesity (lipophilic drug)	↑ V_d
Edema/ascites (hydrophilic drug)	↑ V_d

Clinical use of V_d

Loading Dose = V_d × Target Concentration

A large V_d means you need a large loading dose to "fill the box" and achieve the desired plasma concentration.

3. Half-Life (t½)

Definition

The time for plasma concentration to fall by 50%.

$$t_{1/2} = \frac{0.693 \times V_d}{CL}$$

This is the master equation. Half-life is not an independent variable — it is a dependent result of V_d and CL.

Key implications:

t½ Rule	Clinical Meaning
1 × t½	50% of drug eliminated
2 × t½	75% eliminated
3 × t½	87.5% eliminated
4 × t½	93.75% eliminated
4–5 × t½	~97% eliminated → drug effectively gone
4–5 × t½	~97% steady state achieved with repeated dosing

Terminal vs. Steady-State t½

Steady-state t½: Governs accumulation and decline during a regular dosing interval.
Terminal t½: With prolonged dosing, drug penetrates "deep" secondary compartments (e.g., bone, fat). When dosing stops, drug slowly leaches back, prolonging apparent t½.

Example: Gentamicin has a steady-state t½ of 2–3 hours, but a terminal t½ of 53 hours due to accumulation in kidney proximal tubule cells — explaining its delayed nephrotoxicity and ototoxicity. — Goodman & Gilman's

4. The Master Equation — How All Three Connect

$$\boxed{t_{1/2} = \frac{0.693 \times V_d}{CL}}$$

This means:

t½ increases if V_d increases (more drug hidden in tissues, takes longer to clear)
t½ decreases if CL increases (faster elimination)
A disease can lengthen t½ by either reducing CL or increasing V_d — or both

Classic example: In elderly patients, the t½ of diazepam is prolonged — but clearance does not change with age. The cause is an increased V_d as lean muscle mass decreases and fat increases (diazepam is lipophilic, so it accumulates in fat). — Katzung's Basic and Clinical Pharmacology

5. Real Drug Examples

Drug	V_d (L/kg)	CL (mL/min/kg)	t½	Notes
Digoxin	~7–8	~1.4	~36–48 h	Large V_d: binds muscle Na⁺/K⁺-ATPase & adipose; 667 L in 70 kg patient
Warfarin	~0.14	~0.045	~40 h	Small V_d: highly plasma protein-bound (99%); low extraction → enzyme-sensitive
Chloroquine	~200–800	Variable	~1–2 months	Massive V_d (~15,000 L!): extreme tissue accumulation
Heparin	~0.06	~0.8	~1–2 h	Very small V_d: large molecule stays in plasma
Gentamicin	~0.25	~1.5	2–3 h (steady-state); 53 h (terminal)	Accumulates in renal tubules — terminal t½ explains toxicity
Diazepam	~1–2	~0.38	20–100 h	t½ increases with age due to ↑V_d (↑fat mass), not reduced CL
Theophylline	~0.5	Variable	6–17 h	V_d proportional to body weight (distributes with total body water)
Lidocaine	~1.3	~10	~90–120 min	High hepatic extraction — CL very sensitive to hepatic blood flow

6. Summary Comparison Chart

Parameter       | Low Value Means...          | High Value Means...
----------------|-----------------------------|-----------------------------------------
V_d             | Stays in plasma/blood       | Distributes widely into tissues
                | (heparin, warfarin)         | (chloroquine, digoxin, diazepam)
                |                             |
CL              | Slow elimination            | Fast elimination
                | Longer t½, drug accumulates | Shorter t½, frequent dosing needed
                |                             |
t½              | Short: frequent dosing OR   | Long: infrequent dosing possible
                | loading dose less important | BUT longer to reach steady state
                |                             | AND longer to clear in overdose

7. Clinical Pearls

Renal failure → ↓ CL_renal → ↑ t½ for renally cleared drugs (e.g., gentamicin, digoxin) → dose reduction or interval extension needed.

Liver failure → ↓ CL_hepatic → ↑ t½ for hepatically cleared drugs (e.g., lidocaine, diazepam) → caution with loading doses.

Obesity → ↑ V_d for lipophilic drugs → need weight-adjusted loading dose, but maintenance dose based on clearance (which may not change proportionally).

Protein binding changes (e.g., hypoalbuminemia) → ↓ protein binding → more free drug → apparent ↓ V_d, but free CL may be unchanged — total drug concentration can mislead; monitor free levels for drugs like phenytoin.

Goodman & Gilman's The Pharmacological Basis of Therapeutics — the defining reference for all equations above. Barash, Cullen & Stoelting's Clinical Anesthesia, 9e — compartmental model examples and loading dose calculations. Katzung's Basic and Clinical Pharmacology, 16e — disease-state effects on V_d and CL.

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Emergency & ICU Drugs: Doses, Half-Lives & Key Properties

Sources: Tintinalli's Emergency Medicine, Barash's Clinical Anesthesia 9e, Rosen's Emergency Medicine, Goodman & Gilman's

🔴 VASOPRESSORS & VASOCONSTRICTORS

Drug	Mechanism	IV Bolus Dose	Infusion Dose	Half-Life	Onset	Duration	Key Notes
Epinephrine	α1, β1, β2 agonist	Cardiac arrest: 1 mg IV q3–5 min	0.01–1 mcg/kg/min	<5 min	1–2 min	2–10 min	First-line for anaphylaxis & cardiac arrest; 1:10,000 for IV bolus, 1:1,000 for IM
Norepinephrine	α1 >> β1 agonist	—	0.01–3 mcg/kg/min	1–2 min	Very rapid	1–2 min	First-line vasopressor in septic shock (Surviving Sepsis guidelines)
Dopamine	DA, β1, α1 (dose-dependent)	—	2–20 mcg/kg/min	~2 min	≤5 min	<10 min	No longer first-line in sepsis; higher arrhythmia risk vs NE
Vasopressin	V1 receptor (smooth muscle)	—	0.03–0.04 units/min (fixed dose)	10–20 min	Rapid	≤20 min	Longer t½ than catecholamines — useful adjunct; no inotropic effect
Phenylephrine	Selective α1 agonist	40–100 mcg IV bolus q2–5 min	0.4–9.1 mcg/kg/min	Alpha: ~5 min; Terminal: 2–3 h	Immediate	Minutes	Reflex bradycardia; avoid in cardiogenic shock
Angiotensin II	AT1 receptor	—	20 ng/kg/min (titrate)	<1 min	~5 min	Up to 3 h	For refractory vasodilatory shock; thromboembolic risk 12.9%

🟠 INOTROPES

Drug	Mechanism	IV Dose	Half-Life	Onset	Key Notes
Dobutamine	β1 > β2 > α1 agonist	2–20 mcg/kg/min infusion	2 min	1–10 min	Short-term cardiogenic shock, acute decompensated HF; tachyarrhythmia risk
Milrinone	PDE-III inhibitor (inodilator)	Load 50 mcg/kg over 10 min (optional), then 0.375–0.75 mcg/kg/min	2.3–2.4 h	5–15 min	Vasodilatory — reduces SVR; renal dosing required; longer t½ than dobutamine
Digoxin	Na⁺/K⁺-ATPase inhibitor	0.25–0.5 mg IV load (titrate to 0.75–1.5 mg total)	38 h (parent)	IV: 5–60 min	Rate control AF; narrow TI; toxicity with hypokalemia; V_d = 6–7 L/kg

🟡 ANTIARRHYTHMICS

Drug	Class	IV Dose (Adult)	Half-Life	Onset	Key Indications
Adenosine	Endogenous nucleoside	6 mg rapid IV push → 12 mg if no response → 12 mg again	<10 sec	Seconds	PSVT/SVT termination; ineffective for AF, VT
Amiodarone	Class III (Ia, II, III, IV)	VF/pulseless VT: 300 mg IV push; Stable VT: 150 mg over 10 min, then 1 mg/min × 6 h, then 0.5 mg/min	IV single dose: 9–36 days (!); Chronic oral: 40–55 days	IV: rapid initial effect	Broad-spectrum; multiple organ toxicity with chronic use; huge V_d (66 L/kg)
Lidocaine	Class Ib	1–1.5 mg/kg IV bolus; repeat 0.5–0.75 mg/kg q5–10 min (max 3 mg/kg), then 1–4 mg/min infusion	1.5–2 h	Immediate	VF/VT alternative; hepatic clearance — reduce in liver disease/CHF
Atropine	Muscarinic antagonist	0.5 mg IV q3–5 min (max 3 mg or 0.04 mg/kg)	2.1–3.9 h	IV: immediate	Symptomatic bradycardia; NOT for PEA/asystole routine use
Diltiazem	Class IV (CCB)	0.25 mg/kg IV over 2 min; repeat 0.35 mg/kg if needed; infusion 5–15 mg/h	IV: ~3.4–5 h	IV: 3 min	AF/SVT rate control; contraindicated in WPW, cardiogenic shock
Verapamil	Class IV (CCB)	2.5–5 mg IV over 2 min; repeat 5–10 mg q15–30 min	2–5 h (IV terminal)	3–5 min	SVT conversion; avoid in WPW, wide complex tachycardias
Magnesium sulfate	Membrane stabilizer	1–2 g IV (rapid bolus for arrest; over 15 min if pulse)	~4 h (renally cleared)	Rapid	Torsades de pointes, polymorphic VT with prolonged QT
Isoproterenol	β1/β2 agonist	2–10 mcg/min infusion (titrate)	2.5–5 min	Immediate	Refractory bradycardia, AV block, refractory Torsades; rarely used

🟢 SEDATION & ANALGESIA (ICU)

Drug	IV Dose	Half-Life	Onset	Notes
Propofol	5–50 mcg/kg/min infusion; intubation 1–2 mg/kg	Distribution: 1–8 min; Terminal: 0.5–1 h	15–30 sec	Rapid offset; propofol infusion syndrome with high doses >48 h; monitor triglycerides
Midazolam	0.01–0.05 mg/kg IV; infusion 0.02–0.1 mg/kg/h	1–4 h	2–3 min	Active metabolite (1-OH midazolam) accumulates in renal failure; paradoxical agitation in elderly
Ketamine	Induction 1–2 mg/kg IV; dissociative 0.1–0.5 mg/kg	2–3 h	30–60 sec	Bronchodilator; preserves airway reflexes; dissociative anesthesia; useful in RSI for bronchospasm/hemodynamic instability
Fentanyl	25–100 mcg IV bolus; 25–200 mcg/h infusion	Distribution: 1–6 min; Terminal: 2–4 h	1–2 min	Highly lipophilic → context-sensitive accumulation with prolonged infusions; preferred for hemodynamic instability
Morphine	2–4 mg IV q3–4 h; infusion 2–30 mg/h	2–4 h	5–10 min	Active metabolite M6G accumulates in renal failure → prolonged sedation/resp depression
Dexmedetomidine	0.2–1.5 mcg/kg/h infusion (no bolus required)	2 h	~15 min	α2 agonist; cooperative sedation; minimal respiratory depression; bradycardia risk

🔵 NEUROMUSCULAR BLOCKERS (RSI / ICU)

Drug	Intubation Dose	Half-Life	Onset	Duration	Notes
Succinylcholine	1–1.5 mg/kg IV	<5 min (pseudocholinesterase)	30–60 sec	5–10 min	Depolarizing; fastest onset; contraindicated with hyperkalemia, burns >24h, crush injuries, neuromuscular disease
Rocuronium	0.6–1.2 mg/kg IV	~30 min (distribution); 60–70 min elimination	60–90 sec	30–60 min	Non-depolarizing; reversible with sugammadex; dose 1.2 mg/kg for RSI as succinylcholine alternative
Cisatracurium	0.15–0.2 mg/kg IV; infusion 1–3 mcg/kg/min	22–29 min	2–3 min	40–75 min	Hofmann elimination — organ-independent; preferred in hepatic/renal failure

🟣 OTHER CRITICAL ICU AGENTS

Drug	Dose	Half-Life	Notes
Naloxone	0.4–2 mg IV/IM/IN q2–3 min	60–90 min	Opioid reversal; shorter t½ than most opioids → re-narcotization; may need infusion (2/3 reversal dose/h)
Flumazenil	0.2 mg IV over 15 sec; repeat 0.2 mg q1 min (max 1 mg)	40–80 min	Benzodiazepine reversal; shorter t½ than most benzodiazepines → re-sedation; lowers seizure threshold
Alteplase (tPA)	Stroke: 0.9 mg/kg (max 90 mg); PE/massive: 100 mg over 2 h	~4–5 min	Fibrinolytic; short t½ but irreversible effect until fibrinogen recovers
Heparin (UFH)	80 units/kg bolus, then 18 units/kg/h	1–2 h	Dose-dependent kinetics; reverse with protamine; monitor anti-Xa or aPTT
Sodium bicarbonate	1–2 mEq/kg IV	Short	Severe metabolic acidosis, TCA overdose, hyperkalemia
Calcium gluconate	1–3 g IV slow push	Redistributes	Hyperkalemia, hypocalcemia, CCB toxicity
Insulin (regular)	0.1–0.3 units/kg/h infusion; HyperK: 10 units IV	5–10 min	DKA infusion; hyperkalemia management (with dextrose)

Half-Life Quick Reference — Shortest to Longest

Half-Life	Drug
<1 min	Angiotensin II, adenosine
1–2 min	Epinephrine, norepinephrine, dopamine
2–5 min	Dobutamine, phenylephrine (alpha phase), succinylcholine, alteplase
2–5 min	Isoproterenol
10–20 min	Vasopressin
1–4 h	Midazolam, dexmedetomidine
1–2 h	Heparin (UFH)
2–4 h	Fentanyl (terminal), milrinone, morphine
2–3 h	Ketamine
2.1–3.9 h	Atropine
3–5 h	Diltiazem (IV), verapamil (IV)
38 h	Digoxin
9–36 days	Amiodarone (IV single dose)
40–55 days	Amiodarone (chronic oral)

Clinical Pearl: Drugs with very short half-lives (epinephrine, norepinephrine, adenosine) must be given as continuous infusions or rapid IV pushes for sustained effect. Amiodarone's extreme t½ means loading effects persist for weeks after stopping — and toxic effects (pulmonary, thyroid, hepatic) can develop long after dose reduction.

Sources: Tintinalli's Emergency Medicine: A Comprehensive Study (Tables 19-12, 19-18, 19-21, 20-1 through 20-9); Barash's Clinical Anesthesia 9e; Rosen's Emergency Medicine

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Emergency Drug Reference: Safe Dose, Maximum Dose & Half-Life

Sources: Tintinalli's Emergency Medicine, Morgan & Mikhail's Clinical Anesthesiology 7e, Roberts & Hedges' Clinical Procedures in Emergency Medicine, Barash's Clinical Anesthesia 9e, Goodman & Gilman's

🔴 SECTION 1 — CARDIAC ARREST DRUGS (ACLS)

Drug	Initial / Standard Dose	Repeat Interval	Maximum Dose	Half-Life	Onset	Key Toxicity / Limit
Epinephrine	1 mg IV push	Every 3–5 min	No hard cap in arrest; high-dose (0.1 mg/kg) only after failure of standard therapy	< 5 min	1–2 min	High-dose epi: ↑ myocardial O₂ demand, post-ROSC hypertension, arrhythmias
Amiodarone (VF/pulseless VT)	300 mg IV push	150 mg in 5–10 min (once)	2.2 g/24 h (including maintenance)	IV single dose: 9–36 days	Rapid initial	Hypotension (16%), bradycardia, phlebitis
Lidocaine (VF/VT)	1–1.5 mg/kg IV push	0.5–1.5 mg/kg q5–10 min	3 mg/kg total loading; maintenance 4 mg/min	1.5–2 h	Immediate	Seizures, AV block, cardiac arrest at toxic levels; therapeutic level 1.5–6 mcg/mL
Atropine	0.5–1 mg IV	Every 3–5 min	3 mg total in adults	2.1–3.9 h	IV: immediate	Paradoxical bradycardia at very low doses (<0.1 mg); tachycardia, urinary retention, delirium
Adenosine	6 mg rapid IV push	12 mg after 1–2 min; 12 mg again	12 mg per single dose (pediatric max single dose also 12 mg)	< 10 seconds	Seconds	Transient asystole, bronchospasm, chest pain; use with caution in theophylline users
Vasopressin	40 units IV (single dose) or 0.03 units/min infusion	Single bolus (no repeat needed)	40 units bolus (one dose); infusion typically fixed at 0.03–0.04 units/min	10–20 min	Rapid	Mesenteric/myocardial ischemia at high doses; no chronotropic/inotropic effect
Magnesium sulfate	1–2 g IV (rapid bolus in arrest; over 10–15 min if pulse present)	Can repeat 1–2 g	No strict cap; use clinical caution	~4 h (renal)	Rapid	Respiratory depression, hypotension, cardiac arrest (Mg²⁺ >15 mEq/L); antidote = calcium

🟠 SECTION 2 — VASOPRESSORS (ICU Infusions)

Drug	Starting Dose	Usual Range	Maximum Dose	Half-Life	Onset	Toxicity Ceiling
Norepinephrine	0.01–0.05 mcg/kg/min	0.01–3 mcg/kg/min	No firm max; doses >1 mcg/kg/min = refractory shock territory	1–2 min	Very rapid	Peripheral/digital ischemia, hypertension, arrhythmias; first-line in septic shock
Epinephrine (infusion)	0.01–0.05 mcg/kg/min	0.01–1 mcg/kg/min	No firm max; high doses (>0.5 mcg/kg/min) → severe vasoconstriction	< 5 min	1–2 min	Lactic acidosis (β2 effect → glycogenolysis), tachyarrhythmias, myocardial ischemia
Dopamine	2–5 mcg/kg/min	2–20 mcg/kg/min	20 mcg/kg/min	~2 min	≤5 min	Tachyarrhythmias (contraindication in sepsis per Surviving Sepsis 2021); tissue necrosis on extravasation
Vasopressin (infusion)	0.03 units/min	Fixed: 0.03–0.04 units/min (not titrated)	0.04 units/min	10–20 min	Rapid	Mesenteric/coronary ischemia, hyponatremia; do NOT titrate like catecholamines
Phenylephrine	0.4 mcg/kg/min	0.4–9.1 mcg/kg/min	9.1 mcg/kg/min	Alpha phase ~5 min; terminal 2–3 h	Immediate	Reflex bradycardia, ↓ CO; avoid in cardiogenic shock
Angiotensin II	20 ng/kg/min	20–80 ng/kg/min	80 ng/kg/min	< 1 min	~5 min	Thromboembolic events (12.9%), thrombocytopenia; monitor for DVT/PE

🟡 SECTION 3 — ANTIARRHYTHMICS (Detail)

Drug	Class	Initial Dose	Maintenance / Infusion	Maximum Dose	Half-Life	Onset	Key Safety Limit
Amiodarone (stable VT/AF)	III	150 mg IV over 10 min	1 mg/min × 6 h → 0.5 mg/min × 18 h	2.2 g/24 h total	9–36 days (IV); 40–55 days (oral)	Initial: rapid	QT prolongation, bradycardia, hypotension; pulmonary toxicity with chronic use
Lidocaine	Ib	1–1.5 mg/kg IV bolus	1–4 mg/min infusion	3 mg/kg load; 4 mg/min infusion	1.5–2 h	Immediate	CNS toxicity: tinnitus → seizures → respiratory arrest (>6 mcg/mL)
Procainamide	Ia	20–50 mg/min IV	1–4 mg/min	17 mg/kg total (stop if arrhythmia suppressed, QRS widens >25%, or hypotension)	2.5–4.7 h	Minutes	QT prolongation, lupus-like syndrome (long term), hypotension during loading
Adenosine	—	6 mg rapid IV	N/A (one-time doses)	12 mg per dose (may give twice)	< 10 sec	Seconds	Do NOT use in pre-excitation AF (WPW); bronchospasm in asthma
Atropine	Anticholinergic	0.5 mg IV	Repeat q3–5 min	3 mg total (adults)	2.1–3.9 h	Immediate	Not for Mobitz II or infranodal block; not for PEA/asystole
Diltiazem	IV (CCB)	0.25 mg/kg over 2 min	5–15 mg/h infusion	Repeat bolus: 0.35 mg/kg; infusion max 15 mg/h	IV bolus: 3.4 h; infusion: 4–5 h	3 min	Contraindicated: WPW, wide-complex tachycardia, cardiogenic shock, severe LV dysfunction
Verapamil	IV (CCB)	2.5–5 mg IV over 2 min	Repeat 5–10 mg q15–30 min	20 mg total	IV terminal: 2–5 h	3–5 min	Severe bradycardia/AV block; contraindicated with IV β-blockers
Magnesium	Membrane stabilizer	1–2 g IV over 5–15 min	0.5–1 g/h infusion if needed	Monitor levels; toxic >5 mEq/L	~4 h	Rapid	Loss of DTRs (Mg >7); respiratory arrest (Mg >10); cardiac arrest (Mg >15)
Digoxin	Na⁺/K⁺-ATPase inhibitor	0.25–0.5 mg IV; total load 0.75–1.5 mg	0.125–0.25 mg/day	1.5 mg total load	38 h (parent)	IV: 5–60 min	Narrow therapeutic index (0.5–2 ng/mL); toxicity: nausea, visual halo, VT, bradyarrhythmias

🟢 SECTION 4 — SEDATION & ANALGESIA (ICU/Procedural)

Drug	Induction/Bolus Dose	Infusion Range	Maximum Safe Dose	Half-Life	Onset	Key Toxicity Limit
Propofol	1–2 mg/kg IV (titrate in elderly/sick: 0.5 mg/kg)	5–50 mcg/kg/min (0.3–3 mg/kg/h)	4 mg/kg/h (FDA limit; PRIS risk above this, esp. >48 h)	Distribution: 1–8 min; terminal: 30–60 min	15–30 sec	Propofol Infusion Syndrome: metabolic acidosis, rhabdomyolysis, cardiac failure; lipid overload; pain on injection
Ketamine	Induction: 1–2 mg/kg IV (or 4 mg/kg IM); Dissociation: 0.5–1 mg/kg	0.1–0.5 mg/kg/h for analgesia	No firm cap, titrate to effect; large doses (>2 mg/kg) → prolonged recovery	2–3 h	IV: 30–60 sec; IM: 3–5 min	Emergence reactions (↓ with midazolam); laryngospasm rare; ↑ICP caution (controversial)
Midazolam	0.02–0.05 mg/kg IV slowly	0.02–0.1 mg/kg/h	0.6 mg/kg/h ICU; procedural: 0.1 mg/kg total (titrate)	1–4 h (active metabolite 1-OH accumulates in renal failure)	2–3 min	Respiratory depression, hypotension; paradoxical agitation in elderly; prolonged sedation in renal failure
Lorazepam	0.02–0.04 mg/kg IV (max 2 mg/dose)	0.01–0.1 mg/kg/h	2 mg/dose; 10 mg/day practical ceiling	10–20 h	1–5 min	Propylene glycol toxicity with prolonged high-dose infusions (>72 h); accumulation in elderly
Dexmedetomidine	1 mcg/kg over 10 min (optional load)	0.2–1.5 mcg/kg/h	1.5 mcg/kg/h (FDA label)	2 h	~15 min (infusion)	Bradycardia, hypotension; do not abruptly stop (rebound hypertension); not for >24 h originally (now used longer)
Fentanyl	1–2 mcg/kg IV bolus (25–100 mcg typical)	25–200 mcg/h	No fixed max; titrate to effect; high doses >500 mcg/h → context-sensitive accumulation	Distribution: 1–6 min; terminal: 2–4 h	1–2 min	Chest wall rigidity at high bolus doses (>5 mcg/kg rapid); respiratory depression; accumulation with prolonged infusion (context-sensitive t½)
Morphine	2–4 mg IV q3–4 h (opioid-naïve)	2–30 mg/h infusion	No fixed max; reduce in renal failure (M6G accumulation)	2–4 h	5–10 min	M6G active metabolite → prolonged resp depression in renal failure; histamine release → hypotension
Hydromorphone	0.2–0.6 mg IV q3–4 h	0.5–5 mg/h	No fixed max; 5–8× more potent than morphine	2–3 h	5 min	Respiratory depression, neuroexcitatory metabolites in renal failure

🔵 SECTION 5 — NEUROMUSCULAR BLOCKERS (RSI & ICU)

Drug	Type	Intubation Dose	Maximum / High Dose	Half-Life	Onset	Duration	Key Safety Limit
Succinylcholine	Depolarizing	1–1.5 mg/kg IV	2 mg/kg (for difficult airway)	< 5 min (pseudocholinesterase)	30–60 sec	5–10 min	Absolute contraindications: hyperkalemia, burns >24 h, crush injuries, denervation, neuromuscular disease (K⁺ surge → VF); ↑ IOP/ICP; malignant hyperthermia trigger
Rocuronium	Non-depolarizing	0.6 mg/kg; RSI: 1.2 mg/kg	1.2 mg/kg (reversal = sugammadex 16 mg/kg)	Distribution: ~30 min; elimination: 60–70 min	60–90 sec (0.6 mg/kg); 60 sec (1.2 mg/kg)	30–60 min (dose-dependent)	Accumulates in hepatic failure; reversal always available (sugammadex); no histamine release
Vecuronium	Non-depolarizing	0.1 mg/kg; RSI: 0.2–0.3 mg/kg	0.2–0.3 mg/kg	~80 min (prolonged in hepatic/renal failure)	2–3 min	25–40 min	Accumulates in organ failure; reversal with neostigmine/glycopyrrolate
Cisatracurium	Non-depolarizing	0.15–0.2 mg/kg	0.4 mg/kg	22–29 min	2–3 min	40–75 min	Hofmann elimination — organ-independent; preferred in hepatic AND renal failure; no histamine release
Pancuronium	Non-depolarizing	0.08–0.1 mg/kg	0.1 mg/kg	~2 h	3–5 min	60–90 min	Tachycardia and hypertension (vagolytic); prolonged in renal failure; avoid in CAD

🟣 SECTION 6 — ANTIDOTES & REVERSAL AGENTS

Drug	Standard Dose	Maximum Dose	Half-Life	Onset	Key Point
Naloxone	0.4–2 mg IV/IM/IN; repeat q2–3 min	10 mg (if no response by 10 mg, reconsider opioid etiology)	60–90 min	1–2 min	Shorter t½ than most opioids → re-narcotization common; may need infusion at 2/3 of effective reversal dose per hour
Flumazenil	0.2 mg IV over 15 sec; repeat 0.2 mg q1 min	1 mg total (5 doses of 0.2 mg)	40–80 min	1–2 min	Shorter t½ than benzodiazepines → re-sedation likely; lowers seizure threshold — avoid in BZD-dependent patients or mixed TCA overdose
Sugammadex	Rocuronium reversal: 2 mg/kg (moderate block); 4 mg/kg (deep); 16 mg/kg (immediate RSI reversal)	16 mg/kg	~2 h	Minutes	Binds rocuronium/vecuronium irreversibly; allergic reactions rare but possible; QT prolongation mild
Neostigmine	0.03–0.07 mg/kg IV (with glycopyrrolate)	5 mg total	~80 min	7–10 min	Only reverses moderate block; combined with glycopyrrolate to prevent bradycardia
Protamine	1 mg per 100 units of heparin given in last 2–3 h	50 mg (max single dose)	~7 min	Minutes	Anaphylaxis risk (especially in fish allergy, prior vasectomy); hypotension, bradycardia
Atropine (for organophosphate)	2–4 mg IV q5–10 min	No maximum — titrate to dry secretions	2.1–3.9 h	Immediate	Endpoint is drying of secretions, not tachycardia; large doses (>100 mg over hours) reported in severe poisoning
Calcium gluconate	1–3 g IV slow push (over 5–10 min)	3 g per dose; repeat as needed	Redistributes rapidly	1–3 min	Hyperkalemia, hypocalcemia, CCB overdose, HF toxicity; extravasation → tissue necrosis
Sodium bicarbonate	1–2 mEq/kg IV	Titrate to pH/QRS; no strict max in TCA OD	Short (rapidly distributed)	Immediate	TCA overdose (narrow QRS): target pH 7.45–7.55; hyperkalemia; may cause hypernatremia/alkalosis
Intralipid 20%	1.5 mL/kg IV bolus over 1 min	Bolus × 2, then 0.25 mL/kg/min × 30–60 min; max 10 mL/kg in first 30 min	Rapidly metabolized	Minutes	Local anesthetic systemic toxicity (LAST); lipid sink mechanism; also used in lipophilic drug OD

🩺 SECTION 7 — OTHER CRITICAL EMERGENCY DRUGS

Drug	Indication	Standard Dose	Maximum / Cap	Half-Life	Notes
Alteplase (tPA)	Ischemic stroke	0.9 mg/kg IV (10% bolus, rest over 60 min)	90 mg total	~4–5 min	>90 mg: no additional benefit, ↑ bleeding risk; hold for BP >185/110 before giving
Alteplase (tPA)	Massive PE	100 mg over 2 h	100 mg	~4–5 min	ICH risk ~1–3%; have FFP/cryo ready
Heparin (UFH)	ACS/PE/DVT	80 units/kg bolus, then 18 units/kg/h	No hard cap; target aPTT 60–100 sec (or anti-Xa 0.3–0.7 IU/mL)	1–2 h	Dose-dependent kinetics; HIT risk after ≥5 days; reverse with protamine
Insulin (regular)	DKA infusion	0.1 units/kg/h (no bolus recommended in DKA)	Titrate per protocol; no hard max	5–10 min	Stop when glucose <200 in DKA; severe hypoglycemia risk without dextrose supplementation
Insulin + Dextrose	Hyperkalemia	10 units regular insulin IV + 25–50 g dextrose (D50)	One combined dose; repeat in 30–60 min	5–10 min	Lowers K⁺ by 0.5–1.5 mEq/L within 20–30 min; monitor glucose q1h for 4–6 h
Labetalol	Hypertensive emergency	20 mg IV over 2 min; repeat 40–80 mg q10 min	300 mg total	5–8 h	Contraindicated in acute decompensated HF, severe asthma, >1° AV block
Nicardipine	Hypertensive emergency	5 mg/h infusion; titrate 2.5 mg/h q5–15 min	15 mg/h	2–4 h	Preferred in acute stroke (smooth BP control); no negative inotropy
Hydralazine	Hypertensive emergency (esp. pregnancy)	5–10 mg IV q20–30 min	20 mg IV per episode	3–7 h	Reflex tachycardia; unpredictable response; not recommended as first-line except pregnancy-related HTN
Nitroglycerin	ACS, acute pulmonary edema	5–10 mcg/min IV; titrate up 5–10 mcg/min q3–5 min	200 mcg/min (practical ceiling)	1–4 min	Tolerance develops within 24 h; contraindicated with PDE-5 inhibitors; hypotension at high doses
Nitroprusside	Hypertensive crisis	0.3–0.5 mcg/kg/min; titrate up	10 mcg/kg/min (max); limit duration to <72 h	~2 min	Cyanide toxicity >72 h or renal failure; hydroxocobalamin antidote
Furosemide	Acute pulmonary edema	20–80 mg IV	200 mg single IV dose	~2 h	Ototoxicity at high doses; hypokalemia; alkalosis
Dexamethasone	Croup, cerebral edema, adrenal crisis	Cerebral edema: 10 mg IV then 4 mg q6h; Croup: 0.6 mg/kg (max 10 mg)	Varies by indication	~36–54 h	Hyperglycemia; adrenal suppression; avoid in untreated TB/fungal

⚡ HALF-LIFE RANKED QUICK REFERENCE

t½ Category	Drugs
< 1 min	Angiotensin II, adenosine
1–5 min	Epinephrine, norepinephrine, dopamine, alteplase, succinylcholine, nitroprusside
5–20 min	Vasopressin, phenylephrine (alpha), insulin, protamine
30–90 min	Naloxone, flumazenil, nitroglycerin, furosemide
1–4 h	Propofol (terminal), nicardipine, heparin, milrinone, fentanyl (terminal), dobutamine
2–5 h	Lidocaine, ketamine, midazolam, diltiazem (IV), verapamil (IV), rocuronium
5–10 h	Labetalol
~38 h	Digoxin
9–36 days	Amiodarone (IV single dose)
40–55 days	Amiodarone (chronic oral)

⚠️ Clinical Safety Rules

Adenosine must be given as a rapid flush — slow injection is ineffective (t½ = 10 seconds).

Amiodarone loading effects persist for weeks — organ toxicity (pulmonary, thyroid, hepatic, corneal) can manifest long after the drug is stopped.

Naloxone and flumazenil both have shorter t½ than their targets → anticipate re-sedation and monitor ≥2 h post-dose.

Propofol infusions >4 mg/kg/h or >48 h → risk of Propofol Infusion Syndrome (PRIS) — monitor CK, triglycerides, and lactate.

Succinylcholine is absolutely contraindicated in any condition causing chronic muscle denervation or burns >24 hours old — catastrophic hyperkalemia and VF can result.

Nitroprusside infusions >72 h or in renal failure → cyanide toxicity — limit duration and have hydroxocobalamin available.

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Emergency Drugs HalfLife Poster

Presentation · PPTX

What's Inside (4 Wide-Format Slides)

Design: Dark navy background, color-coded by drug category, gold accents for safety warnings — built for print or projection.

Slide	Contents
Slide 1 — Cover Poster	Title banner, category legend cards (6 color-coded groups), full half-life spectrum bar from <10 sec to 55 days, 5 critical safety alerts
Slide 2 — Cardiac Arrest + Vasopressors	Epinephrine, Amiodarone, Lidocaine, Atropine, Adenosine, Vasopressin, MgSO₄ with initial/repeat/max dose + t½ + toxicity; plus all 6 vasopressors with infusion ranges and max doses
Slide 3 — Antiarrhythmics + Inotropes	9 antiarrhythmics (Amiodarone, Lidocaine, Procainamide, Adenosine, Atropine, Diltiazem, Verapamil, Mg, Digoxin) + 3 inotropes (Dobutamine, Milrinone, Digoxin)
Slide 4 — Sedation / NMBs / Antidotes + Half-Life Ranked Table	7 sedation/analgesia drugs, 4 NMBs with RSI doses and contraindications, 5 antidotes/reversal agents; right column = 21-drug half-life ranking with color gradient from shortest to longest

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