general pharmacology

General Pharmacology205b

Neuromuscular Blocking Agents (NMBAs)

• Cause skeletal muscle weakness or

paralysis for purpose of preventing

movement

Neuromuscular Blocking Agents (NMBAs)

• Cause skeletal muscle weakness or paralysis for

purpose of preventing movement

Two types

1. Depolarizing agents

2. Non-depolarizing agents

Depolarizing Agents

Bind to acetylcholine receptor sites causing a post-synaptic membrane depolarization

Prevention of repolarization causes the post-synaptic ending to become refractory and unexcitable, resulting in muscle flaccidity

Action Prevents acetylcholine from binding at

the receptor site Shorter acting than non-depolarizing

agents Will cause total muscle paralysis in 60 to

90 seconds that lasts from 10 to 15 minutes

Do not have reversing agents

Generic name Proprietary name

Succinylcholine Anectine

Indications- Short acting paralytic ideal for

intubation or similar procedures

Non-Depolarizing AgentsProduce paralysis and muscle weakness by competing with acetylcholine for binding at the receptor sitePrevention of the binding of acetylcholine prevents depolarization of the site, thereby preventing muscle contraction

Action Competitive inhibition of acetylcholine at

muscle post-synaptic receptor site Effects felt in 2 to 10 minutes and last for 30

to 60 minutes May be reversed by cholinesterase

inhibitors, e.g., Neostigmine

Generic Name Proprietary NameTubocurarine d-tubocurarine

Pancuronium PavulonMetocurine MetubineVecuronium Norcuron

Rocuronium Zemuron, Esmeron

Indications- Need for longer term paralysis- Patient-ventilator synchrony- Muscle relaxation during surgery- Indications- Reduction of intracranial pressure- Immobility in trauma patients-- Minimize oxygen consumption

Indications for NMBAs

• Endotracheal intubation

• Muscle relaxation during surgery

• Enhancement of patient-ventilator synchrony

• Reduction of intracranial pressure in intubated patients

• Minimizes oxygen consumption

• Facilitation of procedures or diagnostic studies

• Maintenance of immobility, e.g., trauma patients (Flail Chest)

Depolarizing Agents

• Bind to acetylcholine receptor sites

causing a post-synaptic membrane

depolarization

Depolarizing Agents

• Prevention of repolarization causes the

post-synaptic ending to become

refractory and unexcitable, resulting in

muscle flaccidity

Non-Depolarizing Agents

• Produce paralysis and muscle

weakness by competing with

acetylcholine for binding at the

receptor site


• Prevention of the binding of

acetylcholine prevents depolarization

of the site, thereby preventing muscle

contraction


• Endotracheal intubation

• Muscle relaxation during surgery

• Enhancement of patient-ventilator synchrony

• Reduction of intracranial pressure in intubated patients


• Minimize oxygen consumption

• Facilitation of procedures or diagnostic

studies

• Maintenance of immobility, e.g., trauma

patients

Depolarizing Agents

• Generic name

– Succinylcholine

• Proprietary name

– Anectine

Depolarizing Agents

• Action

– Prevents acetylcholine from binding at the

receptor site

– Shorter acting than non-depolarizing agents

Depolarizing Agents

• Action

– Will cause total muscle paralysis in 60 to 90

seconds that lasts from 10 to 15 minutes

– Do not have reversing agents

Depolarizing Agents

• Indications

– Short acting paralytic ideal for intubation or

similar procedures

Depolarizing Agents

• Side effects and hazards

– May induce sympathomimetic response

• Tachycardia

• Increase in blood pressure

• Vagal response in repeated dosages leading to

bradycardia and hypotension

Depolarizing Agents



• Make provoke release of histamines

• Increase in intracranial pressure in patients with

cerebral edema or head trauma

Depolarizing Agents



• Malignant hyperthermia – caused by genetic defect of

muscle metabolism

– Hypoventilation

Depolarizing Agents

• Route of administration

– Intravenous administration

• Dosage

– 1.0 to 1.5 mg/kg


Generic Name Proprietary Name

Tubocurarine d-tubocurarine

Pancuronium Pavulon

Metocurine Metubine

Vecuronium Norcuron


• Action

– Competitive inhibition of acetylcholine at muscle

post-synaptic receptor site

– Effects felt in 2 to 10 minutes and last for 30 to

60 minutes

– May be reversed by cholinesterase inhibitors,

e.g., Neostigmine


• Indications

– Need for longer term paralysis

– Patient-ventilator synchrony

– Muscle relaxation during surgery


• Indications

– Reduction of intracranial pressure

– Immobility in trauma patients

– Minimize oxygen consumption



– Vagolytic effects including tachycardia, increase

in mean blood pressure, and increase in

release of norepinephrine; seen most with

Pancuronium



– Release of histamine from mast cells

• Vasodilation leading to flushed appearance

• Reflex tachycardia

• Bronchospasm

– Hypoventilation



– Intravenous


• Dosage

– Tubocurarine

• 0.5 – 0.6 mg/kg infused at 0.08 – 0.12 mg/kg/hr

– Pancuronium

• 0.08 – 0.1 mg/kg infused at 1 µg/kg/min

– Vecuronium

• 0.1 – 0.2 mg/kg infused at 1 µg/kg/min

• http://www.youtube.com/watch?v=W60QpiDjKag

http://www.youtube.com/watch?v=W60QpiDjKag

http://www.youtube.com/watch?v=W60QpiDjKag

Narcotics and Analgesics

• Used for the relief of severe pain


• Opioid analgesics – high potency

– Morphine


– Oral: (Adults > 50 kg) – 30 mg q3 – q4 hours

– Intravenous: (Adults > 50 kg)

» Single Dose: 4 – 10 mg q3 – q4 hours

» Continuous: 0.8 – 10 mg/hr

– Intramuscular: 4 – 10 mg q3 – q4 hours


• Opioid Analgesics – high potency

– Oxymorphone - (proprietary name – Numorphan)


– Intravenous: 0.5 mg q3 – 6 hours

– Intramuscular: 1.0 – 1.5 mg q3 – 6 hours



– Fentanyl - (proprietary name – Sublimaze)


– Intravenous: 2 mcg/kg (moderate); 2 – 20 mcg/kg (high)

– Intramuscular: same as IV

– LOLLYPOP



– Methadone - (proprietary name – Dolophine)

– Used to overcome Heroine addiction also


– Oral: 10 mg

– Intravenous: 5 mg

• Methadone is mainly used in the treatment of opioid dependence. It has cross-tolerance with other opioids including heroin and morphine, offering very similar effects and a longer duration of effect. Oral doses of methadone can stabilise patients by mitigating opioid withdrawal syndrome. Higher doses of methadone can block the euphoric effects of heroin, morphine, and similar drugs. As a result, properly dosed methadone patients can reduce or stop altogether their use of these substances.


• Opioid Analgesics – high potency

– Hydromorphone - (proprietary name – Dilaudid)


– Oral: 4 – 8 mg q3 – 4 hours

– Intravenous

» Single dose – 1.5 mg q3 – 4 hours

» Continuous – 0.2 – 30 mg/hr

– Intramuscular: 1.5 mg q3 – 4 hours


• Opioid analgesics – intermediate potency

– Meperidine - (proprietary name – Demerol)


– Oral: 50 – 150 mg q3 – 4 hours

– Intravenous

» Single dose: 50 – 150 mg q3 – 4 hours

» Continuous: 15 – 35 mg/hr

– Intramuscular: 50 – 150 mg q3 – 4 hours


• Opioid analgesics – intermediate potency

– Oxycodone - (proprietary names – Percolone,

Oxycontin; with acetaminophen – Percocet


– Oral: 5 – 10 mg q3 – 4 hours

– Oral: time release capsule – q12 hours


• Opioid analgesics – low potency

– Codeine - (proprietary name – Paveral)


– Oral

» Analgesic: 15 – 60 mg q3 – 6 hours

» Antitussive: 10 – 20 mg q4 – 6 hours

– Intravenous: 15 – 60 mg q4 – 6 hours

– Intramuscular: 15 – 60 mg q4 – 6 hours


• Opioid analgesics – low potency

– Diphenoxylate - (proprietary name – Lomotil)


– Oral: 5 mg 3 to 4 times daily initially, then 5 mg once Daily

as needed


• Opioid analgesics

– Action – not completely understood, but affect

neurotransmission at specific sites in the CNS,

affect autonomic nervous system transmission



– Indications

• Relief of pain

• Fentanyl used as analgesic supplement to general

anesthesia

• Methadone used as substitute for heroin, etc



– Side effects and hazards

• Hypotension

• Transient hyperglycemia

• Depression of respiratory system

• Cough reflex decreased

• Nausea and vomiting



– Contraindications

• Hypersensitivity/allergy to agent

• Head trauma



– Route of administration

• Oral (PO)

• Intravenous (IV)

• Intramuscular (IM)

• Subcutaneous (SubQ)

Narcotic Antagonists

• Action

– Competitive replacement of narcotic from

receptor site

• Indication

– Reversal of the effects of a narcotic

– http://www.youtube.com/watch?v=U1frPJoWt

kw

http://www.youtube.com/watch?v=U1frPJoWtkw

http://www.youtube.com/watch?v=U1frPJoWtkw


• Partial antagonists

– Side effects

• Cause narcotic-like effects in absence of a narcotic

• Increased respiratory depression in non-narcotic

overdose



– Nalorphine - (proprietary name – Nalline)


– Initial dose: IV 5 to 10 mg

– IV drip: 5 to 10 mg in 5% glucose solution



– Levallorphan - (proprietary name – Lorfan)


– IV 1 mg

– May be repeated as needed


• Pure antagonists

– Does not increase respiratory depression if

administered in a non-narcotic overdose


• Pure antagonists

– Naloxone - (proprietary name – Narcan)


– Initial dose: 0.4 to 2 mg IV

– May be repeated at 2 to 3 minute intervals

– May be given IM or subcutaneously if IV unavailable

Sedatives and Hypnotics

• Causes longer generalized depression of

the central nervous system

• http://www.youtube.com/watch?v=68NagUt9DzY

http://www.youtube.com/watch?v=68NagUt9DzY

http://www.youtube.com/watch?v=68NagUt9DzY

Sedatives and Hypnotics• Anti-anxiety agents

– Lorazepam - (proprietary name – Ativan)

http://www.youtube.com/watch?v=oG-LHYO8ggg


– Oral: 2 to 6 mg/d.

– Intramuscular: 0.05 mg/kg

– Intravenous

» Intermittent dose: 0.02 to 0.06 mg/kg q2 to q6 hours

» Infusion rate: 0.01 to 0.10 mg/kg/h

http://www.youtube.com/watch?v=oG-LHYO8ggg


• Anti-anxiety agents

– Midazolam - (proprietary name – Versed)


– Intramuscular: 0.07 to 0.08 mg/kg

– Intravenous (for conscious sedation)

» Intermittent dose: 0.02 to 0.08 mg/kg q30 minutes to

q2 hours

» Infusion rate: 0.04 to 0.2 mg/kg/hr



– Haloperidol - (proprietary name – Haldol)

• Oral: 0.5 to 2 mg BID

• Intramuscular: 2 to 5 mg q4 to q8 hours as needed

• Intravenous

– Intermittent dose: 0.03 to 0.15 mg/kg q30 minutes to q6 hours

– Infusion rate: 0.04 to 0.15 mg/kg/hr

– Haloperidol is a dopamine inverse agonist of the typical antipsychotic/Schizophrenic/Delerium



– Propofol - (proprietary name – Diprivan)

• Induction – 40 mg q10 seconds until induction achieved

• Maintenance – 5 to 80 µg/kg/min

• http://www.youtube.com/watch?v=i1GdGMOJw4c

http://www.youtube.com/watch?v=i1GdGMOJw4c

Sedatives and Hypnotics• Barbiturates

– Thiopental - (proprietary name – Pentothal)


– Intravenous: 3 to 7 mg/kg

– Used in some states for lethal injection


• Barbiturates

– Pentobarbital - (Proprietary Name – Nembutal)

• Route of Administration

– Oral: 20 mg tid

– Intramuscular: 150 to 200 mg

– Intravenous: 50 mg/min (Initial Dose: 100 mg in 70 kg

Adult)


• Barbiturates

– Secobarbital - (proprietary name – Seconal)


– Pre-operative sedation: 200 to 300 mg 1 to 2 hours Before

surgery

– At night: 100 mg PO at hs


• Barbiturates

– Amobarbital - (proprietary name – Amytal)


– Intramuscular: 65 to 500 mg; no more than 5 ml in one

injection

– Intravenous: 65 to 500 mg at rate ≤ 1 ml/min

Sedatives and Hypnotics• Barbiturates

– Phenobarbital


– Oral

» Sedation – 30 to 120 mg/d in two to three divided doses

» Hypnotic – 100 to 200 mg

barbiturate and the most widely used

anticonvulsant worldwide, and the oldest still

commonly used


• Barbiturates

– Phenobarbital


– Intramuscular

» Sedation – 30 to 120 mg 60 to 90 minutes before

surgery

» Hypnotic – 100 to 320 mg


• Barbiturates

– Phenobarbital


– Intravenous

» Same as intramuscular


• Hypnotics

– Methaqualone - (proprietary name – Quaalude)


– Oral: 75 to 300 mg

– More common as a street drug


• Hypnotics

– Flurazepam - (proprietary name – Dalmane)

• Administered orally

– 15 to 30 mg at hs

– In geriatric patients, 15 mg initially, but may be increased


• Hypnotics

– Diazepam - (proprietary name – Valium)


– Oral: 2 to 10 mg bid to qid

– Intramuscular: 2 to 20 mg repeated in three to four hours

– Intravenous: 0.03 to 0.01 mg/kg q30 minutes to q6 hours


• Action

– Depression of ascending reticular activating

system resulting in loss of consciousness


• Indications

– Sleep induction

– Relief of anxiety

– Relief of depression


• Indications

– Anticonvulsant

– Voluntary muscle relaxation


• Side effects

– Drowsiness

– Impaired performance and judgment

– Potential for abuse

– Hangover effect


• Contraindications

– Hypothyroidism

– Hypoadrenalism


• Routes of administration

– Oral (PO)

– Intravenous (IV)

– Intramuscular (IM)

– Subcutaneous (SubQ)

Diuretic Agents• Osmotic diuretics are solutes that oppose the passive movement

of water during sodium transport. The rapid loss of sodium and

water occurs by inhibiting their reabsorption in the proximal

tubule. These low-molecular-weight substances create an

opposing osmotic force and contribute to a decreased fluid

reabsorption and increased urine volume. Osmotic diuretics also

cause sodium excretion to increase because of significant back

diffusion. Because water reabsorption is inhibited and sodium

transport is occurring, a sodium concentration gradient develops.

As a result of the high concentration gradient back diffusion

occurs.

• Alteration of the re-absorption of water within the nephron system

• http://www.youtube.com/watch?v=6Wc4f2KnbYo

• http://www.youtube.com/watch?v=JJAMYHAwCMs&feature=related

http://www.youtube.com/watch?v=6Wc4f2KnbYo

http://www.youtube.com/watch?v=6Wc4f2KnbYo

http://www.youtube.com/watch?v=JJAMYHAwCMs&feature=related

http://www.youtube.com/watch?v=JJAMYHAwCMs&feature=related

Classification of Diuretics

• Osmotic diuretics

– Interfere with the water re-absorption in the

descending loop of Henle and in the proximal

tubule

– Used to treat or prevent acute renal failure


• Osmotic diuretics

– Mannitol

• Route of administration - IV

– Reduction of intracranial pressure – 1.5 to 2 g/kg as a 15%

to 25% solution over 30 to 60 minutes

Mannitol• Mannitol is used to reduce acutely raised intracranial

pressure until more definitive treatment can be applied, e.g., after head trauma. It is also used to treat patients with oliguric renal failure. It is administered intravenously, and is filtered by the glomeruli of the kidney, but is incapable of being resorbed from the renal tubule, resulting in decreased water and Na+ reabsorption via its osmotic effect. Consequently, mannitol increases water and Na+ excretion, thereby decreasing extracellular fluid volume.

• Mannitol can also be used as a facilitating agent for the transportation of pharmaceuticals directly into the brain.


• Carbonic anhydrase inhibitors

– Prevent re-absorption of sodium and bicarbonate

ions in the proximal tubule

– Weak agents used to lower intraocular pressure in

glaucoma

Carbonic anhydrase inhibitors

• suppress the activity of carbonic anhydrase. Their clinical use has been established as antiglaucoma agents, diuretics, antiepileptics, in the management of mountain sickness, gastric and duodenal ulcers, neurological disorders, or osteoporosis



– Acetazolamide (proprietary name – Diamox)

• Route of administration - orally

– Diuresis in CHF – 250 to 375 mg (5 mg/kg) qd in the

morning

– May be used for severe metabolic alkalosis



– Methazolamide - (proprietary name – Neptazane)

• Route of administration - orally

– Reduction of intraocular pressure – 50 to 100 mg bid


• Loop diuretics

– Inhibit absorption of chloride ions in the

ascending loop of Henle

– Used to treat hypertension, acute CHF, chronic

renal failure, ascites


• Loop diuretics

– Furosemide - (proprietary name – Lasix)

• Route of administration - orally or IV

– Acute pulmonary edema – 40 mg IV over 1 to 2

minutes

Lasix• Furosemide, a 'water pill,' is used to

reduce the swelling and fluid retention caused by various medical problems, including heart or liver disease. It is also used to treat high blood pressure. It causes the kidneys to get rid of unneeded water and salt from the body into the urine.

Lasix• The tendency, as for all loop diuretics,

to cause low potassium levels (hypokalemia) has given rise to combination products, either with potassium itself (e.g. Lasix-K) or with the potassium sparing diuretic of amiloride


• Loop diuretics

– Furosemide


– Chronic edema – 20 to 80 mg/d PO initially; may be

given q6 to q8 hrs

– Hypertension – 40 mg PO bid


• Loop diuretics

– Ethacrynic acid - (proprietary name – Edecrin)

• Administered orally or IV

– Edema – initial dose of 50 to 100 mg/d PO; 0.5 to 1.0

mg/kg IV administered slowly over several minutes


• Thiazide diuretics

– Block sodium and chloride ion re-absorption

in the distal tubule

– Used to treat hypertension and CHF



– Chlorothiazide - (proprietary name – Diuril)

• Administered orally or IV

– Edema – 0.5 to 2.0 g PO or IV qd to bid

– Hypertension – 0.5 to 2 g/d PO; IV not recommended



– Chlorthalidone - (proprietary name – Thalitone)


– Edema – 50 to 100 mg/d PO

– Hypertension – 25 – 100 mg/d based on patient

response



– Hydrochlorothiazide - (proprietary name – HydroDiuril)


– Edema – 25 – 200 mg qd PO

– Hypertension – 12.5 – 50 mg PO initially; 25 – 100 mg

qd maintenance



– Methyclothiazide - (proprietary name –

Enduron)


– Edema – 2.5 – 10 mg qd PO

– Hypertension – 2.5 – 5 mg qd PO


• Potassium sparing diuretics

– Block sodium re-absorption in the distal tubule

and collecting duct

– Used to treat chronic liver disease and in CHF

to counteract the hypokalemic effects of other

diuretics



– Spironolactone - (proprietary name – Aldactone)


– Edema – 100 – 200 mg/d PO

– Essential hypertension – 50 – 100 mg/d PO



– Triamterene - (proprietary name – Dyrenium)


– Diuresis – 100 mg bid PO


• Indications

– Used for diuresis in patients with excessive

fluid such as with congestive heart failure,

hypertension, and acute and chronic renal

failure


• Side effects

– Hypokalemia

– Acid-base alterations

– Hyperglycemia

Steroids

• A class of hormonal agents produced

naturally by the body to regulate various

metabolic functions; artificially produced

versions are used to mimic the normal

agents

Steroids

• Actions

– In the context of the ICU, prevention or

suppression of inflammatory responses caused

by hypersensitivity

– Decrease capillary permeability in edema

Steroids

• Indications

– Presence of allergic or non-allergic inflammatory

response

• Asthma

• Chronic obstructive pulmonary disease

Steroids

• Indications

– Suppression of immune response in organ

transplant patients

Steroids

• Side effects from systemic administration

– Cushing’s disease

• Moon face

• Hirsutism

• Muscle wasting

• Hypokalemia

Steroids


– Hypertension

– Atrophy of the adrenal glands

– Obesity

– Suppression of growth

Steroids


– Thinning of skin

– Osteoporosis

– Immunosuppression

– Masks infection

Steroids

• Hydrocortisone

– (proprietary names – Cortaid, Aquacort)

– Routes of administration – oral, topical,

intramuscular, intravenous

• Intramuscular & intravenous: 100 to 500 mg initially,

then q 2 to q10 hours

Steroids

• Cortisone

– (proprietary name –

– Cortone)

– Routes of administration

• Oral: 25 to 300 mg/d

• Intramuscular: 20 to 330 mg/d

Steroids

• Prednisone

– Route of administration

• Oral: initial dose variable depending upon severity of

symptoms; maintenance dose of 5 to 60 mg/d PO

Solu-Medrol• Potent IV steroid for COPD/Asthma

exacerbations• 40, 125, 500 mg doses

Anti-Thrombotic Agents

• Anti-coagulant agents

– Action

• Potentiates the inhibitory effect of anti-thrombin on

Factor Xa and thrombin

• Prevents the conversion of fibrinogen to fibrin

• http://www.youtube.com/watch?v=ac_om5HCjvg&feature=related

http://www.youtube.com/watch?v=ac_om5HCjvg&feature=related

http://www.youtube.com/watch?v=ac_om5HCjvg&feature=related



– Indications

• Prophylaxis and treatment of thrombo-embolic

disorders

• (Pulmonary emboli, stroke, MI…)



– Side effects

• Excessive bleeding

• Hypersensitivity

• http://www.youtube.com/watch?v=Lt0BjNwF6IU

http://www.youtube.com/watch?v=Lt0BjNwF6IU



– Heparin


– Intravenous

» Bolus – 10,000 units

» Continuous infusion – 20,000 to 40,000 units

infused over 24 hours


• Anti-platelet agents

– Action

• Inhibits platelet aggregation

– Indications

• Reduction of risk of myocardial infarction, stroke, and

peripheral vascular disease

• Artrial fibrillation

• The most important antiplatelet drugs are:

• Cyclooxygenase inhibitors – Aspirin

• Adenosine diphosphate (ADP) receptor inhibitors – Clopidogrel (Plavix)– Prasugrel (Effient)– Ticagrelor (Brilinta)– Ticlopidine (Ticlid)



– Side effects

• Increased risk of bleeding

• Safety not established in pregnancy



– Clopidogrel - (proprietary name – Plavix)


– Oral

» Daily – 75 mg PO

» Acute coronary syndrome – 300 mg initially, then 75

mg once daily



– Acetylsalicylic Acid - (proprietary name – Aspirin)


– Oral: for prevention of myocardial infarction – 300 to 325

mg/d; dosage as low as 80 mg/d may be effective


• Thrombolytic agents

– Action

• Converts plasminogen to plasmin, which is then able to

degrade fibrin in clots



– Indications

• Acute myocardial infarction

• Massive pulmonary embolism

• Deep vein thrombosis

• Acute ischemic stroke



– Side effects

• Intracranial hemorrhage

• Bleeding



– Streptokinase - (proprietary name – Streptase)

• Route of administration – intravenous

– Myocardial infarction – 1.5 million units IV

– Deep vein thrombosis, pulmonary emboli – 250,000 units

loading dose, then 100,000 units/hr for 24 hours

general pharmacology

Documents

binding of acetylcholine

acetylcholine receptor

muscle contraction indications

receptor siteshorter

postsynaptic ending

receptor siteprevention

chest depolarizing agentsbind

longer term paralysispatient