| Drug: Acetylcholine (Miochol-E ®) |
| Drug Class: Cholinomimetic (direct acting) |
| Mechanism of Action: The endogenous agonist for muscarinic and nicotinic receptors. Acetylcholine is the primary neurotransmitter responsible for neurotransmission at: 1) all autonomic ganglia (sympathetic & parasympathetic)(nicotinic), 2) all post-ganglionic parasympathetic neurons (e.g. vagal innervation of the heart)(muscarinic), 3) post-ganglionic motor neurons (which innervate skeletal muscle)(nicotinic), 4) sympathetic postganglionic neurons that innervate sweat glands (muscarinic), and 5) preganglionic sympathetic nerves that innervate the adrenal medulla (nicotinic), resulting in the release of epinephrine and norepinephrine into the systemic circulation. Muscarinic receptors mediate their responses by G-proteins. Nicotinic receptors mediate their responses by opening a cationic ion channel that is an intrinsic component of the nicotinic-receptor-channel complex. |
| Clinical Indications: To produce miosis (reduction of size) of the iris in seconds after delivery to the lens in cataract surgery, in penetrating keratoplasty, iridectomy and other anterior segment surgery where rapid miosis may be required. Direct application of acetylcholine to the iris will cause rapid miosis of short duration (by acting as a muscarinic agonist). Topical ocular instillation of acetylcholine to the intact eye causes no discernible response as cholinesterase destroys the molecule more rapidly than it can penetrate the cornea. |
| Side Effects: rare when applied only to the eye |
Pharmacokinetics: After release from the nerve ending, acetylcholine is rapidly inactivated by the enzyme acetylcholinesterase by hydrolysis to acetic acid and choline. |
| Notes: Muscarine and nicotine are naturally occuring alkaloids that were used to pharmacologically identify and characterize receptor subtypes before the endogenous neurotransmitter (acetylcholine or "Vagusstoff") was identified. |
| Reference: www.rxmed.com, www.drugs.com & Katzung's text. |
| Drug: Norepinephrine (Levophed ®) |
| Drug Class: Catecholamine, Sympathomimetic |
| Mechanism of Action: functions as a peripheral vasoconstrictor (by stimulating alpha-1 and alpha-2 adrenergic receptors) and as an inotropic stimulator of the heart (by stimulating beta-1 adrenergic receptors). When given i.v. norepinephrine increases both total peripheral resistance, as well as systolic and diastolic blood pressure. Compensatory vagal reflexes tend to overcome the direct positive chronotropic effects on the heart (since both branches of the ANS innervate the SA node), but do not elminate the positive inotropic effects on the ventricle (which does not have significant vagal innnervation). Norepinephrine is an endogenous catecholamine synthesized in the adrenal medulla that is the biochemical precursor of epinephrine. Norepinephrine is the transmitter of most sympathetic postganglionic fibers of the CNS. |
| Indications: For blood pressure control in certain acute hypotensive states (e.g., pheochromocytomectomy, sympathectomy poliomyelitis, spinal anesthesia, myocardial infarction septicemia, blood transfusion, and drug reactions). As an adjunct in the treatment of cardiac arrest and profound hypotension. |
| Contraindications: (see drug interactions). Norepinephrine should not be given to patients who are hypotensive from blood volume deficits except as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed. If it is used in hypovolemic patients, the following may occur: severe peripheral and visceral vasoconstriction, decreased renal perfusion and urine output, poor systemic blood flow despite “normal” blood pressure, tissue hypoxia, and lactic acidosis. |
| Side Effects: Ischemic injury due to potent vasoconstrictor action and tissue hypoxia. When given as a bolus i.v. there is the potential for a mild bradycardia, probably as a reflex result of a rise in blood pressure, arrhythmias, anxiety, transient headache, respiratory difficulty. |
Pharmacokinetics: When released from nerve terminals, its actions are primarily (75%) terminated by neuronal reuptake. Diffusion and degredation by extracellualr COMT contribute to a lesser extent. When given as an i.v. bolus, redistribution (and associated fall in concentration) also contributes to the decrease in effect as a function of time. |
| Drug Interactions: Cyclopropane and halothane anesthetics increase cardiac automatic irritability and therefore seem to sensitize the myocardium to the action of intravenously administered epinephrine or norepinephrine. Norepinephrine should be used with extreme caution in patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types, because severe, prolonged hypertension may result. |
| Notes: Another synonym for noreinephrine is levarterenol. The British name for norepinephrine is noradrenaline. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Epinephrine (generic) |
| Drug Class: Catecholamine, Sympathomimetic |
| Mechanism of Action: Epinephrine stimulates both alpha 1 & 2 and beta 1 & 2 receptor subtypes on sympathetic effector cells. When given i.v. it is a very potent vasoconstrictor and cardiac stimulant. The rise in systolic blood pressure results from a beta-1 mediated increase in heart rate and ventricular contractility. The rise in diastolic pressure results from stimulation of alpha-1 and alpha-2 receptor mediated vasoconstriction in many vascular beds. Epinephrine also stimulates beta-2 receptors present in skeletal muscle blood vessels, resulting in their dilation. At low doses, at which beta-2 receptor stimulation predominates over alpha receptor stimulation, total peripheral resistance and diastolic pressure may fall. Under physiological conditions, epinephrine released from the adrenal gland functions as a hormone and, via activation of beta-2 receptors, contributes to increased blood flow duirng exercise. Beta-2 stimulation will cause bronchodilation in the lung and activate glycogenolysis in the liver. |
Indications:.
|
| Contraindications: Epinephrine should be used cautiously in patients with hyperthyroidism, hypertension and cardiac arrhythmias. |
| Side Effects: Transient and minor side effects of anxiety, tachycardia, headache, fear and palpitations occur with systemic therapeutic doses, especially in hyperthyroid individuals. Adverse effects such as cardiac arrhythmias and excessive rise in blood pressure may also occur with therapeutic doses or inadvertent overdosage |
Pharmacokinetics: Route of administration depends on the indication for its use. It can be given i.v., s.c., i.m., via an endotracheal tube, or direct injection into the left ventricle. |
| Major drug Interactions: All vasopressors should be used cautiously in patients taking monoamine oxidase (MAO) inhibitors. |
| Notes: The British name for epinephrine is adrenaline |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Dopamine (generic, intropin ®) |
| Drug Class: Sympathomimetic, Catecholamine |
| Mechanism of Action: Dopamine is the immediate metabolic precursor of norepinephrine. At low doses it selectively activates D1 receptors in several vascular beds (e.g. kidney) resulting in vasodilation & a decreased TPR. The D1 mediated effect to increase renal blood flow may be of clinical significance (e.g. in the treatment of shock). Activation of presynaptic D2 receptors may suppress norepinephrine release. At intermediate doses dopamine activates beta-1 receptors in the heart. At high doses dopamine activates alpha receptors leading to vasoconstriction, including the renal vascualr bed. High doses of dopamine may mimic the actions of epinephrine. Dopamine is also a neurotransmitter in certain areas of the central nervous system, especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves. |
| Indications:. For the correction of hemodynamic imbalances present in shock due to myocardial infarction, trauma, endotoxic septicemia, open-heart surgery, renal failure, and chronic cardiac decompensation as in congestive failure |
| Contraindications: Dopamine should not be used in patients with pheochromocytoma or patients with uncorrected tachyarrhythmias or ventricular fibrillation. |
| Side Effects: Cardiac arrhythmias, dyspnea, nausea, vomiting, headache |
Pharmacokinetics: Dopamine’s onset of action occurs within five minutes of intravenous administration, and with dopamine’s plasma half-life of about two minutes, the duration of action is less than ten minutes. However, if monoamine oxidase (MAO) inhibitors are present, the duration may increase to one hour. |
| Major drug Interactions: Patients who have been treated with MAO inhibitors within two to three weeks prior to the administration of dopamine HCl should receive initial doses of 1/10th normal. Tricyclic antidepressants may potentiate the pressor response to adrenergic agents. Cardiac effects of dopamine are antagonized by beta-adrenergic blocking agents. Haloperidol and haloperidol-like drugs suppress the dopaminergic renal and mesenteric vasodilation induced at low rates of dopamine infusion. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Acetylcholine (Miochol-E ®) |
| (See Neurotransmitter section above) |
| Drug: Pilocarpine (generic, Salagen, Isopto Carpine ®) |
| Drug Class: Muscarinic Cholinomimetic (tertiary alkaloid) |
| Mechanism of Action: a cholinergic parasympathomimetic agent exerting a broad spectrum of pharmacologic effects with predominant muscarinic action. |
| Indications: 1) the treatment of symptoms of dry mouth from salivary gland hypofunction caused by radiotherapy for cancer of the head and neck; and 2) the treatment of symptoms of dry mouth in patients with Sjögrens syndrome. |
| Contraindications: In patients with uncontrolled asthma, known hypersensitivity to pilocarpine, and when miosis is undesirable. |
| Side Effects: The most frequent adverse experiences are a consequence of the expected pharmacologic effects of pilocarpine & include sweating, flushing, increased urinary frequency. |
Pharmacokinetics: well absorbed from most sites of administration. Crosses the blood brain barrier (its a tertiary amine). |
| Major drug Interactions: administered with caution to patients taking beta adrenergic antagonists because of the possibility of cardiac conduction disturbances. |
| Notes: A natural alkaloid. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Bethanechol (generic, Urecholine ®) |
| Drug Class: Muscarinic Cholinomimetic |
| Mechanism of Action: It increases the tone of the detrusor urinae muscle, usually producing a contraction sufficiently strong to initiate micturition and empty the bladder. It stimulates gastric motility, increases gastric tone, and often restores impaired rhythmic peristalsis. Because of the selective action of bethanechol, nicotinic symptoms of cholinergic’stimulation are usually absent or minimal |
| Indications:.For the treatment of acute postoperative and postpartum nonobstructive (functional) urinary retention and for neurogenic atony of the urinary bladder with retention |
| Contraindications: Hypersensitivity to bethanechol chloride tablets, hyperthyroidism, peptic ulcer, latent or active bronchial asthma, pronounced bradycardia or hypotension, vasomotor instability, coronary artery disease, epilepsy, and parkinsonism. |
| Side Effects: Early signs of overdosage
are abdominal discomfort, salivation, flushing of the skin (hot feeling),
sweating, nausea and vomiting. Atropine is a specific antidote |
Pharmacokinetics: Bethanechol chloride does not cross the blood-brain barrier because of its charged quaternary amine moiety. The metabolic fate and mode of excretion of the drug have not been elucidated. |
| Major drug Interactions: Special care is required if this drug is given to patients receiving ganglion blocking compounds because a critical fall in blood pressure may occur. Usually, severe abdominal symptoms appear before there is such a fall in the blood pressure. |
| Reference: www.rxlist.com |
| Drug: Nicotine (Nicotrol ® Inhaler) |
Drug Class: Nicotinic Cholinomimetic |
| Mechanism of Action: binds stereo-selectively to nicotinic-cholinergic receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain. Two types of central nervous system effects are believed to be the basis of nicotine’s positively reinforcing properties. A stimulating effect is exerted mainly in the cortex via the locus ceruleus and a reward effect is exerted in the limbic system. At low doses the stimulant effects predominate while at high doses the reward effects predominate.The cardiovascular effects of nicotine include peripheral vasoconstriction, tachycardia, and elevated blood pressure. |
| Indications:.an aid to smoking cessation for the relief of nicotine withdrawal symptoms. |
| Contraindications: patients with known hypersensitivity or allergy to nicotine or to menthol |
| Side Effects: Nicotine toxicity is characterized by nausea, abdominal pain, vomiting, diarrhea, diaphoresis, flushing, dizziness, disturbed hearing and vision, confusion, weakness, palpitations, altered respiration and hypotension. |
Pharmacokinetics: nicotine is well absorbed through the skin |
| Major drug Interactions: may alter the pharmacokinetics of certain concomitant medications, such as tricyclic antidepressants and theophylline. Doses of these and perhaps other medications may need to be adjusted in patients who successfully quit smoking. |
| Notes: Acute tolerance (a reduction in response for a given dose) develops rapidly (less than 1 hour), but not at the same rate for different physiologic effects (skin temperature, heart rate, subjective effects). Withdrawal symptoms such as cigarette craving can be reduced in most individuals by plasma nicotine levels lower than those from smoking. Withdrawal from nicotine in addicted individuals can be characterized by craving, nervousness, restlessness, irritability, mood lability, anxiety, drowsiness, sleep disturbances, impaired concentration, increased appetite, minor somatic complaints (headache, myalgia, constipation, fatigue), and weight gain. |
| Reference: www.rxlist.com |
| Drug: Succinylcholine (Anectine ®) |
| Drug Class: Nicotinic Cholinomimetic & Neuromuscular Blocker |
| Mechanism of Action: Selective for binding to the NMJ subtype of nicotinic receptor. It initially excites skeletal muscle by binding to nicotinic receptors, then prevents contraction by prolonging the time that receptors at the NMJ cannot respond to ACh (block can be divided into two phases: phase I and phase II). |
| Clinical Indications: adjunct to general anesthesia to facilitate ET intubation and relax skeletal muscle during surgery or mechanical ventilation. |
| Contraindications: genetic disorders of plasma pseudocholinesterase, family history of malignant hyperthermia, myopathies with elevated CPK levels, acute narrow-angle glaucoma or penetrating eye injuries. Caution should be used when given to children i.v. due to risk of malignant hyperpyrexia. |
| Side Effects: severe persistent respiratory depression or apnea, arrhythmias, cardiac arrest, anaphylaxis, malignant hyperthermia |
| Pharmacokinetics: given i.v. or i.m. Metabolized by plasma pseudocholinesterase, duration of action 4-30 min depending on route of administration. |
| Major drug Interactions: aminoglycoside antibiotics (additive skeletal muscle blockade), etc. (see PDR) |
| Notes: succinylcholine is the only depolarizing type NMJ blocker in clinical use in the US |
| Reference: www.rxlist.com |
| Drug: Physostigmine, Eserine (generic) |
| Drug Class: Anticholinesterase |
| Mechanism of Action: a reversible anticholinesterase which effectively increases the concentration of acetyicholine at the sites of cholinergic transmission. |
| Indications: To reverse the effect upon the central nervous system, caused by clinical or toxic dosages of drugs capable of producing the anticholinergic syndrome (see Notes). Physostigmine Salicylate Injection can reverse both central and peripheral anticholinergia. |
| Contraindications: Physostigmine should not be used in the presence of asthma, gangrene, diabetes, cardiovascular disease, mechanical obstruction of the intestine or urogenital tract or any vagotonic state, and in patients receiving choline esters and depolarizing neuromuscular blocking agents (decamethonium, succinyicholine). |
| Side Effects: Nausea, vomiting and salivation can be offset by reducing dosage. Can cause a cholinergic crisis. Appropriate antidote is atropine sulfate. |
Pharmacokinetics: Physostigmine contains a tertiary amine and easily penetrates the blood brain barrier, while an anticholinesterase, such as neostigmine, which has a quatemary ammonium ion is not capable of crossing the barrier. |
| Major drug Interactions: For post-anesthesia, the concomitant use of atropine with physostigmine salicylate is not recommended, since the atropine antagonizes the action of physostigmine. |
| Notes: SOME DRUGS WHICH PRODUCE THE
ANTICHOLINERGIC SYNDROME: Amitriptyline, Amoxapine, Anisotropine, Atropine, Benztropine, Biperiden, Carbinoxamine, Clidinium, Cyclobenzaprine, Desipramine, Doxepin, Homatropine, Hyoscine, Hyoscyamine, Hyoscyamus, Imipramine, Lorazepam, Maprotiline, Mepenzolate, Nortriptyline, Propantheline, Protriptyline, Scopolamine, Trimipramine. SOME PLANTS THAT PRODUCE THE ANTICHOLINERGIC SYNDROME: Black Henbane, Deadly Night Shade, Devil’s Apple, Jimson Weed, Loco Seeds or Weeds, Matrimony Vine, Night Blooming Jessamine, Stinkweed. |
| Reference: www.rxlist.com |
Drug: Neostigmine (generic,Prostigmin ®) |
| Drug Class: Anticholinesterase, Cholinomimetic |
| Mechanism of Action: inhibits the hydrolysis of acetylcholine by competing with acetylcholine for attachment to acetylcholinesterase at sites of cholinergic transmission. It enhances cholinergic action by facilitating the transmission of impulses across neuromuscular junctions. It also has a direct cholinomimetic effect on skeletal muscle and possibly on autonomic ganglion cells. Does not cross the blood-brain barrier. |
| Indications:.for the symptomatic treatment of myasthenia gravis. Its greatest usefulness is in prolonged therapy where no difficulty in swallowing is present. In acute myasthenic crisis where difficulty in breathing and swallowing is present, the parenteral form (neostigmine methylsulfate) should be used. The patient can be transferred to the oral form as soon as it can be tolerated. |
| Contraindications: patients with known hypersensitivity to the drug. Because of the presence of the bromide ion, it should not be used in patients with a previous history of reaction to bromides. It is contraindicated in patients with peritonitis or mechanical obstruction of the intestinal or urinary tract. |
| Side Effects: are generally due to an exaggeration of pharmacological effects of which salivation and fasciculation are the most common. Bowel cramps and diarrhea may also occur. For a more complete list, see rxlist.com reference |
Pharmacokinetics: Neostigmine bromide is poorly absorbed from the gastrointestinal tract following oral administration. As a rule, 15 mg of neostigmine bromide orally is equivalent to 0.5 mg of neostigmine methylsulfate parenterally, due to poor absorption of the tablet from the intestinal tract. Neostigmine undergoes hydrolysis by cholinesterase and is also metabolized by microsomal enzymes in the liver. Protein binding to human serum albumin ranges from 15 to 25 percent. |
| Major drug Interactions: Certain aminoglycoside antibiotics, especially neomycin, streptomycin and kanamycin, have a mild but definite nondepolarizing blocking action which may accentuate neuromuscular block. These antibiotics should be used in the myasthenic patient only where definitely indicated |
| Reference: www.rxlist.com |
| Drug: Edrophonium (generic, Tensilon ®) |
| Drug Class: Anticholinesterase |
| Mechanism of Action: a short and rapid-acting anticholinesterase |
| Indications:.1) for the differential diagnosis of myasthenia gravis and as an adjunct in the evaluation of treatment requirements in this disease. It may also be used for evaluating emergency treatment in myasthenic crises. Because of its brief duration of action, it is not recommended for maintenance therapy in myasthenia gravis. 2) useful whenever a curare antagonist is needed to reverse the neuromuscular block produced by curare, tubocurarine, gallamine triethiodide or dimethyl-tubocurarine. It is not effective against decamethonium bromide and succinylcholine chloride. It may be used adjunctively in the treatment of respiratory depression caused by curare overdosage. |
| Contraindications: Known hypersensitivity to anticholinesterase agents; intestinal and urinary obstructions of mechanical type. |
| Side Effects: The myasthenic patient in crisis who is being tested with edrophonium should be observed for bradycardia or cardiac standstill and cholinergic reactions if an overdose is given. Muscarine-like symptoms (nausea, vomiting, diarrhea, sweating, increased bronchial and salivary secretions and bradycardia) often appear with overdosage (cholinergic crisis). An important complication that can arise is obstruction of the airway by bronchial secretions |
Pharmacokinetics: intended for IV and IM use |
| Major drug Interactions: Care should be given when administering this drug to patients with symptoms of myasthenic weakness who are also on anticholinesterase drugs. Since symptoms of anticholinesterase overdose (cholinergic crisis) may mimic underdosage (myasthenic weakness), their condition may be worsened by the use of this drug. |
| Reference: www.rxlist.com |
| Drug: Echothiophate (Phospholine ®) |
| Drug Class: Anticholinesterase |
| Mechanism of Action: a long-acting cholinesterase inhibitor for topical use to enhance the effect of endogenously liberated acetylcholine in the iris, ciliary muscle, and other parasympathetically innervated structures of the eye. It causes miosis, increases the outflow of aqueous humor, causes a fall in intraocular pressure, and potentiation of accommodation. |
| Indications: Treatment of glaucoma (if beta-blockers fail). Because of it's long duration of action, it is useful for "round the clock" control of intraocular pressure. Also indicated for accommodative esotropia (a pediatric use). |
| Contraindications: 1. Active uveal inflammation. 2. Most cases of angle-closure glaucoma, due to the possibility of increasing angle block. 3. Hypersensitivity to the active or inactive ingredients. |
| Side Effects: retinal detachment has been reported in a few cases, stinging, burning, lacrimation, iIris cysts may form, lens opacities, cardiac irregularities |
Pharmacokinetics: Forms an irreversible covalent bond with the ACh binding site on cholinesterase (duration of action is ~100 hrs). |
Major drug Interactions: potentiates other cholinesterase inhibitors such as succinylcholine or organophosphate and carbamate insecticides. Patients undergoing systemic anticholinesterase treatment should be warned of the possible additive effects. |
| Reference: www.rxlist.com |
| Drug: Pralidoxime or 2-PAM (generic, Protopam ®) |
| Drug Class: cholinesterase regenerator, assists in postexposure treatment to organophosphate inhibitor |
| Mechanism of Action: the oxime group (=NOH) in pralidoxime has a very high affinity for the phosphorous atom of oragnophosphates and can cause the bond between the organophosphate agent and the cholinesterase to hydrolyze if the complex has not "aged" or stabilized due to the spontaneous loss of an alkyl group from the organophosphate compound. Pralidoxime's effect on non-aged organophosphate-enzyme complexes causes a reactivation of cholinesterase activity. Because of it's positive charge, pralidoxime does not cross the blood-brain barrier. |
| Indications: used together with atropine to treat poisoning caused by organophosphate cholinesterase inhibitors used as pesticides (e.g., diazinon, malathion, mevinphos, parathion), in chemical warfare (e.g. the “nerve gas” sarin). 2-PAM is not effective against the chemically different "carbamate" type cholinesterase inhibitors (such as neostigmine and pyridostigmine) because carbamates do not have phosphate groups and do not undergo "aging". Because pralidoxime is less effective in relieving depression of the respiratory center, atropine is always required concomitantly to block the effect of accumulated acetylcholine at this site. Pralidoxime relieves muscarinic signs and symptoms, salivation, bronchospasm, etc., but this action is relatively unimportant since atropine is adequate for this purpose. |
| Contraindications: ineffective against carbamate inhibitors of cholinesterase (e.g. pyridostigmine), or against nerve gases that have already inhibited cholinesterase and "aged" to a resistant form. Pralidoxime may may the symptoms of myasthenia gravis worse. The effects may be intensified in patients with kidney disease. |
| Side Effects: excessive doses can induce neuromuscular weakness & other adverse effects. |
| Pharmacokinetics: typically given by i.v. infusion over 15-30 min, although multiple doses given over several days may produce beneficial effects in severe poisoning. |
| Reference: www.rxlist.com |
| Drug: Pyridostigmine (Mestinon ®, Regonol ®) |
| Drug Class: cholinesterase inhibitor (reversible) |
| Mechanism of Action: inhibits the destruction of acetylcholine by cholinesterase |
| Indications: prophylaxis against poisoning by Soman nerve gas (which otherwise produces rapid irreversible aging). Also used in the treatment of myasthenia gravis. Pyridostigmine is needed for adequate protection against soman. If personnel take pyridostigmine in advance of exposure, soman will be prevented from binding to AChE because the AChE binding sites are “occupied” by pyridostigmine, and so aging cannot take place. The armed forces estimate that during a chemical attack, many personnel may be exposed to 5 times the lethal dose (LD) of soman, so a protective ratio (that raises the LD) by at least 5 times is needed. Addition of pyridostigmine allows the protective ratio to exceed 5 for soman (according to studies in monkeys). Clinical trials (pyridostigmine is clinically used in myasthenia gravis) indicate that pyridostigmine is well-tolerated at the doses intended for military use. Pyridostigmine should be started (oral tablets) at least several hours before exposure to soman (8 hours in advance is preferred), and discontinued upon exposure to the nerve gas, at which point atropine and pralidoxime are given at the first indication of exposure. Pyridostigmine pretreatment does not confer an advantage against sarin, based on studies in animals; personnel have enough time to take oxime after exposure to this nerve agent before aging takes place, reactivating the AChE molecule. Indeed, soman is the only nerve agent for which PB is known to be necessary to produce an adequate protective ratio. |
| Contraindications: in mechanical intestinal or urinary obstruction, and particular caution should be used in its administration to patients with bronchial asthma. |
| Side Effects: SLUDE. With overdose it can produce muscarinic & nicotinic symptoms. Muscarinic: nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis and diaphoresis. Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation and weakness. Overdosage may result in cholinergic crisis, a state characterized by increasing muscle weakness which, through involvement of the muscles of respiration, may lead to death. |
| Pharmacokinetics: oral administration. The size and frequency of the dosage should be adjusted to the needs of the individual patient. Pyridostigmine is mainly excreted unchanged by the kidney. |
| Major drug interactions: |
Notes: chemically related to neostigmine, but has a longer duration of action and less GI effects. |
| Reference: http://www.fda.gov/cder/drug/infopage/Pyridostigmine_Bromide/Q&A.htm |
| Drug: Sarin (GB) |
| Drug Class: a human-made chemical warfare agent classified as a nerve agent. Originally synthesized as a pesticide. |
| Mechanism of Action: Sarin is the most volatile of the nerve agents, which means that it can easily and quickly evaporate from a liquid into a vapor and spread into the environment. People can be exposed to the vapor even if they do not come in contact with the liquid form of sarin. Once sarin binds to cholinesterase the chemical stability of it's interaction with the enzyme can become irreversible with time due to the loss of an alkyl group. When this happens it's binding becomes irreversible (aging) and the complex becomes resistant to the effects of oxime regenrators such as pralidoxime. Aging develops with a half-time of 5 hours with sarin. |
| Effects: remember "SLUDE" muscarinic & nicotinic symptoms. Symptoms will appear within a few seconds after exposure to the vapor form of sarin and within a few minutes up to 18 hours after exposure to the liquid form. Symptoms within seconds to hours of exposure: runny nose, watery eyes, small or pinpoint pupils, eye pain, blurred vision, drooling and excessive sweating, cough, chest tightness, rapid breathing, diarrhea, increased urination, confusion, drowsiness, weakness, headache, nausea, vomiting, and/or abdominal pain, slow or fast heart rate, low or high blood pressure. High concentrations may cause loss of consciousness, convulsions, respiratory failure - leading to death. |
Routes of exposure: Following release of sarin into the air, people can be exposed through skin contact or eye contact. They can also be exposed by breathing air that contains sarin. Sarin mixes easily with water, so it could be used to poison water. Following release of sarin into water, people can be exposed by touching or drinking water that contains sarin. Following contamination of food with sarin, people can be exposed by eating the contaminated food. A person’s clothing can release sarin for about 30 minutes after it has come in contact with sarin vapor, which can lead to exposure of other people. |
| Treatment after exposure: decontamination - remove & dispense of contaminated clothing. As quickly as possible, wash skin with large amounts of soap and water. Rinse the eyes with plain water for 10 to 15 minutes if they are burning or if vision is blurred. If sarin has been swallowed, do not induce vomiting or give fluids to drink. Give atropine and pralodoxime STAT as antidotes. Supportive measures such as assisted ventilation, diazepam for convulsions, phentolamine for 2-PAM induced hypertension. |
| Notes: sarin is a clear, colorless, and tasteless liquid that has no odor in its pure form. However, sarin can evaporate into a vapor (gas) and spread into the environment. Sarin is also known as GB. Sarin and other nerve agents may have been used in chemical warfare during the Iran-Iraq War in the 1980s. Sarin was used in two terrorist attacks in Japan in 1994 and 1995. |
| Reference: http://www.bt.cdc.gov/agent/sarin/index.asp |
| Drug: Soman (GD) |
| Drug Class: chemical warfare agent classified as a nerve agent. |
| Mechanism of Action: inhibits the destruction of acetylcholine by cholinesterase. Aging occurs within a half-life of only two minutes with soman. This can make it almost impossible to give pralidoxime rapidly enough to be beneficial after the first noticeable "detection" of symptoms of poisoning are felt. |
| Effects: same as sarin (above) |
| Routes of exposure: same as sarin (above) |
| Treatment after exposure: same as sarin except pralidoxime may be ineffective due to rapid aging caused by soman. |
Notes: Soman is a clear, colorless, tasteless liquid with a slight camphor odor (for example, Vicks Vapo-Rub®) or rotting fruit odor. It can become a vapor if heated. |
| Reference: http://www.bt.cdc.gov/agent/soman/basics/facts.asp |
| Drug: VX |
| Drug Class: chemical warfare agent classified as a nerve agent. |
| Mechanism of Action: same as soman & sarin |
| Effects: same as soman & sarin |
| Routes of exposure: VX can be absorbed through the eyes or the skin of the victim. As little as one drop of VX on the skin can be fatal (as compared to 1 to 10 mls of sarin or soman). The LD50 for humans is estimated to be ~10 mg. |
| Notes: an amber (honey brown) colored, tasteless & odorless, oily liquid with low volatility unless temperatures are high. The "V" of VX signifies it very long persistence compared to sarin and soman. VX decomposes at a rate of ~ 5% a month at 71 °C. |
| Reference: http://www.bt.cdc.gov/agent/vx/index.asp |
| Drug: Atropine (generic) |
| Drug Class: Muscarinic blocker (nonselective) |
| Mechanism of Action: a muscarinic receptor antagonist. It produces a competitive or surmountable antagonism which can be overcome by increasing the concentration of acetylcholine at receptor sites of the effector organ (e.g., by using anticholinesterase agents which inhibit the enzymatic destruction of acetylcholine). The receptors antagonized by atropine are the peripheral structures that are stimulated or inhibited by muscarine (i.e., exocrine glands, smooth and cardiac muscle). Responses to postganglionic cholinergic nerve stimulation also may be inhibited by atropine but this occurs less readily than with responses to injected (exogenous) choline esters. |
| Indications: (1) as an antisialogogue for preanesthetic medication to prevent or reduce secretions of the respiratory tract, (2) to restore cardiac rate and arterial pressure during anesthesia when vagal stimulation produced by intra-abdominal surgical traction causes a sudden decrease in pulse rate and cardiac action, (3) to lessen the degree of atrioventricular (A-V) heart block when increased vagal tone is a major factor in the conduction defect as in some cases due to digitalis, (4) to overcome severe bradycardia and syncope due to a hyperactive carotid sinus reflex, (5) as an antidote (with external cardiac massage) for cardiovascular collapse from the injudicious use of a choline ester (cholinergic) drug, (6) in the treatment of anticholinesterase poisoning from organophosphorus insecticides, (7) as an antidote for the “rapid” type of mushroom poisoning due to the presence of the alkaloid, muscarine, in certain species of fungus such as Amanita muscaria, and (8) may improve the tremor & rigidity of Parkinsonism. |
| Contraindications: Atropine generally is contraindicated in patients with glaucoma, pyloric stenosis or prostatic hypertrophy, except in doses ordinarily used for preanesthetic medication. Atropine Sulfate Injection, USP should be used with caution in all individuals over 40 years of age |
| Side Effects: Most of the side effects of atropine are directly related to its antimuscarinic action. Dryness of the mouth, blurred vision, photophobia and tachycardia commonly occur with chronic administration of therapeutic doses. Anhidrosis also may occur and produce heat intolerance or impair temperature regulation in persons living in a hot environment. Constipation and difficulty in micturition may occur in elderly patients. Occasional hypersensitivity reactions have been observed, especially skin rashes which in some instances progressed to exfoliation. Occasionally, therapeutic doses dilate cutaneous blood vessels, particularly in the “blush” area (atropine flush). Marked excitement and convulsions may occur with toxic doses.The fatal adult dose of atropine is not known; 200 mg doses have been used and doses as high as 1000 mg have been given. (Remember: "blind as a bat, mad as a hatter, dry as a bone, red as a beet, hot as hell") |
Pharmacokinetics: i.v., s.c. or i.m. administration. Atropine disappears rapidly from the blood following injection (half life is 2 hrs) and is distributed throughout the body. Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver; from 13 to 50% is excreted unchanged in the urine. Traces are found in various secretions, including milk. Atropine readily crosses the placental barrier and enters the fetal circulation. Atropine's effect on parasympathetic function declines rapidly in all organs except the eye. Effects on the iris and ciliary muscle persist for more than 3 days. |
| Major drug Interactions: concomitant administration of other drugs having anticholinergic effects (TCA's, antihistamines) may precipitate the complications listed above. |
| Reference: www.rxlist.com & Katzung's text. |
| Drug: Scopolamine (generic, Isopto Hyoscine ®) |
| Drug Class: Antimuscarinic (competitive antagonist) |
| Mechanism of Action: Antimuscarinic drug having more marked central effects, producing drowsiness and amnesia in sensitive individuals. |
| Indications: 1) prevention of nausea and vomiting associated with motion sickness and recovery from anesthesia and surgery. The patch should be applied only to skin in the postauricular area. 2) For mydriasis and cycloplegia in diagnostic procedures. For some pre- and postoperative states when a mydriatic and cycloplegic state is needed in treatment of iridocyclitis. It blocks the responses of the sphincter muscle of the iris and the accommodative muscle of the ciliary body to cholinergic stimulation, producing pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia). 3) Reduction of the tremor of Parkinson's disease. |
| Contraindications: patients with angle-closure (narrow angle) glaucoma, or history of hypersensitivity to scopolamine. |
| Side Effects: Therapeutic doses can cause drowsiness & amnesia, dry mouth, transient impairment of eye accommodation, including blurred vision and dilation of the pupils. Toxic doses can cause excitement, agitation, hallucinations & coma (more likely than with atropine). |
Pharmacokinetics: Scopolamine is rapidly and fully distributed into the CNS where it has greater effects than most other antimuscarinics. Following patch removal, plasma levels decline in a log linear fashion with an observed half-life of 9.5 hours. Less than 10% of the total dose is excreted in the urine as parent and metabolites over 108 hours. |
| Major drug Interactions: Scopolamine should be used with care in patients taking other drugs that are capable of causing CNS effects such as sedatives, tranquilizers, or alcohol. Special attention should be paid to potential interactions with drugs having anticholinergic properties; e.g., other belladonna alkaloids, antihistamines (including meclizine), tricyclic antidepressants, and muscle relaxants. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Tubocurarine (generic, ®) |
| Drug Class: Nondepolarizing neuromuscular blocking agent |
| Mechanism of Action: |
| Indications: Muscle relaxant during surgery or setting of fractures and dislocations; spasticity caused by injury to or disease of CNS. Treat seizures electrically induced or induced by drugs. Diagnosis of myasthenia gravis. |
| Contraindications: Clients in whom release of histamine is hazardous. Use with caution during pregnancy and lactation and in children |
| Side Effects: Most likely of the nondepolarizing drugs to cause histamine release. Allergic reactions. Excessive secretion and circulatory collapse. |
Pharmacokinetics: Given by injection (i.m., i.v.). Narrow margin between therapeutic dose and toxic dose. Onset, IV: 1 min; IM: 15-25 min. Time to peak effect, IV: 2-5 min. Duration, IV: 20-90 min. t1/2: 1-3 hr. About 43% excreted unchanged in urine. |
| Reference: www.healthdigest.org/ |
| Drug: Ipratropium (Atrovent ®) |
| Drug Class: Antimuscarinic |
| Mechanism of Action: a synthetic analog of atropine |
| Indications: administered either alone or with other bronchodilators, especially beta adrenergics, is indicated as a bronchodilator for maintenance treatment of bronchospasm associated with asthma, chronic obstructive pulmonary disease, including chronic bronchitis and emphysema. |
| Contraindications: Ipratropium bromide inhalation aerosol is contraindicated in patients with a history of hypersensitivity to soya lecithin or related food products such as soybean and peanut. |
| Side Effects: include tachycardia, palpitations, eye pain, urinary retention, urinary tract infection and urticaria. A single case of anaphylaxis thought to be possibly related to ipratropium bromide has been reported. Cases of precipitation or worsening of narrow-angle glaucoma and acute eye pain have been reported. |
Pharmacokinetics: The bronchodilation following inhalation of ipratropium bromide is primarily a local, site-specific effect, not a systemic one. Much of an administered dose is swallowed but not absorbed, as shown by fecal excretion studies. The half-life of elimination is about 1.6 hours after intravenous administration. Ipratropium bromide is minimally (0 to 9% in vitro) bound to plasma albumin and a1-acid glycoproteins. It is partially metabolized. |
| Reference: www.rxlist.com |
| Drug: Trimethaphan (Arfonad ®) |
| Drug Class: Short acting, nondepolarizing ganglionic blocker |
| Mechanism of Action: blocks the nicotinc receptor (ganglionic subtype) |
| Indications: Treatment of hypertensive emergencies & dissecting aortic aneurysm, to produce controlled hypotension in neurosurgery to reduce bleeding in the operative field, and in patients undergoing electroconvulsive therapy. |
| Contraindications: |
| Side Effects: cycloplegia, hypotension, postural hypotension, tachycardia, decreased contractility, decreased GI motility, hesitency in urination, urinary retention. |
Pharmacokinetics: inactive orally, given by i.v. infusion. A quaternary drug that does not cross the blood brain barrier (in contrast to mecamylamine, another ganglionic blocker that produces CNS effects such as tremor, choreiform movements, and mental aberrations). |
| Reference: Katzung's text |
| Atropine, 2-PAM, pyridostigmine, sarin, soman, VX (see above) |
| Drugs: Norepinephrine, Epinephrine & Dopamine |
| (See Neurotransmitter section above) |
| Drug: Isoproterenol (generic, Isuprel ®) |
| Drug Class: Nonselective Beta Adrenergic Agonist (Sympathomimetic) |
| Mechanism of Action: Stimulates both beta-1 and beta-2 adrenergic receptors. Intravenous infusion of isoproterenol in man lowers peripheral vascular resistance, primarily in skeletal muscle but also in renal and mesenteric vascular beds. Diastolic pressure falls. Systolic blood pressure may remain unchanged or rise, although mean arterial pressure typically falls. Cardiac output is increased because of the positive inotropic and chronotropic effects of the drug in the face of diminished peripheral vascular resistance. The cardiac effects of isoproterenol may lead to palpitations, sinus tachycardia, and more serious arrhythmias. Isoproterenol relaxes bronchial smooth muscle. |
| Indications: 1) For mild or transient episodes of heart block that do not require electric shock or pacemaker therapy. 2) For serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation). 3) For use in cardiac arrest until electric shock or pacemaker therapy, the treatments of choice, are available. 4) For bronchospasm occurring during anesthesia. 5) As an adjunct to fluid and electrolyte replacement therapy and the use of other drugs and procedures in the treatment of hypovolemic and septic shock, low cardiac output (hypoperfusion) states, congestive heart failure, and cardiogenic shock. |
| Contraindications: by increasing myocardial oxygen requirements while decreasing effective coronary perfusion, may have a deleterious effect on the injured or failing heart. |
| Side Effects: CNS: Nervousness, headache, dizziness. Cardiovascular: Tachycardia, palpitations, angina, Adams-Stokes attacks, pulmonary edema, hypertension, hypotension, ventricular arrhythmias, tachyarrhythmias. |
Pharmacokinetics: Isoproterenol is readily absorbed when given parenterally or as an aerosol. It is metabolized primarily in the liver and other tissues by COMT. Isoproterenol is a relatively poor substrate for MAO and is not taken up by sympathetic neurons to the same extent as are epinephrine and norepinephrine. The duration of action of isoproterenol may therefore be longer than that of epinephrine, but is still brief. |
| Major drug Interactions: Isoproterenol should be used with caution, if at all, when potent inhalational anesthetics such as halothane are employed because of potential to sensitize the myocardium to effects of sympathomimetic amines. |
| Reference: www.rxlist.com |
| Drug: Dobutamine (generic, Dobutrex ®) |
| Drug Class: Beta-1 Selective Sympathomimetic |
| Mechanism of Action: Beta-1 selective adrenergic agonist. It does not cause the release of endogenous norepinephrine, as does dopamine. In animal studies, dobutamine produces less increase in heart rate and less decrease in peripheral vascular resistance for a given inotropic effect than does isoproterenol. |
| Indications: Dobutamine is indicated when parenteral therapy is necessary for inotropic support in the short-term treatment of patients with cardiac decompensation due to depressed contractility resulting either from organic heart disease or from cardiac surgical procedures. |
| Contraindications: Dobutamine is contraindicated in patients with idiopathic hypertrophic subaortic stenosis and in patients who have shown previous manifestations of hypersensitivity to dobutamine. |
| Side Effects: A 10- to 20- mm increase in systolic blood pressure and an increasein heart rate of 5 to 15 beats/minute have been noted in most patients |
Pharmacokinetics: The onset of action of dobutamine is within 1 to 2 minutes; however, as much as 10 minutes may be required to obtain the peak effect of a particular infusion rate. The plasma half-life of dobutamine in humans is 2 minutes. The principal routes of metabolism are methylation of the catechol and conjugation. |
| Major drug Interactions: Do not add dobutamine to 5% Sodium Bicarbonate Injection or to any other strongly alkaline solution. Because of potential physical incompatibilities, it is recommended that dobutamine not be mixed with other drugs in the same solution. Dobutamine should not be used in conjunction with other agents or diluents containing both sodium bisulfite and ethanol. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Tyramine |
| Drug Class: Indirectly Acting Sympathomimetic (a byproduct of tyrosine metabolism) |
| Mechanism of Action: Tyramine is taken up into nerve terminals by the catecholamine reuptake transporter and causes the release of catecholamines from the nerve terminal. |
Pharmacokinetics: Tyramine is readily metabolized by MAO in the liver and is normally inactive when taken orally because of a high first-pass effect (low bioavailability). If administered parentally, or ingested orally when taking MAO inhibitors, it produces effects similar to norepinephrine, and can possibly cause a hypertensive crisis. Tyramine causes the release of catecholamines from a small pool, and repeated exposure may result in tachyphylaxis. |
| Major drug Interactions: Indirectly acting sympathomimetic amines must be taken up into the nerve terminal to promote release. Thus agents that inhibit the uptake pump (for example, cocaine or imipramine) antagonize responses to these agents. Agents that cause depletion of catecholamines from the sympathetic nerve terminals (e.g., reserpine) antagonize indirectly acting agents, such as tyramine, because there is a lack of catecholamines to be released. |
| Note: Tyramine is found in high concentrations in fermented foods such as cheese, sausage, pickled fish & yeast supplements. |
| Reference: Katzung's text |
| Drug: Ephedrine (generic) |
| Drug Class: Direct & Indirectly acting Sympathomimetic |
| Mechanism of Action: Ephedrine has both direct (alpha and beta) agonist effects and indirect (amphetamine or tyramine - like) sympathomimetic effects. |
| Indications:.diet suppressant, bronchodialator, stimulant / energy supplement (increased risk of MI when used in high doses) |
| Contraindications: cardiovascular disease |
| Side Effects: higher than normal incidence of myocardial infarction, stroke and sudden death. Hypertension, insomnia. |
Pharmacokinetics: tachyphylaxis develops with repeated dosing. |
| Notes: Ephedrine occurs in various plants and is the active ingredient in Ma-huang, a popular herbal medication. In Dec 2003, the FDA issued a consumer alert to alert consumers to immediately stop buying and using ephedra products. The alert was based mainly upon a review of recent adverse event reports that indicated an increased risk of stroke, myocardial infarction and sudden death in those using ephedra containing dietary supplements. The FDA also announced a plan to ban the sale of all food supplements containing ephedrine in the near future. |
| Reference: Katzung's text |
| Drug: Dextroamphetamine (Dexedrine ® ) |
| Drug Class: CNS Stimulant |
| Mechanism of Action: increases the release of monoamines (norepinephrine, 5-HT and dopamine) from their storage sites in nerve terminals, competes with monoamines for reuptake, weakly inhibits MAO. Amphetamine causes the intracellular release of dopamine within the terminal & reverses the membrane transporter direction so that dopamine is released into the synapse by reverse transport rather than by ordinary excocytosis. Dextroamphetamine has stronger CNS effects and weaker peripheral action than amphetamine; thus, dextroamphetamine manifests fewer undesirable CV effects |
| Indications: attention-deficit disorders, narcolepsy. |
| Contraindications: lactation. Use for obesity. |
| Side Effects: nervousness, insomnia, palpitations, hypertension, hyperpyrexia, headaches, dizziness, anorexia, weight loss, dryness of the mouth |
Pharmacokinetics: PO, completely absorbed in 3 hr. Duration: PO, 4-24 hr; t1/2, adults: 10-12 hr; children: 6-8 hr. Excreted in urine. Acidification will increase excretion, while alkalinization will decrease it. |
| Major drug Interactions: MAO inhibitors will increase effects & toxicity |
| Notes: schedule II drug with high abuse potential |
| Reference: www.rxlist.com |
| Drug: Cocaine |
| Drug Class: CNS Stimulant |
| Mechanism of Action: relatively low concentrations block monoamine reuptake transport into nerve terminals (Kd = 0.3 uM). Cocaine non-selectively blocks the membrane transporters for norepinephrine, dopamine and serotonin (which are different gene products).* At higher potentially toxic concentrations, cocaine also blocks Na channels (local anesthetic action) (Kd = 8 uM) & cardiac K channels (Kd = 4 uM) (proarrhythmic), and eventually L-type Ca channels (at >30 uM). *Note: the monoamine membrane transporters are most dense in presynaptic nerve terminals, and are different from vesicular transporters (which are blocked by reserpine). |
| Indications: topical anesthesia of the upper respiratory tract (due to its combined vasoconstrictor & local anesthetic properties); use in EM as an ingredient in TAC (tetracaine, adrenaline & cocaine) prior to wound cleaning & suturing. |
| Contraindications: hypersensitivity to ester anesthetics, |
| Side Effects: signs of toxicity (overdosage) include signs of CNS stimulation, tachycardia, hypertension, hyperthermia, mydriasis, cardiac arrhythmias, seizures. NOTE: in animals under the influence of general anesthesia, very high “potentially lethal” plasma concentrations of cocaine (e.g. >30 uM) can cause a fall in blood pressure due to: a) a reduction in cardiac contractility due to cocaine block of L-type Ca channels at very high doses, and b) “local anesthetic” effects on vascular smooth muscle resulting in vasodilation. These cardiovascular effects are “opposite” of those typically seen in a conscious animal given doses similar to those abused by humans (e.g. simultaneous tachycardia & hypertension), which require a functional CNS & result, in large part, from an increase in sympathetic outflow from the CNS. |
Pharmacokinetics: a topical local anaesthetic; Half life is ~50 min. As a drug of abuse the HCl can be sniffed, taken orally or injected IV. The base form (crack or freebase) is typically smoked. |
| Major drug Interactions: MAOI inhibitors would be expected to increase cocaine's effects & toxicity. Ethanol consumption will convert cocaine to cocaethylene, a derivative that has a half life of 3-4 hours and shares a similar pharmacology as cocaine. Most cocaine abusers consume ethanol to prolong their high. This may also increase cocaine's cardiotoxicity. |
| Notes: One of the most addictive drugs known (Schedule II). |
| Reference: www.rxlist.com |
| Drug: Imipramine (Tofranil ®) |
| Drug Class: antidepressant (tricyclic amine) |
| Mechanism of Action: blocks reuptake of norepinephrine & serotonin at nerve endings (therapeutic effects); Na channel blocker, antimuscarinic, antihistamine, alpha receptor blocker |
| Clinical Indications: depression, chronic pain, nocturnal enuresis (peds) |
| Contraindications: Drugs that inhibit monoamine oxidase (MAOI's) taken w/in 14 days, acute recovery period after a myocardial infarction, or history of drug hypersensitivity |
| Side Effects: drowsiness, dry mouth & eyes, constipation, orthotstatic hypotension, mild tremor, sweating, agitation, nausea, tinnitus |
| Pharmacokinetics: PO, metabolized in the liver (P450 - 2D6) 16 hr half life |
| Major drug Interactions: decongestants & local anesthetics w/ sympathomimetics, antihypertensives, CNS depressants, drugs metabolized by P450-2D6. |
| Notes: Several weeks required for therapeutic effect to appear. Concomitant use of MAOI's can cause potentially fatal hyperpyretic cirsis & seizures. Potentially fatal toxicity includes disturbances of cardiac conduction (widening of QRS) and arrhythmias. |
| Reference: www.rxlist.com |
| Drug: Reserpine (generic) |
| Drug Class: Antihypertensive (catecholamine depletor) |
| Mechanism of Action: A selective inhibitor of the catecholamine vesicular uptake transporter in sympathetic nerve terminals, resulting in a depletion of neuronal catecholamine stores. Reserpine's effects produce a reduction in blood pressure due to a decreased cardiac output & decreased peripheral vascular resistance. |
| Indications:.Hypertension |
| Side Effects: Sedation, mental depression (suicidal tendencies), and Parkinsonism symptoms. |
Pharmacokinetics: Reserpine readily crosses the blood brain barrier & depletes cerebral catecholamine stores. This can cause side effects such as those listed above. |
| Note: Reserpine is the active ingredient of a herbal tranquillizer from Rauwolfia serpentina discovered by ancient Indian physicians. |
| Reference: Katzung's text |
| Drug: Bretylium (generic) |
| Drug Class: Antihypertensive & Antiarrhythmic |
| Mechanism of Action: 1) Interferes with the neuronal release of catecholamines. 2) Bretylium also lengthens the duration and effective refractory period in heart tissue, an effect that is most pronouned in ischemic cells (which have shortened action potential durations). |
| Indications: For attempted resuscitation from ventricular fibrillation after lidocaine and cardioversion have failed. |
| Side Effects: precipitation of cardiac arrhythmias at the onset of drug therapy due to its ability to cause the initial release of catecholamines (when used as an antiarrhythmic). Postural hypotension (a sympathoplegic side effect). Nausea & vomiting. |
Pharmacokinetics: available for i.v. use only in the USA. |
| Major drug Interactions: Digitalis toxicity may be aggravated by the initial release of norepinephrine caused by Bretylium. The pressor effects of catecholamines such as dopamine or norepinephrine are enhanced (mechanism unclear). |
| Reference: www.rxlist & Katzung's text. |
| Drug: Guanethidine (Ismelin ®) |
| Drug Class: Antihypertensive, Adrenergic Neuron-blocking Agent |
| Mechanism of Action: In high doses can cause profound sympathoplegia or "pharmacologic sympathectomy". Guanethidine has 4 mechanisms of action: 1) causes an initial release of norepinephrine (tyramine-like effect), followed by replacement of norepinephrine by guanethidine in transmitter vesicles that eventually causes a 2) gradual depletion of norepinephrine stores in the nerve ending (a reserpine-like effect). 3) It's strong interaction with the nerve terminal transporter produces a cocaine-like effect. It also 4) inhibits the release of norepinephrine from nerve terminals (bretylium-like effect). Intially it can produce a pressor effect (due to tyramine & cocaine like actions), but later results in sympathoplegia (due to reserpine & bretylium like effects). |
| Indications: the treatment of more severe cases of hypertension, either alone or as an adjunct, and for the treatment of renal hypertension, including that secondary to pyelonephritis, renal amyloidosis, and renal artery stenosis. |
| Contraindications: guanethidine can cause a hypertensive crisis in patients with pheochromocytoma due to the release of catecholamines (tyramine like action). |
| Side Effects: postural hypotension, diarrhea (from increased GI motility), impaired ejaculation (because of these side effects guanethidine is now rarely used - but it still shows up on the shelf exam!! Hence it's still on the drug list.) |
Pharmacokinetics: guanethidine is too polar to enter into the CNS, and hence has little or no CNS side effects. |
| Major drug Interactions: Tricyclic antidepressants will decrease guanethidine's antihypertensive effects by blocking its uptake into nerve terminals. Concurrent use with other sympathomimetics (OTC cold medications) may produce hypertension. |
| Notes: Q1: Will you "ever" prescribe this drug? (Not likely). Q2: Is guanethedine a nice tool for understanding "the pharmacology of the nerve terminal"? (Yes). Q3: Do I need to know it for the boards? (It still shows up on shelf exams, so.... ?) |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Pargyline |
| Drug Class: Monoamine Oxidase Inhibitor / Antihypertensive |
| Mechanism of Action: pargyline is thought to lower blood pressure by increasing the concentration of octopamine, a false transmitter in peripheral adrenergic nerve terminals. Pargyline inhibits MAO in the GI mucosa and liver and thus allows unimpeded access of dietary tyramine to the systemic circulation. Tyramine is taken up into nerve endings and converted to octopamine which partially replaces norepinephrine in synaptic storage vesicles. Because octopamine is an ineffective adrenergic agonist, sympathoplegia results even though total stores of norepinephrine may be increased. |
| Indications: previously used in the treatment of moderate to severe hypertension. (We now have better drugs). |
| Major drug Interactions: inhibits the metabolism of catecholamines and tyramine inside of presynaptic nerve terminals. Concurrent consumption of tyramine–rich foods can cause a hypertensive crisis. |
| Notes: similar to the situation with guanethedine, pargyline's pharmacology is admittedly "neat" but it no longer has a role in the modern day treatment of hypertension. It could show up on a shelf exam? |
| Reference: an older (7th edition) of Katzung's text. Not covered in the 9th edition. |
| Drug: Methyldopa (Aldomet®) |
| Drug Class: Antihypertensive |
| Mechanism of Action: the antihypertensive effect of methyldopa is believed to be due to its metabolism to alpha-methylnorepinephrine, which then lowers arterial pressure by stimulation of central inhibitory alpha-2 adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity. |
| Indications: may be used in pregnant patients as a replacement for ACE inhibitors & ARBs (which are more efficacious, but are strongly contraindicated in pregnancy). The patient can be switched back to an ACE inhibitor or ARB once pregnancy is over. |
| Notes: Methyldopa is the L-isomer of alpha-methyldopa |
| Reference: www.rxlist.com |
| Drug: Octopamine |
| Drug Class: False neurotransmitter. |
| Mechanism of Action: Dopamine beta-hydroxylase converts tyramine to octopamine. Octopamine can be taken up into storage vesicles in nerve terminals, and then be released by nerve stimulation. However, it exerts only a "small effect" on postsynaptic receptors compared to norepinephrine. |
| Notes: Typically exists in only trace amounts in the mammalian CNS, but accumulates when MAO is inhibited (e.g. by pargyline). First identified in the octopus. Octopamine plays an important role in the innervtebrate nervous system where its role is analogous to that of norepinephrine (NE) in vertebrates, and it is responsible for the "fight or flight" effect and fat mobilizing. |
| Drug: Dobutamine (generic, Dobutrex ®) |
| Drug Class: Beta-1 Selective Sympathomimetic |
| (See above) |
| Drug: Albuterol (Ventolin, Combivent, Proventil ®) |
| Drug Class: Beta- 2 Adrenergic Agonist |
| Mechanism of Action: Adrenergic agonist with a selectivity for beta-2 receptors. The prime action of beta-adrenergic drugs is to stimulate adenyl cyclase, the enzyme which catalyzes the formation of cyclic-3 ,5 -adeno-sine monophosphate (cyclic AMP) from adenosine triphosphate (ATP). The cyclic AMP thus formed mediates the cellular responses. |
| Indications: To produce bronchodilation. For the prevention and relief of bronchospasm and for the prevention of exercise-induced bronchospasm. |
| Contraindications: a history of hypersensitivity to albuterol |
| Side Effects: Manifestations of overdosage may include tremors, seizures, anginal pain, hypertension, hypokalemia, tachycardia with rates up to 200 beats/min. |
Pharmacokinetics: aerosol and capsule formulations. Albuterol is longer acting than isoproterenol in most patients by any route of administration because it is not a substrate for the cellular uptake processes for cate-cholamines nor for catechol-O-methyl transferase. Studies in asthmatic patients have shown that less than 20% of a single albuterol dose was absorbed following IPPB (intermittent positive-pressure breathing) or nebulizer administration. Albuterol does not readily cross the blood brain barrier. |
| Major drug Interactions: Other sympathomimetic aerosol bronchodilators or epinephrine should not be used concomitantly with albuterol. Albuterol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic anti-depressants, since the action of albuterol on the vascular system may be potentiated. |
| Reference: www.rxlist.com |
| Drug: Terbutaline (Brethine, Bricanyl ®) |
| Drug Class: Beta- 2 Adrenergic Agonist |
| Mechanism of Action: (same as albuterol) |
| Indications: for the prevention and reversal of bronchospasm in patients with bronchial asthma and reversible bronchospasm associated with bronchitis and emphysema. |
| Contraindications: hypersensitivity |
| Side Effects: similar to those commonly seen with other sympathomimetic agents. All these reactions are transient in nature and usually do not require treatment. |
Pharmacokinetics: typically given by s.c. injection. |
| Major drug Interactions: (same as with albuterol) |
| Reference: www.rxlist.com |
| Drug: Phenylephrine (generic, Neo-Synephrine ®) |
| Drug Class: Synthetic Alpha-Selective Adrenergic Agonist; Nasal decongestant |
| Mechanism of Action: a powerful postsynaptic alpha-receptor stimulant with little effect on the beta receptors of the heart. In therapeutic doses, it produces little if any stimulation of either the spinal cord or cerebrum. A singular advantage of this drug is the fact that repeated injections produce comparable effects. |
| Indications: for the maintenance of an adequate level of blood pressure during spinal and inhalation anesthesia and for the treatment of vascular failure in shock, shock-like states, and drug-induced hypotension, or hypersensitivity. It is also employed to overcome paroxysmal supraventricular tachycardia, to prolong spinal anesthesia, and as a vasoconstrictor in regional analgesia. Also used as a mydriatic & decongestant. |
| Contraindications: hypertension, ventricular tachycardia, or in patients who are hypersensitive. |
| Side Effects: Headache, reflex bradycardia, excitability, restlessness, and rarely arrhythmias |
Pharmacokinetics: Given by s.c., i.m. or i.v. injection. Also present in some nasal drop formulations. It produces vasoconstriction that lasts longer than that of epinephrine and ephedrine. It is not a catechol and is not inactivated by COMT. Responses are more sustained than those of epinephrine, lasting 20 minutes after intravenous and as long as 50 minutes after subcutaneous injection |
| Major drug Interactions: The pressor effect of sympathomimetic pressor amines is markedly potentiated in patients receiving monoamine oxidase inhibitors (MAOI) |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Clonidine (Catapres ®) |
| Drug Class: Alpha-2 Selective Adrenergic Agonist |
| Mechanism of Action: stimulates alpha-2 adrenoreceptors in the brain stem. This action results in reduced sympathetic outflow from the central nervous system and in decreases in peripheral resistance, renal vascular resistance, heart rate, and blood pressure. Selective for alpha-2 over alpha-1 receptors. |
| Indications: treatment of hypertension |
| Contraindications: hypersensitivity |
| Side Effects: dry mouth, dizziness, constipation |
Pharmacokinetics: Clonidine hydrochloride, acts relatively rapidly. The patient’s blood pressure declines within 30 to 60 minutes after an oral dose, the maximum decrease occurring within 2 to 4 hours. |
| Major drug Interactions: may potentiate the CNS- depressive effects of alcohol, barbiturates or other sedating drugs. May produce bradycardia & depress sinus node function in patients on digitalis, calcium channel blockers and beta-blockers. |
| Reference: www.rxlist.com |
Alpha Receptor Blockers
| Drug: Phenoxybenzamine (Dibenzyline ®) |
| Drug Class: Alpha-1 & Alpha-2 Nonselective Adrenergic Antagonist |
| Mechanism of Action: a long-acting, adrenergic, alpha-1 & alpha-2 nonselective receptor blocking agent which can produce and maintain "chemical sympathectomy" by oral administration. Phenoxybenzamine binds covalently to alpha receptors. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. (Although the clinical relevance is unclear, phenoxybenzamine also inhibits the presynaptic reuptake of released norepinephrine, and blocks H-1 histamine, acetylcholine and serotonin receptors as well as alpha receptors.) |
| Indications: Pheochromocytoma, to control episodes of hypertension and sweating. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. |
| Contraindications: conditions where a fall in blood pressure is undesirable |
| Side Effects: Postural hypotension, tachycardia, inhibition of ejaculation, nasal congestion, miosis, drowsiness, GI irritation, shock (overdose). |
Pharmacokinetics: the half-life of intravenously administered drug is approximately 24 hours. Demonstrable effects with intravenous administration persist for at least 3 to 4 days, and the effects of daily administration are cumulative for nearly a week. |
| Major drug Interactions: interactions will occur with compounds that stimulate both alpha- and beta- adrenergic receptors (i.e., epinephrine) to produce an exaggerated hypotensive response and tachycardia. |
| Reference: www.rxlist.com |
| Drug: Phentolamine (Regitine ®) |
| Drug Class: Nonselective Alpha Receptor Antagonist |
| Mechanism of Action: Phentolamine blocks both alpha-1 and alpha-2 receptors. It produces vasodilator effects on vascular smooth muscle, and less marked, positive inotropic and chronotropic effects on cardiac muscle (baroreceptor reflex mediated). Although the clinical significance is unclear, phentolamine also blocks H-1 and H-2 histamine receptors, serotonin and muscarinic receptors. |
| Indications: 1) for the prevention or control of hypertensive episodes that may occur in a patient with pheochromocytoma as a result of stress or manipulation during preoperative preparation and surgical excision. 2) for the preventionor treatment of dermal necrosis and sloughing following intravenous administration or extravasation of norepinephrine. 3) for the diagnosisof pheochromocytoma by the phentolamine blocking test. |
| Contraindications: Myocardial infarction, history of myocardial infarction, coronary insufficiency, angina, or other evidence suggestive of coronary artery disease; hypersensitivity to phentolamine or related compounds. |
| Side Effects: Acute and prolonged hypotensive episodes, tachycardia, and cardiac arrhythmias |
Pharmacokinetics: Not well absorbed if taken orally, and is given either i.m. or i.v.. It produces an alpha-adrenergic block of relatively short duration ( half-life in the blood of 19 minutes following intravenous administration). |
| Reference: www.rxlist.com |
| Drug: Prazosin (generic, Minipress®) |
| Drug Class: Selective Alpha-1 Receptor Blocker, Antihypertensive |
| Mechanism of Action: competitively blocks alpha-1 adrenergic receptors. The peripheral vasodilator effect of prazosin is confined mainly to the level of the resistance vessels (arterioles). Unlike conventional alpha-blockers, the antihypertensive action of prazosin is usually not accompanied by a reflex tachycardia. |
| Indications: the treatment of hypertension. It can be used alone or in combination with other antihypertensive drugs such as diuretics or beta-adrenergic blocking agents. |
| Side Effects: dizziness, orthostatic hypotension |
Pharmacokinetics: Taken orally. Following oral administration, human plasma concentrations reach a peak at about three hours with a plasma half-life of two to three hours. The drug is highly bound to plasma protein |
| Reference: www.rxlist.com |
| Drug: Doxazosin (generic, Cardura ®) |
| Mechanism of Action: alpha-1 selective blocker (similar to prazosin) |
| Pharmacokinetics: long half life (22 hrs), once a day dosing. |
| Drug: Butoxamine * |
| Drug Class: Beta-2 Selective Adrenergic Antagonist |
| Mechanism of Action: Competitive antagonist at beta-2 adrenergic receptors |
| Indications: It is used primarily in animal and tissue experiments to characterize beta-2 receptor involvement and identify beta-2 receptors. * Not available for clinical use. |
| Reference: Katzung's text |
| Drug: Yohimbine (generic, Yocon ®) |
| Drug Class: Selective Alpha-2 Receptor Blocker |
| Mechanism of Action: Yohimbine blocks presynaptic alpha-2-adrenergic receptors.This effect can increase sympathetic outflow and potentiate the release of norepinephrine from nerve endings, leading to activation of alpha-1 and beta-1 receptors in the heart and peripheral vasculature, with a consequent rise in blood pressure. |
| Indications: no established clinical role. Theoretically it could be useful in autonomic insufficiency by promoting neurotransmitter release by blocking presynaptic alpha-2 receptors. |
| Side Effects: Yohimbine exerts a stimulating action on the mood and may increase anxiety. |
| Major drug Interactions: Yohimbine can reverse teh antihypertensive effects of an alpha-2 receptor agonist such as clonidine, a potentially serious adverse drug interaction.. |
| Reference: www.rxlist.com , Katzung's & Goodman & Gilman's texts |
Other alpha blockers in Top 200
| Terazosin (generic, Hytrin ®) - for hypertension & BPH (reference) |
| Tamsulosin (Flomax ®) - for hypertension & BPH (reference) |
| Drug: Propranolol (generic, Inderal ®) |
| Drug Class: Nonselective Beta Receptor Blocker |
| Mechanism of Action: Competitively blocks both beta-1 and beta-2 adrenergic receptors. When access to beta-receptor sites is blocked by Propranolol HCl, the chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation are decreased proportionately. |
| Indications: 1) the management of hypertension. It may be used alone or used in combination with other antihypertensive agents, particularly a thiazide diuretic. 2) the long-term management of patients with angina pectoris. 3) cardiac arrhythmias (atrial tachyarrhythmias induced by catecholamines, digitalis, thyrotoxicosis, or associated with Wolff-Parkinson-White syndrome; for the control of ventricular rate in patients with atrial flutter or fibrillation when digoxin is ineffective or contraindicated, ventricular arrhythmias caused by catecholamines or digoxin). 4) prevention of sudden death and reinfarction after an MI. 5) treatment of migraines. 5) management of hypertrophic subaortic stenosis. 6) adjunct therapy with alpha blockers in treatment of pheochromocytoma. 7) management of familial or hereditary essential tremor. |
| Contraindications: in 1) cardiogenic shock, 2) sinus bradycardia and greater than first degree block, 3) bronchial asthma |
| Side Effects: bradycardia; congestive heart failure; intensification of AV block; hypotension; paresthesia of hands, light-headedness; mental depression manifested by insomnia, lassitude, weakness, fatigue |
Pharmacokinetics: Propranolol is almost completely absorbed from the gastrointestinal tract, but a portion is immediately bound by the liver. Peak effect occurs in one to one-and-one-half hours. The biologic half-life is approximately four hours.There is no simple correlation between dose or plasma level and therapeutic effect, and the dose-sensitivity range as observed in clinical practice is wide. The principal reason for this is that sympathetic tone varies widely between individuals. Since there is no reliable test to estimate sympathetic tone or to determine whether total beta blockade has been achieved, proper dosage requires titration. |
| Major drug Interactions: Patients receiving catecholamine-depleting drugs such as reserpine should be closely observed if propranolol is administered. Caution should be exercised when patients receiving a beta blocker are administered a calcium-channel blocking drug. |
| Reference: www.rxlist.com |
| Drug: Metoprolol (generic, Lopressor, Toprol ®) |
| Drug Class: Beta-1 Selective Receptor blocker. |
| Mechanism of Action: a beta1-selective (cardioselective) adrenoceptor blocking agent. This preferential effect is not absolute, however, and at higher plasma concentrations, metoprolol also inhibits beta2-adrenoreceptors, chiefly located in the bronchial and vascular musculature. Metoprolol has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at plasma concentrations much greater than required for beta-blockade. |
| Indications: Hypertension & Angina Pectoris |
| Contraindications: sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure. |
| Side Effects: fatigue, dizziness, depression, bradycardia |
Pharmacokinetics: Available in oral and oral sustained-release formulatons. |
| Major drug Interactions: reserpine (additive effect) |
| Warning: In patients with ischemic heart disease exacerbations of angina pectoris and, in some cases, myocardial infarction have occurred following abrupt cessation of therapy with certain beta-blocking agents. If treatment is to be discontinued, the dosage should be reduced gradually over a period of 1-2 weeks |
| Reference: www.rxlist.com |
| Drug: Pindolol (generic, Visken ®) |
| Drug Class: Nonselective Beta Adrenergic Antagonist |
| Mechanism of Action: a synthetic non-selective beta-adrenergic receptor blocking agent with intrinsic sympathomimetic activity at therapeutic doses, and may produce less bradycardia. |
| Indications: treatment of hypertension |
| Contraindications: 1) bronchial asthma;
2) overt cardiac failure; 3) cardiogenic shock; 4) second and third degree
heart block; 5) severe bradycardia. |
| Side Effects: Most adverse reactions have been mild |
| Major drug Interactions: reserpine (additive effect) |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Labetalol (generic, Normodyne, Trandate ®) |
| Drug Class: Adrenergic Receptor Blocking Agent (alpha-1, beta-1 & beta-2) |
| Mechanism of Action: A racemic mixture of two pairs of isomers that produces adrenergic receptor block with both selective alpha1-adrenergic and nonselective beta-adrenergic receptor blocking actions in a single substance. One isomer is a potent alpha-1 blocker, and one is a potent nonselective beta blocker. Labetalol produces a greater amount of beta vs. alpha blockade at therapeutic doses. Labetalol produces dose-related falls in blood pressure without reflex tachycardia and without significant reduction in heart rate, |
| Indications: management of hypertension |
| Contraindications: in bronchial asthma, overt cardiac failure, greater-than-first-degree heart block, cardiogenic shock, severe bradycardia, other conditions associated with severe and prolonged hypotension, and in patients with a history of hypersensitivity |
| Side Effects: dizziness, nausea, fatigue, postural hypotension |
Pharmacokinetics: Oral and parenteral formulations. Plasma half life is 6 to 8 hours. |
| Reference: www.rxlist.com |
Drug: Bisoprolol (Zebeta ®): |
| Mechanism of Action: beta-1 selective |
| Pharmacokinetics: long half life. Once a day dosing. |
| Reference: www.rxlist.com |
Other beta blockers in Top 200:
| Atenolol (generic, Tenormin ®): beta-1 "cardioselective" (reference) |
| Caravedilol (Coreg ®): alpha & beta blocker (reference) |
| Timolol (generic, Blocadren, Timoptic ®): non-selective beta (reference) |
| Drug: Angiotensin II |
| Drug Class: Vasoactive peptide |
| Mechanism of Action: Exerts important actions at several sites in the body, including vascular smooth muscle, adrenal cortex, kidney & brain by activating angiotensin receptors. Through its actions, the renin-angiotensin system plays a key role in regulating fluid & electrolyte balance & arterial blood pressure. Excessive activity can result in hypertension & disorders of fluid & electrolyte homeostasis. In particular for this PBL, Ang II is shown to be a very potent pressor agent (40 times more potent than norepinephrine). |
| Pharmacokinetics: Ang I is converted to Ang II by ACE (Angiotensin Coverting Enzyme, a dipeptidyl carboxypeptidase. The plasma half life of Ang II is only 15-60 seconds |
| Other drugs used in this PBL have been covered above. |