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36 Cards in this Set
- Front
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Discuss sympathomimetics in general:
example clinical uses-- (5) |
*Imitate the effects of the sympathetic nervous system, activating alpha or beta receptors or both.
*Most agents directly stimulate receptors rather than increasing amounts of available endogenous catecholamines (i.e., norepinephrine) *Example Clinical Uses: Nasal congestion (Alpha-1) Bronchospasm (Beta-2) Anaphylaxis (Beta-2 and Alpha-1) Cardiovascular collapse (Alpha-1 and Beta-1) Overactive bladder (Beta-3...new drug) |
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Epinephrine:
what receptors does it activate? |
*Potent agonist for Alpha-1, Beta-1 and Beta-2 receptors
Systemic (intravenous) administration, causes: 1) Significant direct cardiac effects (Beta-1): increase in chronotropic (increase SA firing-->HR), dromotropic (increase AV conduction) and inotropic (increase contractility) effects on the heart. 2) Blood pressure effects (Alpha-1-->increase) at higher doses; some Beta-2 (decrease) at lower doses. 3) Bronchodilation (Beta-2). *Other effects based on receptor stimulation should be anticipated-- the effects will be systemic, beyond your target therapy. |
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Norepinephrine:
what receptors does it activate? What do you do if you accidentally inject NE outside of a blood vessel? |
*Potent agonist for Alpha-1 receptors; Beta-1 agonism
*With systemic IV administration, causes significant increase in BLOOD PRESSURE (NO Beta-2 effects to counteract) and significant increase in INOTROPY. Your HR might not actually increase (multiple receptor effects)! *Clinical Pearl: IV administration of any Alpha-1 agonist can cause significant NECROSIS if extravasation occurs. Prevention of this adverse effect by CAREFUL TECHNIQUE is essential. Phentolamine (an Alpha blocker) is administered locally if extravasation occurs. |
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Dopamine:
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*Precursor of NE but also direct agonist for Beta-1 and Alpha-1 receptors. Additionally stimulates dopamine D-1 receptors in mesenteric, renal, and coronary vasculature causing VASODILATION.
*Dose-related effects: Low (1-2 mcg/kg/min): renal/mesenteric vasodilation. Medium (5-10 mcg/kg/min): increased heart rate, inotropy. High (10-20 mcg/kg/min) increased vasoCONSTRICTION, HR, inotropy. *Clinical Pearl: Low dose dopamine has limited effects on improving renal function; At high dose, increased vascular resistance predominates over any vasodilatory effects |
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Other Representative Sympathomimetics:
Isoproterenol and Dobutamine-- what receptors do they stimulate? |
Uses:
*Intravenous: cardiogenic shock with primary increase in contractility (rather than increase in peripheral resistance); Increase heart rate with isoproterenol. *Inhaled Isoproterenol: previous use for asthma patients but newer agents are selective for Beta-2 receptors and do not cause the same cardiac side effects. *Note: Although both increase contractility, in patients with cardiogenic shock, dobutamine less likely to cause reflex tachycardia than isoproterenol. |
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Other Representative Sympathomimetics:
Ephedrine, Phenylpropanolamine, and Pseudoephedrine: what receptors do they stimulate? |
*Considerations:
All these agents cause significant Alpha-1 stimulation (vasoconstriction) and can significantly raise BP increasing risk of stroke. *Ephedrine is banned by the FDA- beware of herbal products containing like compounds. *Phenylpropanolamine (PPA)was commonly used as an OTC decongestant and appetite suppressant. PPA is now banned by the FDA because of blood pressure/stroke risk. *Pseudoephedrine is sold OTC behind the counter due to its use as a precursor for methamphetamine. |
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Other Representative Sympathomimetics:
Terbutaline, Albuterol, and Salmeterol-- what receptors do they stimulate? |
*Uses:
*Inhalation: As bronchodilators in the treatment of airways disease such as asthma and COPD. Drugs differ with regards to onset of action and duration of effect. *Example: Salmeterol cannot be used for acute management of asthma because of its slow onset. *Oral: less frequently used dosage form due to increase risk of adverse effects. |
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Sympathomimetics: Adverse Events from ß1 overstimulation: 4
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*Tachycardia, increased myocardial oxygen demand, arrhythmias, cardiac damage.
*Clinical Pearl: Although Beta-1 agonists such as dobutamine can be used in the short-term management of decompensated heart failure, intermittent infusions to treat chronic heart failure increase overall mortality. |
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Sympathomimetics: Adverse Events Due to Beta-2 over-stimulation: 4
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*Skeletal muscle tremors, tachycardia, arrhythmias, hypokalemia.
*Clinical Pearl: While less common with inhaled administration (rather than oral) of Beta-2 agonists, these side effects may still occur. |
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Sympathomimetics: Adverse Events Due to Alpha-1 over-stimulation: 4
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*Severely elevated blood pressure, increasing myocardial oxygen demand, predisposing to stroke and cardiac damage
*CNS effects--agitation, headaches. |
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Alpha Sympatholytics (Alpha Blockers): Alpha-1 receptor selective agents:
how do they work? uses? 2 |
*Bind to alpha receptors and block the effects of endogenous agonists.
*Alpha-1 receptor selective agents: -Representative: prazosin, terazosin, doxazosin -Uses: Hypertension: decreases vascular resistance Benign prostatic hyperplasia (BPH): improves urinary flow. *Caution: Orthostatic hypotension; syncope with first use or an increase in dose. |
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Alpha Sympatholytics (Alpha Blockers): Combined Alpha-1 and Alpha-2 receptor blockers--
use? adverse effects? Caveat? |
*Representative: phentolamine, phenoxybenzamine
*Use: pheochromocytoma *Adverse effects: Significant hypotension causing reflex stimulation of the heart resulting in tachycardia, arrhythmias and myocardial ischemia. *Caveat to sympatholytics: central acting Alpha-2 agonists (e.g., clonidine) reduce CNS efferent sympathetic outflow, reducing blood pressure as well. |
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Beta Sympatholytics (Beta-Blockers):
how do they work? How are they distinguished among each other? 5 traits |
*Bind to beta receptors and block the effects of endogenous agonists.
*Beta Blockers are distinguished by the following properties: -Likelihood to block only Beta-1 receptors (Selectivity) -Ability to act as a beta-agonist (Intrinsic Sympathomimetic Activity; ISA) -Ability to cause concurrent Alpha-1 blockade (vasodilating effect) -Metabolism and Elimination (Pharmacokinetics, esmolol is short acting, nadolol long acting) -Likelihood to cross into CNS (Lipophilicity) |
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Beta Sympatholytics (Beta-Blockers): Discuss Selectivity considerations--
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*Property is useful when needing to avoid risk of BRONCHOCONSTRICTION.
*Clinical Pearl: Selectivity is dose-related; maximum doses lose selectivity. |
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Beta Sympatholytics (Beta-Blockers): DISCUSS ones with ISA--
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*Partial beta-agonism that occurs at times of low sympathetic tone (e.g., during sleep).
*Property is useful when patients with HTN treated with beta-blockers have excessively low heart rates at night. *Property NOT USEFUL in patients with ischemic heart disease, where overall benefit related to lowered heart rate. |
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Beta Sympatholytics (Beta-Blockers): discuss ones that have concurrent alpha-1 blockade--
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*Property allows for broader scope of antihypertensive actions.
*Patients treated with beta-blockers for other cardiovascular disease may experience a relatively greater reduction in blood pressure. |
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Cardiovascular Indications for Beta-Blockers (Beta-1 blockade):
Discuss HTN and ischemic heart disease-- |
*Hypertension
Commonly used antihypertensive (primary effect to reduce cardiac output); may be less desirable as first line therapy. *Ischemic Heart Disease -Chronic Angina Pectoris: reduces cardiac workload; decreases symptoms. -Acute Coronary Syndromes: decreases workload and ischemia; decreases mortality if given long-term. |
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Cardiovascular Indications for Beta-Blockers (Beta-1 blockade)
Discuss systolic heart failure as an indication-- How do the drugs help? Dosing considerations? |
*Decreases long-term mortality by blocking effects of high circulating levels of norepinephrine. Results in reduced mortality from both cardiac arrest and progressive heart failure.
*Clinical Pearl: In patients with systolic HF, doses MUST be titrated very slowly to avoid an exacerbation of heart failure symptoms (i.e., initiate with 1/10 of target dose, increasing every 2 weeks). *carvedilol and metroprolol succinate are the ones. |
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Cardiovascular Indications for Beta-Blockers (Beta-1 blockade)
Discuss arrhythmias and prevention of SCD as indications-- mechanism: Caveat drug? |
*Mechanism of benefit is from blocking effects of sympathetic nervous system (not direct membrane-stabilizing effects).
*Prevention of sudden death (e.g., ventricular fibrillation) in patients with systolic heart failure and patients with myocardial infarction. *Treatment of supraventricular arrhythmias by causing Beta-1 blockade of the AV node (SA node). *Caveat: Sotalol is an Class III antiarrhythmic that also has significant beta-blocking properties. |
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Some Other Uses of Beta-Blockers:
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*Glaucoma
-Instillation of beta-blockers (e.g., ophthalmic TIMOLOL) decreases intraocular pressure. -Clinical Pearl: Case reports have demonstrated that ophthalmic preparations may have enough systemic absorption to cause adverse beta-blocking effects (such as acute worsening of heart failure symptoms). *Thyroid Storm *Performance anxiety (“stage fright”) *Migraine prophylaxis |
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Adverse Effects of Beta-Blockers:
3 categories |
*May be dependent/modified by characteristics of beta-blocker (e.g., Beta-1 selectivity)
*Direct Cardiac Effects: -Acute decompensation of systolic heart failure especially with large doses. -Symptomatic AV nodal block/ sinus bradycardia. *Bronchoconstriction: -More likely to occur with NON-SELECTIVE beta-blockers but be careful with higher doses of Beta-1 selective drugs. Should generally avoid in patients with asthma. *Dyslipidemias: -Decreased HDL; may be less likely with ISA-containing beta-blockers. |
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Adverse Effects of Beta-Blockers:
DM considerations: peripheral vasoconstriction: CNS effects: |
*Decreased recognition of hypoglycemia in DM:
-Most important in patients with hard to control insulin-dependent diabetes. -If patients have cardiac conditions requiring beta-blockade, DM is usually NOT a contraindication. *Peripheral vasoconstriction: -More likely to occur with non-selective beta-blockers (ß2 receptors). *CNS side effects: -Nightmares; sedation (propanolol). -May be less common with use of beta-blockers having lower lipid solubility. |
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Beta-Blockers: Important Considerations when discontinuing beta blockers:
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*Patients should not abruptly discontinue their beta-blockers on their own: can increase risk of ischemic events.
*Up-regulation of beta-receptors during chronic therapy is a possible mechanism. *In patients admitted to the hospital with decompensated heart failure, beta-blockers are continued or re-instituted as soon as possible. *In those patients requiring IV beta-agonists (NE, dopamine) for acute heart failure, higher doses may be needed in patients receiving chronic beta-blockade. |
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Parasympathomimetics (Cholinergic Drugs):
How do they increase the effect of the PNS? |
Direct action: Stimulate muscarinic receptors
Indirect action: Inhibit acetylcholinesterase |
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Direct acting muscarinic agonists (examples):
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*Choline esters:
Carbachol Bethanechol Methacholine Acetylcholine ( cannot be used clinically- rapidly hydrolysed) *Alkaloids: Pilocarpine |
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Clinical Use of Direct-Acting Muscarinic Agonists- Examples: 3 conditions; list drugs for each
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*Glaucoma
-Reduce intraocular pressure through increasing outflow of aqueous humor (e.g., pilocarpine) *Xerostomia -Inceases salivary secretion (e.g., pilocarpine; cevimeline) *Gastric atony /Urinary retention -Improve gastrointestinal and urinary function in patients without obstruction (e.g., bethanechol) |
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Indirect acting parasympathomimetics (examples):
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*Edrophonium
-Short-lived binding (MINUTES) to the active site *Physostigmine, neostigmine, pyridostigmine -Medium duration of action (MINUTES to HOURS) due to covalent bonding *Organophosphates used as insecticides or as topical treatments (e.g., parathion, malathion) and nerve gases (e.g., sarin, soman) -Long duration of action (DAYS) due to covalent phosphorylated active site -Can undergo aging, whereby the bond becomes more stable over time *Newer Acetylcholinesterase Inhibitors that cross the BBB (alzheimer's): tacrine, donepezil, rivastigmine, galantamine |
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Clinical Use of Indirect-Acting Parasympathetic Agonists:
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*Conditions benefited by direct-acting agents
-Glaucoma, xerostomia, gastric atony/urinary retention *Myasthenia gravis -Increase acetylcholine at neuromuscular junctions -neostigmine, pyridostigmine *Alzheimer’s disease -tacrine, donepezil, rivastigmine, galantamine *Others -Prophylaxis against nerve gas poisoning (physostigmine; temporary) -Antimuscarinic poisoning with atropine and others |
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Adverse Effects of Direct-Acting and Indirect-Acting Muscarinic Agonists:
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*Just extensions of pharmacologic effects.
*Cardiovascular: -Bradycardia -Hypotension *Bronchial/Pulmonary: -Bronchoconstriction -Glandular hypersecretion *Gastrointestinal: -Distress -Increased acid secretion |
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Organophosphate Insecticide Poisoning: signs and symptoms--
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*Signs and Symptoms (nicotinic and muscarinic)
-Cardiovascular: hypotension, severe bradycardia, and arrhythmias. -Pulmonary: respiratory distress and failure. -GI: nausea, vomiting, abdominal cramps, diarrhea, incontinence. -Eyes: miosis, reduced vision, ocular pain. -CNS: confusion, seizures, central respiratory failure, coma. |
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Organophosphate Insecticide Poisoning: management--
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*Decontamination
*Atropine for muscarinic side effects (also, it can cross the BBB at high doses). *Pralidoxime (2-PAM) = cholinesterase reactivator- doesn’t enter CNS and efficacy is time dependent due to aging of the bond. *Respiratory support |
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Antimuscarinic Drugs:
Actions-- Direct effects-- |
*Actions
-Block effects of exogenous and endogenous muscarinic agonists. *Direct effects: -Cardiac: increased heart rate, conduction velocity through AV node, block of reflex bradycardia. -Lungs: bronchodilation, reduced bronchial secretions. -GI/GU: inhibit tone, inhibit gastric acid secretion. -Eyes: mydriasis, cycloplegia. -CNS: excitation or depression. -Other: anhydrosis and xerostomia. |
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Antimuscarinic Drugs: Examples and Uses--
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*Alkaloids (atropine, scopolamine).
*Usual doses of atropine have little CNS effects; scopolamine has better permeation of blood-brain barrier at therapeutic doses (used for motion sickness). *Intravenous atropine is used for significant bradycardia. *Anti-muscarinic effects of atropine are dose related. |
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Antimuscarinic Drugs: Examples and Uses of Tertiary Amine Derivatives--
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*Characterized by good CNS penetration/eye penetration.
*Benztropine and trihexylphenidyl: -Parkinson’s Disease (improve effects of relative cholinergic excess). -Treatment of extrapyramidal side effects (relative reduction in dopamine) of antipsychotics. *Dicyclomine, oxybutynin: Antispasmodics for G/U. Helps alleviate patients peeing/pooping their pants. *Homatropine, cyclopentolate: Topical mydriatic agents (get your eyes dilated). |
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Antimuscarinic Drugs: Examples and Uses of Quaternary Ammonium Derivatives--
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*Bronchodilators administered by aerosol; Low systemic absorption; do not cross blood-brain barrier.
Frequently used in combination with beta-agonists like albuterol. |
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Indications for using beta blockers:
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HTN
Ischemic heart disease Systolic heart failure Arrhythmias and SCD Thyroid storm Performance anxiety Migraine prophylaxis |
