7-30 Sympathomimetic Drugs Flashcards
What are the 5 clinical uses of epinephrine?
bronchial asthma
anaphylactic shock/epi pen
glaucoma
infiltration with local anesthetics
cardiac resuscitation
topical hemostatic
How does epinephrine work as a drug to treat asthma?
Bronchial Asthma; Administered by inhalation (nebulizer)
Acts as a bronchodilator (ß2)
vasoconstrictor (a1)
and an inhibitor of antigen-induced release of histamine (ß2).
Racemic epinephrine mostly used in pediatric asthma.
How does epinephrine work as a drug to treat anaphylactic shock?
Anaphylactic Shock (usually SC injection) and related immediate (Type I) IgE-mediated reactions.
Pharmacological actions include: for initial treatment
bronchodilation, decreased edema, decreased antigen-induced release of histamine and alleviation of hypotension
Drug of choice because of efficacy on a1, b2 adrenergic receptors.
How does epinephrine work to treat glaucoma?
Glaucoma; lowers intraocular pressure (mechanism uncertain) Administered topically – rarely used now.
How does epinephrine work in conjunction with a topical anaesthetic?
Prolongs action via vasoconstriction
prevents toxicity of anaesthetic
How is epinephrine used to do cardiac resuscitation?
Cardiac Resuscitation (Administer IV). Rarely used.
How is Epi used as a topical hemostatic?
Topical Hemostatic; effective only against bleeding from arterioles and capillaries. Ineffective on large vessels.
What are some adverse effects associated with epinephrine?
Adverse Effects:
Arrhythmias; may develop in conjunction with halogenated hydrocarbons (i.e. certain gaseous anesthetics) e.g. halothane
B.P.; cerebral hemorrhage
Necrosis; anoxia at site of injection
CNS effects; fear, anxiety, headache
What are the contraindications to epinephrine?
Contraindications:
Hypertension
Shock; further compromises blood flow to vital organs
Hyperthyroidism; increased incidence of arrhythmias
Angina Pectoris; increased work and oxygen demand
Asthmatics with degenerative heart disease
What are the uses for NE as a drug?
Use; manage hypotension during spinal anesthesia
What are the effects of NE as a drug?
Pharmacological Effects: agonist at alpha1 and 2 and beta1 receptors (Very weak Beta2 effects)
Heart: direct; positive inotropic and chronotropic effects indirect; reflex bradycardia (blocked by atropine) ‑ secondary to vasoconstriction.
Net effect: positive inotropic and negative chronotropic effects.
Blood Vessels: only an alpha1 effect (no Beta2 effect because of low potency)
Vasoconstriction: Net Effect on Blood Pressure: always increased
Metabolic Effects: alpha1, weak glycogenolysis and beta3, lipolysis
What are the side effects associated with norepinephrine?
Side effects: similar to Epi:
Arrhythmias; may develop in conjunction with halogenated hydrocarbons (i.e. certain gaseous anesthetics) e.g. halothane
B.P.; cerebral hemorrhage
Necrosis; anoxia at site of injection
CNS effects; fear, anxiety, headache
What are the contraindications associated with epinephrine?
Same as epi:
Contraindications:
Hypertension
Shock; further compromises blood flow to vital organs
Hyperthyroidism; increased incidence of arrhythmias
Angina Pectoris; increased work and oxygen demand
Asthmatics with degenerative heart disease
What is the receptor selectivity of isoproterenol?
Synthetic agent, Receptor selectivity; agonist at Beta1, Beta2 and Beta3 receptors
What are the pharmacological effects of isoproterenol?
Heart; increased HR and force of contraction
Blood Vessels; vasodilation of blood vessels in skeletal muscle
Blood Pressure; increased systolic no change or slight decreased diastolicdecrease in mean atrial B.P.
Smooth Muscle; relaxes bronchial and uterine smooth muscle
CNS: insignificant
Metabolic; Increased FFA`s
Effects on blood glucose less than Epi because this agent releases insulin (b2) and thus opposes the b2 effect (glycogenolysis) in the liver.
What are the clinical uses of isoproterenol?
Bronchial Asthma; aerosol.
Heart Block; Intracardial injection, i.v. bolus and infusion.
Cardiogenic shock after myocardial infarction; increases C.O. and blood flow to all organs (not drug of choice).
What are the side effects associated with isoproterenol?
Common: tachycardia, headache, flushing of skin
Serious: arrhythmias, anginal pain
What effect does dopamine have at adrenergic receptors?
agonist at Beta1 adrenergic and D1 dopaminergic receptors at low and high doses.
In addition higher doses stimulate alpha1 adrenergic receptors which will override the dopaminergic effect.
What are the pharmacological effects of dopamine?
Heart; mild positive inotropic and chronotropic effects compared to Isoproterenol.
Blood Vessels; vasodilation of mesenteric and renal vascular beds (dopamine receptors). Blocked by chlorpromazine and other Dopamine receptor antagonists.
Higher doses stimulate alpha adrenergic receptors and overcome the vasodilatory effects.
What are the clinical uses of dopamine?
Treatment of:
shock
CHF
How is dopamine helpful in treating shock?
Shock; increases C.O. and enhances perfusion of vital organs (Monitor B.P. carefully).
How is dopamine useful in treating CHF?
Chronic Congestive Heart Failure; increases C.O. without increasing total peripheral resistance
Fenoldopam is a synthetic dopamine (D1) agonist – can be used to treat hypertension
Bromocriptine is a synthetic dopamine (D2) agonist sometimes used to treat Parkinson’s disease or prolactinemia.
What is the effect of dobutamine on adrenergic receptors?
Classified as a selective beta1 adrenergic agonist. This agent is only a partial agonist in comparison to norepinephrine and therefore the efficacy is accordingly less.
What are the pharmacological effects of dobutamine?
Pharmacological Effects; Primarily induces mild stimulation of the pump with little vascular effects. Observe a weak positive inotropic effect with lesser positive chronotropic effects
What are the clinical uses of dobutamine?
Acute myocardial infarction; effects on HR and systolic pressure are less than with other catecholamines.
Dobutamine increases cardiac output in patients with cardiogenic shock with lesser incidence of arrhythmias than with dopamine.
When is dobutamine contraindicated?
idiopathic hypertrophic subaortic stenosis
What are the physiological effects of phenylephrine?
Pharmacological Effects can be predictable from knowledge of alpha1 receptor responses.
In vasculature observe constriction. Although this agent does not directly modulate myocardium, a reflex bradycardia occurs due to vasoconstriction. Why can the reflex bradycardia be blocked with atropine?
What are the clinical uses of phenylephrine?
Nasal Decongestant ‑ Vasoconstrictor
Infiltration with Local Anesthetics
Pressor Agent; spinal anesthesia
Paroxysmal atrial tachycardia; induces reflex bradycardia
Glaucoma; decreases production of aqueous humor and/or out flow
Mydriasis; no effect on accommodation
What is clinical use of midodrine?
Midodrine (Pro Amatine) An N-acetamide derivative of methoxamine. Used orally for orthostatic hypotension that is disabling.
What is the pharmacology associated with beta 2 adrenergic receptor agonists?
General Properties:
Selectivity stimulate beta2 adrenergic receptors. However the selectivity is dose‑dependent. There is about a 10 fold greater selectivity for beta2 than beta1 receptors.
Generally these agents have a longer duration of action than catecholamines because they are not as rapidly metabolized as catecholamines. Some agents in this class are also effective orally.
In some patients, rapid tolerance may develop. Although receptor down regulation has been hypothesized to be responsible, the mechanism remains unclear.
What are 5 examples of beta 2 adrenergic receptor agonists?
Albuterol
Salmeterol, Formoterol
Metaproterenol
Terbutaline
Ritrodrine/Yutopar
How does albuterol work? What is it used for?
relatively selective agent for beta2 (10X)
used for bronchial asthma: acute (aerosol), chronic (p.o.)
What are the contraindications with albuterol? Side effects?
desensitization may occur (mechanism unclear)
side effects: muscle tremors, tachycardia, headaches, hypoglycemia, hypokalemia
What is salmeterol used for?
long acting, selective for beta2
used to treat nighttime asthma and prophylaxis of asthma as inhaler
What is the mechanism for amphetamines?
Mechanism; mainly indirect; releases NE from adrenergic nerve endings and will inhibit net NE reuptake by competition. Amphetamines comprise a large group of drugs.
- Adderall, for ADHD; Benzedrine; racemic mixture of d, l‑amphetamine
- Dexedrine (d‑amphetamine)
What are the pharmacological effects for amphetamines?
CNS; stimulation results in increased alertness, confidence, ability to concentrate and a decreased sense of fatigue
Cardiovascular; vasoconstriction, positive inotropic effect, negative chronotropic effect. Effects are usually small and vary with drugs.
Smooth Muscle; mild constriction of sphincter of the bladder
Metabolism; effects last for several hours and are effective p.o.
What are the clinical uses for amphetamines?
Narcolepsy,
ADHD
Obesity: Tolerance develops rapidly to the appetite suppressant or anorexic effects.
What are the side effects associated with amphetamines?
Side Effects;
CNS; insomnia delirium, anxiety
Cardiovascular; arrhythmias anginal pain
GI; nausea, vomiting
Toxicity
Acute; convulsions, coma, death
Chronic; abnormal mental state, weight loss, psychotic reactions
Tolerance; develops to anorexic and mood effects
How do you treat amphetamine poisoning?
Amphetamines are weak bases and therefore acidity‑urine with ammonium chloride to prevent reabsorption.
What are the pharmacological effects of ephedrine/pseudoephedrine?
Metabolism; not hydrolyzed by COMT or MAO, therefore useful orally and long acting.
Pharmacological Effects (longer duration and less efficacy than Epi)
CNS; some stimulatory effects
Cardiovascular; mild positive inotropic effect, heart rate unchanged, weak vasoconstriction
Bronchioles; sustained but moderate relaxation
What are the clinical uses of pseudephedrine?
Pressor agent in spinal anesthesia
Nasal decongestant
Severe acute bronchospasm by parenteral administration
What are the side effects associated with ephedrine?
Side Effects; anxiety, insomnia, palpitations
