Adrenergic Drugs Flashcards
Direct-acting Selective Adrenergic Agonists
- a1-phenylephrine
- a2-clonidine
- B1-dobutamine
- B2-terbutaline
Responses are not reduced by prior treatment w/ reserpine or guanethidine. Response may be potentiated by cocaine, reserpine and guanethidine.
Direct-acting Non-selective Adrenergic Agonists
- a1 a2-oxymetazoline
- B1 B2-isoproterenol
- a1 a2 B1 B2-epinephrine
- a1 a2 B1-norepinephrine
Responses are not reduced by prior treatment w/ reserpine or guanethidine. Response may be potentiated by cocaine, reserpine and guanethidine.
Mixed-acting Adrenergic Agonists
- ephedrine (a1 a2 B1 B2 and releasing agent)
Response is reduced by prior treatment w/ reserpine or guanethidine.
Indirect-acting Adrenergic Agonist Releasing Agents
- amphetamine
- tyramine
Responses are abolished by prior treatment w/ reserpine or guanethidine
Indirect-acting Adrenergic Agonists Uptake Inhibitor
- cocaine
Indirect-acting Adrenergic Agonist MOA Inhibitors
- selegiline
Indirect-acting Adrenergic Agonist COMT Inhibitors
- entacapone
Alpha1 Receptors Actions
- alpha 1 postsynaptic receptors mediate smooth muscle contraction
Alpha2 Receptors Actions
- presynaptic receptors negative feedback inhibition of neuronal NE release
- extrajunctional receptors (noninnervated) which respond to circulating catecholamines, mediate smooth muscle contraction
- central postsynaptic receptors in braine stem mediate reduction in sympathetic outflow
Order of Adrenergic Agonist Potentcy
Although the naturally occuring catecholamines cannot distinguish b/w a1 and a2 subtypes, many synthetic drugs do
- EPI>NE>DA (dopamine)>ISOP (isoproterenol)
Beta1 Receptors Actions
- B1 postsynaptic receptors mediate cardiac stimulation and renin release
- ISOP>EPI=NE>DA
Beta2 Receptors Actions
- B2 postsynaptic receptors mediate smooth muscle relaxation
- ISOP>EPI>NE
NE Receptors w/ Major Pharmacological Effects
- a1 and 2 (a1 is clinically significant), B1 (variable)
- NE inactivated after PO adm; duration of action is extremely short due to MAO and COMT metabolism
- Clinical indications: used in shock (IV) to inc. BP, slow drip
- Adverse effects: inc. BP/hypertensive crisis/hemorrhage, reflex bradycardia, excessive nasal dryness, blurred vision, IV infiltration > tissue necrosis (may be treated w/ alpha antagonist phentolamine)
EPI Receptors w/ Major Pharmacological Effects
- a1 and 2
- B1 and 2
ISOP Receptors w/ Major Pharmacological Effects
- B1 and 2
- very little alpha (clinically nonsignificant)
Structure activity relationships of sympathomimetic amines
- C-3, C-4 (catecholamines): COMT metabolizes (short drug action)
- C-3, C-5 (B2 selectivity): COMT does not metabolize (long duration of action)
- lack of OH group: increases lipid solubility for CNS penetration and COMT does not metabolize (long duration of action)
- Nitrogen substitution: increases beta selectivity
- Alpha-carbon substitution: MAO does not metabolize (long drug action)
Alpha-1 agonist intracellular actions
- Stimulates Gq and increases IP3 and DAG, further enhances intracellular calcium, causes vasoconstriction (pressor effects)
Phenylephrine
- PO, nasal, IV; pressor decongestant, mydriatic
- Stimulates alpha1 receptors, little or no beta effect; primarily vasoconstrictor
- Not a catecholamine, duration of action: 30-60min
Clinical Indications
- IV to inc BP
- PO or intranasally as decongestant
- Opthalmic drops for mydriasis
Adverse Effects
- Cardiovascular system (CVS)- increase in blood pressure, cardiac failure and arrhythmia
- Infiltration necrosis after parenteral administration
- Rebound nasal congestation
Naphazoline and Oxymetazoline
- Naphazoline: a1 agonist
- Oxymetazoline: non-selective alpha agonist
- PO or intranasally as nasal decongestant
- Relief of redness of eye (naphazoline, oxymetazoline)
Clonidine
- Alpha2 agonist
- Stimulates presynaptic a2 receptors in CNS to decrease sympathetic outflow to the periphery
Clinical Uses
- Hypertenstion
- Withdrawal symptoms from opiates, tobacco smoking, and benzodiazepines
Side Effects
- Lethargy, sedation, constipation and dry mouth
- Abrupt discontinuance causes reboud hypertension
Ephedrine and pseudoephedrine
- Mixed acting agonists; PO, decongestant
- Ephedrine-containing herbal supplements banned du to life-threatening cardiovascular reactions
- Phenylephrine has replaced pseudophedrine in many oral decongestants, since pseudoephedrine has been misused to make meth
Other indirect or mixed action adrenergic agonists
- Phentermine: PO; anoretic
- Phenylpropanolamine: PO, decongestant, anorectic
Beta1 receptor intracellular actions
- Stimulation activates Gs protein to increase intracellular cAMP, which further increases intracellular Ca to increase contractility in heart and renin release in kidney
Beta2 receptor intracellular actions
- Present in smooth muscle; stimulation results in activation of Gs protein to increase intracellular cAMP and phosphorylation of myosin light chain kinase (MLCK) and cause muscle relaxation
Isoproterenol
Drug Effects
- Non-selective, stimulates beta1 and 2, parenteral, inhalation, sublingual
- Causes vasodilation within the skeletal muscles, resulting in a drop in total peripheral resistance and a concurrent drop in diastolic pressure
- Chronotropic actions resulting in a rise in systolic pressure
- Glycogenolysis and hyperlipidemia and myometrial relaxation
Clinical Indications
- Mainly used to treat heart block, bradycardia, ventricular arrhythmia (torsades de pointes); In disorder such as asthma and shock, isoproterenol largely has been replaced by other sympathomimetic drugs
Adverse Effects
- Tachycardia, palpitations, arrhytmias, inc BP, tremors
- CNS stimulation/anxiety in overdoses
Dobutamine
- Selective beta1 agonist at therapeutic doses
- Incs force > heart rate at therapeutic conc.; different isomers have opposing effects on alpha 1 receptors
- Used parenterally in acute CHF
- Development of tolerance w/ prolonged use
- Adverse effects: develop ventricular arrhythmia
Terbutaline
- Selective beta2 agonist
- PO, SC, inhalation or parenteral (IV), lasts 3-6hrs
- Relaxes smooth muscle, bronchodilation, relax uterus in premature labor, vasodilation skeletal muscle blood vessels
Clinical Indications
- Use for asthma, acute bronchospasm; inhibit the uterine contractions assoc. w/ premature labor
Adverse Effects
- Tremor, tachycardia (at higher doses can cause some beta-1 stimulation on heart)
Albuterol
- Selective beta2 agonist
- PO, inhalation, short-acting
Epinephrine (ADRENALINE)
- Parenteral; inhalation, IM, SC
- alpha and beta receptor stimulator
- alpha1 stimulation: causes a rise in systolic blood pressure due to regional vasoconstriction
- alpha2 stimulation: causes decreased release of insulin
- beta1 stimulation: causes a rise in systolic pressure due to an increased cardiac output (heart rate and contractility increase)
- beta2 stimulation: causes a drop in diastolic pressure due to skeletal muscle vasodilation, bronchorelaxation, hyperglycemic effect (increased glycogenolysis in liver), and increased release of glucagon
- Lipolysis: hydrolyzes triglycerides to free fatty acids and glycerol
Clinical Indications
- Blood pressure, heart (cardiac stimulant), smooth muscle (asthma), mast cells (antiallergic effect, especially for anaphylaxis), topical hemostatic agent (eg. bleeding peptic ulcers), calorigenic effect (metabolic); hyperglycemis, inc. free fatty acids, insulin- alpha vs. beta effect
Adverse Effects
- CVS- ventricular arrhytmias
- CNS- headache, restlessness
Dopamine (INTROPIN)
- IV infusion
Peripheral dopamine receptors (dopaminergic)
- Renal- vasodilation
- Mesenteric- vasodilation
Dose-response relationship of dopamine and receptors
- Low-dose- dopaminergic (vasodilation)
- Medium dose- beta1 (force>rate)
- High dose- alpha (vasoconstriction)
Uses
- Circulatory shock
- Acute heart failure
Adverse effects
- Tachycardia, anginal pain, arrhythmias, headache
Fenoldopam
- An intravenous dopamine D1 agonist used for the acute treatment of severe hypertension
Tyramine
- Indirect sympathomimetic
- Releases norepinephrine from storage granules, thus producing both alpha and beta stimulation
- Leads to tachyphylaxis, because of depletion of norepinephrine stores after repeated use
- Hypertensive crisis (cheese effect) in patients who are taking MAO inhibitors when tyramine is ingested (fermented foods, wine)
- Often used experimentally to understand mechanisms
Amphetamine
- Indirect sympathomimetic
- Releases norepinephrine, epinephrine and dopamine (brain)
Uses
- CNS stimulant: stimulates mood and alertness
- Appetite suppression
- ADHD disorder in children: methylphenidate is preferable
Adverse Effects (due to sympathomimetic effects)
- Nervousness, insomnia, anorexia
- Growth inhibition (children)
Adrenergic non-selective alpha receptor antagonists
- Phenoxybenzamine
- Phentolamine
Adrenergic alpha1-selective antagonists
- Prazosin
Adrenergic non-selective beta receptor antagonists
- Nadolol
- Pindolol
- Propanolol
- Timolol
Adrenergic beta1-selective antagonists
- Acebutolol
- Esmolol
- Metoprolol
Adrenergic non-selective beta receptor antagonist
- Carvedilol
- Labetalol
Drugs which block both alpha-1 and 2 receptors
- Phenoxybenzamine
- Phentolamine
Main pharmacologic effects
- blood vessels
- heart
Drugs which block only alpha-1 receptors
- Prazosin
Alpha blockers therapeutic uses
- Diagnosis and treatment of pheochromocytoma
- Shock
- Peripheral vascular disease (Raynaud’s)
- Hypertension
- Vasodilator therapy in CHF
- Urinary obstruction
Alpha blockers adverse effects
- Nasal stuffiness
- Miosis
- Postural hypotension
- Reflex tachycardia
- Inhibition of ejaculation
- Diarrhea
- Epinephrine reversal
Beta blockers chart
Factors related to the use of beta blockers
- Selectivity- beta blockers can precipitate severe bronchospasm in patients w/ obstructive pulmonary disease and can mask symptoms of hypoglycemia in insulin-dependent diabetics
- In low doses effects are mostly limited to the heart. In doses used to treat hypertension, can cause bronchospasm, but are still less likely to mask the symptoms of hypoglycemia
- Lipid solubility
- Membrane- stabilizing activity
- Intrinsic sympathomimetic activity (partial agonists) beta-blockers w/ partial agonist (intrinsic sympathomimetic) activity not only block the access of catecholamines to beta-receptors but also partially activate the receptors. They cause less slowing of the heart rate at rest than other beta-blockers and may be less likely to cause serum lipid abnormalities
Beta blockers pharmacologic effects
- Heart
- Blood pressure
- CNS
- Metabolic
- Uterus
- Renin
Beta blockers Therapeutic uses
- Hypertension
- Cardiac arrhythmias
- Angina pectoris
- Glaucoma
- Migraine
- Pheochromocytoma
- Decrease mortality after MI
Beta blockers adverse effects/potential problems
- GI hyperactivity
- Cardiovascular: CHF, angina, arrhythmia, hypotension; should avoid abrupt drug withdrawal
- Respiratory distress/asthma
- CNS: insomnia, nightmares, depression
- Aggravation of peripheral vascular disease
- Hypoglycemia, especially following insulin administration
Labetalol and carvedilol
- Selective alpha-1 blocker and nonselective beta blocker
Uses
- Labetalol: IV for hypertension and hypertensive emergencies, pheocromocytoma
- Carvedilol: used for heart failure
Adverse Effects
- Combination of alpha/beta blockade, hepatic injury
Reserpine
- Adrenergic neuronal blocker
- MOA: blocks vesicular amine transporters
Pharmacologic effects
- Cardciovascular
- CNS
Therapeutic uses
- Systemic hypertension
Adverse effects
- Orthrostatic hypotension, sedation, depression
Guanethidine and Gunadrel
- MOA: displaces NE from storage vesicles; acts as false transmitter
Therapeutic Uses
- Systemic hypertension
Adverse Effects
- Orthrostatic hypotension, sedation
