Module 4 Flashcards
CNS Drugs
Direct-acting cholinomimetic agents
bind to and activate muscarinic or nicotinic receptors
Indirect-acting cholinomimetic agents
inhibit acetylcholinesterase allowing natural acetylcholine to bind to muscarinic or nicotinic receptors
How does acetylcholine affect the eye?
has a parasympathetic effect which causes miosis (pupil constriction) and accommodation
How does acetylcholine affect the cardiovascular system?
has a parasympathetic effect which results in a decrease in inward calcium current and slowing of the pacemaker rate
How does acetylcholine affect the respiratory system?
has a parasympathetic effect causing contraction of smooth muscle in the bronchial tree and increased secretion by glands in tracheobronchial mucosa
How does acetylcholine affect the GI system?
has a parasympathetic effect causing increased motor and secretory activity of the gut and stimulation of salivary and gastric glands
How does acetylcholine affect the GU system?
has a parasympathetic effect causing contraction of the detrusor muscle in the bladder and relaxation of the trigone and sphincter muscles allowing urination
How do indirect-acting cholinomimetics affect the CNS?
cause diffuse EEG activation and subjective alert response improvement
How do indirect-acting cholinomimetics affect the cardiovascular system?
mimics effects of vagal nerve activation on the heart and causes negative chronotropy, dromotropy, and inotropy (decreased cardiac output)
How do indirect-acting cholinomimetics affect the neuromuscular junction?
increase the strength of skeletal muscle contraction
Acetylcholine MOA
direct-acting cholinergic agonist that binds to both muscarinic and nicotinic receptors causing widespread systemic effects limiting its utility (causes a brief decrease in heart rate and cardiac output as well as lowered BP due to M3 activation which dilates blood vessels, increases salivation and intestinal motility, increases bronchial secretions and contraction, and detrusor muscle activation)
Bethanechol MOA
direct-acting cholinergic agonist with strong muscarinic activity which lacks nicotinic activity
Bethanechol clinical uses
used in genitourinary disease (atonic bladder) to stimulate the detrusor muscle resulting in urination
Pilocarpine MOA
direct-acting cholinergic agonist with primarily muscarinic activity (activity occurs within minutes, lasts 4-8 hours)
Pilocarpine clinical uses
used topically in ophthalmology to produce rapid miosis and contraction of the ciliary muscle, particularly useful in the treatment of glaucoma, and can also be used to promote salivation in patients with xerostomia
Why is Pilocarpine the drug of choice for angle-closure glaucoma?
It acts on muscarinic receptors of the iris causing it to contract which leads to pupil constriction and movement of iris away from the angle. This process opens trabecular meshwork around the canal of Schlemm resulting in an immediate drop in intraocular pressure due to increased drainage of aqueous humor.
Edrophonium MOA
an indirect-acting cholinergic agent which binds reversibly to acetylcholinesterase, preventing hydrolysis of Ach
Edrophonium clinical uses
used primarily in the diagnosis of myasthenia gravis, which transiently increases the concentration of Ach in the NMJ, resulting in a rapid increase in muscle strength
Pyridostigmine MOA
inhibitor of acetylcholinesterase
Pyridostigmine clinical uses
used in the chronic management of myasthenia gravis (duration of action is 3-6 hours - must be taken 4-5 times/day for a therapeutic effect on MG)
Physostigmine MOA
binds reversibly to acetylcholinesterase and stimulates muscarinic and nicotinic receptors of the ANS as well as nicotinic receptors of the NMJ causing miosis, hypotension, and bradycardia
Physostigmine clinical uses
used to treat atropine overdose
Echothiophate MOA
irreversible indirect-acting cholinergic agonist that covalently binds to a phosphate group on acetylcholinesterase, permanently inactivating it (an organophosphate) - can only be reversed with high doses of atropine
Echothiophate clinical uses
only used topically in the treatment of ocular hypertension in chronic glaucoma and causes intense miosis which can cause cataracts at high doses (limiting its use)
Organophosphate MOA
irreversible inhibitors of acetylcholinesterase with both muscarinic and nicotinic receptor activity
Pralidoxime clinical uses
used to reverse organophosphate toxicity which only reactivates acetylcholinesterase in the periphery (cannot reverse CNS effects)
Atropine MOA
an anti-muscarinic agent, highly selective for muscarinic receptors, that acts centrally and peripherally on salivary, bronchial, and sweat glands
How does atropine affect the eye?
causes mydriasis and cycloplegia in the eye and reduces lacrimation
How do anti-muscarinic agents like atropine affect the respiratory system?
causes bronchodilation and reduced airway secretions in the respiratory system
How do anti-muscarinic agents like atropine affect the cardiovascular system?
causes tachycardia, reduces the PR interval, blocks vasodilation of coronary arteries in the heart
How do anti-muscarinic agents like atropine affect the gastrointestinal system?
decreases salivary and gastric acid secretions and prolongs gastric emptying
How do anti-muscarinic agents like atropine affect the genitourinary system?
relaxes ureteral and bladder wall smooth muscle and may cause urinary retention
How do anti-muscarinic agents like atropine affect the CNS?
has a minimal effect
What are the general effects of cholinergic antagonists?
blurry vision and mydriasis, decreased lacrimation, salivation, and sweating, confusion, constipation, and urinary retention
Atropine clinical uses
used topically to induce mydriasis and cycloplegia, IV form can be used to reverse dangerous bradycardia and to block secretions in the upper and lower respiratory tract before surgery, also used to reverse the effects of organophosphate toxicity and mushroom poisoning
Scopolamine MOA
an anti-muscarinic agent that has a greater effect on the CNS in comparison to atropine
Scopolamine clinical uses
administered in a patch to combat motion sickness on cruises and can be sedating
Ipratropium MOA
a short-acting synthetic analog of atropine (muscarinic antagonist) that is a powerful bronchodilator, tiotropium is the long-acting form of ipratropium
Ipratropium clinical uses
administered via inhalation alone or in combination with a long-acting beta-adrenoceptor agonist to treat COPD
Tiotropium MOA
a long-acting synthetic analog of atropine that is a powerful bronchodilator
What receptors do ganglionic blockers affect?
block nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia
Nicotine MOA
a non-selective ganglionic blocker that blocks the entire output of the ANS at the nicotinic receptor causing depolarization of autonomic ganglia resulting in stimulation followed by paralysis of all ganglia (also results in dopamine and norepinephrine release)
Rocuronium/vecuronium MOA
at low doses these non-depolarizing neuromuscular blockers competitively block Ach at nicotinic receptors preventing depolarization of the cell membrane and resulting in inhibition of muscle contraction, Neostigmine and Edrophonium can be used as antidotes
Rocuronium/vecuronium clinical uses
administered IV or IM during surgery to facilitate tracheal intubation and provide complete muscle relaxation allowing for more rapid recovery from anesthesia than other sedating agents (smaller muscles paralyzed first, including facial and ocular, then larger muscles later including fingers, limbs, neck and trunk, muscles of respiration are affected last)
Succinylcholine MOA
a depolarizing neuromuscular blocker that causes cell membrane depolarization resulting in an initial discharge that produces transient fasciculations in the muscle itself followed by flaccid paralysis. After the membrane repolarizes, the receptor is desensitized to the effect of any remaining Ach in the cell membrane which allows for continued paralysis
Succinylcholine clinical uses
administered IV and used when rapid endotracheal intubation is required during the induction of anesthesia and can also be used in ECT treatment (used less often than non-depolarizing agents due to potential complications)
Succinylcholine complications
malignant hypothermia, apnea from prolonged paralysis of the diaphragm, and hyperkalemia by increasing potassium release from intracellular stores
Oxybutynin/Solifenacin/Tolterodine MOA
muscarinic antagonists that competitively bind to muscarinic receptors in the bladder resulting in reduced frequency of bladder contractions, reduced intravesical pressure, and increased bladder capacity, Solifenacin is a more selective M3 muscarinic receptor antagonist (all are metabolized by cytochrome P450 system)
Solifenacin/Tolterodine clinical uses
administered orally and used for the management of overactive bladder and urinary incontinence
Oxybutynin clinical uses
administered orally and used for the management of overactive bladder, urinary incontinence, and neurogenic bladder
What tissues contain alpha-1 adrenoceptors?
vascular smooth muscle, pupillary dilator muscle in the iris, pilomotor smooth muscle (erects hair), the prostate, and the heart
What tissues contain alpha-2 adrenoceptors?
postsynaptic CNS neurons, platelets, adrenergic and cholinergic nerve terminals, vascular smooth muscle, and fat cells
What are the effects of stimulating alpha-1 adrenoceptors?
causes contraction of vascular smooth muscle, dilation of pupils, erected hair, contraction of the prostate, and increased force of contraction of the heart
What are the effects of stimulating alpha-2 adrenoceptors?
causes platelet aggregation, inhibited neurotransmitter release at adrenergic and cholinergic nerve terminals, contraction of vascular smooth muscle, and inhibited lipolysis of fat
What tissues contain beta-1 adrenoceptors?
the heart and juxtaglomerular cells (kidneys)
What tissues contain beta-2 adrenoceptors?
the respiratory system, uterus, vascular smooth muscle, skeletal muscle, and the liver
What tissues contain beta-3 adrenoceptors?
the bladder and fat cells
What are the effects of stimulating beta-1 adrenoceptors?
increases the force and rate of contraction in the heart and increases renin release in the kidneys
What are the effects of stimulating beta-2 adrenoceptors?
promotes vascular and bronchial smooth muscle relaxation, potassium uptake in skeletal muscles, and glycogenolysis in the liver
What are the effects of stimulating beta-3 adrenoceptors?
relaxes the detrusor muscle preventing urination and activates lipolysis in fat cells
Cardiovascular effects of alpha-1 agonist
arterial and venous vasoconstriction counteracted by autonomic baroreflex mechanism (carotid bulbs) resulting in a rise in BP, increase in vagal tone, and a decrease in HR
Phenylephrine
alpha-1 agonist used clinically to treat nasal congestion
Cardiovascular effects of alpha-2 agonist
when administered locally causes vasoconstriction and when administered systemically reduces BP
Cardiovascular effects of beta-1 agonist
increases cardiac output by increasing the contractability of the heart and heart rate through direct activation of the sinus node resulting in increased chronotropy (heart rate), dromotropy (conduction velocity), and inotropy (contractability/rate of relaxation) of the heart.
Isoproterenol MOA
a pure beta agonist that activates beta-1 and beta-2 adrenoceptors but has no effect on alpha adrenoceptors, beta-2 adrenoceptor activation causes vasodilation causing MAP to typically decrease (its non-selectivity makes it clinically unpopular but can be used to treat AV nodal block)
Cardiovascular effects of beta-2 agonist
causes vasodilation in blood vessels resulting in a decrease in peripheral vascular resistance
Bronchial effects of beta-2 agonist
causes bronchial smooth muscle relaxation and bronchodilation (important agent in the treatment of asthma)
Epinephrine MOA
a mixed alpha and beta agonist where beta effects predominate at low doses and alpha effects predominate at higher doses - a potent vasoconstrictor and cardiac stimulant
Epinephrine clinical uses
used for resuscitation during cardiac arrest, bronchospasm, and anaphylaxis, and to produce local vasoconstriction for subcutaneous injection to minimize bloody oozing
Norepinephrine MOA
a mixed agonist of both alpha-1, alpha-2, and beta-1 adrenoceptors and has little effect on beta-2 receptors (little compensatory vasodilation takes place) - results in increased peripheral resistance, increased diastolic and systolic BP, and maintained positive inotropic effects
Norepinephrine clinical uses
used only as a pressor (very effective) for treatment of shock in an ICU setting
Dopamine MOA
a metabolic precursor of norepinephrine that activates alpha and beta adrenoceptors causing vasoconstriction at high doses through alpha-1 receptor activation and increasing inotropic and chronotropic effects at low doses through beta-1 receptor activation, it also binds to dopamine receptors causing vasodilation in mesenteric and renal vasculature
Dopamine clinical uses
used in the treatment of septic and cardiogenic shock in an ICU setting, also used in treating patients with hypotension and severe heart failure who are oliguric (low urine output) by increasing blood flow to the kidneys
Dobutamine MOA
a beta-1 agonist that increases cardiac rate and output with few other vascular effects (no peripheral vascular constriction)
Dobutamine clinical uses
used as a pressor in states of acute heart failure and inotrope after cardiac surgery, also can be used as a stimulant for cardiac stress testing
Phenylephrine MOA
primarily an alpha-1 agonist causing vasoconstriction and increased systolic and diastolic BP, induces reflex bradycardia
Phenylephrine clinical uses
used as a pressor in ICU settings, especially in patients with rapid HR
Amphetamine/methamphetamine/methylphenidate MOA
indirect-acting sympathomimetics that cause the release of catecholamines like dopamine and norepinephrine at nerve terminals and result in a powerful CNS stimulatory effect, also activate alpha and beta-1 adrenoceptors
Amphetamine/methamphetamine/methylphenidate clinical uses
used in management of ADD/ADHD, weight loss, and narcolepsy
Cocaine MOA
indirect-acting sympathomimetic that blocks cellular reuptake of norepinephrine into the adrenergic neuron leading to increased norepinephrine in the synapse and increased sympathetic activity, it also blocks the reuptake of dopamine and serotonin
Ephedrine/Pseudoephedrine MOA
alpha and beta agonists that also indirectly cause the release of stored norepinephrine from nerve endings, ephedrine causes an increase in both systolic and diastolic BP through vasoconstriction and increased cardiac output
Ephedrine clinical use
can treat hypotension and has mild CNS stimulation but is largely replaced by epinephrine or isoproterenol
Pseudoephedrine clinical use
treats nasal congestion via vasoconstriction
Albuterol MOA
short-acting beta-2 agonist that causes bronchodilation
Albuterol clinical uses
used to treat asthma and COPD
Albuterol adverse effects
can cause tremor, restlessness, anxiety, and tachycardia (caution in patients with underlying arrhythmias due to slight beta-1 activation)
Salmeterol/Formoterol MOA
long-acting beta-2 agonists that cause bronchodilation
Salmeterol/Formoterol clinical use
used alone to treat asthma or coupled with inhaled corticosteroids to treat COPD
Which sympathomimetic agent has the greatest effect on total peripheral vascular resistance?
phenylephrine causes a significant increase in total peripheral vascular resistance (PVR)
Which sympathomimetic agent has the greatest effect on skeletal muscle vascular resistance?
isoproterenol causes a significant decrease in skeletal muscle vascular resistance
Which sympathomimetic agent has the greatest effect on cardiac output?
isoproterenol causes a significant increase in both heart contractability and heart rate which results in a larger cardiac output ^^^
How do alpha antagonists affect the cardiovascular system?
cause a lowering of peripheral vascular resistance and blood pressure, often also causing orthostatic hypotension and reflex tachycardia
Phenoxybenzamine MOA
irreversible alpha antagonist which binds covalently to alpha adrenoceptors causing a long-duration blockade, inhibits the reuptake of released norepinephrine by presynaptic adrenergic nerve terminals
Phenoxybenzamine clinical use
used in the treatment of pheochromocytoma, a tumor of the adrenal medulla or sympathetic ganglion cells that secretes catecholamines norepinephrine and epinephrine, which attenuates catecholamine-induced vasoconstriction
Phenoxybenzamine adverse effects
reflex tachycardia and increased cardiac output
Prazosin/Terazosin MOA
highly selective alpha-1 antagonist which relaxes both arterial and venous smooth muscle leading to decreased peripheral vascular resistance and BP, it also relaxes smooth muscle in the prostate
Prazosin/Terazosin clinical uses
used to treat hypertension but not considered first-line drugs due to inferior cardiovascular outcomes compared to other anti-hypertensives
Prazosin/Terazosin adverse effects
can cause exaggerated orthostatic response and syncope with the first dose but it can be minimized by using very low doses initially that are given at bedtime
Tamsulosin MOA
selective alpha-1 antagonist with higher affinity for alpha-1A and alpha-1D subtypes (which are more present on prostate smooth muscle than in the heart) than for alpha-1B subtype
Tamsulosin clinical use
has greater potency in inhibiting contraction in prostate smooth muscle than in vascular smooth muscle compared with other alpha-1-selective antagonists, has less effect on standing blood pressure in patients
Propranolol MOA
a nonselective beta-1 and beta-2 antagonist that diminishes cardiac output and depresses SA and AV nodal activity making it useful in decreasing cardiac workload and minimizing angina, bradycardia limits its use at high doses
Propranolol clinical uses
used mainly in hypertension and angina management and for the treatment of social or situational anxiety and tremor, also is a good prophylactic agent for migraine and is used to decrease sympathetic activity in thyrotoxicosis
Metoprolol/Atenolol/Esmolol/Nebivolol MOA
selective beta-1 antagonists which are most selective at lower doses and primarily lower BP in hypertension and increase exercise tolerance in angina
Metoprolol/Atenolol/Esmolol/Nebivolol clinical uses
safer than propranolol in patients with bronchoconstrictive disorders such as asthma or COPD due to their beta-1 selectivity and have little effect on peripheral vascular resistance and carbohydrate metabolism (safer in insulin-dependent diabetics and those with peripheral vascular disease who require a beta-blocker), metoprolol also is commonly used in the management of CHF
Acebutolol MOA
partial selective beta-1 antagonist with some additional beta-1 agonist activity and with overall weak sympathomimetic activity resulting in a diminished effect on heart rate and a modest decrease in cardiac output
Pindolol MOA
partial nonselective beta antagonist with some additional beta-1 agonist activity and with overall weak sympathomimetic activity resulting in a diminished effect on heart rate and a modest decrease in cardiac output
Acebutolol/Pindolol clinical use
most effective in managing hypertension in patients with moderate bradycardia
Labetalol/Carvedilol MOA
nonselective alpha and beta antagonists that block alpha-1 and beta adrenoceptors causing hypotension with less significant tachycardia
Labetalol/Carvedilol clinical use
Labetalol is often used in hypertensive emergencies to lower BP rapidly; Carvedilol useful in the chronic management of heart failure to lower cholesterol and decrease vascular wall thickening (have beneficial effects on myocardial remodeling and in decreasing the risk of sudden death in HF patients)
Timolol/Nadolol MOA
potent nonselective beta antagonists
Timolol clinical use
used primarily in the chronic management of glaucoma (not acute attacks) and diminishes aqueous humor production by the ciliary body - onset is within 30 minutes and effects last 12-24 hours
Nadolol clinical use
used primarily to reduce angina frequency and intensity
What are the affects of nonselective beta-blocker on the lungs, vessels, kidneys, and heart?
causes bronchoconstriction in the lungs, increased peripheral vascular pressure through constriction of vascular smooth muscle, decreased blood flow in the kidneys, and decreased cardiac output - decreased BP and HR (example: Propranolol)
What are the affects of selective beta-1-blocker on the lungs, vessels, kidneys, and heart?
causes decreased blood flow in the kidneys and decreased cardiac output and BP (example: Metoprolol)
General adverse (undesirable) effects of beta-blockers
can cause decreased glycogenolysis resulting in fasting hypoglycemia, decreased HDL and increased VLDL which may increase CAD risks, sexual impairment, and CNS effects like fatigue, depression, and weakness
