Pharm ANS

A 60-year-old immigrant from Latin America was told she had hypertension and should be taking antihypertensive medication. She decides to take an herbal medication from an online "holistic pharmacy." One week after starting the medication, she is found unconscious in her apartment. In the emergency department, her blood pressure is 50/0 mm Hg and heart rate is 40 bpm. Respirations are 20/min; pupils are slightly constricted. Bowel sounds are present. Which of the following would be the most effective cardiovascular stimulant? (A) Amphetamine (B) Clonidine (C) Isoproterenol (D) Norepinephrine (E) Tyramine

"Herbal" medications often contain potent synthetic drugs in addition to (or instead of) the advertised constituents. This patient shows signs of sympathetic autonomic failure: hypotension, inappropriate bradycardia, constricted pupils. These signs are compatible with a large overdose of a drug that causes marked depletion of stored catecholamine transmitter such as reserpine, an obsolete but inexpensive antihypertensive agent. The indirect-acting agents (amphetamines and tyramine) act through catecholamines in (or released from) the nerve terminal and would therefore be ineffective in this patient. Clonidine acts primarily on presynaptic nerve endings although it can activate α2 receptors located elsewhere. Isoproterenol would stimulate the heart but has no α-agonist action and might exacerbate the hypotension. Norepinephrine has the necessary combination of direct action and a spectrum that includes α1, α2, and β1 effects. The answer is D.

What enzyme makes ACh?

Achetylcholine transferase

Atropine

Atropine Alice antagonist at muscarinic receptors

Ephedrine

Causes release of stored catecholamines. Ephedrine is used to treat the following conditions: Nasal congestion Urinary incontinence Hypotension

Full activation of the parasympathetic nervous system is likely to produce which of the following effects? (A) Bronchodilation (B) Decreased intestinal motility (C) Increased thermoregulatory sweating (D) Increased pupillary constrictor tone (miosis) (E) Increased heart rate (tachycardia)

D

Alpha-Methyldopa

DOC during pregnancy for HTN. Prodrug that is converted to analog of norepinephrine; acts on alpha 2 autoreceptors in brainstem to decrease NE release = less sympathetic tone hepatic metabolism; liver disease is a precaution. Liver fxn tests only a concern if 3x normal or greater! In <1% of cases it causes hemolytic anemia

Where do you find M3 receptors?

Effector Cells: - smooth muscle contraction: circular muscle of the eye (miosis), ciliary muscle (zonula fibers relax = lens accommodation), bronchoconstriction, GI tract peristalsis, UG system contraction of detrusor muscle, relaxation of trigone and sphincters (=urination), uterine contraction - glands: cause secretion (lacrimation, acid secretion from parietal cells, bronchus mucous secretion, gallbladder contraction) - vascular endothelium: cause dilation of blood vessels via Nitric Oxide Gq

Which one of the following drugs has a very high affinity for the phosphorus atom in parathion and is often used to treat life-threatening insecticide toxicity? (A) Atropine (B) Benztropine (C) Bethanechol (D) Botulinum (E) Cyclopentolate (F) Neostigmine (G) Pralidoxime

G

Where do you find Nm receptors?

NMJ - cause skeletal muscle contraction (NMJ blockers bind here to produce skeletal muscle paralysis) ion channel

Nicotine

Nn and Nm agonist Remember adrenal medulla has nicotinic receptors, so you can activate norepi and epi, and see effects on CV system, GI, etc. ... = side effect can be increased BP

What alpha antagonists do we know?

Phentolamine: reversible alpha 1 and 2 antagonist -- vasodilation (phantom comes and goes... reversible) Phenoxybenzamine: irreversible alpha 1 antagonist (phoenix tattoo; tattoos are irreversible) Prazosin - alpha 1 Tamsulosin - alpha 1, specifically approved for BPH

A crop duster pilot has been accidentally exposed to a high concentration of a highly toxic agricultural organophosphate insecticide. If untreated, the cause of death from such exposure would probably be (A) Cardiac arrhythmia (B) Gastrointestinal bleeding (C) Heart failure (D) Hypotension (E) Respiratory failure

Respiratory failure, from neuromuscular paralysis or CNS depression, is the most important cause of acute deaths in cholinesterase inhibitor toxicity. The answer is E.

Where do you find beta 3 receptors?

adipose cells Gs increases lipolysis

What effect does cholinergic stimulation have on smooth muscle of vasculature? Via what receptor?

causes vasodilation via NO activity (plays role in erection) M3

What effect does cholinergic stimulation have on the urogenital system? Via what receptor?

contraction of the detrusor muscle and relaxation of the urinary sphincters = urination contracts uterus M3

What effect does cholinergic stimulation have on the GI tract? Via what receptor?

increases peristalsis, increases acid secretion from parietal cells, increases gallbladder contraction M3

Pindolol

partial agonist (in the beta blocker section) "agonizing pin" in sketchy, kid pokes heart balloon with pin and it makes annoying noise in the audience has intrinsic sympathomimetic activity. useful when you don't want complete beta blockade (avoids bronchospasm) used for tx of HTN, useful in heart failure, heart block, or bronchospasm when you want maintenance of adequate sympathetic tone "attenuates sympathetic tone but doesn't eliminate it entirely" also partial agonist at serotonin receptors, may augment SSRI effects precautions: diabetes, abrupt discontinuation (causes ischemia, MI)

Phentolamine

phantom in phantom of the alpha non-selective, reversible competitive alpha blocker (short-acting) inhibits vasoconstriction; used to prevent hypertensive episodes that may occur in a pt w/pheochromocytoma during surgery used to prevent dermal necrosis following extravasation of alpha agonists Adverse rxns: dizziness, orthostatic hypotension, reflex tachycardia, NVD, nasal congestion Precautions: MI, angina, etc.

Phenoxybenzamine

phoenix tattoo in phantom of the alpha irreversible alpha 1 blocker (it's a nitrogen mustard like alkylating agents in cancer drugs) Used for pheochromocytoma surgery -- given days in advance to normalize BP since it's long-acting can also treat BPH bc alpha 1 receptors are found in smooth muscle and normally cause contraction... antagonism causes relaxation clinical effects are vasodilation, decreased pupillary dilation is lipophilic and can accumulate in fatty tissues

What does amphetamine do?

promotes catecholamine release from presynaptic terminal vesicles via "reverse transport" (acts as reuptake transporter substrate, gets taken up into NET or DAT, then flushes 5HT, DA, and NE out into the synapse) also inhibits NE, dopamine, and serotonin uptake transporters used for ADHD or narcolepsy, off label for obesity metabolized by CYPs and MAO then excreted renally (renal excretion sensitive to changing urine pH) Adverse rxns: insomnia, restlessness, anorexia; CV: tachycardia, angina Precautions: anorexia, CV issues, MAO inhibitors, hyperthyroid, and glaucoma bc it can increase IOP

Albuterol

short acting beta 2 agonist

Where do you find alpha 1 receptors?

smooth muscle: contraction -- radial muscle of eye (mydriasis), trigone of bladder and urinary sphincters (urinary retention), decreased GI motility, arteriole and venous smooth muscle (vasoconstriction), contracts uterus glands: contraction of seminal vesicles and vas deferens = ejaculation liver: increases glycogenolysis and GNG Gq

Where do sympathetics originate?

thoracic and lumbar parts of the spinal cord = thoracolumbar autonomic system specifically: T1-T12 and L1-L5

What amino acid precursor are dopamine, NE, and epinephrine made from?

tyrosine

Dobutamine

"just do bugling" beta 1 agonist with slight beta 2 effects increases heart contractility and stroke volume w/modest chronotropic effects the R isomer is a potent beta 1 agonist and alpha 1 antagonist; the S isomer is a weaker mixed beta agonist and alpha 1 agonist metabolized in liver by COMT and glucuronidation to inactive metabolites Adverse rxns: PVCs, tachycardia, angina Precautions: idiopathic hypertrophic subaortic stenosis (hypertrophy of left ventricle to the point that when the heart contracts the muscle tissue occludes the exit of blood thru the aorta), arrhythmias, hypovolemia Has short half-life, so not very useful for chronic use. Main use is in the hospital if pt has acute cardiac failure and organs are getting poor perfusion.

Norepinephrine

"north-facing" scout alpha 1 and alpha 2 agonist, has a little bit of beta 1 effect (alpha 1 causes reflex bradycardia, this wins out over the slight beta 1 increased HR effect bc norepinephrine has a greater effect at alpha receptors) increases MAP with reflex bradycardia

Where do you find Nn receptors?

ANS ganglia (cause AP) adrenal medulla (cause secretion of catecholamines) ion channel

A 65-year-old woman with impaired renal function and a necrotic ulcer in the sole of her right foot is admitted to the ward from the emergency department. She has long-standing type 2 diabetes mellitus and you wish to examine her retinas for possible vascular changes. Which of the following drugs is a good choice when pupillary dilation—but not cycloplegia— is desired? (A) Isoproterenol (B) Norepinephrine (C) Phenylephrine (D) Pilocarpine (E) Tropicamide

Antimuscarinics (tropicamide) are mydriatic and cycloplegic; α-sympathomimetic agonists are only mydriatic in the eye. Isoproterenol has negligible effects on the eye. Norepinephrine penetrates the conjunctiva poorly and would produce intense vasoconstriction. Pilocarpine causes miosis. Phenylephrine is well-absorbed from the conjunctival sac and produces useful mydriasis for 10-30 minutes. The answer is C.

Which of the following is an accepted therapeutic indication for the use of antimuscarinic drugs? (A) Atrial fibrillation (B) Botulinum poisoning (C) Chronic obstructive pulmonary disease (COPD) (D) Glaucoma (E) Postoperative urinary retention

Atrial fibrillation and other arrhythmias are not responsive to antimuscarinic agents. Botulinum poisoning is associated with parasympathetic blockade. Parkinson's disease, not Huntington's, is partially responsive to antimuscarinic drugs. Antimuscarinic drugs tend to cause urinary retention and may precipitate or exacerbate glaucoma. Bronchospasm is mediated in part by vagal outflow in many patients with COPD and in some with asthma. The answer is C.

Mr Green is a 60-year-old man with poorly controlled hypertension of 170/110 mm Hg. He is to receive minoxidil. Minoxidil is a powerful arteriolar vasodilator that does not act on autonomic receptors. Which of the following effects will be observed if no other drugs are used? (A) Tachycardia and increased cardiac contractility (B) Tachycardia and decreased cardiac output (C) Decreased mean arterial pressure and decreased cardiac contractility (D) Decreased mean arterial pressure and increased salt and water excretion by the kidney (E) No change in mean

Because of the compensatory responses, a drug that directly decreases blood pressure through a decrease in peripheral vascular resistance will cause a reflex increase in sympathetic outflow, an increase in renin release, and a decrease in parasympathetic outflow. As a result, heart rate and cardiac force will increase. In addition, salt and water retention will occur. The answer is A.

Bethanechol

Beth the construction worker muscarinic agonist, no nicotinic activity. Used for post-operative ileus to increase urination and GI motility precautions: bradycardia, asthma, hyperthyroidism, peptic ulcer, urinary tract obstruction

Which one of the following drugs causes vasodilation that can be blocked by atropine? (A) Benztropine (B) Bethanechol (C) Botulinum toxin (D) Cyclopentolate (E) Edrophonium (F) Neostigmine (G) Pralidoxime

Bethanechol (Chapter 7) causes vasodilation by directly activating muscarinic receptors on the endothelium of blood vessels. This effect can be blocked by atropine. Indirectly acting agents (AChE inhibitors) do not typically cause vasodilation because the endothelial receptors are not innervated and acetylcholine is not released at this site. Pralidoxime is a distracter in this answer list. The answer is B.

A 3-year-old child has been admitted to the emergency department having swallowed the contents of 2 bottles of a nasal decongestant. The active ingredient of the medication is a potent, selective α-adrenoceptor agonist drug. Which of the following is a sign of α-receptor activation that may occur in this patient? (A) Bronchodilation (B) Cardiac acceleration (tachycardia) (C) Pupillary dilation (mydriasis) (D) Renin release from the kidneys (E) Vasodilation of the blood vessels of the skin

C

Parasympathetic nerve stimulation and a slow infusion of bethanechol will each (A) Cause ganglion cell depolarization (B) Cause skeletal muscle end plate depolarization (C) Cause vasodilation (D) Increase bladder tone (E) Increase heart rate

Choice (E) is not correct because the vagus slows the heart. Parasympathetic nerve stimulation does not cause vasodilation (most vessels do not receive parasympathetic innervation), so choice (C) is incorrect. Ganglion cells and the end plate contain nicotinic receptors, which are not affected by bethanechol, a direct-acting muscarinic agonist. The answer is D.

Which of the following is the primary second-messenger process in the contraction of the ciliary muscle when focusing on near objects? (A) cAMP (cyclic adenosine monophosphate) (B) DAG (diacylglycerol) (C) Depolarizing influx of sodium ions via a channel (D) IP3 (inositol 1,4,5-trisphosphate) (E) NO (nitric oxide)

Cholinomimetics cause smooth muscle contraction mainly through the release of intracellular calcium. This release is triggered by an increase in IP3 acting on receptors in the endoplasmic reticulum. The answer is D.

What receptors are active at the radial, circular, and ciliary muscles of the eye and what are their effects?

Circular: M3 (muscle contraction = miosis) and Beta2 (muscle relaxation = mydriasis.. small effect) Radial: alpha 1 (contraction, remember it's Gq... mydriasis effect stronger than Beta 2) Ciliary: M3 (contraction --> opens trabecular meshwork and allows lens to become more round for accommodation) and Beta2 (muscle relaxation, ligament stretches, lens flattens)

For which drug is idiopathic hypertrophic subaortic stenosis a precaution?

Dobutamine IHSS: hypertrophy of the left ventricle to the point that when the heart contracts the muscle tissue occludes the exit of blood through the aorta. Use caution bc then there's no route for exit of blood through the heart If you administer a beta agonist and this happens then where does the blood go when you increase CO? ouch

Two new synthetic drugs (X and Y) are to be studied for their cardiovascular effects. The drugs are given to three anesthetized animals while the blood pressure is recorded. The first animal has received no pretreatment (control), the second has received an effective dose of a long-acting ganglion blocker, and the third has received an effective dose of a long-acting muscarinic antagonist. Drug X caused a 50 mm Hg rise in mean blood pressure in the control animal, no blood pressure change in the ganglionblocked animal, and a 75 mm mean blood pressure rise in the atropine-pretreated animal. Drug X is probably a drug similar to (A) Acetylcholine (B) Atropine (C) Epinephrine (D) Hexamethonium (E) Nicotine Drug Y causes an increase in HR with no blocker, a decrease in HR with a ganglion blocker, and no change with the muscarinic blocker. Drug Y is probably a drug similar to (A) Acetylcholine (B) Edrophonium (C) Hexamethonium (D) Nicotine (E) Pralidoxime

Drug X causes an increase in blood pressure that is blocked by a ganglion blocker but not by a muscarinic blocker. The pressor response is actually increased by pretreatment with atropine, a muscarinic blocker, suggesting that compensatory vagal discharge might have blunted the full response. This description fits a ganglion stimulant like nicotine but not epinephrine, since epinephrine's pressor effects are produced at α receptors, not in the ganglia. The answer is E. Drug Y causes an increase in heart rate that is blocked by a muscarinic blocker but reversed by a ganglion blocker. The fact that a ganglion blocker reverses the unknown drug's effect suggests that the control response (tachycardia) involves the baroreceptor reflex. The description fits a direct-acting muscarinic stimulant such as acetylcholine (given in a dosage that causes a significant drop in blood pressure). An indirect-acting cholinomimetic (cholinesterase inhibitor, B) would not produce this pattern because the vascular muscarinic receptors involved in the depressor response are not innervated and are unresponsive to indirectly acting agents. The answer is A.

Mr Green, a 54-year-old banker, had a cardiac transplant 6 months ago. His current blood pressure is 120/70 mm Hg and heart rate is 100 bpm. Which of the following drugs would have the least effect on Mr Green's heart rate? (A) Albuterol (B) Epinephrine (C) Isoproterenol (D) Norepinephrine (E) Phenylephrine

Heart transplantation involves cutting of the autonomic nerves to the heart. As a result, autonomic nerve endings degenerate, and cardiac transmitter stores are absent for 2 years or longer after surgery. Therefore, indirect-acting sympathomimetics are ineffective in changing heart rate. All the drugs listed are direct-acting, and all but phenylephrine have significant effects on β receptors. Phenylephrine usually causes reflex bradycardia, which requires intact vagal innervation. The answer is E. (Note that denervation may result in upregulation of both β1 and β2 receptors so that direct-acting β agonists may have a greater than normal effect.)

What does alpha-methyltyrosine do? What's the one precaution to know?

It inhibits tyrosine hydroxylase (it's a tyrosine analog) = can't convert tyrosine to DOPA, can't make norepi and epi --> effective in treating pheochromocytoma side effect is transient sedation, anxiety, depression, drooling, hallucinations; diarrhea, crystalluria bc it's excreted in urine Precaution = ALCOHOL, want fluid intake to produce urine output of 2 L so you don't get crystals

Which of the following is an expected effect of a therapeutic dose of an antimuscarinic drug? (A) Decreased cAMP (cyclic adenosine monophosphate) in cardiac muscle (B) Decreased DAG (diacylglycerol) in salivary gland tissue (C) Increased IP3 (inositol trisphosphate) in intestinal smooth muscle (D) Increased potassium efflux from smooth muscle (E) Increased sodium influx into the skeletal muscle end plate

Muscarinic M1 and M3 receptors mediate increases in IP3 and DAG in target tissues (intestine, salivary glands). M2 receptors (heart) mediate a decrease in cAMP and an increase in potassium permeability. Antimuscarinic agents block these effects. The answer is B.

A 30-year-old man has been treated with several autonomic drugs for 4 weeks. He is now admitted to the emergency department showing signs of drug toxicity. Which of the following signs would distinguish between an overdose of a ganglion blocker versus a muscarinic blocker? (A) Cycloplegia (B) Dry skin in a warm environment (C) Miosis (D) Postural hypotension (E) Tachycardia

Neither ganglion blockers nor muscarinic blockers cause miosis; they cause mydriasis. Both classes of cholinoceptor blockers increase resting heart rate and cause cycloplegia, because these are determined largely by parasympathetic tone. Similarly, both can cause dry skin, since this requires cholinergic transmission. Postural hypotension, on the other hand, is a sign of sympathetic blockade, which would occur with ganglion blockers but not muscarinic blockers (Chapter 6). The answer is D.

A 3-year-old child is admitted to the emergency department after taking a drug from her parents' medicine cabinet. The signs suggest that the drug is an indirect-acting cholinomimetic with little or no CNS effect and a duration of action of about 2-4 h. Which of the following is the most likely cause of these effects? (A) Acetylcholine (B) Bethanechol (C) Neostigmine (D) Physostigmine (E) Pilocarpine

Neostigmine is the prototypical indirect-acting cholinomimetic; it is a quaternary (charged) substance with poor lipid solubility; its duration of action is about 2-4 h. Physostigmine is similar but has good lipid solubility and significant CNS effects. The answer is C.

What alpha agonists do we know?

Phenylephrine = alpha 1 Norepinephrine = alpha 1 and alpha 2 Clonidine = alpha 2 agonist -- inhibition of sympathetic tone and reduced BP Alpha-methyldopa = alpha 2 agonist -- DOC for HTN in pregnant women

A 27-year old compulsive drug user injected a drug he thought was methamphetamine, but he has not developed any signs of methamphetamine action. He has been admitted to the emergency department and antimuscarinic drug overdose is suspected. Probable signs of atropine overdose include which one of the following? (A) Gastrointestinal smooth muscle cramping (B) Increased heart rate (C) Increased gastric secretion (D) Pupillary constriction (E) Urinary frequency

Tachycardia is a characteristic atropine overdose effect. Bradycardia is sometimes observed after small doses. None of the other choices are typical of atropine or methamphetamine overdose. The answer is B.

A group of volunteers are involved in a phase 1 clinical trial of a new autonomic drug. When administered by intravenous bolus, the blood pressure increases. When given orally for 1 week, the blood pressure decreases. Which of the following standard agents does the new drug most resemble? (A) Atropine (B) Clonidine (C) Phentolamine (an α blocker) (D) Phenylephrine (E) Propranolol (a β blocker)

The dual blood pressure effects of the drug suggest that initially it is causing a direct α-agonist vasoconstrictor effect, but when given for a week, it is accumulating in a blood pressure-controlling center, eg, the CNS, and reducing sympathetic outflow. The answer is B.

A mystery drug increases systolic BP, diastolic BP, cardiac output, and HR. Which of the following drugs does the new experimental agent most resemble? (A) Atropine (B) Epinephrine (C) Isoproterenol (D) Phenylephrine (E) Physostigmine

The investigational agent caused a marked increase in systolic and diastolic pressures and a moderate increase in pulse pressure (from 40 to 60 mm Hg). These changes suggest a strong alpha effect on vessels and an increase in stroke volume, a β-agonist action in the heart. The heart rate increased significantly, reflecting a β response. Note that the stroke volume also increased (cardiac output divided by heart rate—from 70.2 to 81.7 mL). The drug behaves most like a mixed α and β agonist. The answer is B.

Your 30-year-old patient has moderately severe new onset asthma, and you prescribe a highly selective β2 agonist inhaler to be used when needed. In considering the possible drug effects in this patient, you would note that β2 stimulants frequently cause: (A) Direct stimulation of renin release (B) Hypoglycemia (C) Itching due to increased cGMP (cyclic guanine monophosphate) in mast cells (D) Skeletal muscle tremor (E) Vasodilation in the skin

Tremor is a common β2 effect. Blood vessels in the skin have almost exclusively α (vasoconstrictor) receptors. Stimulation of renin release is a β1 effect. Beta2 agonists cause hyperglycemia and have little effect on cGMP. The answer is D.

Epinephrine

agonist at alpha and beta receptors used for anaphylactic shock - increases systolic and diastolic pressure, heart rate and contractility, and causes bronchodilation at low doses has more beta effects, high doses has more alpha effects

What effect does adrenergic stimulation have on smooth muscle of vasculature? Via what receptor?

alpha 1 and alpha 2 = constriction of smooth muscle Beta 2 = relaxation in liver and skeletal muscle = decreased TPR and increased blood flow to these tissues. Beta 2 activation decreases diastolic pressure.

Tamsulosin

alpha 1 antagonist specifically approved for BPH bc it's selective for the specific alpha 1 receptor that makes up 70% of the alpha 1 receptors in the prostate also used to pass kidney stones (from renal) long-acting, food decreases bioavailability so take on empty stomach! metabolized by CYP3A4 and CYP2D6 Causes CNS dizziness, syncope, orthostatic hypotension, abnormal ejaculation Caution with PDE5 inhibitors bc they're also vasodilators = effects are additive

Prazosin

alpha 1 antagonist, long acting, reversible used to treat HTN, used off label to treat BPH: relaxes prostate and bladder neck = urination will see first dose syncope, so take at night. Complete antihypertensive effects may not occur for 4-6 weeks metabolized in the liver causes impotence bc smooth muscle contraction is important for ejaculation and alpha 1 antagonism blocks it Precautions: angina bc inducing hypotension may make it worse; syncope is bad if you need to be alert for your job. Caution with PDE5 inhibitors bc they're also vasodilators = effects are additive

What effect does adrenergic stimulation have on the GI system? Via what receptor(s)?

alpha 1 causes contraction of GI sphincters = inhibits GI activity Beta 2 causes decreased acid secretion, relaxed gallbladder, relaxation of smooth muscle and decreased motility

What effect does adrenergic stimulation have on metabolism?

alpha 2 - DECREASED insulin release from pancreatic beta cells Beta 2 - promotes GNG and glycogenolysis; K+ is taken up into skeletal muscle. INCREASED insulin release from beta cells (so muscles can have access to more glucose). Beta 3 - stimulates lipolysis in adipocytes

Activation of what receptors causes platelet aggregation?

alpha 2s

Carvedilol

alpha and beta antagonist -- the carved wooden candle holder on stage at the brahms lullaby beta blocker sketch; holds an extinguished alpha 1 candle used for chronic heart failure to manage HTN bc decreases vasoconstriction, lowers BP, and increases ejection fraction beta 1 blockade prevents reflex tachycardia normally associated with alpha 1 blockers and prevents tachycardia associated with sympathetic compensatory mechanisms in heart failure CYP2D6 metabolism Never abruptly discontinue the drug Contraindications: asthma bc you block beta 2s, and IV inotropes bc you can cause dysrhytmias Increases survival in heart failure pts

What effect does adrenergic stimulation have on the UG system? Via what receptor(s)?

alpha one causes constriction of the sphincters and trigone = urinary retention; causes contraction of seminal vesicles and vas deferens = ejaculation Beta 1 causes renin release from the kidney Beta 2 relaxes the detrusor = urinary retention

Yohimbine

antagonist at central alpha 2s = causes more release of NE --> increased sympathetic outflow = increased penile blood flow to help with erection not used in women, but if it were it would be category D for pregnancy precautions: angina, HTN, etc

Where do you find D2 dopamine receptors?

axon terminals as autoreceptors = less dopamine release cholinergic neurons in the gut = decreased GI motility

Metoprolol

beta 1 selective antagonist "A BEAM" in Sketchy shining on the beta 1 bugler -- A-tenolol, B-, E-, A-, and M-etoprolol are the beta 1 antagonists Reduces CO and HR, but increases ejection fraction, causes decrease in both systolic and diastolic BP has extensive first pass metabolism - CYP2D6 Don't abruptly discontinue bc can cause myocardial ischemia Precautions: bradycardia, hepatic disease, raynaud's, diabetes bc decreases sympathetic response to low blood sugar

Atenolol

beta 1 selective antagonist "A BEAM" in Sketchy shining on the beta 1 bugler -- A-tenolol, B-, E-, A-, and M-etoprolol are the beta 1 antagonists used for HTN, angina, arrhythmia

What effect does cholinergic stimulation have on the bronchioles? Via what receptor?

bronchoconstriction, increases mucous secretion M3

What effect does adrenergic stimulation have on the the eye? Via what receptor(s)?

causes contraction of radial muscle = mydriasis (alpha 1) circular muscle relaxation = mydriasis (B2.. only a slight effect) relaxation of ciliary smooth muscle which stretches zonula fibers = lens becomes more flat, opposite of lens accommodation (B2) Beta 2s increase aqueous humor production (which is why the beta blocker Timolol is used for open angle glaucoma bc it decreases aqueous humor production)

What effect does cholinergic stimulation have on the eye? Via what receptor?

circular muscle contraction = miosis ciliary muscle contraction; the zonula fibers relax, so the lens forms a more spherical shape = lens accommodation lacrimation M3

Clonidine

claw guy in phantom of the alpha alpha 2 agonist in the brainstem = results in decreased sympathetic outflow; treats HTN (also accounts for adverse effect of sedation) used as epidural agent for opioid-refractory cancer pain bc it's not blocked by opioid antagonists, can be used for ADHD, tourette's causes orthostatic hypotension, bradycardia, GI dryness, NV, constipation don't abruptly withdraw bc you get too fast of a rebound in catecholamines = severe HTN Precaution: breastfeeding, CV disease bc hypotensive effects may cause ischemia

Where do parasympathetics originate?

cranial nerves and sacral spinal cord = craniosacral autonomic system specifically: CN nuclei III, VII, IX, and X; sacral segments S2-S4

Phenelzine

example of a MAO inhibitor, used as second line tx for depression

Phenylephrine

flannel friends alpha 1 agonist causes increased MAP (arterial and venous vasoconstriction), reflex bradycardia, mydriasis used to treat nasal congestion bc of vasoconstriction in the nose; can treat shock bc of increase in TPR degraded by MAO parenteral drug administration can cause angina, HTN, anxiety, insomnia (that's why CV diseases like CAD, MI, angina etc are precautions) Precaution: narrow angle glaucoma bc it causes mydriasis, hyperthyroidism

Where do you find M2 receptors?

heart --> decrease HR at the SA node, reduce conduction velocity thru AV node, and reduce heart contractility Gi

Where do you find beta 1 receptors?

heart ventricles: increases HR, conduction velocity, and contractility kidney: increases renin release from JGA Gs

Where do you find beta 2 receptors?

heart: increases HR and contractility liver and skeletal muscle: increases GNG and glycogenolysis pancreatic beta cells: increases insulin release relaxes smooth muscle (bc Gs coupled, causes increased cAMP; PKA inhibits myosin light chain kinase.. compared to alpha 1 which is Gq coupled so it causes contraction): - mydriasis via circular muscle relaxation, - flattens lens for distance vision, - bronchodilation, - decreased GI motility, - increased aqueous humor production, - relaxed detrusor = urinary retention, - relaxes uterus, - decreases diastolic pressure, - decreases gastric acid secretion Gs

Activation of which receptors causes increased insulin release from beta cells, and which cause decreased insulin release?

increased insulin release = beta 2s decreased insulin release = alpha 2s

Isoproterenol

iso-pro-tunnel tent in sympathomimetics sketch beta agonist - beta 1 and 2 increased contractility of the heart and increased HR, decreased diastolic bc of beta 2 effects increased insulin release Precaution heart block: you don't want to stimulate beta 1 receptors if passing the signal thru the ventricles is blocked, this produces dysrhythmias Diabetes precaution: hypoglycemia causes increased sympathetic response

What does cocaine do? What's a non-obvious adverse rxn to remember?

it inhibits reuptake by the presynaptic terminal of norepi, epi, serotonin, and dopamine. produces local vasoconstriction AND anesthesia; good as a local anesthetic effective as anesthetic bc it blocks voltage-gated Na channels in axons = prevents propagation of APs down pain fibers. (remember ester-type anesthetics can cause allergic reactions) Peripheral NET inhibition = sympathetic stimulation--HTN, tachycardia, and mydriasis. Central DAT inhibition = arousal, addiction, and seizures. Beta blockers make cocaine HTN even worse (unopposed alpha-1 stimulation). Don't use if seizure disorder, CV disease (will cause angina), or inflammation at the site of application (vasoconstriction can cause damage)

Atomoxetine Why shouldn't you use it if you have narrow angle glaucoma?

kid watching tv with atom on it under the dock in indirect sympathomimetics selective inhibitor of NET (norepinephrine reuptake transporter), treats ADHD extensive CYP2D6 metabolism, excreted 80% in the urine (precaution = hepatic disease) side effects: increases NE tone, preferentially in the CNS (insomnia, headache, restlessness, decreased libido); peripherally - tachycardia, HTN, NV, constipation, problems w/ejaculation, urinary hesitancy Don't use w/MAO inhibitors or if you have narrow-angle glaucoma bc rarely it will cause mydriasis Don't use if underlying CV issues black box warning bc of suicidal ideation

Salmeterol

long acting beta 2 agonist

Neostigmine

neon sign inhibits acetylcholinesterase (quaternary amine = no CNS penetration)

Where do you find M1 receptors?

nerve endings (e.g. CNS), cause a slow EPSP; antagonists reduce tremors and rigidity in Parkinson's Gq

Where do you find alpha 2 receptors?

nerve endings: decreased NE release (= decreased sympathetic tone) some smooth muscle contraction pancreatic beta cells: decreased insulin release platelets: aggregation Gi

Tubocurarine

non-depolarizing neuromuscular blocker

Timolol

non-selective beta blocker Timmy the beta 2 tuba player with the eyeball mute and lots of spit leaking out of his spit valve agent of choice for open-angle glaucoma bc reduces production of aqueous humor metabolized in the liver, precaution is hepatic disease Precaution: diabetes, raynaud's, bronchospasm, asthma, bradycardia Can see adverse rxns with pain in the eye, or CNS effects. Also if you get systemic absorption.

Propranolol

non-selective beta blocker decreases HR and CO, systolic and diastolic BP treats HTN, angina, tachycardia, MI, prophylaxis for MI, prophylaxis for migraine, anxiety, agitation, panic attack adverse rxns: dizziness, fatigue, depression, NVD **if you abruptly discontinue it you can get an MI, arrhythmia, or severe HTN precautions: asthma, bronchospasms, pulmonary edema, bradycardia, AV block, hepatic disease (bc hepatic metabolism), Raynaud's, diabetes (bc blocks sympathetic response when they have low blood sugar)

What does VMAT do? What drug can target it?

transports norepi into vesicles to store them there reserpine inhibits VMAT = depletion of transmitter stores

What does tyramine do?

tyramine displaces stored catecholamines (similar effect to amphetamines) found in fermented foods avoid if taking a MAO inhibitor (e.g. Phenelzine) bc it can interact with MAO inhibitors to cause hypertensive crisis due to inhibition of NE breakdown

What enzymes convert tyrosine to epinephrine?

tyrosine hydroxylase converts tyrosine to DOPA, DOPA is decarboxylated to dopamine, and inside the vesicle dopamine is hydroxylated to norepinephrine by Dopamine beta hydroxylase PNMT converts norepinephrine to epinephrine

Where do you find D1 dopamine receptors?

vascular smooth muscle in the kidney Gs -- PKA inhibits MLCK = smooth muscle relaxation = dilates blood vessels and increases GFR