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102 Cards in this Set

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Direct cholinergic agonists?
acetylcholine (cis-N, trans-M), carbachol (N,M), methacholine (M), bethanechol (M), succinylcholine (N2 @NMJ), cevimeline (M), pilocarpine (M)

N=nicotinic, M=muscarinic
1.) rapid decrease in MAP if given i.v.
2.) used to induce rapid miosis before or after Sx on anterior chamber (20-60 minutes)
used to induce slow miosis (4-8 hrs)
used to induce bronchial asthma
selective for GU/GI system
given p.o. low F
Tx: postoperative or neurogenic paralytic ileus and/or urinary retention ( 1.0 hour duration).
Contraindicated: asthma, COPD, peptic ulcer, CHF and hyperthroidism (decrease ERP)
N2-agonist @NMJ
i.v. causes single contraction followed by flaccid paralysis (3-10 minutes)
Degraded by plasma cholinesterases (genetic variants can lead to greater than 1 hour paralysis)
muscarinic agonist
tertiary natural amine
Primary use: glaucoma (contracts ciliary muscle increasing iridocorneal angle and lining up trabeculae in C of S for easier AH flow), fixes accomodation, night blindness
Secondary: Sjogren's syndrome
Degraded by liver
Contraindicated as in bethanechol
Tx for dry mouth, eyes of Sjogren's
SE's: GI cramps, sweating, incontinence and rhinitis
What drugs decrease the formation of aqueous humor for Tx glaucoma?
timolol-B1 & B2-blocker, causes bradycardia & bronchoconstriction.
betaxolol- Beta1 blocker, can cause bradycardia
acetylzolamide (nasty oral) and dorzolamide(topical)-CA inhibitors
apraclonidine- alpha2-agonist, Tx for ocular hypertension following trabeculoplasty.
What drugs increase the normal outflow of AH for Tx glaucoma?
epinephrine- alpha 1-agonist
dipivefrin-lipid solution that converts to epi in anterior chamber. Both cause mydriasis.
isofluophate and echothiophate are irreversible AChase inhibitors that increase ciliary muscle contraction (lines up those trabeculae).Pilocarpine- lines up trabeculae by increasing iridocorneal angle (decrease IOP 20%)
What drug increases uveoscleral outflow for Tx glaucoma?
latanoprost (PGF-2a)
decrease IOP 20%
What drugs are used together for the emergent Tx of glaucoma?
mannitol (osmotic diuretic) causes cellular dehydration and decrease in IOP.
acetylzolamide- decrease formation of AH.
pilocarpine- alignment of trabeculae in Canal of Schlemn for easy flow.
Rx for treatment of open-angle glaucoma?
1.)- decrease AH production
Beta-antagonists (betaxolol, timolol)
CA inhibitors (acetylzolamide, dorzolamide)
alpha2-agonists (apraclonidine)
2.)- Increase AH flow
alpha1-agonists (epinephrine, dipivefrin)
pilocarpine, isoflouphate
3.)-increase uveoscleral flow
PGF2a analogs (latanoprost)

Additive effect: One drug from 1+2+3 (3 different mechanisms)
What are the indirect cholinergic agonists?
physostigmine, neostigmine, pyridostigmine---> intermediate acting
carbamates. edrophonium---> short acting alcohol.
cabaryl, isoflurophate, parathion, malathion, dimpylate---> irreversible organophosphates
*tertiary carbamate, CNS effects*
reversible cholinesterase inhibitor. Tertiary, natural. Carbamoylates AChase, t 1/2 15-30 mins. Tx Alzheimer's and anticholinergic poisoning.
Reversible AChase inhibitor
*quarternary carbamate, no CNS effects*
carbamoylation of AChase @ N & M sites. Directs N2-agonist. Increases ACh @ NMJ (N2) and heart/salivary glands. Tx: paralytic ileus, GI/GU atony, myasthenia gravis, reversal of muscle paralysis from blocking agents (pancuronium).
Reversible Chase-inhibitor
*quarternary carbamate, no CNS effects*
MOA same as neostigmine. Long-term Tx for myasthenia gravis. Mild-> pyridostigmine + corticosteroids, Moderate-> pyridostigmine + thymectomy, Severe-> pyridostigmine + azathioprine.
Reversible AChase inhibitor
*quarternary carbamate, no CNS effects*
Inhibits AChase at all peripheral sites but mostly at NMJ. Quaternary amine. Extremely short t 1/2 (iv, im). Dx for myasthenia gravis. Distinguishes "myasthenic" vs. "cholinergic" crisis (pg 253 notes). Reversal of paralysis from neuromuscular blockade.
Reversible AChase inhibitor
*tertiary carbamate, CNS effects*
carbamate insecticide used at home. Use atropine for poisoning. Lipid soluble-->CNS
isoflurophate (DFP)
-Irreversible AChase inhibitor.
Phosphorylates active site. Tx for intractable glaucoma. If poisoned use atropine + pralidoxime (2-PAM), which facilitates the hydrolysis of inactive ACh and does not penetrate CNS.
-Irreversible AChase inhibitor
-phosphorylates active site.
-Tx for intractable glaucoma.
If poisoned: atropine + pralidoxime (2-PAM), which facilitates the hydrolysis of inactive ACh and does not penetrate CNS.
Irreversible AChase inhibitor
-common cause of illness & death
- If poisoned: atropine + pralidoxime (2-PAM), which facilitates the hydrolysis of inactive ACh and does not penetrate CNS.
-Irreversible AChase inhibitor
-safer than parathion
-mammals have carboxyesterase to break it down.
-used for mosquitos and head lice.
- If poisoned: atropine + pralidoxime (2-PAM), which facilitates the hydrolysis of inactive ACh and does not penetrate CNS.
Irreversible AChase inhibitor
-insecticide for lawn and garden.

- If poisoned: atropine + pralidoxime (2-PAM), which facilitates the hydrolysis of inactive ACh and does not penetrate CNS.
What are the effects of cholinergic agonists?
Muscarinic- miosis, blurry vision, bradycardia, cough, bronchoconstriction, pulmonary edema, GI cramping, diarrhea, involuntary defecation, sweating, lacrimation, salivation, urinary frequency increase and incontinence.

Nicotinic- Sk muscle- fasciculations, cramping, weakness. Sympathetic ganglia-tachycardia, hypertension.
Treatment of choice for Alzheimer's?
*tertiary carbamate, CNS effects*
-CNS AChase inhibitor.
Decreases apathy, hallucinations, anxiety and behavioral problems.

SE's- cramping, diarrhea, fatigue, insomnia and anorexia.
What drugs increase CYP 450 levels?
phenobarbital, rifampin, phenytoin, carbamazepine, ethanol (chronic use), benzopyrene (cig's)
What drugs decrease the levels of CYP 450?
cimetidine, ketoconazole, isoniazid, erythromycin, ethanol (acute), grapefruit juice.
What do these drugs have in common?

They all prevent the phosphodiesterase-mediated breakdown of cAMP to 5'-AMP downstream of Beta-receptor signaling. Additive effect with albuterol (Beta 2 agonist-> bronchodilator for Tx asthma)
How does Beta-2 stimulation lead to bronchodilation?
Beta-2 receptor stimulation leads to phosphorylation and inhibition of myosin-light chain kinase thus preventing the phosphorylation of myosin for myosin/actin contraction.
How does sildenafil (Viagra) work?
Sildenafil inhibits phosphodiesterase-5 (PDE 5) from breaking down cGMP to 5'-GMP leading to higher cGMP levels, which activates a myosin-light chain phosphatase. Myosin light chain phosphatase dephosphorylates myosin preventing contraction and promoting smooth muscle relaxation in the corpus cavernosa.
What do you use to acidify urine to increase the excretion of a weak base?
Ammonium chloride
What do you use to alkalinize urine to increase the excretion of a weak acid?
acetylzolamide (increases excretion of HCO3-)
What drugs may be metabolized differently due to the genetic differences in N-acetyltransferase?
sulfapyridine-hepatic damage and blood dyscrasias
isoniazid-peripheral neuropathy
procainamide-lupus like

Tertiary Muscarinic Antagonists
**Cross BBB, breast milk, placenta**

atropine, scopolamine, homatropine, cyclopentolate, tropicamide, benztropine, trihexyphenidyl, biperidin, dicyclomine, hyoscyamine, oxybutynin, tolterodine, solifenacin, diphenylhydramine.
Quaternary Muscarinic Antagonists
**Cannot penetrate CNS**

N-methylatropine, methylscopolamine, N-methylhomatropine, ipratropium, glycopyrrolate, propantheline, trospium.

*Ones with methyl- and Tiny PIG*
What are the pharmacological effects of muscarinic antagonists?
Eye-relaxtion of sphincter muscle (mydriasis) and ciliary muscle (cycloplegia). Cardiac- increased depolarization rate, heart rate, conduction velocity and decreased ERP. Bronchial relaxation. Decreased GI motility (constipation). Relaxation of detrusor and contraction of internal sphincter. Decreased, salivation, tearing and sweating. Decrease in bronchial and gastirc secretion.
Tertiary Belladona alkaloid(methylatropine is quaternary with no CNS effects). From small to large dose sensitivity is: glands->heart-> bladder, bowel-> eye. CNS effects are not seen at pharmacological dosing.

Perioperative use: decreases the production of saliva/pulmonary secretions. Counteracts bradycardia induced by ocular pressure, visceral traction, carotid sinus stimulation or injection of multiple doses of succinycholine. Reversal of neuromuscular blockade (atropine/edrophonium).
Opthalmology: mydriasis and cycloplegia to determine refractive error. Inflammation and cataract Sx.
Cardiac: reversal of digoxin AV block (adults) and bradycardia in kids to increase CO.
Gastro: in Lomotil to prevent addiction to diphenoxylate.
Myasthenia: prevents SE's of neostigmine & pyridostigmine.
Parkinson's: can block M-receptors centrally to decrease overactive stimulation.
Organophosphate poisoning: (atropine sulfate) for central and peripheral reversal.
Perioperative use: decreases the production of saliva/pulmonary secretions. Counteracts bradycardia induced by ocular pressure, visceral traction, carotid sinus stimulation or injection of multiple doses of succinycholine. Reversal of neuromuscular blockade (glycopyrrolate/neostigmine).
Tertiary (methscopolamine is quaternary with no CNS effects).
Perioperative use: tranquilizer during parturition (in the past).

Opthalmology: Mydriasis and cyloplegia to determine refractive error.

Motion sickness: reduces excessive M-activity in vestibular nuclei and reticular formation at the price of antegrade amnesia!
Opthalmology: used to induce mydriasis for fundascopic examination of retina and optic disk. Variation in concentration due to eye color.
Opthalmology: Mydriasis and cycloplegia for dertermination of refractive error.
GI: prevents bowel spasm and decreases pain due to Irritable Bowel Syndrome (IBS). Same as dicyclomine.
GI: prevents bowel spasm and decreases pain due to Irritable Bowel Syndrome (IBS). Same as hyoscyamine.
What are some of the SE's of antimuscarinic use in older patients with overactive bladder?
Blockade of central M-receptors may lead to drowsiness, somnolence, dizziness, disorientation and hallucinations.
-once daily
-blocks muscarinic receptors and exerts an antispasmodic effect on detrusor. SE's: drowsiness, dry mouth, somnolence and dizziness.
-twice daily
-relaxes detrusor.
SE's: somnolence, dry mouth, blurred vision and constipation.
-twice daily
-relaxes detrusor
-No CNS, but may have peripheral anti-M effects (ie: constipation, dry mouth).
Selective M3-antagonist
-relaxes detrusor
-Increase in Q-Tc interval (increases repolarization time for ventricles). May lead to Torsade de Pointes, which can ultimately cause v-fib.
-Fewer CNS effects and less dry mouth.
Selective M3-antagonist
Tertiary. Once-daily.
-relaxes detrusor.
-No CNS or CV effects. Less dry mouth.
Used in COPD to improve ventilation by relaxing bonchial smooth muscle.
What drugs are central muscarinic antagonists that can be used to treat Parkinson's?
*Tertiary to reach CNS*


Effect: decreased tremor > regidity > akinesia.

SE's such as cycloplegia, constipation urinary retension and dry mouth limit their use.
Describe the toxicity of atropine-like drugs.
Overdose: red as a beet, hot as a pistol, mad as a hatter and dry as a desert.

CNS: nervousness, excitation, confusion, hallucinations, weakness, giddiness, muscualr incoordination, hypertension, maniacal tendencies.

PNS: dry mouth, thirst, difficulty swallowing, hot-dry skin, dilated pupils (mydriasis), photophobia, blurred vision (cyloplegia), tachycardia, urinary retention, absense of bowel sounds (constipation).
How do you treat atropine-like overdose?
Gastric lavage, cardiorespiratory support, decrease body temp, Foley catheter to empty bladder, keep room dark, benzo's for sedation.
What is the mechansim of action (MOA) of the Nicotinic (N1) receptor antagonists (ganglion blocking agents)?
Competitive blockade of N-1 cholinergoc receptors in autonomic ganglia prevent all parasympathetic and sympathetic activity from reaching effector organs.
What is the effect of N1-ganglion blockade on the sympathetic nervous system?
arteriodilation lowers TRP, venodilation lowers preload, decreased CO, increase depolarization time, hypotension (decreased CO & TPR), decreased sweating (sympathetic stimulation of M1-receptors on sweat glands), no ejaculation.
What is the effect of N1-ganglion blockade on the parasympathetic nervous system?
tachycardia, mydriasis and cycloplegia. Decreased: salivation/lacrimation, GI motility and secretion, pancreatic secretion. Constipation and urinary retention. No erection.

(for USMLE)
Nicotinic ganglion-blocker (i.v.).
Reduces hypertension during head and neck Sx. Can induce histamine release--->vasodilation---->decrease in TPR---->decrease in BP.

(for USMLE)
Nicotinic ganglion-blocker.
Reduces hypertension associated with spinal cord injuries.
- plant alkaloid
- stimulates peripheral N1 & N2 receptors.
- stimulates N1 in CNS to release DA into the nucleus accumbens (addiction happens here).
Pharmacological Effects:
Smoking--> nicotine reached brain in 8-10 seconds.
Naive person:
Increased alertness, facilitation of memory, decreased aggression, decreased appetite, decreased skeletal muscle tone, increased tremor. Transient increase in HR. Decrease in skin temp due to vasoconstriction. Toxic in pesticide doses.
What are the effects of chronic nicotine use?
increase LDL, decrease HDL
increased platelet adhesion, coronary disease, peripheral vasculature disease, neutrophil inflammation in capillaries, escape of albumin (decreased oncotic pressure), insulin resistance, dysrhythmias, cancer, depression, facial wrinkling (increase P450 via benzopyrene leads to decrease in estrogen), cataracts, ulcer (GET THE PICTURE?)

Quit using nicotine gum, patch and Bupropion (antidepressant)
catecholamine released from the adrenal medulla. "Fight or Flight."

i.v.-Decrease in TPR & DBP (B2), increase in contractility (B1), increased venous return (B2-liver constrictors). Overall increase in CO & SV (SBP).
DOC bronchodilator in anaphylactic shock (B2).

Lowers IOP in glaucoma (alpha 1). Vasoconstrictor with local anesthetics (alpha 1). Relieves priapism (DOC).
SE's- anxiety, cerebral hemorrhage, pulmonary edema, arrythmia.
catecholamine released from presynaptic terminal.

i.v.-B1 and B2 cause increased contractility and increased venous return, however, alpha increases afterload (DBP) by arteriolar vasoconstriction. Reflex bradycardia. SV increase but CO remains the same.
Use as vasopressor agents when CO and tissue perfusion are normal (ie:spinal shock). Vasoconstrictor with local anesthetics.
synthetic adrenergic drug
all alpha1

increase in TPR & DBP. Reflex bradycardia. Systemic vasoconstrictor.

Relieves nasal congestion with increase in rebound vasodilation. Produces mydriasis for fundascopic exam.
synthetic catecholamine
all B

i.v.-like epi without the alpha activity. Large fall in TPR and DBP with increase flow to renal and GI. Large increase in SV & CO.

Increases AV conduction in AV block. Positive chronotropic and inotropic agent in cardiac arrest.

effects are dose dependent after MI. low (<2ug/kg/min)- increase in renal BF (D1) with an increase in GFR and hemodynamic diuresis. intermediate (2-10 ug/kg/min)- increase in cardiac contractility (B1) with little effect on HR. Increase in CO accentuates RBF and water excretion. Large dose (>10 ug/kg/min)- increase in TPR and afterload (alpha1). Increased venous return (alpha1) places increased demand on heart. Reverse with dobutamine or Na-nitroprusside (releases NO).

Used to increase BP following septic shock and increased CO after MI.
synthetic catecholamine
B1> or equal B2

-increased SV, but not HR like dopamine (good for heart failure patients). No increase in TPR & DBP. Causes venodilation and decrease in venous return and decreased cardiac filling pressure after MI.
What are the B2-agonists that are used to induce rescue bonchodilation in asthma, COPD and bonchitis?
salmeterol, terbutaline, albuterol, pirbuterol.

Relaxes uterus to delay parturition and allows for external eversion to correct for breech.
alpha agonist

nasal decongestant (vasoconstrictor). Lasts longer than phenylephrine. **Rebound vasodilation**
indirect-adrenergic agonist

in many foods: wine, beer, cheese. Causes release of NE stores in noradrenergic terminals. No clinical use. Contraindicated if on an MAO-inhibitor.
Lipid soluble and can freely enter CNS.
Causes release and prevents uptake of NE:

mixed agonist, lipid soluble-->CNS.

direct B1, B2 and release of NE, which acts on alpha and B.

bronchodilation and increased AV conduction (B). Nasal decongestion, mydriasis and increase in BP (alpha).

Reverses hypotention during anesthesia.

Nasty diet pills.

isomer of ephedrine with less CNS excitation and less of an increase in HR and BP.


What are the adverse effects of catecholamines and sympathomimetic amines?
arrythmia (B), angina (B), renal ischemia (alpha), cerebral bleeds (increase in BP), pulmonary edema (with increase afterload), anxiety (epinephrine), tremor (B), rebound nasal vasodilation (alpha), insomnia & psychiatric disturbances(amphetamines)
How to differentiate the CV effects of the adrenergic agonists?

ISO & DA increase RBF. NE & E decrease RBF.


ISO decreases DBP. DA causes no change. NE increases DBP and E decreases DBP.
reserpine & guanethidine
reserpine- depletion of NE stores in presynaptic bulb. Leads to decreased NE release and, therefore, vasodilation with a corresponding decrease in TPR/DBP. Renal retention of water. Increased GI activity and prolactin secretion. No longer used therapeutically to lower BP. SE's- sedation, failure to ejaculate, man boobs, supersensitivity to catecholamines via upregulation of alpha and B receptors.

guanethidine- inhibition of NE release by action potential. Decreases TPR and DBP. Salt retention due to decreased renal perfusion. Not used as a Tx for hypertension anymore. SE's- orthostatic hypertension, sexual dysfunction, supersensitivity to catecholamines.
guanethidine & bretylium
inhibit the exocytosis of NE by an action potential
cocaine and amphetamines
block reuptake of NE
Name the alpha receptor blockers?
prazosin, ergotamine, phenoxybenzamine, phentolamine, tamsulosin, yohimbe, lebetolol
Tx for migraine headaches. Partial alpha-agonist that constricts cerebral vessels.

SE's- apontaneous abortion, muscle pain and gangrene.
noncompetitive covalent alpha-blocker
Tx for malignant, pheochromocytoma (NE secreting tumor). Blocks NE vasoconstrictor effects to maintain BP.
Used along with a beta-blocker in pheochromocytoma Sx to reduce BP effects following manipulation of the tumor.

Part of "triple-P" cocktail (phentolamine, papaverine (PDE-inhibitor), alprostadil (PGE1-analog)) for injectable impotence Tx.
alpha1-selective blocker
reduction in BP without increase in HR like phentolamine. Tx: hypertension, pheochromocytoma, Reynaud's syndrome, frostbite and BPH.
alpha-a1-selective blocker
Tx: DOC to decrease urinary obstruction due to BPH.
central alpha2-blocker that reduces baroreceptor arc and increases sympathetic output to cause tachycardia, tremor and slight increase in BP. Does not treat impotence as marketed.
What are the adverse effects of the alpha-blockers?
orthostatic hypotension, angina (phentolamine and phenoxybenzamine due to reflex tachycardia), failure to ejaculate or retrograde ejaculation, miosis, nasal congestion, abdominal cramping, water/salt retention.
What is the concept of balanced vasodilation when using alpha-blockers to ameliorate hypertension in patients with normal cardiac function?
Alpha-blockers decrease preload by venous dilation and this decreases SV. They also decrease afterload via arteriole vasodilation (TPR) and this will increase SV. The effects on SV cancel and do not change CO.
Describe epinephrine reversal?
A large bolus of epi can cause a rise in BP. The effects of epi on vasoconstriction can be blocked by an alpha-antagonist and this will lower BP. (pg 308 of notes)
Name your B-blockers right now!!!!
The "olol's"
labetolol (both alpha and B), atenolol, betaxolol, metoprolol, esmolol, labetolol, propranolol, timolol.
What are the more cardioselective B-blockers?
"BAM on the heart" -high B1 selectivity:

What are the pharmacological effects of the B-blockerino's?
CV: decreased HR, conduction, dp/dt, O2 demand. Slowly developing decrease in BP (mechanism not known).
Kidney: renin release decreased and plasma AT-II levels drop.
Lungs: increased airway resistance *Use contraindicated in asthmatics/COPD*
Digits: cold hands
Eye: decrease in formation of AH for Tx glaucoma. Not propranolol (anesthetic).
Metabolic: blocks B1-lipolysis and B2-glycogenolysis (hypoglycemia). Careful monitoring with diabetics.
What are B-blockers used for?
CV: supraventricular arrythmia associated with stress, anxiety and thyrotoxicosis. Prevents sudden death from previous MI by 25-40%. Decrease BP. Improved CO in diastolic dysfunction (filling).
Thyroid: thyrotoxicosis
Eye: glaucoma
Essential tremor: decreases tremors of 8-12 Hz that are associated with caffeine, lack of sleep, hangovers and stenuous exercise.
Head: migraine headache incidence.
Liver: reduction in portal hypertension (propanolol) and risk from hemmorhage of varices.
What are some of the adverse effects from using B-blockers?
Lung: contraindicated in asthma and COPD (prevents bronchodilation).
Metabolism: Masks the signs of hypoglycemia, which are mediated by Epi. Can cause hypertension since only alpha receptors remain for epi to stimulate (increase TPR).
Skin: decreased blood flow. Contraindicated in Reynaud's. Smoking makes this worse.
Exercise intolerance and ED.
What are the sympatholytic drugs?
They directly or indirectly decrease the release of NE from peripheral neurons and lower BP by a decrease in TPR (no vasoconstriction).

reserpine (card #79)
guanethidine (card #79)
How does alpha-methlydopa work?
Once transported into central noradrenergic neurons by the aromatic amino acid pumo, it is converted to alpha-methyl-NE, which is not degraded by MAO. alpha-methyl-NE stimulated alpha-2 receptors in the rostral ventrolateral medulla to cause a decrease in presynaptic sympathetic nerve activity. *Mimics increased baroreceptor firing to decrease HR.* This all results in decreased sympathetic activity and NE release.
What are the pharmacological effects of alpha-methyldopa?
CV: decreased TPR, HR.
Kidney: water/salt retention. Renin and ATII decrease.
Pituitary: prolactin secretion increases.
What is the use of alpha-methyldopa?
Tx: hypertension in children and pregnant women (not a teratogen).
What are the side effects of alpha-methyldopa use?
sedation, somnolence, dry moth, nasal congestion, edema, orthostatic hypotension (no that bad, pg 319), positive Coomb's test (can't type blood), man-boobs and amenorrhea in women.
a botanical alkaloid
-blocks Na-channels in sensory pain fibers.
-noncompetitive blockade of NE reuptake.
-increases central sympathetic flow
-euphoria and addiction from DA release into Nucleus Accumbens.
What is the therapeutic use of cocaine?
Provides local anethesia for ocular and nasal Sx.
What are the toxic effects of cocaine?
Cardiac dysrthymia due to blocked Na-channels and an increase in HR (not good for a heart). Rapid MI and MI feelings. Pulmonary edema. Stroke. Seizures. Sudden death (even first time use).