Pharmacology Flashcards
<p>What conditions can be exaberated with use of cholinomimetric agents?</p>
<p>COPD</p>
<p>Asthma</p>
<p>Peptic ulcers</p>
<p>What is the function of Bethanechol and what type of activity <strong>(nicotinic/muscarinic)</strong>does it have?</p>
<p><strong>Function:</strong>Activates the bladder (smooth muscle)</p>
<p><strong>Activity:</strong>Muscarinic</p>
<p><strong>NOTE:</strong>Bethanechol is resistant to AChE</p>
<p>Bethanechol should be prescribed in cases of \_\_\_\_\_\_\_\_.</p>
<p>Urinary retention</p>
<p>List the direct agonists of AChE.</p>
<p>Bethanechol</p>
<p>Carbachol</p>
<p>Methacholine</p>
<p>Pilocarpine</p>
<p>Which class of receptor are muscarinic receptors?</p>
<p>G- protein</p>
<p><b>NOTE:</b>M1= Gq; M2= Gi; M3= Gq</p>
<p>What is the major function of M1 (muscarinic) receptors?</p>
<p>Mediates higher cognitive functions, stimulates enteric nervous system</p>
<p>What is the major function of M2(muscarinic) receptors?</p>
<p>Decrease heart rate and cotnractility of<strong>atria</strong></p>
<p><strong>REMEMBER:</strong>M2 receptors are only present on the atria and the SA and AV nodes</p>
<p>What is the major function of M3 (muscarinic) receptors?</p>
<ul>
<li>Increase exocrine gland secretions</li>
<li>Increase gut peristalsis</li>
<li>Increase bladder contraction, bronchoconstriction</li>
<li>Increase pupillary sphincter muscle contration, ciliary muscle contraction (accommodation)</li>
<li>Increase insulin release, endothelium-mediated vasodilation</li>
</ul>
<p>What is the function of carbochol?</p>
<p>Constricts pupil and relieves intraocular pressure in open-angle glaucoma</p>
<p><strong>NOTE:</strong>Carbochol has both nicotinic and muscarinic activity</p>
<p>Metacholine acts as a challenge test for diagnosis of \_\_\_\_\_\_\_\_\_.</p>
<p>Asthma</p>
<p>What is the function of methacholine?</p>
<p>Stimulates muscarinic receptors in airway when inhaled</p>
<p>Which direct cholinomimetric agents are resistant to AChE?</p>
<p>Bethanechol</p>
<p>Carbochol</p>
<p>Pilocarpine</p>
<p></p>
<p>What is the function of pilocarpine?</p>
<ul>
<li>Contracts ciliary muscle of eye, pupillary sphincter</li>
</ul>
<p><strong>NOTE:</strong>Contraction of ciliary muscle treats<strong>open-angle glaucoma</strong>and contraction of pupillary sphincter treats<strong>closed- angle glaucoma</strong></p>
<p>Of the 4 direct acetylcholine agonists, which can cross the blood-brain barrier?</p>
<p>Pilocarpine</p>
<p>In what cases is pilocarpine administered?</p>
<ul>
<li>Open-angled glaucoma</li>
<li>Close-angled glaucoma</li>
<li>Xerostomia (Sjogren syndrome)</li>
</ul>
<p>What is the G-protein class for each of the sympathetic receptors?</p>
<p><strong>a1-</strong>q</p>
<p><strong>a2-</strong>i</p>
<p><strong>B1-</strong>s</p>
<p><strong>B2-</strong>s</p>
<p><strong>B3-</strong>s</p>
<p>What are the major functions of a1 receptors?</p>
<ul>
<li>Increase vascular smooth muscle contraction</li>
<li>Increase pupillary dilator muscle contraction (mydriasis)</li>
<li>Increase intestinal and bladder sphincter muscle contraction</li>
<li></li>
</ul>
<p>What are the major functions of a2receptors?</p>
<ul>
<li>Decrease in sympathetic (adrenergic) outflow</li>
<li>Decrease in insulin release</li>
<li>Decrease in lipolysis</li>
<li>Increase in platelet aggregation</li>
<li>Decrease in aqueous humor production</li>
</ul>
<p>What are the major functions of B1receptors?</p>
<ul>
<li>Increase in heart rate</li>
<li>Increase in contractility</li>
<li>Increase in renin release</li>
<li>Increase in lipolysis</li>
</ul>
<p>What are the major functions of B2receptors?</p>
<ul>
<li>Vasodilation</li>
<li>Bronchodilation</li>
<li>Increase lipolysis</li>
<li>Increase insulin release</li>
<li>Increase glycogenolysis</li>
<li>Decrease in uterine tone (tocolysis)</li>
<li>Increase in aqueous humor production</li>
<li>Increase in cellular K+ uptake</li>
</ul>
<p>What are the major functions of B3receptors?</p>
<ul>
<li>Increase in lipolysis</li>
<li>Increase in thermogenesis in skeletal muscle</li>
<li>Increase in bladder relaxation</li>
</ul>
<p>What is the mechanism of action of Gq class proteins?</p>
<p>1. Phospholipase is activated by aGq receptor</p>
<p>2.<strong>Phospholipase C</strong>converts PIP2 to DAG and IP3</p>
<p>3.<strong>IP3</strong>then diffuses through the cytosol to bind toIP3receptors, particularlycalcium channelsin thesmooth endoplasmic reticulum(ER).</p>
<ul>
<li>This causes the cytosolic concentration of <strong>calcium to increase</strong>, causing a cascade of intracellular changes and activity.</li>
</ul>
<p>4. Ca2+ acts with DAG to produce <strong>p</strong><strong>rotein kinase C</strong></p>
<p>Which receptors are of the Gq protein class?</p>
<p>H1 (Histamine)</p>
<p>a1 (sympathetic)</p>
<p>V1 (vasopressin)</p>
<p>M1 (muscarinic)</p>
<p>M3 (Muscarinic)</p>
<p><strong>MNEMONIC:</strong>Have 1 M &M</p>
<p><strong>NOTE:</strong>Receptors in the Gq protein class stimulate<strong>smooth muscle contraction</strong></p>
<p>What is the mechanism of action of Gs receptors?</p>
<p>1. Gs receptors stimulate adenyl cyclase</p>
<p>2. Adenyl cyclase converts ATP into<strong>cAMP</strong></p>
<p>3. cAMP activates<strong>protein kinase A</strong></p>
<ul>
<li>Sequesters Ca2+ in sarcoplasmic reticulum (heart)</li>
<li>Inhibits myosin light-chain kinase (smooth muscle)</li>
</ul>
Which receptors are on the Gs protein class?
B1
B2
B3
D1
H2
V2
What is the mechanism of action for Gi receptors?
Gi inhibits Adenylyl cyclase
Which receptors are of the Gi protein class?
M2 (muscarinic)
a2 (sympathetic)
D2 (Dopamine)
MNEMONIC: People who are 2 MAD inhibit themselves
When should albuterol be administered? What about salmeterol?
Albuterol= Acute asthma/COPD
Salmeterol= Serial (long- term) asthma/ COPD
Which direct sympathomimetics have both B2 and B1 action with the B2 action being greater than the B1 action?
Albuterol
Salmeterol
Terbutaline
When should terbutaline be administered?
Acute bronchospasm in asthma and tocolysis (inhibition of uterine contractions)
Which sympathomimetic only has a1 action?
Midodrine
When should midodrine be administered?
In cases of autonomic insufficiency and postural hypotension
NOTE: Midodrine may exacerbate supine hypertension
What is the mode of action of isoproterenol?
B1=B2
When should isoproterenol be administered?
Electrophysiologic evaluation of tachyarrythmias
NOTE: Isoproterenol can worsen ischemia
What is the mode of action of epinephrine?
B>a
What is the mode of action of norepinephrine?
a1>a2>B1
What is the mode of action for phenylephrine?
a1>a2
When should epinephrine be administered?
- Anaphylaxis
- Asthma
- Open-angle glaucoma
NOTE: The alpha effect predominates at low doses
What is the mode of action of dobutamine?
B1>B2, a
When should dobutamine be administered?
- Heart failure
- Cardiogenic shock (inotropic> chronotropic)
- Cardiac stress testing
When should norepinephrine be administered?
- Hypotension
- Septic shock
When should phenylephrine be administered?
- Hypotension (vasoconstrictor)
- Ocular procedures (mydriatic)
- Rhinitis (decongestant)
- Ischemic priapism
Which drugs are anticholinesterases (indirect agonist)?
Donepezil
Rivastigmine
Galantamine
Edrophonium
Neostigmine
Physostigmine
Pyridostigmine
Which anticholinesterases are first line for Alzheimer's disease?
Donepezil
Rivastigmine
Galantamine
What is the function of edrophonium?
Used to diagnose myasthenia gravis 0.0
Used to diagnose myasthenia gravis
NOTE: This has been replaced by anti-AChR Ab (anti-acetylcholine receptor antibody) test
Which of the anitcholinesterases cannot cross the CNS?
Neostigmine
Pyridostigmine
When should neostigmine be administered?
- Postoperative and neurogenic ileus (muscles of your intestines stop contracting) and urinary retention
- Myastenia gravis
- Reversal of neuromuscular junction blockage (postoperative)
What is the function of physostigmine?
Antidote for anticholinergic toxicity
NOTE: Physostigmine can freely cross the blood-brain barrier
Which drugs are used along side pyridostigmine to control its side effects?
Glycopyrrolate
Hyoscyamine
Propantheline
What is the function of pyridostigmine?
- Treats myasthenia gravis (long term)
- Increases muscle strength
What is the primary cause of anticholinesterase poisoning?
Organophosphates that irreversibly inhibit AChE
NOTE: Organophosphates are commonly used as insecticides and as a result anticholinesterase poisoning
What are the muscarinic effects of anticholinesterase poisoning?
- Diarrhea
- Urination
- Miosis
- Bronchospasm
- Bradycardia
- Emesis
- Lacrimation
- Sweating
- Salivation
MNEUMONIC: DUMBBELLS
Muscarinic effects caused by anticholinesterase poisoning can be reversed by ____________.
Atropine
NOTE: Atroprine acts as a competitive inhibitor and can cross the BBB to relieve CNS symptoms
What are the nicotinic effects of anticholinesterase poisoning?
Neuromuscluar blockage
Nicotinic effects of anticholinesterase are reversed by ________.
Pralidoxime, which regenerates AChE if given early
NOTE: Pralidoxime does not readily cross the BBB
What are the CNS effects of anticholinesterase poisoning?
Respiratory depression
Lethargy
Seizures
Coma
What are the muscurinic antagonists? Which organ systems are affected?
Eye
- Atropine
- Homatropine
- Tropicamide
CNS
- Benztropine
- Trihexyphenidyl
- Scopolamine
GI, Respiratory
- Glycopyrrolate
GI
- Hyoscyamine
- Dicyclomine
Respiratory
- Intratropium
- Tiotropium
Genitourinary
- Oxybutaynin
- Solifenacin
- Tolterodine
What muscarinic antagonists affect the eye? What is their function?
Antagonists: Atropine, Homatropine, Tropicamide
Function: Produces mydriasis (dilation of pupil and cycloplegia (paralysis of ciliary muscle)
What muscarinic antagonists affect the CNS? What is the function of each?
Antagonists: Benztropine, trihexyphenidyl
- Function: Treats Parkinson disease and acute dystonia
Antagonists: Scopolamine
- Function: Motion sickness
Which muscarinic antagonists affect the GI and respiratory system?
Antagonists: Glycopyrrolate
- Function
- Nonoral: Preoperative uste to reduce airways secretion
- Oral: Drooling, peptic ulcers
Which muscarinic antagonists affect the GI system?
Antagonists: Hyoscyamine, dicyclomine
- Function: Antispasmodics for irritable bowel syndrome
Which muscarinic antagonists affect the respiratory system?
Antagonist: Ipratropium, tiotropium
- Function: COPD, asthma
Which muscarinic antagonists affect the genitourinary system?
Antagonist: Oxybutynin, solifenacin, tolterodine
- Function: Reduce bladder spasms and urge urinary incontinence (overactive bladder)
What affect does atropine have on the following systems?
Eye
Airway
Stomach
Gut
Bladder
Eye
- Increases pupil dilation
- Cycloplegia
Airway
- Bronchodilation
- Decrease in secretions
Stomach
- Decrease acid secretion
Gut
- Decrease motility
Bladder
- Decrease urgency in cystitis
NOTE: Atropine reduces the effects (DUMBELLS) of anticholinesterases, but not the nicotinic effects
What are the adverse effects of atropine?
- Increase in body temp (due to decrease in sweating)
- Increase in HR
- Dry mouth
- Dry, flushed skin
- Cyclopegia
- Constipation
- Disorientation
MNEUMONIC: Hot as a hare, dry as a bone, red as beet, blind as a bat, mad as a hatter, full as a flask
NOTE: Can cause acute angle-closure glaucoma in in elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia, and hyperthermia in infants
_____ is inversely related to the affinity of the enzyme for its substrate.
Km
______ is directly propertional to the enzyme concentration.
Vmax
What affect do competitive inhibitors have on Vmax, Km, and pharmocodynamics?
Vmax: Unchanged
Km: Increased
Pharmocodynamics: Decrease potency
What affect do irreversible competitive inhibitors have on Vmax, Km, and pharmocodynamics?
Vmax: Decrease
Km: Unchanged
Pharmocodynamics: Decrease in efficacy
What affect do noncompetitive inhibitors have on Vmax, Km, and pharmocodynamics?
Vmax: Decrease
Km: Unchanged
Pharmacodynamics: Decrease efficacy
What is bioavailabilty (F)?
Fraction of administered drug reaching systemic circulation unchanged
NOTE: IV, F=100%; Oral. F<100% due to incomplete absorption and first pass metabolism
Vd
Theoretical volume occupied by the total amount of drug in the body relative to its plasma concentration
Vd= (amount of drug in the body)/ (plasma drug concentration)
The apparent volume distribution of drug can be altered by ______ and _______ disease.
Liver; kidney
NOTE: Protein binding will decrease, so Vd will increase.
When is Vd low?
When a high percentage of drug is bound to plasma proteins.
Ex: Plasma/ intravascular
When is Vd high?
When a high percentage of a drug is being sequestered in tissues.
NOTE: This raises the possibility of displacement by other agents .
Clearance
The volume of plasma cleared of drug per unit time.
NOTE: Clearance may be imparied with defects in cardiac, hepatic, or renal function
CL= (rate of elimination of drug)/ (plasma drug concentration); CL= Vd X Ke (elimination constant)
Half- life
The time required to change the amount of drug in the body by 1/2 during elimination.
t1/2= (0.7 X Vd)/ CL
NOTE: Time to steady state depends primarily on t1/2 and is independent of dose and dosing frequency.
In _________ kinetics, a drug infused at a constant rate takes 4-5 half-lives to reach steady state.
First order kinetics
NOTE: It takes 3.3 half-lives to reach 90 % of the steady state level
Loading dose
(Cp X Vd)/ (F)
Cp= target plasma concentration at steady state
NOTE: In renal disease, maintenance dose is decreased and loading dose is usually unchanged.
Maintenance dose
(Cp X CL x T)/ (F)
Cp= target plasma concentration
T= dosage interval (time between doses), if not administered continuously
NOTE: In renal or liver disease, maintence dose decreases and loading dose is usually unchanged.
Additive drug interactions
Effect of substance A and B together is equal to the sum of their individual effects
EX: Aspirin and acetaminophen
Permissive drug interactions
Presnce of substance A is required for the full effects of substance B
EX: Cortisol on catecholamine responsiveness
Synergestic drug interactions
Effect of substance A and B together is greater than the sum of their individual effects
EX: Clopidogrel with aspirin
Tachyphylactic drug interactions
Acute decrease in response to a drug after initial/ repeated administration
EX: Nitrates, niacin, pheylephrine, LSD, MDMA
What effect does a competitive antagonist have on potency and efficacy?
Potency: Decrease
Efficacy: No change
NOTE: A competitive antagonist can be overcome by increasing the agonist concentration.
EX: Diazepram (agonist) + flumazenil (competitive antagonist) on GABAA receptor
What effect does a noncompetitive antagonist have on potency and efficacy?
Potency: Decrease
Efficacy: Decrease
NOTE: A noncompetitive antagonist cannot be overcome by increasing agonist concentration
EX: Norepinephrine (agonist) + phenoxybenzamine (noncompetitive antagonist) on a- receptors
Zero-order elimination
Rate of elimination is constant regardless of Cp. Cp decreases linearly with time. Capacity-limited elimination
EX: Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations)
First-order elimination
Rate of first-order elimination is directly proportional to the drug concentration. Flow-dependent elimination
NOTE: Cp decreases exponentially with time
*Applies to most drugs
Which drugs eliminate via zero-order elimination?
Phenytoin, Ethanol, and Aspirin
How is TCA toxicity generally treated?
With sodium bicarbonate to overcome the sodium channel-blocking activity of TCAs
NOTE: This is not true in cases of accelerating drug elimination
Phase I Drug metabolism
Reduction, Oxidation, Hydrolysis with cytochrome P-450 usually yield slightly polar, water-soluble metabolites, which are often still active
NOTE: Geriatric patients lose phase I first
Phase II
Conjugation (methylation, glucuronidation, acetylation, sulfation) usually yields very polar, inactive metabolites, which are renally excreted.
NOTE: Patients who are slow acetylators have increase side effects from certain drugs, because a decrease rate of metbolism.
What is the therapeutic window?
Dosage range that can safely and effectively treat disease
Therapeutic index
T50/ ED50
(Median toxic dose)/ (Median effective dose)
NOTE: Safer drugs have higher TI values. Drugs with lower TI values frequently require monitoring
EX: Warfarin, Theophylline, Digoxin
________________ are part of the sympathetic pathway but are innervated by cholinergic fibers.
Sweat glands
Where are NN receptors found?
Autonomic ganglia
Adrenal medulla
Where are NM found?
Neuromuscular junction of skeletal muscle
What are the clinical applications of amphetamine?
Narcolepsy, obesity, ADHD
Indirect sympathomimetics
Amphetamine
Cocaine
Ephedrine
Characteristics of amphetamine
Indirect general agonist
Reuptake inhibitor
Releases stored catecholamines
What are effects of cocaine?
Causes vasoconstriction and local anesthesia
NOTE: Caution when giving B-blockers if cocaine intoxication is suspected (can lead to unopposed a1 activation, which can lead to extreme hypertension and coronary vasospasm)
Characteristics of cocaine
Indirect general agonist
Reuptake inhibitor
Characteristics of ephedrine
Indirect general agonist
Releases stored catechlamines
What are the clinical applications of ephedrine?
Nasal decongestion (pseudoephedrine)
Urinary incontinence
Hypotension
How do norepinephrine and isoproterenol differ?
Norepinephrine
- Increases systolic and diastolic pressures as a result of a1 mediated vasoconstriction
- Increases mean arterial pressure
- Reflex bradycardia
Isoproterenol
- B2 mediated vasodilation
- Decrease in mean arterial pressure
- Increase in heart rate through B1 and reflex activity
List a2 agonistsTiza
Clonidine
Guanfacine
a-methydopa
Tizanidine
What are the clinical applications of clonidine?
- Hypertensive urgency (limited situations)
- ADHD
- Tourette syndrome
- Symptom control in opoid withdrawl
What are the clinical applications of guanfacine?
Hypertensive urgency (limited situations)
ADHD
Tourette syndrome
Symptom control in opoid withdrawl
What are the adverse effects of clonidine?
- CNS depression
- Bradycardia
- Hypotension
- Respiratory depression
- Miosis
- Rebound hypertension with abrupt cessation
What are the clinical applications of a-methyldopa?
Hypertension in pregnancy
What are the adverse effects of a-methyldopa?
- Positive direct Coombs hemolysis
- Drug-induced lupus
What is the clinical application for tizanidine?
Relief of spasticity
What are the adverse effects of tizanidine?
Hypotension
Weakness
Xerostomia (dry mouth)
List the nonselective a-blockers
- Phenoxybenzamine
- Phentolamine
What are the clinical applications of phenoxybenzamine?
Pheochromocytoma (used preoperatively) to prevent hypertensive (catecholamine) crisis
NOTE: Phenoxybenzamine is an irreversible nonselective a-blocker
What is the clinical application of phentolamine?
Given to patients of MAO inhibitors who eat tyramine-containing foods and for severe cocaine induced hypertension (2nd line)
What are the irreversible effects of phentolamine?
- Orthostatic hypotension
- Reflex tachycardia
List the a1 selective blockers?
Prazosin
Terazosin
Tamsulosin
NOTE: They all have an -osin ending
What are the adverse effects of a1 selective blockers?
- 1st-dose orthostatic hypotension
- Dizziness
- Headache
What are the a2 selective blockers?
Mirtazapine
What are the clinical applications of mirtazapine?
Depression
What are the adverse effects of mirtazapine?
- Sedation
- Increase in serum cholesterol
- Increase in appetite
What response does epinephrine have to mirtazapine?
Epinephrine response exhibits reversal of mean arterial pressure from a net increase to a net decrease (the B2 effect)
What response does phenylephrine have to mirtazapine?
Response is supressed
List B1 selective blockers
- Acebutolol (partial agonist)
- Atenolol
- Betaxolol
- Bisoprolol
- Esmolol
- Metoprolol
List nonselective B blockers
- Nadolol
- Pindolol (partial agonist)
- Propranolol
- Timolol
List drugs that act as both a and B blockers
Carvedilol
Labetalol
_____________ combines cardiac-selective B1- adrenergic blockage with stimulation of B3 receptors.
Nebivolol
What is the clinical application of timolol?
Decrease production of aqueous humor, to treat glaucoma
Which B-blockers treat heart failure?
- Bisoprolol
- Carvedilol
- Metoprolol
NOTE: They act by decreasing motality
What is the clinical application of propranolol?
Control symptoms of hyperthyroidism
- Decrease heart rate
- Decrease tremor
Which B-blockers treat supraventricular tachycardia?
Metroprolol, esmolol
NOTE: They act by decreasing AV conduction velocity (class antiarrhythmic)
Which B-blockers treat variceal bleeding?
Nadolol, propranolol, carvedilol
NOTE: They act by decreasing hepatic venous pressure gradient and portal hypertension
B-blockers are administered for which conditions?
- Angina pectoris
- Glaucoma
- Heart failure
- Hypertension
- Hyperthyroidism
- Hypertrophic cardiomyopathy
- Myocardial infarction
- Supraventricular tachycardia
- Variceal bleeding
How do B-blockers act to treat angina pectoris?
- Decrease heart rate and contractility, resulting in decrease in O2 consumption
How do B-blockers act to treat hypertension?
- Decrease cardiac output
- Decrease renin secretion (due to B1-receptor blockade on JG cells)
How do B-blockers act to treeat hypertrophic cardiomyopathy?
- Decrease heart rate
- Increase filling time, relieving obstruction
How do B-blockers act to treat myocardial infarction?
- Decrease O2 demand (short-term)
- Decrease mortality (long-term)
What are the adverse effects of B-blockers?
- Erectile dysfunction
- Cardiovascular (bradycardia, AV block, HF)
- CNS (seizures, sleep alterations)
- Dyslipidemia
- Asthma/ COPD exacerbations
____________ (insulin/glucagon) treats B-blocker toxicity.
Glucagon
