a. most common receptor used in drug mechanisms
b. mechanism resembles receptor tyrosine kinases
c. growth hormone, erythropoietin, interferon
d. production of intracellular second messengers
e. intracellular receptor
f. opening and closing regulated by ligand binding
g. regulated allosterically by a ligand binding to extracellular domain
h. binds and stimulates protein tyrosine kinase
i. insulin, EGF, PDGF, ANP, TGFb
j. beta-adrenoreceptors, glucagon receptors, thyrotropin
k. acetylcholine, serotonin, GABA, glutamate
1. lipid soluble ligand receptor - e. intracellular receptor
2. transmembrane receptors - g. regulated allosterically by a ligand binding to extracellular domain,h. binds and stimulates protein tyrosine kinase, i. insulin, EGF, PDGF, ANP, TGFb
3. cytokine receptors - b. mechanism resembles receptor tyrosine kinases, c. growth hormone, erythropoietin, interferon
4. ligand gated channels - f. opening and closing regulated by ligand binding, k. acetylcholine, serotonin, GABA, glutamate
5. GPCRs - a. most common receptor used in drug mechanisms, d. production of intracellular second messengers, j. beta-adrenoreceptors, glucagon receptors, thyrotropin
What are the 3 ways in which receptors are regulated?
rapid desensitization: decreased ability of receptor to respond to stimulation by drug
resensitization: recovery after agonist is removed
downregulation: removal of receptor upon repeated (or persistent) drug-receptor interaction
What is the equilibrium dissociation equation?
Kd = [D][R]/[DR] = Koff/Kon
Kd = equilibrium dissociation constant for drug-receptor complex
[D] = free drug concentration
[R] = free receptor concentration
[DR] = drug-receptor complex concentration
Response is directly proportional to the amount of _____ (3 words) that is formed. When all of the receptors are bound to the drug, there is a _____ response.
drug-receptor complex; maximum
Why do pharmacologists us logarithmic plots (i.e. the log-concentration-response curve)?
allows for plotting over a larger concentration range
helps in comparing drugs
Match the following.
1. efficacy
2. potency
a. EC50
b. Emax
c. comparison of EC50 values for 2 or more agonists
d. measure of the maximum response obtained with the highest concentrations of agonist
1. efficacy - b. Emax, d. measure of the maximum response obtained with the highest concentrations of agonist
2. potency - a. EC50, c. comparison of EC50 values for 2 or more agonists
True or false. Greater potency for a drug means that the concentration needed for the response is greater.
False, Greater potency for a drug means that the concentration needed for the response is smaller.
a. inactivate receptor molecule or act on a downstream site; decrease maximum response of agonist
b. constitutive receptor activity; effect is opposite to agonist
c. ligand that binds to a receptor to directly activate a signaling pathway to turn on downstream effectors that produce the response
d. agent that binds to a receptor but cannot produce conformational change necessary to trigger downstream events
e. bind reversibly to receptor
f. produce an effect with lower efficacy than the standard agonist
g. shifts graph to the right
h. shifts graph downward
1. agonist - c. ligand that binds to a receptor to directly activate a signaling pathway to turn on downstream effectors that produce the response
2. partial agonist - f. produce an effect with lower efficacy than the standard agonist
3. antagonist - d. agent that binds to a receptor but cannot produce conformational change necessary to trigger downstream events
4. competitive antagonist - e. bind reversibly to receptor, g. shifts graph to the right
5. non-competitive antagonist - a. inactivate receptor molecule or act on a downstream site; decrease maximum response of agonist, h. shifts graph downward
6. inverse antagonist - b. constitutive receptor activity; effect is opposite to agonist
Give an example of a structure-activity relationship.
congeners: produced by adding on longer hydrocarbon chains (i.e. ACh > PrCh, BuCh)
analogs: produced when the oxygen of the esteric linkage in ACh is replaced by sulfur (i.e. ACh > AtCh)
What are the 5 mechanisms by which drugs cross biological membranes?
passive diffusion
aqueous channels in intercellular junctions (i.e. tight junctions)
lipid cell membranes
active pumps or co-transporters
cellular endocytosis/exocytosis
What equation is used to calculate the total drug concentrations in compartments of differing pH separated by a membrane (i.e. ph trapping)?
Henderson-Hasselbalch equation
pH = pKa + log (unprotonated/protonated)
_____ will accumulate in basic compartments. This is how _____ is absorbed from the stomach into more alkaline plasma.
Acids; aspirin
_____ will accumulate in acidic compartments and they are not absorbed from the stomach into the plasma because of pH trapping.
Bases
Match the following.
1. oral
2. sublingual
3. rectal
4. IV
5. topical
6. inhalation
7. IM
8. subcutaneous
a. mins to hours; small volumes, risk of irritation
b. immediate; irreversible, increased risk of adverse effects
c. hours; small quantity, limited absorption, risk of irritation
d. minutes to days; pain, irreversible, precluded from anticoagulant therapy; avoids 1st pass metabolism
e. 20-60 minutes; 1st pass metabolism, requires patient compliance
f. immediate; gas, vapor or small particles
g. minutes to hours; inconvenient; alternative to oral
h. immediate; small quantities; avoids 1st pass metabolism
2. sublingual - h. immediate; small quantities; avoids 1st pass metabolism
3. rectal - g. minutes to hours; inconvenient; alternative to oral
4. IV - b. immediate; irreversible, increased risk of adverse effects
5. topical - c. hours; small quantity, limited absorption, risk of irritation
6. inhalation - f. immediate; gas, vapor or small particles
7. IM - d. minutes to days; pain, irreversible, precluded from anticoagulant therapy; avoids 1st pass metabolism
8. subcutaneous - a. mins to hours; small volumes, risk of irritation
What is the volume of distribution equation? Calculate 8000 mg of a drug administered IV with a concentration of drug at t = 0, of 200mg/L.
Vd = amt/Ct=0
Vd = 8000 mg/200 mg/L = 40 L
Vd = volume distribution
amt = amount
Ct=0 = concentration of drug at time zero
What 2 factors determine drug distribution (Vd) in the body?
lipid solubility:
high - measured plasma concentration of drug is low ->> high Vd
low - measured plasma concentration of drug is high ->> low Vd
binding to plasma proteins: results in a lower Vd
If a 70 kg person has a Vd range of 5-10 L, what does this mean in terms of drug distribution?
B. drug is highly charged or bound to plasma protein
If a 70 kg person has a Vd range of 20-40 L, what does this mean in terms of drug distribution?
D. drug is moderately lipid soluble
If a 70 kg person has a Vd of 40 L, what does this mean in terms of drug distribution?
D. drug is lipid soluble enough to distribute to total body water
If a 70 kg person has a Vd of >40 L, what does this mean in terms of drug distribution?
C. drug is highly lipid soluble and is sequestered in fat, nervous tissue and muscle
True or false. CNS-active drugs will generally have a very large Vd and will be eliminated by hepatic drug metabolism.
true
What 2 factors determine whether a drug is eliminated by renal excretion or hepatic metabolism?
extensive protein binding: slows down renal and liver metabolism and elimination because these systems only work on free, unbound drug
high lipid solubility: liver metabolism; easy entry into liver cells
True or false. Hydrophobic drugs are metabolized via the kidney, while hydrophilic drugs are metabolized via the liver.
False, hydrophobic drugs are metabolized via the liver, while hydrophilic drugs are metabolized via the kidney.
What is "1st pass metabolism" and what are its consequences?
linking of the GI blood flow into the portal circulation along with the presence of the metabolizing system in the liver
consequence: drugs may be chemically altered (and perhaps inactivated) before it reaches systemic circulation
What is the definition of drug kinectic order? Give the rate equation.
dependence of rate of a process on the exponent of the drug concentration
rate = constant * [drug]^n
n = kinectic order
What factors affect the flux of drugs across biological membranes?
concentration difference across membrane
area
permeability coefficient: lipid solubility
size
thickness
What is drug metabolism and why is it necessary?
process of converting lipophilic chemicals into hydrophilic chemicals that can be readily excreted in the urine or bile; prevents toxic buildup
What are the 4 major reasons why drug metabolism is clinically important?
there are genetic differences in drug-metabolizing genes among individuals
toxic metabolites can form as a result of drug metabolism (i.e. acetaminophen, MPTP)
major source of drug-drug interactions (i.e. terbenafine + strong inhibitors of CYP3A4 (ketoconazole, erythromycin) > buildup of terbenafine > cardiotoxicity)
drug pharmacokinetics may be altered during pathophysiological conditions > need to adjust dose or select alternative drug
What are the 4 types of drug metabolism reactions? and what phases are they a part of?
Phase I:
oxidation
reduction
hydrolysis
Phase II:
conjugation
True or false. Biotransformation is generally catalyzed by enzymes.
true
What are the major sites of drug metabolism in the body?
liver
intestine
kidney
lung
skin
nasal epithelium
What role do bacteria play in drug metabolism?
some drug metabolic reactions (i.e. reduction) are catalyzed by enzymes in gut microflora (mainly anaerobic bacteria in colon)
How are "inducible" drug-metabolizing enzyme responses mediated?
xenobiotic-sensing receptors
What are the 3 "xenobiotic-sensing receptors" that mediate induction of xenobiotic-metabolizing enzymes and what are their prototype ligands?
All of the following are descriptive of phase I metabolic oxidation except:
A. generally catalyzed by intestinal microflora (phase I metabolic reduction)
Which of the following is descriptive of phase I metabolic oxidation:
D. hydroxylation, epoxidation of double bond, heteroatom(S-, N-, I-) oxygenation or N-hydroxylation, and heteroatom (O-, S-, N-) dealkylation
All of the following are descriptive of phase I metabolic reduction except:
B. catalyzed by flavin monooxygenases
Which of the following is descriptive of phase I metabolic reduction:
B. catalyzed by NAD(P)H-quinone oxidoreductase-1 and NAD(P)H-quinone-2
What 2 major enzymes are involved in phase I metabolic hydrolysis?
carboxylesterases (CE)
epoxide hydrolases
Epoxide hydrolases are generally considered to be _____ enzymes, but can play a role in bioactivation.
detoxification
What are the 6 major conjugation reactions involved in Phase II metabolism?
glucuronidation
sulfation (sulfonation)
glutathione conjugation
acetylation
methylation
amino acid conjugation
All of the following are descriptive of phase II metabolic glucuronidation except:
D. substrates are aliphatic alcohols, phenols, amines, N-oxides, and N-hydroxyls, but not carboxylic acids (sulfation)
All of the following are descriptive of phase II metabolic sulfation (sulfonation) except:
A. substrates are aliphatic alcohols, phenols, amines, N-oxides, N-hydroxyls and carboxylic acids (not carboxylic acids!!!)
All of the following are descriptive of phase II metabolic glutathione conjugation except:
B. reaction occurs in microsome only (occurs in cytosol, microsomes and mitochondria)
All of the following are descriptive of phase II metabolic acetylation except:
A. epoxides, arene oxides, nitro groups and hydroxylamines are all substrates (amines are the only substrates)
All of the following are descriptive of phase II metabolic methylation except:
A. acetyl coenzyme A is a cofactor (S-adenosylmethionine (SAM) is the cofactor)
What is kinetic order? and what equation is used to descrie it?
depedence of rate of a process on the exponent of the drug concentration
rate = constant * [drug]^n
n = rate order
Match the following.
1. zero order
2. first order
a. renal excretion under normal conditions
b. hepatic metabolism under normal conditions
c. straight-line behavior on non-logarithmic plotting graph
d. straight-line behavior on a logarithmic plotting graph
e. alcohol elimination
f. aspirin overdose
g. rate of process is directly dependent on drug concentration
h. process is not dependent on the drug concentration and proceeds at a constant rate
i. constant amount lost per unit time
j. constant percent of fraction lost per unit time
k. drug administration
l. drug elimination in overdose
m. approach an end-point at a proportional rate
n. approach an end-poiny at a constant rate
1. zero order - c. straight-line behavior on non-logarithmic plotting graph, e. alcohol elimination, f. aspirin overdose, h. process is not dependent on the drug concentration and proceeds at a constant rate, i. constant amount lost per unit time, k. drug administration, l. drug elimination in overdose
2. first order - a. renal excretion under normal conditions, b. hepatic metabolism under normal conditions, d. straight-line behavior on a logarithmic plotting graph, g. rate of process is directly dependent on drug concentration, j. constant percent of fraction lost per unit time, m. approach an end-point at a proportional rate
True or false. A first order plot will have an exponential curve on a non-logarithmic graph and straight line behavior on a logarithmic graph.
true
True or false. A zero order plot will have straight line behavior on a non-logarithmic graph and an exponential curve on a logarithmic graph.
true
What is the equation for rate of drug input?
rate of drug input = f (D/T)
What equation is used to determine the elimination rate of a drug under normal conditions?
Michaelis-Menten equation; E = (Vmax * C)/ (Km + C)
E = elimination rate
Vmax = maximum rate of drug elimination
Km = drug concentration at which rate of elimination is 1/2 Vmax
C = concentration of drug in plasma
True or false. The concept of half-life applies to both zero and first order.
False, the concept of half-life only applies to first order.
What is half-life and what is its significance?
time required for amount of drug to decrease to 1/2 of the starting amount; half-lives can vary between individuals based on their renal and hepatic function and needs to be considered in dosing schedule
What equation is used to express the relationship between half life (t1/2) and the elimination rate constant (Ke)? Are they directly or inversely related?
Ke = 0.7/half life; inversely
What is the plateau principle, how is it used and what is its relationship to drug accumulation?
used to achieve steady state with drug accumulation (some drug is still left over when the next dose is given - this needs to be accounted for) so that rate of input and rate of loss per day are equal
What equation can be used to determine loading dose when the time interval to achieve steady state levels may be too long if there is a serious, painful, or even life-threatening condition and the half-life of the drug is too long?
loading dose = Css * Vd
Css = average concentration at steady state
Vd = volume distribution
What equation is used for "maintenance of a dose" at the steady state level?
DOSEmaintenance = clearance * Css
Css = average concentration at steady state
What is a very useful concept for the determination of a dosing regimen? What equation is used to calculate this value?
clearance = (Vd)(Ke)
Vd = volume distribution
Ke = elimination constant
What equation is used to determine total body clearance?
CLtotal = CLliver + CLkidney + CLother
How do you determine when the steady state is achieved in a regular dosing regimen?
after four half-lives (4 * t1/2)
What is the steady state equation?
f(D/T) = (Css)(CL)
f(D/T) = input rate
All of the following can affect drug metabolism rate except:
F. all the above true
True or false. Only a few drugs have adverse effects, while most of them do not.
False, all drugs produce adverse effects.
All of the following should be reason to routinely monitor serum drug levels except:
A) a. patient response is sufficient
What is a "therapeutic window"?
range of plasma concentration that lies in the effective range without going to a toxic range
Pharmocogenetics is:
B. the study of genetic basis for variation in drug response
a. a sub-disciplineof pharmacogenetics that employs tools for surveying the entire genome to assess genetic determinants of drug response (pharmacogenomics)
c. a variation in DNA sequence that is present at a frequency of at least 1% in a population (polymorphisms)
All of the following are true of SNPs except:
B. the CYP3A5*3 allele contains a SNP in intron 3 that creates an alternative splice site, which results in introduction of an early stop codon and production of an active protein (produces an inactive protein)
All of the following are true of haplotype except:
A. it is the proportion of individuals carrying a variant allele that express an associated phenotype (penetrance)
_____ (2 words) occurs when the genotype present at one locus is independent of the genotype at a second locus, while _____ (2 words) occurs when the genotypes at two loci are not independent of one another.
Linkage equilibrium; linkage disequilibrium
What are some practical applications of pharmacogenetics?
better screening of potential drug candidates for efficacy, toxicity, and side effects in clinical trials
better identification of therapeutic dose
improved ability to select potential protein targets for drug development
better ability to identify patients who might be at increased risk for therapeutic failure or development of an adverse drug reaction
How are pharmacogenetic traits identified?
by using a "reverse genetic, genotype-to-phenotype approach"
genomics-based technologies
patient drug response
Match the following.
1. autosomal recessive
2. codominant
3. dominant
a. heterozygous exhibit a phenotype that is intermediate to that of homozygotes for the common allele and homozygotes for the variant allele
b. most common pattern
c. responsible gene is located on an autosome and a distinct phenotype is evident only with nonfunctional alleles on both chromosomes
d. exhibits gene dosage effect
e. normal allele dominates over mutant allele
f. distinct phenotype is evident with one nonfunctional allele
g. no dominance of one allele over another
1. autosomal recessive - c. responsible gene is located on an autosome and a distinct phenotype is evident only with nonfunctional alleles on both chromosomes, e. normal allele dominates over mutant allele
2. codominant - a. heterozygous exhibit a phenotype that is intermediate to that of homozygotes for the common allele and homozygotes for the variant allele, b. most common pattern, d. exhibits gene dosage effect, g. no dominance of one allele over another
3. dominant - f. distinct phenotype is evident with one nonfunctional allele
True or false. Monogenic traits are often possible to predict phenotype based on genotype, while multigenic traits have a large number of possible genotypes that will produce a broad range of phenotypes and do not reveal any distinct groups.
true
What are the 3 types of polymorphisms?
single nucleotide polymorphisms (SNPs)
insertions/deltions (Indels)
copy number variations (CNVs)
All of the following are true of polymorphisms in non-coding regions except:
C. promoter and enhancer regions may alter cis-elemenents that regulate translation (regulate transcription of genes)
a. base pair change does not result in amino acid change
b. base pair change introduces a stop codon
c. base pair change results in amino acid change
1. non-synonymous (missense) - c. base pair change results in amino acid change
2. synonymous (sense) - a. base pair change does not result in amino acid change
3. Nonsense - b. base pair change introduces a stop codon
How can a SNP affect protein function?
some SNPs can create an alternative splice site, which results in introduction of an early stop codon and production of an inactive protein
What 4 factors determines the clinical relevance of a pharmacogenetic polymorphism?
frequency and penetrance of a variant allele
narrowness of therapeutic index or sharpness of dose-response curve
limited availability of alternative clearance pathways
absence of alternative drugs
What types of genes are involved in pharmacogenetic traits?
genes that encode determinants of a drugs pharmacokinetics
genes that encode drug receptors and targets
genes that are involved in the disease being treated but do not directly interact with a drug (modifiers)
Give 3 examples of pharmacogenetic traits.
CYP2D6 - debrisoquine polymorphism
NAT2 - acetylation polymorphism
ADH2 - polymorphisms in ethanol metabolism
All of the following are true of glial cells except:
B. microglia produce myelin and insulate nerve cell axons (oligodendrocytes and Schwann cells produce myelin and insulate nerve cell axons)
All of the following are true of glial cells except:
A. Schwann cells regulate the properties of the post-synaptic terminal at the nerve-muscle synapse (pre-synaptic terminal)
All of the following are true of neurons except:
B. dendrites contain voltage gated sodium channels and convey action potentials (dendrites DO NOT contain voltage gated sodium channels and convey action potentials, but they do contain ionotrophic neurotransmitter receptors and voltage-gated calcium channels which propagate an electrical signal to the soma. Axons generate action potentials, which are generated at the axon hillock.)
What 6 steps of synaptic transmission are targeted for pharmacological intervention?
1. synthesis of NT from precursor (targeted by DOPA decarboxylase) and storage in vesicles (targeted by VMAT)
2. action potential that depolarizes pre-synaptic nerve terminal (targeted by local anesthetics)
3. depolarization activates voltage-dependent calcium channels and calcium enters pre-synaptic terminal (targeted by antibiotics like streptomycin and gentamycin)
4. influx of calcium leads to fusion of vesicles with pre-synaptic membrane and release of NT into synaptic cleft (targeted by botulinum toxin A and black widow spider venom)
5. NT diffuses across cleft and binds to post-synaptic receptors (ionotropic or metabotrophic receptors)
6. removal of NT via enzymes in cleft, recycling or degradation of post-synaptic intracellular signaling molecules (targeted by Dopamine, NE and serotonin transporters, and MAO and COMT)
What molecules are the primary excitatory and inhibitory NTs in the CNS?
amino acids:
excitatory - glutamate and aspartate
inhibitory - glycine and GABA
What molecules are the primary modulatory NTs in the CNS?
biogenic amines:
dopamine
NE
Epinephrine
histamine
serotonin
What molecule is considered to be an "atypical" NT in the CNS and why?
NO - it is made on demand and released by diffusion rather than being stored and released by synaptic vesicles
What are 2 examples of peptide NTs?
opioid peptides
tachykinins
All of the following are true in regards to fast excitatory synaptic transmission except:
D. all of the above are true
All of the following are true in regards to metabotrophic G protein-coupled receptors except:
E. a and c (activation of beta-adrenergic receptors leads to an increase in AC; activation of alpha-2-adrenergic receptors leads to a decrease in AC)
All of the following are true except:
G. all of the above are true
Glutamate activates _____ and _____ receptors, while acetylcholine activates _____ and _____ receptors.
a. iris (radial muscle)
b. ciliary muscle
c. heart (sympathetic autonomic nervous system)
d. heart contractility
e. blood vessels of skin
f. blood vessels of skeletal muscle
g. blood vessels of kidney
h. endothelium
i. bronchiolar smooth muscles
j. walls of GI tract
k. esophageal sphincters
l. gastric secretions
m. bladder
n. GU sphincters
o. uterus
p. penis
q. pilomotor smooth muscle
r. apocrine sweat glands
s. eccrine sweat glands
t. liver metabolism
u. fat metabolism
v. kidney
1. sympathetic, contraction, alpha-1 receptors - a. iris (radial muscle), n. GU sphincters
2. sympathetic, contraction, alpha receptors - e. blood vessels of skin, o. uterus
3. sympathetic, relaxation, beta receptors - b. ciliary muscle
4. sympathetic, relaxation, beta-2 receptors - f. blood vessels of skeletal muscle, i. bronchiolar smooth muscles, j. walls of GI tract, m. bladder, o. uterus
5. sympathetic, relaxation, M receptors - f. blood vessels of skeletal muscle
6. sympathetic, relaxation, D1 receptors - g. blood vessels of kidney
7. sympathetic, relaxation, alpha-2 receptors - j. walls of GI tract
8. sympathetic, accelerates, beta-1 and beta-2 receptors - c. heart (sympathetic autonomic nervous system)
9. sympathetic, increases, beta-1 and beta-2 receptors - d. heart contractility
10. sympathetic, ejaculation, alpha receptors - p. penis
11. sympathetic, increases, alpha receptors - r. apocrine sweat glands
12. sympathetic, increases, M receptors - s. eccrine sweat glands
13. sympathetic, gluconeogenesis, beta-2 and alpha receptors - t. liver metabolism
14. sympathetic, glycogenolysis, beta-2 and alpha receptors - t. liver metabolism
15. sympathetic, lipolysis, beta-3 receptors - u. fat metabolism
16. sympathetic, renin release, beta-1 receptors - v. kidney
a. iris (circular muscle)
b. ciliary muscle
c. heart (sympathetic autonomic nervous system)
d. heart contractility
e. endothelium
f. bronchiolar smooth muscles
g. walls of GI tract
h. esophageal sphincters
i. gastric secretions
j. bladder
k. GU sphincters
l. uterus
m. penis
1. Parasympathetic, contraction, M3 receptors - a. iris (circular muscle), b. ciliary muscle, f. bronchiolar smooth muscles, g. walls of GI tract, j. bladder, l. uterus
2. Parasympathetic, contraction, M receptors - h. esophageal sphincters
3. Parasympathetic, relaxation, M3 receptors - k. GU sphincters
5. Parasympathetic, decreases, M2 receptors - d. heart contractility
6. Parasympathetic, EDRF release, M3 receptors - e. endothelium
7. Parasympathetic, increases, M1 receptors - i. gastric secretions
8. Parasympathetic, erection, M receptors - m. penis
Which of the following agonists are prototypical drugs used for modulating cholinergic function in patients:
A. ACh
Which of the following antagonists are prototypical drugs used for modulating cholinergic function in patients:
E. more than one of the above (atropine and d-tubocurarine, also mecamylamine)
Which of the following anticholinesterases are prototypical drugs used for modulating cholinergic function in patients:
C. neostigmine
What agent is known for its ability to block ACh release into the synaptic cleft:
B. botulinum toxinA
What agent is used for the regeneration of ACh:
B. pralidoxime
All of the following are muscle relaxants except:
a. baclofen
b. dantrolene
c. cyclobenzaprine
e. all of the above are true
e. all of the above are true
What agonist is known for its ability to block depolarization of cholinergic neurons:
B. succinylcholine
All of the following applications of cholinergic pharmacology are true except:
D. ACh is used to treat sinus bradycardia (atropine is used to treat sinus bradycardia)
Which of the following applications of cholinergic pharmacology are true:
E. more than one of the above (b and c are true)
Which of the following agents can be used as "nerve gas" in chemical warfare:
A. sarin
Which ion is important in ACh release?
calcium
Which agent inhibits the rate-limiting step for the uptake and synthesis of choline into the nerve terminal:
B. hemicholiniums
What agent inhibits the packaging of ACh into secretory vesicles:
E. vesamicol
What agent prevents the activation of the nerve terminal:
B. local anesthetics
What agent interferes with the influx of calcium into the nerve terminal:
B. streptomycin
What agent modifies exocytosis at the synaptic membrane:
G. more than one of the above (c and e)
All of the following are possible side effects of agents that affect cholinergic activity except:
A. atropine - miosis, difficulty with near vision, elevated intraocular pressure (mydriasis not miosis)
All of the following are possible side effects of agents that affect cholinergic activity via muscuranic receptors except:
B. atropine - increased gastric emptying (decreased gastric emptying and GI tract motility, constipation)
All of the following are true of agents that affect cholinergic activity via muscuranic receptors except:
D. tolterodine is a quaternary amine that is metabolized by the liver (tolterodine is a tertiary amine)
All of the following are possible side effects of agents that affect cholinergic activity via muscuranic receptors except:
A. pilocarpine - dry mouth (increased salivary secretion and sweating - used to treat dry mouth)
All of the following are possible side effects of agents that affect cholinergic activity via nicotinic receptors except:
D. all of the above are true
All of the following are possible side effects of non-depolarizing nicotinic blocking agents except:
A. d-tubocurarine - rapid and transient decrease in blood pressure
True or false. Succinylcholine is a phase I depolarizing blockade and cardiac arrest and/or muscle soreness are possible side effects.
true
All of the following are true of spasmolytics except:
C. tizanidine is an atypical alpha-1-adrenoceptor agonist and increases both pre- and post-synaptic inhibition (tizanidine is an atypical alpha-2-adrenoceptor agonist)
What are the 3 components of potential changes in postganglionic cell bodies?
fast EPSPs - mediated by nAChRs, mecamylamine or d-tubocurarine blocks this early EPSP
IPSP - mediated by accessory cells in ganglion (SIF cells) and ACh stimulation of inhibitory M2 receptors; control or prevent excessive neurotransmission
slow EPSPs - mediated by M1 receptors and peptide co-transmitter receptors
What is the most common side effect seen with hexamethonium?
orthostatic hypotension
All of the following are true of reversible anticholinesterase agents except:
a. physostigmine is a tertiary amine methyl carbamate that may be used topically to treat glaucoma
b. neostigmine is a quaternary amine that is used in the management of myasthenia gravis and has no significant effects on the CNS
c. edrophonium is used as a diagnostic agent in myasthenia gravis
d. pyridostigmine is used in the chronic treatment of myasthenia
f. all of the above are true
f. all of the above are true
How do you differentiate between myasthenia crisis from cholinergic crisis in your patient? What would you expect in each case and how long would the effects last?
give a small test dose of edrophonium; cholinergic crisis would improve, myasthenia crisis would worsen; the test will last a few minutes
All of the following are true of reversible anticholinesterase agents used to treat Alzheimer's disease except:
D. all of the above are true
All of the following are possible side effects of irreversible anticholinesterases except:
G. hypertension (hypotension)
What agents should be used in the treatment of organophosphate poisoning and why?
pralidoxime; promotes regeneration of AChE
supportive measures - supporting respiration and BP, benzodiazepines to control seizures
Author
davis.tiff
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174964
Card Set
GENERAL PRINCIPLES OF PHARM - CHOLINERGIC PHARMACOLOGY (DR. PODGORSKI, DR. KOCAREK, DR. KAPATOS, DR.
