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FA Pharmacology

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pujomora's version from 2016-06-09 05:05

Enzyme kinetics

Question Answer
Km is inversely related to
(Michaelis-Menten kinetics)
affinity of enzyme for substrate
Vmax is directly proportional toenzyme concentration
enzymatic reactions that have cooperative kinetics havesigmoid curve
y-intercept inversely proportional to
(Lineweaver-Burk plot)
Vmax
the further to the right the x-intercept, the greater the
(Lineweaver-Burk plot)
Km
the further to the right the x-intercept, the lower the
(Lineweaver-Burk plot)
affinity
competitive inhibitor effect on Vmaxnone
competitive inhibitor effect on Kmincrease
noncompetitive inhibitor effect on Vmaxdecrease
noncompetitive inhibitor effect on Kmnone
Lineweaver-Burk plot1/[S] (x axis) vs. 1/V (y axis)
slope=Km/Vmax
Competitive inhibitor changes and doesn't changeIncreases Km
Doesn't change Vmax
Noncompetitive inhibitor changes and doesn't changeDecreases Vmax
Doesn't change Km
Km =[S] at (1/2)Vmax
"Mnemonic" to remember competitive vs. noncompetitive inhibitors on Lineweaver-Burk plotCompetitive inhibitors cross each other competitively, whereas noncompetitive inhibitors do not.
Which is overcome by ↑ [S] - competitive or noncompetitive inhibitors?competitive
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Pharmacokinetics

Question Answer
bioavailabilty of IV med100%
formula for volume of distributionamount of drug in body/plasma drug concentration
low Vdblood, large/charged molecules, plasma protein bound
medium VdECF, small hydrophilic molecules
high Vdall tissue, small lipophilic molecules, especially if bound to tissue protein
half-life is a property offirst-order elimination
number of half-lives it takes a drug infused a constant rate to reach steady state4-5 half-lives
half-life formula(0.7 x Vd)/CL
clearance formula(rate of elimination of drug)/plasma drug concentration or Vd x Ke (elimination constant)
loading doseCp x Vd/F
maintenance doseCp x CL/F
in renal or liver diseasemaintenance dose decreases, loading dose unchanged
time to steady state is independent of dosing frequency or sizedepends on half-life
Cp =target plasma concentration
What kind of drugs can be altered by liver and kidney disease?plasma protein-bound drugs (↓ protein binding, ↑ Vd)
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Elimination

Question Answer
examples of zero-order elimination drugsPhenytoin, Ethanol, Aspirin (at high or toxic concentrations)
(a PEA is shaped like a 0)
examples of weak acid drugsphenobarbital, methotrexate, aspirin
treat overdose of weak acid drugs withbicarbonate; trapped in basic environments
example of weak base drugamphetamines
treat overdose of weak base drugs withammonium chloride; trapped in acidic environment
phase I of drug metabolismreduction, oxidation, hydrolysis with P-450 usually yields slightly polar, water soluble active metabolites
geriatric patients lose this phase of metabolism firstphase I
phase II metabolismconjugation (glucuronidation, acetylation, sulfation) yields very polar, inactive metabolites (renally excreted)
slow acetylators are affected in this phase of metabolismphase II
Explain zero-order eliminationa constant amount of the drug is excreted over a period of time
2.5 units/h is eliminated
Explain first-order eliminationa constant percent of the drug is eliminated over a period of time
50% every hour (10 units to start, 5 units eliminated in the first hour, 2.5 units eliminated in the 2nd, etc)
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Efficacy, potency, receptor binding, and therapeutic index/window

Question Answer
high-efficacy drugsanalgesics, antibiotics, antihistamines, decongestants
high-potency drugschemotherapy, antihypertensives, antilipids
therapeutic index formulaLD50/ED50
drugs with low TIsdigoxin, lithium, theophylline, warfarin
therapeutic windowminimum effective dose to minimum toxic dose
competitive inhibitors effect on potency/efficacy↓ potency
noncompetitive inhibitors effect on potency/efficacy↓ efficacy
A=drug
A+C=drug + allosteric activator
A+B = drug + competitive antagonist
A+D = drug + noncompetitive antagonist
A+D can also be a drug+partial agonist, but the potency doesn't necessarily have to be the same in that case
Example of competitive antagonistDiazepam + flumazenil on GABA receptor
Example of noncompetitive antagonistNE + phenoxybenzamine on α-receptors
Example of partial agonistMorphine (full agonist) + buprenorphine (partial agonist) at opioid μ-receptor
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Nicotinic, muscarinic, ACh, NE, parasympathetics, sympathetics

Question Answer
ACh works where?Pre/post ganglionic receptors in parasympathetic nervous system
Preganglionic receptors in both parasymp & sympathetic nervous systems
Post ganglionic receptors in sympathetic sweat glands
Skeletal muscle NMJ
NE works where?Post ganglionic receptors in sympathetic nervous system
end organ effects after it's produced by the adrenal medulla
Nicotinic receptors are where?1st synapse of efferent parasympathetics ( Nn )
sympathetic ganglion ( Nn )
adrenal medulla ( Nn )
skeletal muscle ( Nm )
Muscarinic receptors are where?parasympathetic organs
Sympathetic sweat glands
They all use ACh as the NT
Nicotinic ACh receptor typeligand gated Na/K channels
Muscarinic ACh receptor typeG-protein coupled, act through second messengers
Parasympathetic organs NT and M or N?ACh, M
1st synapse of efferent parasympathetics NT and M or N?ACh, N
Sympathetic sweat glands NT and M or N?ACh, M
Sympathetic organs NT and M or N?NE, α/β
Renal vasculature NTDopamine
Sympathetic ganglion NT and M or N?ACh, N
Adrenal medulla NT and M or N?ACh, N
Skeletal muscle NT and M or N?ACh, N
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Autonomic drugs

Question Answer
alpha-1 receptor G protein classq
alpha-1 receptor fnsvascular smooth muscle contraction
dilate pupils (mydriasis)
contract intestinal and bladder sphincters
alpha-2 G proteini
alpha-2 fnsincrease platelet aggregation
decrease insulin release
decrease lipolysis
decrease sympathetic outflow
beta-1 G proteins
beta-1 fnsincrease heart rate
increase contractility
increase renin release
increase lipolysis
beta-2 G proteins
beta-2 fns↑↑ sympathetic effects
vasodilate
bronchodilate
increased heart rate
increased contractility
increased lipolysis
increased insulin release
decrease uterine tone
relax ciliary muscles
increase aqueous humor production
M1 receptor G proteinq
M1 fnsCNS, enteric nervous system
M2 G proteini
M2 fndecrease heart rate and contractility of atria
M3 G proteinq
M3 fnincrease exocrine gland secretions
increase gut peristalsis
increase bladder contraction
bronchoconstriction
miosis, ciliary muscle contraction (accomodation)
D1 G proteins
D1 fnrelaxes renal vascular smooth muscle
D2 fnmodulates transmitter release, esp in brain
D2 G proteini
H1 G proteinq
H1 fnincrease nasal and bronchial mucus production
contraction of bronchioles
pruritus and pain
H2 G proteins
H2 fnincrease gastric acid secretion
V1 G proteinq
V1 fnvascular smooth muscle contraction
V2 G proteins
V2 fnincrease water permeability and reabsorption in collecting tubules of kidney
Sympathetic receptorsα1, α2, β1, β2
But α2 controls/limits the sympathetic outflow
Parasympathetic receptorsM1, M2, M3
Mnemonic for g-protein classes of automic receptorsQiss and qiq till you're siq of sqs (super qinky sex)
Gq mechanismphospholipase C -> lipids to PIP2. PIP2 -> DAG -> protein kinase C. PIP2 also -> IP3 -> increased calcium -> smooth muscle contraction
Gs mechanismAdenylate cyclase -> ATP to cAMP -> protein kinase A -> increased calcium in heart, stops myosin light chain kinase (smooth muscle)
Gi mneumonicMAD 2's
Gq mneumonicHAVe 1 M&M
Gi mechanismINHIBITS: Adenylate cyclase -> ATP to cAMP -> protein kinase A -> increased calcium in heart, stops myosin light chain kinase (smooth muscle)
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Autonomic drugs - a functions-based approach

Question Answer
↑ vascular smooth muscle contractionα1, V1
↑ pupillary dilator muscle contraction (mydriasis)α1
↑ intestinal and bladder sphincter muscle contractionα1
↓ sympathetic outflowα2
↓ insulin releaseα2
↓ lipolysisα2
↑ platelet aggregationα2
↑ HRβ1, β2
↑ contractilityβ1, β2
↑ renin releaseβ1
↑ lipolysisβ1, β2
Vasodilationβ2
Bronchodilationβ2
↓ uterine tone (tocolysis)β2
Ciliary muscle relaxationβ2
↑ aqueous humor productionβ2
CNS stimulationM1
Eneteric nervous system stimulationM1
↓ HRM2
↓ contractilityM2
↑ exocrine gland secretions (lacrimal, gastric acid)M3, H2 (gastric acid)
↑ gut peristalsisM3
↑ bladder contractionM3
BronchoconstrictionM3, H1
↑ pupillary sphincter muscle contraction (miosis)M3
Ciliary muscle contraction (accommodation)M3
Relaxes renal vascular smooth muscleD1
Modulates transmitter release, esp. in brainD2
↑ nasal and bronchial mucus productionH1
PruritusH1
PainH1
↑ H20 permeability/resorption in the collecting tubules of the kidneyV2
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Cholinomimetic agents

DrugClincal applicationsAction
bethanecholpostoperative ileus
neurologic ileus
urinary retention
activates bowel and bladder smooth muscle
resistant to AChE
carbacholglaucoma
pupillary contraction
relief of intraocular pressure
carbon copy of acetylcholine
↑ pupillary sphincter muscle contraction (miosis)
ciliary muscle contraction (accommodation)
↑ lacrimal gland secretion
pilocarpineopen and closed angle glaucoma
potent stimulator of sweat, tears, saliva
Acts on M3 receptors
contracts ciliary muscle (open angle)
contracts pupillary sphincter (closed angle)
resistant to AChE
Methacholinechallenge test for asthma diagnosisstimulates muscarinic receptors in airway when inhaled (M3) → bronchoconstriction
neostigminepostoperative and neurogenic ileus and urinary retention, postoperative reversal of NMJ block, myasthenia gravisincreases endogenous ACh
pyridostigminemyasthenia gravis (long acting) does not penetrate CNSincrease endogenous ACh, increase strength
edrophoniumdiagnosis of myasthenia gravis (extremely short acting)↑ endogenous ACh
physostigmineanticholinergic toxicity (atropine overdose)
crosses blood brain barrier
↑ endogenous ACh
"Phyxes" atropine overdoes
donepezilalzheimer's disease↑ endogenous ACh
things to watch for in all cholinomimeticsexacerbation of COPD, asthma, and peptic ulcers-
antidote to organophosphate poisoningatropine + pralidoxime (regenerates AChE)-
organophosphate poisoningirreversibly inhibits AChE. common in farmers from insecticides-
DUMBBELSS of organophosphate poisoningdiarrhea
urination
miosis
bronchospasm
bradycardia
excitation of skeletal muscle and CNS
Lacrimation
Sweating
Salivation
-
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Rapid fire: Direct vs indirect cholinomimetic

Question Answer
BethanecholDirect cholinomimetic
CarbacholDirect cholinomimetic
PilocarpineDirect cholinomimetic
MethacholineDirect cholinomimetic
NeostigmineIndirect cholinomimetic
PyridostigmineIndirect cholinomimetic
EdrophoniumIndirect cholinomimetic
PhysostigmineIndirect cholinomimetic
DonepezilIndirect cholinomimetic
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Cholinergic drugs

ABC

 

LabelAnswer
AHemicholinium
BVesamicol
CBotulinum
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Muscarinic agonists

DrugOrgan systemClinical application
AtropineEyeproduces mydriasis, cycloplegia
HomatropineEyeproduces mydriasis, cycloplegia
TropicamideEyeproduces mydriasis, cycloplegia
benztropineCNSparkinson's (park your benz)
scopolomineCNSmotion sickness
ipratropiumRespiratoryCOPD, asthma
tiotropiumRespiratoryCOPD, asthma
OxybutyninGUreduce urgency in mild cystitis, reduce bladder spasms
parenteral application of glycopyrrolateGI, respiratorypreoperative, to reduce airway secretions
oral application of glycopyrrolateGI, respiratorydrooling, peptic ulcer
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Atropine

Question Answer
medical use of atropineto treat bradycardia and for ophthalmic applications
effect of atropine on eyepupil dilation, cycloplegia
effect of atropine on airwaydecrease secretions
effect of atropine on stomachdecrease acid secretion
effect of atropine on gutdecreased motility
effect of atropine on bladderdecreased urgency in cystitis
toxicity of atropine in elderlyacute angle-closure glaucoma
toxicity of atropine in men with BPHurinary retention
toxicity of atropine in infantshyperthermia
toxicities of atropineincreased body temp (decreased sweating), rapid pulse, dry mouth, dry flushed skin, cycloplegia, constipation, disorientation
random plant that causes mydriasisJimson weed
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