Shared Flashcard Set

Details

IT Test 2 Fall 2012
Cholinergic, Adrenergic, Direct and Indirect, Agonist, Antagonist
124
Pharmacology
Professional
09/16/2012

Additional Pharmacology Flashcards

 


 

Cards

Term
N-Acetyltransferase
Definition
Higher risk of Neurotoxicity with ISONIAZID
Term
Thiopurine-S-methyltransfrase
Definition
Higher hematopoietic toxicity AZATHIOPRINE and 6-MERCAPTOPURINE
Term
TA(TATA Box) Repeats in Promoter Region
Definition
Higher risk of toxicity for IRINOTECAN

UDP-glucuronosyl-transferase(UGT1A1) has lower expression
Term
Glutathione-S-transferase
Definition
Higher toxicity with anti-cancer drugs
Term
Aldehyde dehydrogenase
Definition
Impaired function causes facial flushing with alcohol
Term
Butyrylcholinesterase (pseudocholinesterae)
Definition
Prolonged muscle relaxant response to Succinylcholine
Term
P-glycoprotein
Definition
Member of ATP-binding cassette family (ABCB1)
Toxicity for anti-cancer drugs and digoxin
Term
Variation in a anion transporter
Definition
Statins and methorexate adverse effects increased
Term
Variations in cation transporter
Definition
Influence effect of Metformin
Term
Receptors that signal through Gq
Definition
M1 M3 M5 Alpha1 (Increases intraceullular Ca2+)
Term
Receptors that signal through Gi
Definition
M2 M4 Alpha 2 (Opens K+ and REDUCES cAMP)
Term
M1 and M4 location
Definition
CNS neurons
Term
M2 Location
Definition
Myocardium
Term
M3 Location
Definition
Smooth Muscle, Vascular Endothelium, Excorine Glands
Term
Receptors that Signal through Gs
Definition
All Beta receptors (B1, B2, B3) ad D1 (Elevates cAMP)
Term
B1 Location
Definition
Heart and Renal Tubes
Term
B2 Location
Definition
Lung and Various Smooth muscle
Term
B3 Location
Definition
Adipocytes
Term
B1 Function
Definition
INCREASED Heart rate and Force of Contraction
INCREASED blood flow to skeletal muscle
INCREASED Renin release from Kidney
Term
B2 Function
Definition
Relaxation of Bronchilar Smooth Muscle

INCREASED Gluconeogenesis and GLycogenolysis in Liver
Term
B3 Function
Definition
INCREASED lipolysis in fat cells
Term
A1 Function
Definition
DECREASED Blood flow to skin and viscera
Vasoconstriction on vascular smooth muscle (skin and splanchnic)

INCREASED Gluconeogenesis and Glycogenolysis in liver
Term
M2 Function
Definition
Parasympathetic reduces heart rate
Term
M3 function
Definition
INCREASED Blood flow to skeletal muscle

Contraction of bronchiolar smooth muscle

Constriction of pupils in eyes due to contraction of ciliary Muscles
Term
Renin Production Regulated by which system and receptor?
Definition
Sympathetic Nervous System , B1 receptor
Term
Location of Sensory Input for Afferent Fibers
Definition
Hypothalamus and Medulla
Term
Location of Baroreceptors typically found
Definition
Carotid Sinus and Aortic Arch
Term
Phenylephrine
Definition
Alpha1-adrenoceptor Agonists

INCREASE in Systolic and Diastolic

Nasal Decongestion (Dose too high you lose this selectivity)
Term
Midodrine
Definition
Alpha1-adrenoceptor Agonists

INCREASE in Systolic and Diastolic

Orthostatic HYPOtension
Term
Clonidine
Definition
Alpha2-Adrenoceptor AGONIST

Treats Hypertension

Suppresses sympathetic tone through negative feedback of Alpha2 pre-ganglionic
Term
Dobutamine
Definition
Beta1-Adrenoceptor AGONIST

Treats Acute Heart Failure

Positive Inotrophic and Chronotropic (HR). Chronotropic less prominent

Increase in Cardiac Output
Term
Albuterol
Definition
Beta2-Adrenoceptor Agonist

Treats Asthma and COPD

Relaxes bronchial Smooth Muscle

MILD INCREASE in HR and Force of Contraction

Vasodilation in some vascular Beds of Skeletal Muscle

Inhalation dose minimizes effects on Heart and Vascular Beds
Term
Isoproterenol
Definition
Similar Potency for B1 and B2 receptors, NO EFFECT on Alpha

Vasodilator EXCEPT on Blood vessel in skin

Positive Chronotropic and Inotropic

REDUCTION in Diastolic, little effect on Systolic
Term
Norepinephrine
Definition
Alpha1, Alpha2, B1 (less for B2)

Vasoctriction, Increase in BP

Reduction in HR due to Baroceptor reflex
Term
Epinephrine
Definition
Alpha1, Alpha2, B1 and B2 recpeotrs

Inotropic effect but is equaled out due to baroceptor reflex

Increase in cardiac OUTPUT

Increase in Systolic, little effect on Diastolic
Term
Prazosin
Definition
(Minipress)

Alpha 1-Adrenoceptor Antagonist

Treats Hypertension & Hyperplasia of prostate

Vaasodilation on Vascular Smooth muscle

DECREASE in peripheral arterial resistance

DECREASE in venous tone

Decrease in mean Arterial Pressure primarily due to Diastolic
Term
Propanolol
Definition
(Inderal)

Beta1 Antagonist

Similar potency for B1 and B2 receptor. B2 less selection

Negative Inotropic and Chronotropic Effects
ACUTE EFFECT: INCREASE in peripheral resistance

CHRONIC EFFECT: DECREASE in peripheral resistance to decrease BP

Suppression of Renin
Term
Metoprolol
Definition
Beta1-Antagonist

Negative Inotropic and Chronotropic Effects

Treats Hypertension

Suppresses Renin release
Term
Other Effects of B1 antagonist besides anti-hypertension?
Definition
Contraction of Bronchial Smooth Muscle (Mainly propanolol)
Term
B1 can what effect on asthma patients?
Definition
Problematic effects since it causes bronchial smooth muscle contraction
Term
Acetylcholine
Definition
(Miochol-E)

Direct-Acting Cholinergic Agonist


Naturla transmitter, short acting and non-selective, interacts with muscarinic AND nicotinic

M3 Receptor
Term
Methacholine
Definition
Direct-Acting Cholinergic Agonist

Interactis with Muscarinic Receptors due to Methyl group

M3 Receptor
Term
Carbachol
Definition
(Carboptic)

Direct-Acting Cholinergic

Resistant to Cholinesterase and is NON-selective

Treats Glaucoma

M3 Receptor
Term
Bethanechol
Definition
(Urecholine)

Resistant to Cholinesterase and SELECTIVE for muscarinic receptors

Treats Urinary Retention

M3 Receptor
Term
How do Cholinergic drugs work?
Definition
Cause vasodilation through M3 reeptor. Vascular Endothelium releases NO and DECREASES BP. Baroreceptors stimulate sympathetic and INCREASE heart rate
Term
Organ Effects of Direct Acting Cholinergic Agonists

Cardiovascular System
Definition
Vasodilation through M3 receptors in Vascular endothelium that release NO

Decrease in BP

Reflex INCREASE in Heart rate with Low doses
Term
Organ Effects of Direct Acting Cholinergic Agonists

Eye
Definition
Contraction of Iris Circular Muscle (constriction of pupil)

Contraction of Ciliary Muscle (Accommodation)
Term
Organ Effects of Direct Acting Cholinergic Agonists

Respiratory System
Definition
Contraction of Bronchial Smooth Muscle

Stimulation of Glandular Secretion (mucus in lung)
Term
Organ Effects of Direct Acting Cholinergic Agonists

GI Tract
Definition
INCREASED motility and relaxation of sphincters (Increase movement of food through GI tract)

Stimulation of secretion from salivary and gastric glands
Term
Organ Effects of Direct Acting Cholinergic Agonists

Urinary Bladder
Definition
Contraction of Bladder and Relaxation of Sphincter (Voiding of Bladder)
Term
Edrophonium
Definition

(Tensilon)

 

Indirect-Cholinergic Agonist

 

Short Acting Drug

 

Treats Myasthenia Gravis Inhibits

 

cholinesterase which will increase ACh

Term
Neostigmine
Definition
(Prostigmin)

Treats Myasthenia Gravis

Inhibits cholinesterase which will increase ACh
Term
Indirect Acting Cholinergic Agonist have what side effects?
Definition
DIRECTLY cause bradycardia

Reduces Cardiac Output
Term
Atropine
Definition
Cholinergic Antagonist

Used in Ophthalmology

Selective for all muscarinic ACh receptors

Tertiary Amine
Term
Ipratropium
Definition
(Atrovent)

Selective for ALL muscarinic ACh

Treats Asthma and COPD

Quaternary Amine
Term
Why does it matter that Ipratropium is a tertiary amine?
Definition
Makes it much more limited and more lipohilic, which allows it to be used for COPD and asthma
Term
Cholinergic Antagonist given at too high doses can have an effect on?
Definition
Cardiovascular System
Term
Cholinergic Antagonist Organ System Effects

Cardiovascular Effects
Definition
Minimal effect on BP or heart rate at NORMAL dosage

Slight Tachycardia may occur
Term
Cholinergic Antagonist Organ System Effects

Eye
Definition
Relaxation of Iris circular Muscle (dilation of pupil)

Relaxation of Ciliary Muscle (loos of accommodation)
Term
Cholinergic Antagonist Organ System Effects

Respiratory System
Definition
Relaxation of bronchial smooth muscle

Inhibition of Glandular secretion (decrease secretion of mucous)
Term
Cholinergic Antagonist Organ System Effects

GI Tract
Definition
Reduced Motility

Inhibition of secretion from salivary gland
Term
Cholinergic Antagonist Organ System Effects

Urinary Bladder
Definition
Relaxation of Bladder muscles
Term
Cholinergic Antagonist Organ System Effects

Secretory Glands
Definition
Inhibits secretion
Term
Pharmacogenetics
Definition
Study of Genetic basis for Variation in drug response
Term
Pharmacogenomics
Definition
Assess the contribution from multiple genes on drug reponse
Term
Phenotype-Gentoype approach
Definition
Find the phenotype first, then use a pedigree to tract back
Term
Genotype-Phenotype approach
Definition
Find the Genotype first,then see what phenotype it expresses
Term
Locus
Definition
Location on chromosome where gene resides
Term
Allele
Definition
Specific DNA sequence at a particular Locus
Term
Haplotype
Definition
Particular combination of alleles at nearby loci on a chromosome that tend to be inherited together
Term
Linkage Disequilibrium
Definition
Tendency for alleles at nearby loci to be inherited together
Term
SNP occurring in promoter region?
Definition
INCREASE or DECREASE mRNA expression
Term
SNP in 5-UTR?
Definition
Alter gene regulation
Term
SNP in 3-UTR?
Definition
Alters mRNA stability and Protein expression
Term
SNP at exon-intron splicing site?
Definition
Causes alternative splicing
Term
VNTR stands for what and is normally found where?
Definition
Variable Number of Tandem Repeats, Normally found in non-coding regions
Term
Indel is what?
Definition
Insertion or deletion of one or more nucleotide in DNA sequences
Term
Genetic Variation is greatest in what group?
Definition
African Population
Term
Hardy-Weinberg Equilibrium
Definition
Evaluates effect of polymorphic variants in a specific gene.
Term
Genome Wide Associated Study
Definition
Used to discover unanticipated gene effects. Powerful approach to identify novel pharmacogenetic contribution
Term
Limitations of Genome Wide Associated Study
Definition
Has a high rate of False positive findings
Term
Functional Studies
Definition
Validates significance of potentials causative genetic variants.

Used for Drug transporters and metabolizing Enzymes
Term
Functional Studies are particularly useful when?
Definition
Doing non-synonymous coding SNP and indel it can identify loss of function and gain of function variants
Term
CYP450 Phase what?
Definition
Phase I
Term
CYP450 Predominant Enzymes
Definition
CYP3A4/5, CYP2D6, CYP2C9
Term
Prominent effects on Pharmacokinetics due to poor metabolizer polymorphism
Definition
INCREASED risk of toxicity of antidepressant and anti-psychotic drugs

Reduced analgesic effect of Codeine (pro-drug for morphine)

Reduced anti-neoplastic action of Tamoxifen (pro-drug for endoxifen)

Metabolism of Other drugs also affected
Term
Enzymes with prominent role in Wafarin Metabolism
Definition
CYP2C9 and Vitamin K Epoxidase
Term
This enzyme causes 10-fold reduction in Wafarin clearance
Definition
CYP2C9*3
Term
CYP2C9*3 affects what drugs?
Definition
NSAIDs, Warfarin, Phenytoin, Tolbutamide
Term
2 Poor metabolizer variants of CYP2C19
Definition
CYP2C19*2 & *3
Term
Ultra-rapid metabolizer of CYP2C19
Definition
CYP2C19*17
Term
Phase I Biotransformation
Definition
Increases Hydrophilicity

Inactivate Drug

Provides a Handle for Phase II
Term
Major Phase I Enzymes
Definition
CYP450 and FMO
Term
Phase II Biotransformation
Definition
Increases Hydrophilicity

Inactivates Drug

ADDS a recognition element for Active excretion
Term
Phase I Reactions
Definition
Oxidation
Hydroxylation
Reduction
Hydrolysis
Term
Oxidation on Carbon Susceptibility
Definition
Methyl Substituents on Skeleton easily accessible for oxidation to form alcohol --> carboxylic Acids

Longer-chain substituents the terminal carbon and penultimate carbon are most exposed which make them susceptible to oxidation

Aliphatic rings, most exposed region is likely to be oxidized

Activated carbon atoms next to sp2 or sp carbon MORE likely to be oxidized

Methyl--> Primary Alcohol --> aldehyde --> COOH

Oxidation of carbon Next to N,O,S
Term
Aromatic Hydroxylation Predominate form
Definition
Predominate form is PARA position, with some ortho formed
Term
Oxidation of Amines
Definition
Aromatic amines --> aromatic Nitro groups
N(OH)HCHRR--> O2N-CHRR

Aromatic Primary Amines --> aromatic Nitro groups
AR-NH-OH-->AR-NO2
Term
Oxidation of FMO
Definition
Oxidation of Nitrogen, Sulfur, Phosphorus (NPS)
Term
Oxiation pathway of Aldehyde, Carboxylic and Alcohol
Definition
Alcohol --> Aldehyde --> Carboxylic Acid
Term
Reduction
Definition
Ketones, Aldehyde, Azo and Nitro
Term
Reduction of Disulfide bridge forms?
Definition
Two Thiols
Term
Phase I Ester/Amide hydrolysis, which is hydrolyzed faster?
Definition
Esters are faster hydrolyzed than amides, Esters readily react with water
Term
Phase II Conjugation Metabolisms
Definition
Glucuronic Acid Conjugation
Sulfate Conjugation
Amino Acid Conjugation
Acetylation
Methylation
Glutathione Conjugation
Term
Phase II Most important conjugation?
Definition
Glucuronic Acid
Term
Glucuronidation Most susceptible functional groups
Definition
Amines, PHenols, Alcohols, Hydroxylamines, Carboxylic Acid, Sulfonadmides, Amides and Thiols
Term
Which one is the metabolite after conjugation with glucuronic acid?
Definition
C1, (Carbon next to oxygen)
Term
Sulfate Conjugation, Most susceptible functional groups
Definition
Phenols, Alcohols, Aryl Amines and N-hydroxy compounds
Term
Sulfate conjugation competes with which Phase II?
Definition
Glucuronidation
Term
Sulfate Conjugation is catalyzed by what enzyme?
Definition
Sulfotransferase with co-factor PAPS which donates the Sulfur
Term
Where does the sulfate for PAPS come from?
Definition
AA Cys or Met
Term
How does Amino acid Conjugation work?
Definition
Drug with a Carboxylic acid is activated by CoA-thioester and links it to a amino acid
Term
Acetylation occurs in what functional groups?
Definition
Nitrogen (amines)
Term
Methylation occurs in what functional groups?
Definition
Oxygen and Nitrogen
Term
Methylation receives it's methyl from where?
Definition
Methionine
Term
Glutathione/Mercapturic Acid Conjugates interact with?
Definition
Electrophilic Functional Groups :Epoxides, Alkyl Halides, Sulfonates, Disulfides, Radical species
Term
Which group on Glutathione interacts?
Definition
Thiol group
Term
Glutathione takes place Especially where in the body?
Definition
Liver, Kidney
Term
Glutathione reactions are catalyzed by what enzyme?
Definition
Glutathione Transferase
Term
Antidote for APAP
Definition
Acetylcysteine
Term
Why is acetylcysteine a antidote for APAP?
Definition
Its the precursor for glutathione
Term
CYP2C9
Definition
Wafarin
Phenytoid
NSAIDS
Tolbutamide
Term
CYP2C19 poor metabolizer
Definition
Mephenytoin INCREASED toxicity
Omeprazole INCREASED efficacy
Clopidrogel DECREASED efficacy
Term
CYP2D6
Definition
INCREASED risk of Toxicity of Anti-depressant and Anti-psychotic

Reduced analgesic effect of Codeine

Reduced antineoplastic action of Tamoxifen
Supporting users have an ad free experience!