Term
|
Definition
Higher risk of Neurotoxicity with ISONIAZID |
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Term
Thiopurine-S-methyltransfrase |
|
Definition
Higher hematopoietic toxicity AZATHIOPRINE and 6-MERCAPTOPURINE |
|
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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 |
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Term
|
Definition
Impaired function causes facial flushing with alcohol |
|
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Term
Butyrylcholinesterase (pseudocholinesterae) |
|
Definition
Prolonged muscle relaxant response to Succinylcholine |
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Term
|
Definition
Member of ATP-binding cassette family (ABCB1) Toxicity for anti-cancer drugs and digoxin |
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Term
Variation in a anion transporter |
|
Definition
Statins and methorexate adverse effects increased |
|
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Term
Variations in cation transporter |
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Definition
Influence effect of Metformin |
|
|
Term
Receptors that signal through Gq |
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Definition
M1 M3 M5 Alpha1 (Increases intraceullular Ca2+) |
|
|
Term
Receptors that signal through Gi |
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Definition
M2 M4 Alpha 2 (Opens K+ and REDUCES cAMP) |
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Term
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Definition
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Term
|
Definition
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Term
|
Definition
Smooth Muscle, Vascular Endothelium, Excorine Glands |
|
|
Term
Receptors that Signal through Gs |
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Definition
All Beta receptors (B1, B2, B3) ad D1 (Elevates cAMP) |
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Term
|
Definition
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Term
|
Definition
Lung and Various Smooth muscle |
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Term
|
Definition
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Term
|
Definition
INCREASED Heart rate and Force of Contraction INCREASED blood flow to skeletal muscle INCREASED Renin release from Kidney |
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Term
|
Definition
Relaxation of Bronchilar Smooth Muscle
INCREASED Gluconeogenesis and GLycogenolysis in Liver |
|
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Term
|
Definition
INCREASED lipolysis in fat cells |
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Term
|
Definition
DECREASED Blood flow to skin and viscera Vasoconstriction on vascular smooth muscle (skin and splanchnic)
INCREASED Gluconeogenesis and Glycogenolysis in liver |
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Term
|
Definition
Parasympathetic reduces heart rate |
|
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Term
|
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 |
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Definition
|
|
Term
Location of Baroreceptors typically found |
|
Definition
Carotid Sinus and Aortic Arch |
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Term
|
Definition
Alpha1-adrenoceptor Agonists
INCREASE in Systolic and Diastolic
Nasal Decongestion (Dose too high you lose this selectivity) |
|
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Term
|
Definition
Alpha1-adrenoceptor Agonists
INCREASE in Systolic and Diastolic
Orthostatic HYPOtension |
|
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Term
|
Definition
Alpha2-Adrenoceptor AGONIST
Treats Hypertension
Suppresses sympathetic tone through negative feedback of Alpha2 pre-ganglionic |
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Term
|
Definition
Beta1-Adrenoceptor AGONIST
Treats Acute Heart Failure
Positive Inotrophic and Chronotropic (HR). Chronotropic less prominent
Increase in Cardiac Output |
|
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Term
|
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 |
|
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Term
|
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 |
|
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Term
|
Definition
Alpha1, Alpha2, B1 (less for B2)
Vasoctriction, Increase in BP
Reduction in HR due to Baroceptor reflex |
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Term
|
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 |
|
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Term
|
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 |
|
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Term
|
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 |
|
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Term
|
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 |
|
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Term
|
Definition
(Miochol-E)
Direct-Acting Cholinergic Agonist
Naturla transmitter, short acting and non-selective, interacts with muscarinic AND nicotinic
M3 Receptor |
|
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Term
|
Definition
Direct-Acting Cholinergic Agonist
Interactis with Muscarinic Receptors due to Methyl group
M3 Receptor |
|
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Term
|
Definition
(Carboptic)
Direct-Acting Cholinergic
Resistant to Cholinesterase and is NON-selective
Treats Glaucoma
M3 Receptor |
|
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Term
|
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) |
|
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Term
|
Definition
(Tensilon)
Indirect-Cholinergic Agonist
Short Acting Drug
Treats Myasthenia Gravis Inhibits
cholinesterase which will increase ACh |
|
|
Term
|
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 |
|
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Term
|
Definition
Cholinergic Antagonist
Used in Ophthalmology
Selective for all muscarinic ACh receptors
Tertiary Amine |
|
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Term
|
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
|
|
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
|
|
Term
|
Definition
Study of Genetic basis for Variation in drug response |
|
|
Term
|
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
|
Definition
Location on chromosome where gene resides |
|
|
Term
|
Definition
Specific DNA sequence at a particular Locus |
|
|
Term
|
Definition
Particular combination of alleles at nearby loci on a chromosome that tend to be inherited together |
|
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Term
|
Definition
Tendency for alleles at nearby loci to be inherited together |
|
|
Term
SNP occurring in promoter region? |
|
Definition
INCREASE or DECREASE mRNA expression |
|
|
Term
|
Definition
|
|
Term
|
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 |
|
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Term
|
Definition
Insertion or deletion of one or more nucleotide in DNA sequences |
|
|
Term
Genetic Variation is greatest in what group? |
|
Definition
|
|
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
|
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
|
Definition
|
|
Term
CYP450 Predominant Enzymes |
|
Definition
|
|
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
|
|
Term
CYP2C9*3 affects what drugs? |
|
Definition
NSAIDs, Warfarin, Phenytoin, Tolbutamide |
|
|
Term
2 Poor metabolizer variants of CYP2C19 |
|
Definition
|
|
Term
Ultra-rapid metabolizer of CYP2C19 |
|
Definition
|
|
Term
Phase I Biotransformation |
|
Definition
Increases Hydrophilicity
Inactivate Drug
Provides a Handle for Phase II |
|
|
Term
|
Definition
|
|
Term
Phase II Biotransformation |
|
Definition
Increases Hydrophilicity
Inactivates Drug
ADDS a recognition element for Active excretion |
|
|
Term
|
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
|
Definition
Aromatic amines --> aromatic Nitro groups N(OH)HCHRR--> O2N-CHRR
Aromatic Primary Amines --> aromatic Nitro groups AR-NH-OH-->AR-NO2 |
|
|
Term
|
Definition
Oxidation of Nitrogen, Sulfur, Phosphorus (NPS) |
|
|
Term
Oxiation pathway of Aldehyde, Carboxylic and Alcohol |
|
Definition
Alcohol --> Aldehyde --> Carboxylic Acid |
|
|
Term
|
Definition
Ketones, Aldehyde, Azo and Nitro |
|
|
Term
Reduction of Disulfide bridge forms? |
|
Definition
|
|
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
|
|
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
|
|
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
|
|
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
|
|
Term
Methylation occurs in what functional groups? |
|
Definition
|
|
Term
Methylation receives it's methyl from where? |
|
Definition
|
|
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
|
|
Term
Glutathione takes place Especially where in the body? |
|
Definition
|
|
Term
Glutathione reactions are catalyzed by what enzyme? |
|
Definition
|
|
Term
|
Definition
|
|
Term
Why is acetylcysteine a antidote for APAP? |
|
Definition
Its the precursor for glutathione |
|
|
Term
|
Definition
Wafarin Phenytoid NSAIDS Tolbutamide |
|
|
Term
|
Definition
Mephenytoin INCREASED toxicity Omeprazole INCREASED efficacy Clopidrogel DECREASED efficacy |
|
|
Term
|
Definition
INCREASED risk of Toxicity of Anti-depressant and Anti-psychotic
Reduced analgesic effect of Codeine
Reduced antineoplastic action of Tamoxifen |
|
|