Term
|
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
|
Definition
| Impaired function causes facial flushing with alcohol |
|
|
Term
| Butyrylcholinesterase (pseudocholinesterae) |
|
Definition
| Prolonged muscle relaxant response to Succinylcholine |
|
|
Term
|
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
|
Definition
|
|
Term
|
Definition
|
|
Term
|
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
|
Definition
|
|
Term
|
Definition
| Lung and Various Smooth muscle |
|
|
Term
|
Definition
|
|
Term
|
Definition
INCREASED Heart rate and Force of Contraction
INCREASED blood flow to skeletal muscle
INCREASED Renin release from Kidney |
|
|
Term
|
Definition
Relaxation of Bronchilar Smooth Muscle
INCREASED Gluconeogenesis and GLycogenolysis in Liver |
|
|
Term
|
Definition
| INCREASED lipolysis in fat cells |
|
|
Term
|
Definition
DECREASED Blood flow to skin and viscera
Vasoconstriction on vascular smooth muscle (skin and splanchnic)
INCREASED Gluconeogenesis and Glycogenolysis in liver |
|
|
Term
|
Definition
| Parasympathetic reduces heart rate |
|
|
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 |
|
Definition
|
|
Term
| Location of Baroreceptors typically found |
|
Definition
| Carotid Sinus and Aortic Arch |
|
|
Term
|
Definition
Alpha1-adrenoceptor Agonists
INCREASE in Systolic and Diastolic
Nasal Decongestion (Dose too high you lose this selectivity) |
|
|
Term
|
Definition
Alpha1-adrenoceptor Agonists
INCREASE in Systolic and Diastolic
Orthostatic HYPOtension |
|
|
Term
|
Definition
Alpha2-Adrenoceptor AGONIST
Treats Hypertension
Suppresses sympathetic tone through negative feedback of Alpha2 pre-ganglionic |
|
|
Term
|
Definition
Beta1-Adrenoceptor AGONIST
Treats Acute Heart Failure
Positive Inotrophic and Chronotropic (HR). Chronotropic less prominent
Increase in Cardiac Output |
|
|
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 |
|
|
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 |
|
|
Term
|
Definition
Alpha1, Alpha2, B1 (less for B2)
Vasoctriction, Increase in BP
Reduction in HR due to Baroceptor reflex |
|
|
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 |
|
|
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 |
|
|
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 |
|
|
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 |
|
|
Term
|
Definition
(Miochol-E)
Direct-Acting Cholinergic Agonist
Naturla transmitter, short acting and non-selective, interacts with muscarinic AND nicotinic
M3 Receptor |
|
|
Term
|
Definition
Direct-Acting Cholinergic Agonist
Interactis with Muscarinic Receptors due to Methyl group
M3 Receptor |
|
|
Term
|
Definition
(Carboptic)
Direct-Acting Cholinergic
Resistant to Cholinesterase and is NON-selective
Treats Glaucoma
M3 Receptor |
|
|
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) |
|
|
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 |
|
|
Term
|
Definition
Cholinergic Antagonist
Used in Ophthalmology
Selective for all muscarinic ACh receptors
Tertiary Amine |
|
|
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 |
|
|
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 |
|
|
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 |
|
|
