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38 Cards in this Set
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- Back
- 3rd side (hint)
What is first order elimination?
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rate of elimination is proportional to the concenration.
the higher the concentration of drug the greater amount of drug is eliminated per unit time. this is the more common type of elimination |
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What is zero-order elimination?
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the rate of elimination is constant
independent of concentration this is the less common type of elimination |
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What is Vd?
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Vd describes how large a blood volume would be required to contain the entire ADMINISTERED dose at the measured concentration of drug in the blood
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What is the Henderson-Hasselbalch Eq.?
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pKa= pH + log [RH]/[R-] for acids
pKa= pH + log [BH+]/[B] for bases |
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How does ionization affect solubility?
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At low pH, weak bases are in ionized form which makes them less lipid soluble and cannot cross membranes.
For ex. a drug that is a weak base cannot cross the membrane of the stomach because the pH of the stomach is really low and the weak base will be predominantly in it's ionized form. Weak Acids are in the ionized form at high pH. For ex., in the high pH environment of the small intestines a drug that is a weak acid will predominantly in its ionize form therefore it will not cross the membrane of the small intestine. ionized forms of drugs are less lipid soluble |
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Name some factors that influence the distribution of absorbed drug?
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1. regional diff in blood flow (eg. brain vs. kidney?)
2) tissue mass 3) transport mechanism 4)permeability charachteristics 5) ion-trapping 6) nonspecific binding |
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What is the difference between drugs that exhibit one compartment vs two compartment distribution?
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One Compartment Distribution
- rapid equilibrium is achieved btwn plasma and tissue distribution following a drug administration. -------------------------------- Two compartment -rapid distribution to a central compartment (plasma) followed by slow distribution to other tissues/binding sites (2nd compartment). causes a biexponential [plasma] time profile repetitive administration, steady-state concentrations are achieved only after 5-6 elimination half-lives. Ex. Digoxin, Lidocaine, Phenytoin An administered dose is given and when steady state is achieved distribution continues and elimination starts. |
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Volume of Distribution?
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volume of distribution (Vd) is a measure of how evenly the drug is distributed in the body
Vd= Dose/Cο Vd= total drug in the body÷plasma concentration of the drug Vd tells us the ability of drugs to distribute into the tissues. A large Vd signifies that most of the drug is being sequestered in some organ or compartment |
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What is bioavailability?
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the fraction of the administered dose that reaches the systemic circulation unchanged
drug may have imcomplete bioavailability if it undergoes first-pass metabolism |
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What is drug elimination half-life?
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the time required to eliminate one-half of the body content of a drug.
dependent on Vd and Clearance of Elimination t1/2 = 0.69 x Vd x CL When Vd is constant t1/2 is proportional to CL |
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What is steady-state concentration?
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Steady-State Concentration, Css =
Dosing Rate/Elimination Clearance There is a direct proportionality btwn dosing rate and steady-state plasma concentration This is true for most drugs used in medicine because most drugs follow first-order kinetics of elimination. ** First-Order Kinetics of Elimination: the rate of drug elimination is protoprtional to the amount of drug present in the body. |
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Describe the steps in Phase I Reactions
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parent drug is converted to a more POLAR metabolite by introducing or unmasking a functional group on the molecule so that it can then be usually excreted.
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Describe the steps in Phase II Reactions
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some phase I metabolites are not eliminated rapidly & subject to phase II
endogenous substrate combines w/ the functional group derived from phase I rxns result: high polar conjugate which is easily eliminated by the body |
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What is the role of Cytochrome P450?
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Plays a critical role in Phase I reactions
-microsomal oxidation reaction RH--> cyp 450 + oxidation steps --> ROH remember Phase I rxn convert a parent drug (RH) to a more polar electrolyte by introducing or unmasking a functional group (in this case OH) so it can be excreted. |
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What factors affect drug metabolism?
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1. Drug-age interaction
neonates and elderly have slow biotransformation 2. Drug-drug interactions competition induction- pharmacokinetic tolerance enzyme inducer may stimulate metabolism simultaneously administered drug- decrease therapeutic effectiveness 3. Drug-endogenous substance interactions 2 drugs compete for same substrate eg. glucuronic acid for conjugation 4. Drug-disease interactions liver disease (eg. cirrhosis and cancer) can impair microsomal oxidation ->slow metabolism heart disease can limit blood flow to the liver can slow down the hepatic metabolism of a drug. 5. Drug-genetic interactions mutation in genes coding for enzymes that metabolize drugs |
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How does protein binding affect drug distribution?
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low protein binding generally leads to a large volume of distribution (drug being sequestered in some tissue or organ)
high protein binding = low Vd |
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what is the function of administering a loading dose?
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loading dose can be used with certain medications to achieve an immediate therapeutic response
especially for drugs with long half-lives and for patients with critical disease states is usually higher than maintenance dose LD(mg) = Css x Vd(L/kg) x Wt(kg) NOTE: Loading Dose does not bring you to steady state any FASTER |
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what is the function of administering a maintenance dose?
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maintains desired concentration
MD(mg)= Vd (L/kg) x Wt(kg) x (Cmax-Cmin) |
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Detail some drug-drug interactions that affect absorption
Sucralfate + digoxin Ciprofloxacin + Aluminum hydroxide Itraconazole Tobramycin in an ascitic pt |
●Sucralfate + digoxin
-Sucralfate coats stomach so digoxin is not absorbed drug administration must be spaced ●Ciprofloxacin+ AlOH -Chelation decreases absorption -drug administration must be spaced ●Itraconazole + raniditine -raniditine decreases stomach pH which decreases absorption of Itraconazole |
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Describe the neurochemistry of Autonomic nerves
what neurotransmitter is released by pregnaglionic postganglionic exceptions |
Neurochemistry of Autonomic nerves
Pre-ganglionic cells release Ach Post-ganglionic parasympathetic release Ach Post-ganglionic sympathetic release NE Adrenal gland releases EPI and NE Exceptions: sympathetic fibers innervating sweat glands and some skeletal muscle vascular smooth muscle release Ach |
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Functional Effects of Parasympathetics on
eye heart bronchioles GI tract bladder |
Eye: Pupillary Constriction (miosis)
Heart: Negative Chronotropy (decr. in hr) Bronchioles: Constriction GI tract: Increased Motility Bladder: Stimulates Emptying (a lot of muscarinic receptors on the bladder) |
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Functional Effects of Sympathetics on
eye heart bronchioles blood vessels GI tract bladder metabolic functions |
Eye: Pupillary Dilation
Heart: Increased Chronotropy and Inotropy Bronchioles: Relaxation Blood vessels: Constriction and Relaxation GI: Decreased Motility Bladder: Inhibits Emptying Metabolic functions: Increased Blood Sugar |
calcium funny current of the SA node leads to faster depolarization??? review
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Describe the Autonomic influences on the eye
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Sphincter (para)
Dilator (symp) Ciliary Muscle (para) Ciliary Body (symp) |
sphincter cells are circular shaped cells that are innervated by para
dilators are innervated by sym nerves and its response is mediated by alpha receptors ciliary m. changes shape of lens to accomodate for near objects, these express muscarinic receptors (para) the ciliary body produces aqueous humor and is mediated by beta receptors (symp) |
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Types of adrenoreceptors, some of the peripheral tissues in which they are found and the major effects of their activation
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α1
tissue: most vascular smooth muscle, pupillary dilator muscle actions: increase vascular resistance, contracts pupil α2 tissue: adrenergic and cholinergic nerve terminals, some vascular sm. muscle action: inhibits transmitter release and contracts some vascular smooth muscle β1 tissue: heart, JG cells Actions: stimulates heart rate and force of contraction, stimulate renin release from JG cells (leads to angiontensin II which increases Blood Pressure and can cause hypertension) β2 tissues: Respiratory, uterine and vascular smooth muscle, liver, pancreatic B cells, somatic motor nerve terminals (voluntary) actions:relaxes resp., uterine, and vasc. sm. muscle, stimulates glycogenolysis, stimulates insulin release (cells are able to take the glucose in )and causes tremor in voluntary muscle. Dopamine 1 acts on renal and other splanchnic blood vessels to relax them and reduce resistance Dopamine 2 acts on nerve terminals to inhibit adenylyl cyclase |
Beta 3 receptors are found on fat cells and stimulate lipolysis
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Describe the alpha 1 signal cascade
α1 adrenergic signaling, e.g. in vascular smooth muscle |
agonist binds alpha-1 receptor which causes the GDP to be phosphorylated to GTP.
Phospholipase C cleaves releases IP3 and DAG IP3 acts to free stored Calcium which stimulates Ca-dependent protein kinase to become activated protein kinase which produces biological effects in vascular smooth muscle you have actin and myosin interaction leading to contraction. DAG stimulates protein kinase C to become actived PKC |
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Describe the alpha 2 signal cascade
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when an agonist bind to an alpha-2 receptor(alpha-i) GDP is phosphorylated to GTP which inhibits adenylyl cyclase--> ATP is not cleaved to cAMP and biological effect is inhibited
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MLCK when phosphorylated becomes inactive
MLCK is needed to phosphorylate myosin-LC so that Myosin-LC-PO4 can become activated and actin can bind to it leading to contraction |
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α2 signaling e.g. in adrenergic in nerve terminal
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agonist binds to alpha-2 receptor in the noradrenergic nerve terminal, this inhibits NE release. This is a form of Negative Feedback..when NE is release some is recycled by reuptake and soem NE binds to the alpha-2 receptor to inhibit NE release.
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α2 signaling e.g. in vascular smooth muscle constriction
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alpha-2 agonist inhibits ATP being cleaved to cAMP which would stimulate MLCK phosphorylation
MLCK then goes down another pathway to stimulate myosin light chain by phosphorylation which leads to myosin light chain phosphorylation (actin binds and muscle contracts) and Myosin Light Chain relaxation |
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β1 receptor signaling in cardiac pacemaker cells
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agonist binds beta receptor which phosphorylates Gs GDP to GTP this stimulates adenylyl cyclase so that ATP is cleaved to cAMP
Biological effect is phosphorylation of L-type calcium channels and increased calcium current during phase 4 depolarization |
cAMP can bind to If funny current channels which causes increase opening time of that current and more current generated during hyperpolarization. This increases the heart rate.
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β1 receptor signaling in cardiac myocyte
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Biological effect is phosphorylation of calcium channel that increases open probability time, leads to increased SR calcium release
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β2 receptor signaling in smooth muscle
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β2 stimulates ATP cleavage to cAMP
cAMP stimulates phosphorylation of MLCK some MLCK is timulated to bind actin and produce contraction |
opposite of alpha-2
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What are some Direct Acting Sympathomimetics:
Endogenous Compounds |
Norepinephrine
Epinephrine Isoproterenol |
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Relative Potency of Direct Acting
Sympathomimetics |
α1-receptors EPI≥NE>>Iso
α2-receptors EPI≥NE>>Iso β2-receptors Iso>Epi>>NE β1-receptors Iso>Epi=NE |
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Cardiovascular effects of direct acting sympathomimetics
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need notes
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Endogenous Adrenergic Agents
Epinephrine (stimulates α1, α2, β1 and β2) |
Physiological effects:
Low rates lower diastolic BP Increase CO Higher rates Increase TPR and CO Indications Anaphylaxis Cardiac Arrest Bronchospasm Toxicity Arrhythmias Cerebral hemorrhage Anxiety Cold extremeties Pulmonary Edema Contraindications Later term pregnancy |
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Norepinephrine (stimulates α1, α2 and β1 receptors)
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Physiological effects:
Increase diastolic BP Increase CO Increase TPR Decrease HR (baroreflex) Overall increase MAP Indications: Limited to shock Toxicity: Arrhythmias Ischemia Hypertension Contraindications: Late term preganancy and pre-existing vasoconstriction |
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Dopamine (stimulates D1,D2, β1, α1 and α2)
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Physiological effects:
Low rates Decreases TPR (D1 receptor) Increases CO (β1) Higher rates Increases MAP and TPR (α1) Toxicity: Low BP (at low infusion rates) Ischemia (high infusion rates) Indications: Cardiogenic Shock Contraindications: Pheochromocytoma Tachyarrhythmias Ventricular fibrillation |
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Synthetic Sympathomimetics
Isoproterenol (stimulates β1 and β2 receptors) |
Physiological effects:
Decrease TPR (β2 receptor) Increase CO (β1) Small increase in MAP Bronchodilation (β2) Toxicity: Arrhythmias Indications Bradycardia/heart block when TPR is high Bronchospasm w/ anesth Contraindications: Tachyarrhythmias Angina |
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