New User Special Price Expires in

Let's log you in.

Sign in with Facebook


Don't have a StudySoup account? Create one here!


Create a StudySoup account

Be part of our community, it's free to join!

Sign up with Facebook


Create your account
By creating an account you agree to StudySoup's terms and conditions and privacy policy

Already have a StudySoup account? Login here


by: Theresa Emard

Pharmacology BMS 450

Theresa Emard
GPA 3.65

Douglas Ishii

Almost Ready


These notes were just uploaded, and will be ready to view shortly.

Purchase these notes here, or revisit this page.

Either way, we'll remind you when they're ready :)

Preview These Notes for FREE

Get a free preview of these Notes, just enter your email below.

Unlock Preview
Unlock Preview

Preview these materials now for free

Why put in your email? Get access to more of this material and other relevant free materials for your school

View Preview

About this Document

Douglas Ishii
Class Notes
25 ?




Popular in Course

Popular in Biomedical Sciences

This 19 page Class Notes was uploaded by Theresa Emard on Monday September 21, 2015. The Class Notes belongs to BMS 450 at Colorado State University taught by Douglas Ishii in Fall. Since its upload, it has received 60 views. For similar materials see /class/210039/bms-450-colorado-state-university in Biomedical Sciences at Colorado State University.

Similar to BMS 450 at CSU

Popular in Biomedical Sciences


Reviews for Pharmacology


Report this Material


What is Karma?


Karma is the currency of StudySoup.

You can buy or earn more Karma at anytime and redeem it for class notes, study guides, flashcards, and more!

Date Created: 09/21/15
25 January Routes of Administration The route influences the rate of onset and magnitude of response Eat something 9 GI tract 9 liver may inactivate drugs first pass effect drugs which are rapidly biotransformed molecular structure changed are inactivated do not want to give these orally Parenteral route not orally avoids first pass effect side effects on GI tract binding to GI contents biotransformation in GI tract Parenteral Topical Route Percutaneous through the skin Hydrophilic ionic polar excluded Lipophilic molecules can diffuse through plasma membranes hydrophilic blocked unless there is a transporter Lipophilic penetrates by passive diffusion Steroids DMSO carbon tetrachloride organic pesticides Role of surface area greater surface area greater effect Alveolar membrane pulmonary endothelium Lipophilic passive diffusion General anesthetics aerosols leaded gas Particle size lt2 um Problems irritation dose regulation Topical Mucosal Membranes Vagina urethra conjunctiva nasal Lipophilic via passive diffusion Parenteral Intranasal Drugs with transporters at bloodbrain barriers Nose is highly vascularized Counter current cooling of brain Aerosol droplet size is important Uptake from blood into cerebrospinal fluid Example insulin Appropriate dose avoids hypoglycemia Parenteral Injection ntradermal id Liquids Oils Suspensions Slow release possible Absorption same as sc subcutaneous and im intramuscular Subcutaneous sc Liquids Oils Suspensions Solid pellets pumps insulin pump Absorption generally slow and even Problems irritation tissue slough severe pain high density of sensory receptors Intramuscular im Liquids oils suspensions Absorption 10 30 min faster than sc slower than iv Less irritating or painful than sc Less hazardous than iv Problems potential for nerve damage hemorrhage septic abscess necrosis and gangrene Nevertheless often preferred over sc and iv Uptake After id sc or im Lipophilic drugs Passive diffusion across endothelial cells into capillaries Small ionic polar molecules can squeeze through pores Large polar molecules proteins Excluded from pores Via lymphatics into blood Manipulation of Drug Absorption Rate limiting perfusion at sc injection site Overdose decrease rate of perfusion ice pack tourniquet Increase absorption exercise massage heat site hyaluronidase enzyme breaks down connective tissue Decrease absorption immobilize tourniquet cool site epinephrine vasoconstriction Parenteral injection intravenous Advantages Rapid emergencies Complete bioavailability not an issue Circumvents first pass effect Avoids sensory nerve endings Absorption rate can be exactly regulated Minimizes fluctuation in drug levels Safer for drugs with small TR therapeutic ratio Drugs with short halflives Large drug volumes can be delivered Must be sterile pyrogen free not causing inflammation and isotonic Tonicity concentration of non penetrating solutes sodium chloride Disadvantages Only soluble drugs in aqueous solutions except rapidly soluble suspensions Embolism clog can occur if using solids oils precipitates Hypotonic potential hemolysis Prolonged infusions vessel damage No margin for error if wrong drug concentration tonicity precipitation or anaphylaxis Drug Bolus iv push Wave of concentrated drug even salts Chemoreceptors at carotid arch or carotid sinus Potential for profound fall in bp cardiac irregularities compromised respiration Prudent approach to iv Donot use iv push except where required and known to be safe Circulation time about 1 min Particularly with unfamiliar drug Inject relatively slowly Convulsion loss of consciousness Partial vs completely empty syringe Parenteral injection Other ntraarterial Diagnostic Local targeting of drug cancer ntrathecal Spinal subarachnoid space Spinal anesthesia CNS infections Nonlipophilic drugs ntraperitoneal generally experimental Large surface area risky Emergency toxicology Enteral Route of Administration Via alimentary canal Buccal or Sublingual cheek under tongue High vascularity Lipophilic drugs Avoids first pass effect Cons distasteful or irritating drugs Rectal Lipophilic solution suppository Avoids first pass effect Useful ifvomiting or unconscious Cons poor diffusion binding irritation 23 January Importance of quotPrinciplesquot Potential for harm as well as good Literally thousands of drugs Basis for understanding use of any new drug Package inserts are for quotnormalquot subjects How does one adapt treatment to diseased animals different age or species different body weights revised schedules revise dose in event of underoverdosing Iatrogenic disease 100000 wrong human prescriptions annually 10 20 of serious hospital admissions Drug input absorption amp distribution 9 steadystate drug concentration 9 receptors beneficial toxic and output biotransformation elimination Some PK pharmacokinetic Variables Affecting Drug Input Drug form Route of administration Bioavailability Dose and schedule Absorption rate Biotransformation Drug distribution tissue perfusion rate Drugdrug interactions protein binding on trapping Some PK Variables Affecting Drug Output Biotransformation Enzyme induction Protein binding Drugdrug interactions Liver function Kidney function ion trapping Disease Physiological state age pregnancy shock Individual genetics Some PD pharmacodynamics Variables Affecting Drug Response Drug concentration and affinity Efficacy agonist antagonist partial agonist Receptors for beneficial response Occupancy and response Spa re receptor systems Up and down regulation Receptor families and subtypes Second messenger systems Receptors for toxic response Some things to think about What are the variables that determine drug concentration in the body Which variables can be manipulated for clinical advantage Begin with a gualitative understanding of the variables Review and practice math and chemistry skills and do problem sets Develop a guantitative understanding of the variables Review conversion factors Volumes 1000 pi 1 ml 1000 mi 1 L Weights 1000 ug 1 mg 1000 mg 1 g 1000 g 1 Kg Conversions 1 ugml 1 mgL 1 ml water 1 g standard conditions 10 vv 10 ml drug per 100 ml liquid 10 ww 10 g drug per 100 g powder 10 wv 10 g drug per 100 ml liquid Review chemistry and math Know what 1 M 1 mM and 1 uM mean Know how to do dilution problems Know logarithmic functions y e X Syllabus review pages 26 31 page 8c Q3 amp 4 First a few definitions Pharmacology the science of drugs in the body Pharmacy dispensing of drugs Pharmacokinetics rate Pharmacodynamics action of drug in body Pharmacognosy finding active ingredients Active pharmaceutical ingredient API molecular structure Pharmaceutical process Formulation Bioavailability Route and schedule of administration Compliance Formulations and Equivalence Formulation API various additives quotexcipientsquot Chemical equivalence same API in formulations Biological equivalence same API levels in tissues T39 r 39 I 39 39 same I I 39 response to API in clinical trials Clinical trial placebo controlled doubleblind multicenter 10 100 million Bioavailability Med Letter Natl Formulary US Pharmacopia Primary proof therapeutic equivalence Secondary proof biologic equivalence Caveat generics vs brand Drug Forms amp Absorption Gases passively diffuse into blood high bioavailability Liquids usually don t have bioavailability problems Suspensions smaller particles dissolve more rapidly presented to the body more quickly Solids Polymorphism crystal vs amorphous Particle size Solvates chloroformate vs asolvate solvent helps dissolving Solubility constant rate it goes into solution pH determines extent of ionization Oilwater partition coefficient Lipophilic vs hydrophilic ionization polarity Determines rate of entering cells Drug Formulations and Bioavailability Tablets Binding agents Compression force Lubricants Pills Hard dissolves faster vs soft gelatin capsules Enteric coatings Time release capsules Tablets and pills designed for average GI transit time Greatest likelihood of bioavailability problems Shelf life 30 January Drug Distribution Back diffusion would oppose drug distribution Lipophilic drug can passively diffuse through membrane but could do the same in the opposite direction Serum albumin binding sites for drugs 119 positive charges 96 negative charges Many lipophilic sites Many other serum proteins Bound drug is not available to act inactive Equilibrium between bound and unbound Buffering system Drug binding prevents back diffusion Lipophilic drugs have low solubility in water but can piggyback on serum proteins faster Consequences of Protein Binding Proteinbound drug is generally inactive Only free drug is active Protein binding provides a drug reservoir and buffers against drug elimination Drugdrug competition Dicoumarol anticoagulant 97 bound Aspirin compete for binding Free drug increased from 3 to 6 Greater tendency to bleed less coagulation Drugmetabolite competition Thiopental anesthetic 75 bound Free fattyacids elevated in diabetes Displace bound thiopental Free active thiopental increased Increased depth of anesthesia Elevated FFA diabetes fasting anorexia bacterial infections Proteinbiirubin heme product binding Sulfonamides antibiotics compete Free active biirubin levels are increased May cause kernicterus in newborn Bilirubin enters brain Encephalopathy Seizures Potentially fatal Protein binding reduces rate of biotransformation and rate of removal from body through kidneys Effect on biotransformation at liver 80 13 pores Binding generally slows biotransformation Depends on how tightly bound the protein is how rapid dissociation is Effect on glomerular filtration and excretion 80 13 pores Generally slows filtration and excretion But penicillin for example rapidly dissociates so is quickly eliminated Regulation of Serum Protein Levels Serum albumin is produced in the liver Factors that regulate serum protein levels can alter free active drug concentrations Pregnancy steroids Hepatitis hepatocarcinoma alcoholism Fetus aged Therapeutic adjustments must be made Distribution Rate to Tissues The central compartment Brain heart liver lung and kidneys Rapid perfusion and distribution The peripheral compartment Adipose tissue tendons cartilage Slow perfusion and distribution Other compartments Muscle skin Intermediate perfusion and distribution Redistribution Drug Permeation nto Tissues The reverse of absorption into capillaries Lipophilic by diffusion across endothelial cells Polarionic by passing through 30 13 pores Serum albumin 68 kDa gt 30 13 retained in bloodstream Insulin 58 kDa 16 A Drug Permeation Exceptions Brain and spinal cord Tight junctions between endothelial cells Generally devoid of pores Excludes ionicpolar drugs except through transporters llBloodbrain barrier BBB Lipophilic drugs by passive diffusion Exclusion limit gt450 daltons Heroin inactive vs morphine active Heroin is more lipophilic is rapidly metabolized to morphine CNS infections capillaries can get leaky Placenta Tight endothelial junctions Similar to CNS Ionicpolar drugs generally excluded Lipophilic drugs can reach placenta Ethanol barbiturates heroin Immature liver and kidneys Teratogenesis Hamburg Univ birth defects 1949 1950 none 1960 30 1961 154 Thalidomide OTC in 1959 teratogenic causes birth defects Agent Orange herbicide E embryonic age days after conception 21 22 ears cranial nerves E24 27 arms E28 29 legs E34 36 anorectal stenosis First trimester organogenesis species specific Drug Accumulation Drug binding is not always reversible Irreversible binding leads to drug accumulation Highly lipophilic compounds Want to stay in membranes DDT accumulates in food chain Vitamin A can become toxic Tetracycline deposits in bone and teeth Growth retardation Carbon tetrachloride Forms covalent bonds liver necrosis Complete Problem Set 1 Complete review of p29 34 Do Problem Set 1 Answers to be posted later 28 January Enteral Route Oral Convenient economical generally safe Trained personnel not required Compliance needed Conscious and not vomiting Disadvantages bioavailability Irritation drug inactivation acid Biotransformation in gut drugs with poor solubility Potential first pass effect Stomach pH low high acid fluid short duration Limited surface area 10 30 absorption Favors absorption of weak acids ion trapping Small intestine Microvilli 120 square meters Most important region for drug absorption Favors absorption of weak bases ion trapping pH 5 8 Large intestine colon No villi paste low diffusion Few transporters Low drug absorption Considerations Too fast poor absorption with slow dissolving drugs Too slowly acid may degrade biotransformation Absorption of Oral Drugs Passive diffusion Lipophilic drugs downhill transport Not concentration dependent Concentration inside with equal concentration outside Reach equilibrium across membrane Uptake proportional to concentration Uptake nonsaturable Carriermediated facilitated transport Ionicpolar Concentration dependent will saturate Transporters Downhill transport Equilibrium will occur Active transport carriermediated Polar or ionic drugs uphill transport Use ATP against concentration gradient Saturates with drug concentration Energydependent can be inhibited Cyanide dinitrophenol Amount inside can exceed amount outside Pinocytosis ATP dependent Uptake of drug into vesicles Minor mechanism of drug absorption Problem sets see handout syllabus page 29 34 on trapping Drugs that are weak acids or weak bases can distribute assymetrically on either side of a biological membrane if there is a pH difference across the membrane This has important consequences for therapeutics as well as toxicology HendersonHasselbach equation pH pKa log proton acceptorproton donor pH pKa log proton acceptorproton donor 10 Kl proton acceptorproton donor


Buy Material

Are you sure you want to buy this material for

25 Karma

Buy Material

BOOM! Enjoy Your Free Notes!

We've added these Notes to your profile, click here to view them now.


You're already Subscribed!

Looks like you've already subscribed to StudySoup, you won't need to purchase another subscription to get this material. To access this material simply click 'View Full Document'

Why people love StudySoup

Jim McGreen Ohio University

"Knowing I can count on the Elite Notetaker in my class allows me to focus on what the professor is saying instead of just scribbling notes the whole time and falling behind."

Jennifer McGill UCSF Med School

"Selling my MCAT study guides and notes has been a great source of side revenue while I'm in school. Some months I'm making over $500! Plus, it makes me happy knowing that I'm helping future med students with their MCAT."

Bentley McCaw University of Florida

"I was shooting for a perfect 4.0 GPA this semester. Having StudySoup as a study aid was critical to helping me achieve my goal...and I nailed it!"


"Their 'Elite Notetakers' are making over $1,200/month in sales by creating high quality content that helps their classmates in a time of need."

Become an Elite Notetaker and start selling your notes online!

Refund Policy


All subscriptions to StudySoup are paid in full at the time of subscribing. To change your credit card information or to cancel your subscription, go to "Edit Settings". All credit card information will be available there. If you should decide to cancel your subscription, it will continue to be valid until the next payment period, as all payments for the current period were made in advance. For special circumstances, please email


StudySoup has more than 1 million course-specific study resources to help students study smarter. If you’re having trouble finding what you’re looking for, our customer support team can help you find what you need! Feel free to contact them here:

Recurring Subscriptions: If you have canceled your recurring subscription on the day of renewal and have not downloaded any documents, you may request a refund by submitting an email to

Satisfaction Guarantee: If you’re not satisfied with your subscription, you can contact us for further help. Contact must be made within 3 business days of your subscription purchase and your refund request will be subject for review.

Please Note: Refunds can never be provided more than 30 days after the initial purchase date regardless of your activity on the site.