2. Pharmacokinetics Flashcards
Pharmacokinetics
- In lay terms it’s what the ____ does to the drug
- Processes that affect how much drug ultimately reaches the ____ and how ____ it stays around the receptor and the body.
- These include the processes of drug ____, drug ____, drug ____ and drug ____.
- Many adverse drug interactions involve the ability of one drug to effect the ____ of another drug.• DD > only ____amount of drug actually gets to the receptors
• DB > all drugs are ____; don’t get rid they cause bad effects
• DE > DB process makes drugs more ____ soluble less lipid soluble more readily excreted (primary organ: ____)
• Really bad one interactions > interference with ____ and ____ of another drug
○ One drug has a low therapeutic index; difference bt effective and lethal doses are not that great
body receptor long absorption distribution biotransformation elimination PK
type poisons water kidney DB elimination
Absorption – How do we get the drug into the body?
Typically can’t reach receptors unless drug enters ____
- Oral (PO) route - by mouth. Typically the ____, and most convenient (people don’t like needles). However has ____ onset to effect and is least ____.
a) Before being absorbed into blood stream from stomach and small intestine drug must disintegrate and ____ into solution. A lot of drug is lost in this process.
i. Speed up aspirin absorption and lose less drug by first dissolving in warm ____ or use ____t formulation like Alka Seltzer
ii. For ibuprofen use the ____ formulation
iii. For drug irritating to stomach add ____ coat but this will ____down
absorption
b. Gastric emptying time: Time it takes for drug to pass from stomach to ____ where most absorption takes place. Faster and more complete for
____ than solids.
c. Lipid solubility – highly ____ soluble drugs can go right through gastrointestinal
membranes. More ____ drugs need to find pores to squeeze through.• Usually prescribe by mouth > blood levels build up slowly
blood stream safest slowest predictable dissolve water effervescent liquigel enteric slow small intestine liquids lipid polar
Factors Effecting Oral Absorption Continued
d. pH effects. Many drugs are weak ____ (i.e. aspirin) or weak ____ (i.e. lidocaine)
Most drug absorption takes place in ____ where pH is closer to neutral and there is a large surface area with villi and microvilli and drugs can even be absorbed against pH gradients.
• Low pH > uncharged and more readily absorbed in the \_\_\_\_ • Weak base - opioids, local anesthetics (anti-arrythmic properties bc there's Na+ in heart) ○ Picks up \_\_\_\_, becomes charged and is not \_\_\_\_ well
acids bases small intestine stomach H+ absorbed
pH effects important for some injectable drugs like local anesthetics!!!
• Not injecting right into nerve, but closely so it diffuses through the sheath and the individual nerve fibers and membranes • Inject into an inflamed area > the pH is \_\_\_\_ > local anesthetic (weak base) > charges up, picks up \_\_\_\_ and won't get into nerve membrane • Henderson-hasselbach equation for a weak base*** ○ pKa > pH where \_\_\_\_ molecules are charged and uncharged; never changes for a \_\_\_\_, but diff molecules have diff pKa's ○ pH of the environment (interstitial fluid, around nerves is 7.4) ○ Drop pH \_\_\_\_ units > 99% charged, and 1% uncharged > hard to get someone numb ○ Both charge and uncharge are \_\_\_\_, but charge doesn't get in
low hydrogen half pKA two active
Factors Affecting Oral Absorption Continued
e. Some drugs are permanently charged such as ____ and streptomycin
f. Some drugs destroyed by stomach acid such as ____ and insulin
g. Other foods and drugs can impair absorption such as the ability of ____ antibiotics to chelate foods and drugs with divalent and trivalent cations(____, Mg++, ____, Fe++, ____).
• Always charged, irrespective of pH • Streptomycin - used IV to treat \_\_\_\_ - good against gram- aerobic infections, cannot be given orally because it stays \_\_\_\_ indefinitely ○ Early penicillin had this problem • B-lactam nicked > loses \_\_\_\_ > pH can do it • Penicillin G is totally \_\_\_\_; insulin gets \_\_\_\_, it's a protein • Tetracycline antibiotics drug interaction with dairy products (Ca++) ○ Like to grab on, chelation to div/trivalent cations > do not get \_\_\_\_ (70-95%) ○ Mg++/Al++ in antacids (mylanta, MgOH and AlOH) § Side effect of Al: constipation § Side effect of Mg: diarrhea ○ Fe++ supplements for \_\_\_\_ ○ Bi++ > \_\_\_\_ > helical bacti pylorai killer > GI ulcers
curare penicillin G tetracycline Ca++ Al+++ Bi++ Tb charged acidity injectable degraded absorbed anemia peptobismal
Factors Affecting Oral Absorption Continued
h. First pass effect: First places drug goes after passing the stomach is the ____ and then absorption into the portal circulation.
____ in the small intestine and the liver can inactivate a significant amount of drug after ____ absorption. For example the opioid morphine can be inactivated ____% after oral administration compared to injection. Makes oral dosing with these high first pass drugs somewhat ____. Obviously you need to give higher doses than with ____.
* If you hear first pass effect, it’s usually oral or rectal * If you have someone with opioid induced nausea and vomiting, you can’t get a pill down them * Sometimes depositories are the best route * No oral morphine > depending on the individual > it goes to liver after stomach/SI > 60-90% inactivated (\_\_\_\_) > makes dosing unpredictable * With injection, there is no \_\_\_\_ effect - it is in the \_\_\_\_
small intestine enzymes oral 60-90 unpredictable injections
gluconerated
first pass
bloodstream
Other routes of drug administration
- Rectal Route –suppositories for ____ drugs. There is a ____ effect. Tell patients to take the ____ foil off before inserting and that they shouldn’t be swallowed.
- Intravenous route – inject drug right into blood stream. No issues with disintegration, food interactions, acid destroying the drug or ____ effect. However it is also the most ____ route because once the drug is in the blood stream there is no way to get it out in case of an overdose.
b. Route is ____ – give small incremental doses and watch the effects rapidly come on like sedating patient with midazolam( Versed®). When you get to where you want to be, you stop administering the drug.
c. Quick way to get ____ drugs (lidocaine for ventricular arrhythmias) into the system
d. Quick way to induce ____ with i.v. general anesthetics like ____ (Diprivan®) or fentanyl (Sublimaze®). ____ seconds or less.
e. Antibiotics administered through this route for ____-threatening infections- Through rectal mucosa, some ends up in liver > some first pass effect
- IV is most ____, but most dangerous
- Accidentally eat something > give activated charcoal, or induce vomiting (ipicach syrup - stimulates cholinergic and dopaminergic input into the vomiting center); some things you don’t want to induce vomiting (like bleach, if aspirated can form permanent scaring)
- Conscious sedation > you don’t want to knock him out; can’t do with oral drug
- IV anesthesia comes on very quickly; fentanyl is an ____
antinausea/vomiting
first pass
tin
first pass dangerous titratable emergency general anesthesia propofol thirty life
predictable
opioid
Other routes of drug administration
- Inhalation–usually takes a few ____ depending on properties of drug
a) Some ____ anesthetics (sevoflurane) as quick as ____ minutes. Nitrous oxide as sedative within 1 – 3 minutes for effect.
b) Route for N2O is ____
c) Inhale small particles called ____ for antiasthmatic drugs (mainly β2 agonists like ____ (Proventil®).• Sevoflurane > dissipates quickly (comes on quick too)
○ Sevo is really a ____ at RT; NO is a real gas
• The ones that come on the quickest have the lowest ____
◦ Anesthetic gases behave according to ____ gradients
◦ Low blood solubility with gases means quick ____, quick offset
Nitrous oxide is like getting a buzz within 1-3 minutes
◦ Nitrous oxide is not used by itself because it is ED 50…its median effective dose is about ____
○ Ed50 - 100% NO - 0% oxygen - people used to die; not bc NO was poison, but bc they were getting no ____
• Hope the small particles are ____ enough so they stay put for antiasthmatics
minutes gaseous 2 titratable aersols albuterol
liquid blood solubility partial pressure onset 100% O2 big
Other routes of administration
- Sublingual – allow tablet to dissolve under tongue and be absorbed by ____. Usually takes a few ____ to come on. Sublingual ____ (Nitrostat®) for angina attack.
- Intramuscular and subcutaneous – takes a few minutes to ____ minutes depending on ____ and ____ drug is in.
a. Sustained release ____
b. Insulin
c. ____ for anaphylaxis (within a few minutes)• NG ____ everything (not just the coronaries) so the heart doesn’t have to work as hard, and you decrease myocardial oxygen demand
○ Angina - chest pain bc the ____ are blocked up
• Gives off a lot of NO > vasodilator > postural hypotension
• A lot of blood supply, comes on ____; not much > comes on slower
• Sustained release peni > IM > ____ and syphilis > slowly leeches out over a longer period
• Insulin - is ____
• Epi > anaphylactic 1:1000 (1 mg/mL)
veins minutes nitroglycerin thirty blood supply vehicle penicillin epinephrine
vasodilates coronaries qicker gonorrhea subcutaneous
Other routes of administration
- Submucosal injections – local ____ with vasoconstrictors (epinephrine). In this case we add the epinephrine to keep local anesthetic blood levels relatively low and levels at the site of injection high. High blood levels of locals lead to toxicity. Also used for injections of ____ (Oraverse®) to speed up recovery from local.
- Epidural and Spinal – used for obstetric ____ anesthesia during child birth. Also for ____ drugs that have difficulty getting into brain where a tumor is located (spinal administration).
- High levels around nerve, and not a lot around blood
- Don’t want to use mesylate after surgery > onset of pain quicker
- Epidural - outside the ____ (give a lot of anesthetic, 20 mL)
- Spinal - into the ____ - typically done below ____
anesthetic phentolamine mesylate local cancer chemotherapeutic dura mater CSF L2
Other routes of administration
Topical – most drugs do not penetrate intact skin with a few exceptions. Mainly penetrate ____ skin or mucous membranes.
a. ____ or lidocaine for topical soft tissue mucosal anesthesia before injection
b. ____® (benzocaine) for sunburn pain
c. ____ (Benadryl®) for insect bite
d. ____ – eutectic mixture of local anesthetics. A mixture of lidocaine and prilocaine in very ____ soluble vehicle. Will penetrate intact skin in 30 minutes to one hour for venipuncture in kids. A related dental product is ____® - place it in gingival pockets before scaling and root planning.
e. ____ patch (Transderm Scop) - patch placed behind ear to prevent ____ sickness. Takes a couple of hours to work. Mechanism of action is its ____ (antimuscarinic effect).
• Drugs must be v \_\_\_\_ soluble to drive through the skin • Benzocaine, overdoses causing \_\_\_\_ ○ Prilocaine also does it ○ Tremors, seizures, low BP, and maybe respiratory depression are common symptoms • Scopoalamine - muscarinic cholinergic antagonist - takes time to work
intact benzocaine solarcaine diphenhydramine EMLA lipid Oraqiz scopolamine motion anticholinergic lipid methemoglobenmia
Vomiting Center
• Motion sickness > blocks \_\_\_\_ receptors only • Vestibular system going crazy in the ear, and maybe you ate something before you got on the airplane • Drug induced vomiting > block \_\_\_\_ and \_\_\_\_ • \_\_\_\_ is a big DA blocking agent • All end in -setron ○ Given before cancer chemotherapy • People who go up in space take a combo of \_\_\_\_ and something that releases \_\_\_\_
muscarinic cholinergic DA SE promethazine anticholinergic NE
Motion Sickness
• Want anticholinergic (muscarinic receptor antagonist)
– ____(Benadryl®)
– ____ (Dramamine®)
– ____ (Bonine®)
– ____ (Transderm Scop®)
diphenhydramine
dimenhydrimate
maclizine
scopolamine
Distribution - Where do drugs go after they are absorbed
First thing that happens when drug gets into blood stream is it gets diluted by ____ and in many cases by extracellular and intracellular fluid. If we look at body as 3 compartment model – total body water is about ____ Liters.
Not all drugs distributed ____ in the 3 compartments (plasma = ____L, extracellular = ____L, intracellular = ____L)
VD stands for apparent volume of distribution or how much ____ the drug appears to be dissolved in.
• Plasma, fluid bt cells (EC fluid) and fluid inside (IC fluid) • Put all \_\_\_\_ and ground the up > 28 L • Different drugs distribute differently in these compartments > apparent volume of distribution ○ Will not have to calculate, but understand clinically ○ Amount of drug you put in over the initial concentration of drug in the BS
blood 40 equally 3 9 28
fluid
cells
• Take blood samples as plasma cxn goes down due to drug getting diluted, some biotrans, gets eliminated > you get a relatively ____ and extrapolate back to ____ and get initial cxn
○ Don’t know for sure, but ____
straight line
y-axis
relative
