7. Drug Variability Flashcards
Variability Attributed to Biological System
- ____
- Age
- ____
- Genetics
- ____
- Species
Variability Attributed to Condition of Administration
- ____ and route of ____
- previous exposure to ____
- other ____ or ____ on board
weight and body composition
sex
general state of health
dose administration drug drugs foods
• Two categories in how we respond to drugs > vraibility attributed to biolgical system (patient, animal) and to the conidtion of administration (how you give it, interacting drugs/foods on board, previous exposure to drug [drug allergy])
• Same dose of a drug in 150 lb adult will have a bigger bang in a ____ lb child; drugs are dosed ____ based, an adult dose and then the child dose is typically 1/5 the adult
○ For locals, max doses are all weight based (for lidoc is ____mg/lb > a 50lb kid can receive ____mg (4 cylinders), 150lb adult can receive ____mg (13 cylinders)
• Cancer chemo agents are dosed on ____ and ____ area (height aetc.)
• Age > things don't work as well (kidney, liver, metabolic capacity, excretion (via creatin clearance)) ○ Less eff \_\_\_\_ and \_\_\_\_, esp with multiple doses, drugs can accumulate ○ \_\_\_\_ output goes down > less \_\_\_\_ to liver/kidney per unit time > indirectly slows down metbaolis/excreiton ○ For CNS depressents, increased \_\_\_\_ > for opioids/benzos > bigger bang for buck; for geriatric patients, start \_\_\_\_ and go slow Can also \_\_\_\_ receptor sensi > \_\_\_\_ receptor > old people and asthma >may need more \_\_\_\_
30 weight 3.2 160 500 weight body surface
biotransformation
excretion
cardiac
blood
receptor sensitivity low decrease B2 albuterol
• Sex > there are drugs where you see diff in responses, there’s an agonist antagonist opioid (pentazosin) > a lot of ____ (nightmares, etc., mainly by ____) > stimualtes one opioid receptor (at ____) and antagonises the ____ (where classic opioids bind)
○ For women, they have a better ____ effect of this drug
• Genetics > atypical \_\_\_\_; malginant \_\_\_\_, hereditatry \_\_\_\_ ○ Opioids > 2D6 (cytochrome P450), codeine is a prodrug, has to be demethylated to \_\_\_\_ for itsa ctviity; low in 2D6, codeine becomes devoid of \_\_\_\_ efffects bc you don’t form active metabolic of morphine ○ Kids with tonsillectomies with a lot of 2D6 > therapetuic dosees of codeine going into resp depression > overmethylating into \_\_\_\_ and too much of active metabolite § Don’t use codeine on kids under ages of 12 warning § Now giving them mrore addictive things • General state of heatlh > \_\_\_\_ of liver from drinking; and drugs that casue hepatotoxicity on overdose now you're worrying about high therapeutic doses (like acetomen) ○ Poor \_\_\_\_ function > as we age, NSAIDS accumulate; and other target organs for NSAID is the kidney and then a cycle where drug builds up and causing more kidney damage (knocks prostaglandin) ○ \_\_\_\_ > with a beta blocker > asthmatic attack ○ Allergy to \_\_\_\_ > give amox you'll get a reaction
dysphoria
kappa
mu
analgesic
cholinesterases
hypothermia
methemoglobenmia
morphine
analgesic
morphine
cirrhosis
renal
asthma
penicillins
- Species > gold standard injectible opioid > morphine > 10mg good for pain; but the analgesic effect in a rat is 10mg, in human it’s the same > while you see same qualtiitve effects, but they’re more resisant tot ____ in rats
- Dose/route administration > benzo that relates to diazpoem (have to dissolve in propylene glycol, can be thrombofphlobitis) > metolazopam > major ____ sedation drug > its ____ soluble, and lacks ____ metabolites, ____ half life; gave a 1mg/2mg orally > may take the edge off; gave 4/6mg orally > drowsy; take 4/6mg given IV slowly > deeper state of ____ (conscious sedation), load 20mg then you can knock out the ____ (general anesthetic state)
CNS depressants IV water active shorter sedation patient
• Previous exposure to drug > drug allergy > allergic reaction look nothing like ____ of the drug > allergic rxn from bee sting is the ____ you see from amox/ibuprofen; food allergies, histamine icn persisatalsis > diarrhea too
○ Can lead to tolerance > need more and more drug to get the same effect > two ways > ____ (drug inc own metabolism, see with barb’s > they’re substrates/inducers of P450), and ____ (postsyn receptors downregulate); weird type of tolerance > ____ > rapid development of tolerance > drugs that work indirectly > don’t stimulat e areceptor, work by increasing ____ relaease (amphetamine stimulatants > causing a release of NE in the brain from presyn nerve fibers; but you hit will several doses, theyres no more ____ to come out)
• Other drugs and food on board > \_\_\_\_ on milk and antacids ○ Drug that blocks cytochrome P450 enzyme > grapefruit juic > levels of \_\_\_\_ go high > muscle aches, rhabdomyelesis (muscle breakdown products clog up kidney tubules) ○ Interaction bt monoaminoxidase inhibiotrs (third line drugs to treat depression) and \_\_\_\_; end result of MAOI and eating foods with these AA > \_\_\_\_ and \_\_\_\_
phamacologic effects same metabolism pharmacodynamics tachyphylaxis NE NE tetracycline statins tyramine cardiac arrythmias hypertensive crisis
MAO Inhibitors (MAOIs) • Major use is in treating \_\_\_\_ – \_\_\_\_ line drugs • The names – \_\_\_\_ (Nardil ®) – Tranylcypromine (Parnate®) – \_\_\_\_ (Marplan®)
• First line > \_\_\_\_ • Second line > \_\_\_\_ or there's a new cateogry but don't have tricyclinc structure > dual \_\_\_\_ reupatek inibiotrs (symbalta) ○ Some antidepressants are used in \_\_\_\_ pain
depression
3rd
phenelzine
isocarboxazid
SSRI
tricyclic antidepressants
NE/SE
chronic
Some Foods Containing Tyramine
- ____ cheese and other aged cheese
- Pickled Foods
- ____ beverages
- Processed meats
- ____ and sour cream
- Avocados, bananas, raspberries
- Miso soup and ____
- Not a ____ AA in our body, but it in a lot of food products
- Tyramine is an indrect ____ (like amphetamines) hits presynap nerve termianls if it can get tot hem > like ones containin EPI/DA > when hits, it spills out ____ > instead of being a totally controleld reelase its less ____
cheddar
alcoholic
yogurts
soy sauces
natural
sympamematic
NT
controlled
The Interaction Pt. 1
• MAO is also in the ____ (not just nerve terminals) > degrades ____
• On MAOI > excess of tyramine > absorbed into BS > makes its way to ____
gut
tyramine
nerve terminals
The Interaction Pt. 2
• Nerve terminal in CNS but also in periphery, in soemone that’s not on a MAOI • MAOI inibiotrs on depression its in the \_\_\_\_; blocks MAO in nerve temrianls in brain > accumulation in nerve terminal, and for every AP you get 2 coming out ○ Can also help in periphery • Depression > imbalance of SE and NE; and with MAOI you spit out more in the CNS and peirpehral, but its still a \_\_\_\_ rleease ○ MAOI happens in \_\_\_\_ hours, while other ones take 2-3 weeks; in 2 weeks theres' a a downregualtion of \_\_\_\_ receptors • If eat food product that contains tyramine > if it gets out of the gut, and now nervetemrianls are loaded with NE > will hit presynpatic termianls (not just in the brain, \_\_\_\_ nerve fibers) > eveyrthing spills out > massive amount of NE hitting \_\_\_\_ receptors on BV and \_\_\_\_ receptors on heart > cardaic \_\_\_\_, and hypertensive \_\_\_\_ ○ IV tyramine > a little bump in \_\_\_\_; bypassing MAO in stomach ○ Two things > its making through the \_\_\_\_, and bc they're on MAO the nevre temrianls are loaded with NT and get bumped and they all get \_\_\_\_ ○ Shouldn’t take efedrin like drugs (pseudofed) > MAOI with nasal congestion, \_\_\_\_ can kill you (do saem thing as tyarmine) • Food drug interaction - worse than \_\_\_\_
brain controlled 24-48 post-syn post ganglion alpha beta arrythmias crisis
BP
stomach
spilled
pseudofed
tetracycline
• ____ - atypical cholinesterases
• Methemoglobenemia > took a blod sample and do coxsymmetry > 99.5% of hemoglobin is in ____ state (Fe++, readily carries xoygen and drops off in tissues), and .5% would be in met state (____ state, Fe+++, less electronegative, and doesn’t let go of oxygen)
○ When onverdose on strong oxidizing drugs (nitroglycerin, last you want for someone on angina attack) > clinical signs when met is ____%+, patient turns blue; once it reaches ____% they have trouble libreathing
○ Two LA on overdose that are oxidizing > convert Fe++ to Fe+++ (____ and oragel/ambosaol) > pea size amount around aching tooth and if you put more on them
○ Injectible local of ____ > metbaolite > o-toludene > sstrong oxidizing agent
○ Overdoses of cipro > prevent traveler’s diarrhea
Small number of inidivudals that walk around with 5% of met; but now a therapeutic dose of a strong ____ agent can send them into methemoglobinemia
succinylcholine reduced oxidized 10 20 benzocaine prilocaine oxidizing
• Acute intermittent porhiria > form abnormal amounts of ____ > get attacks where they form severe abdominal pain and have seizures; cytochrome P450 system induces rings, and drugs that induce them (____, phneobarbitols, ____) > have actue intermitti portpheria > can trigger the enzymes that stimualte the produciton of these rings
• Malginant hyperthermia*** > rare, runs in ____ bc its genetics > did you or sibiling or parent have a weird response to general anesthesia
○ People get expoxed to a drug known as a triggering agnetn > ____ (a volatile GA liquid at RT and heat then it forms a gas), ____ (depolarizing blocker) > when expose,d massive release intenrally of ____ fro inside calcium stores in skeletal muscles (from ____) causes the muscles (____ first) to become ____, then ____ builds up in body > 107/108 degrees, not compatible with life very long
○ Thrown in ____ water baths; but there is a drug > ____ > muscle relaxers but difff from succ/curare > this one stops internal release of ____; this use to be 70% lethal, but now down to under ____% lethal, can pick it up befor eit happens based on a godo medical history
○ Develop arrtyhmias, sodium potassium imbalances
precursor hemoglobin rings rifampin barb's families halothane succinylcholine Ca++ SR masseter rigid heat ice dandroline Ca++ 5
• Genetic polymorphisms
○ ____ - codeines/tramadol > repsonsible for dethymlating both drugs into active ____
§ Codeine inactive, but still get the ____ but vomintitng
§ Tramadol > parent moleucle has ____ activity (inc in CNS), and the ____ metbaolite (demthatbrotole ) sitmualtes ____ opioid receptors
○ Where low in ____ > these drugs wont work as well as far as ____ goes
○ With tramadol > bc it has SE activity > if you give other drugs that block 2D6 > and you give ____, then tramadol accumualtes, and then other drugs block reuptake of seortinin > ____ > ____, irregular ____
• Codeine/tosileectomies > ____ of 2D6 > therapetuic doses of codeine, but form too much morphine and then they die > ____ for opiods overdose > don’t respond to ____ building up in your body
2D6 metabolite constipation SE demethylated mu
2D6
pain relief
SSRI
serotonin syndrome
seizures
heartbeats
overexpressors
respiratory depression
CO2
