1. Pharmacology Introduction Flashcards
• What is a pharmacologist?
– Someone who studies the effects of chemicals on ____ tissue. When that chemical is a potential useful therapeutic agent it is considered a ____.
• Pharmacologist is not a pharmacist ○ Some pharmacoogists have \_\_\_\_ degrees ○ Some are "frauds" - like the oral medicine folks
living
drug
clinical
Branches of Pharmacology
- Basic – studying the effects of drugs on whole ____ or ____ culture. Looking at things like drug effects of voltage gated calcium channels or tumerogenesis signaling. These are critical studies before we start testing drugs in ____. Gives us some idea if they may work or are safe.
- Clinical – the study of drugs in ____. Are they relatively safe, do they work, what are the proper ____, how are they ____ in the body
- Two subclasses of pharmacology
- In development of drugs - done on animals and tissue culuture first, if unsafe, doesn’t move onto humans
- Once drug company gets and IND, submits to FDA, then once accepted it can be studied on people (or it can be declined, or want mores data)
animals tissue humans humans dosages processed
Subranches of Pharmacology 1 - Pharmacokinetics
• Within basic and clinical pharmacology there are studies of drug ____ processes, drug ____ (where does the drug go – most of it doesn’t reach the receptor), drug ____ – typically processes that make the drug more ____ soluble, more readily excreted, and less active.
Lots of adverse drug interactions involve ____. One drug inhibiting or speeding up the metabolism of another drug. And drug elimination processes – primary organ of a lot of drug elimination is the ____. Again we have ways of using one drug to speed up the elimination of another drug in the case of poisoning.
absorption
distribution
biotransformation
water
biotransformation
kidney
• Within clinical > pharmacokinetics (what the body does to drug) and biotransformation
• Pharmacokinetics - wat processes are needed to get pill in body; drugs are not in body until it enters the BS
○ Exceptions: antioboitc sto treat ____ infections, antacids (maylox/myelanta)
• Distribution - where does the drug go once it gets in - 1/100th gets to ____
○ Some other places than receptors - cans et up for drug-drug interactions, where drugs don’t mix
○ One place where drugs like to go - stick to ____ (albumin) - becomes a depot site for drug > then one drug can block another durg off the plasma proteins and rasie to t toxic leaveels
• Biotransformation - metabolism, but that implies active to inactive, but that doesn’t always happen
○ If don’t ianctive the drug, they may the drug more ____ soluble/lipid soluble more polar more easily excreted/removed
○ If drugs build up > toxicity
• Final part of pharmoacokinetics - excretion > ____, but can also show up in sweat/____/breast milk; Breast milk is a clinical concern for those treating breast feeding women
• adverse reactions has to do with pharmacokinetics > two major areas > biotrasnformation (one drug block metabolism of another, or speeding it up), and also where drugs can block the active secreiton of other drugs in the renal tubule system (kidney); ex: common ____ to inhibit secretion of lithium from renal tubule system (major bipolar, a lot of AD reactions bc low therapeutic index; diff bt effective and lethal is small - if one drugs blocks excretion then trouble - kidney damamge, tremors, seizures, etc.)
• Overdoses - speed up elimination
GI receptors plasmid protein water kidney feces NSAIDS
Subranches of Pharmacology 2
• Pharmacodynamics – the ____ of the drug at the ____ level. What receptors does it bind. Is it an agonist or antagonist? Are their potential drug interactions at the receptor level? Also dose-response relations – typically as you give more drug you get a bigger effect.
• What the drug does to the body - what's going on a t the receptor level ○ Autonomic/somatic system ○ Epi and beta blockers can add up to a sever \_\_\_\_ event • Dose response relations two types: 90% - \_\_\_\_ (the more you give, th emore the effect); and \_\_\_\_ (all or none) ○ Calc therapeutic index - ratio of lethal dose over effective dose ○ Sleeping aid - how much to kill 50% of individuals, and then over how much it took to put him to sleep ○ The higher the \_\_\_\_ - the safer the drug (relative safety, doesn't tell what drug \_\_\_\_)
effect receptor hypertensive graded quantal TI does
Sub-Branches of Pharmacology 3
- Toxicology - all drugs whether prescription or over the counter drugs have potential toxic effects. Sometimes seen mainly on overdose but also can be seen at ____ with drugs that have a ____ therapeutic index.
- Often the toxic effects of drug are just an extension of their ____ effects.
- Some examples• Can see toxic effects with therapetuic indexes - even with wide TI you can see side effects (more often seen with narrow)
○ Benedryl - 20-30 TI, need to take 20-30X eff does to see dose > but with a therapetuic dose you still see ____; mehcniams explains - antihistamine and anticholinergic; histamine and AcH in brain is excitatory and casues drowsiness
therapeutic indexes
narrow
drowsiness
Examples of toxic (side) effects of drugs 1
- Warfarin (Coumadin®) – many people with ____ on this drug. Inhibits synthesis of ____. MAJOR TOXICITY = ____
- Diazepam (Valium) – many people take this for ____. Remember it enhances ____ influx into nerve cells. MAJOR TOXICTY = ____• Warfarin - low TI (3-4)
○ Binds to VitK epoxide receptor1 complex
○ ____ - too much > bleeding (intenral bleeding)
§ Can occur in GI and brain > hemorrhagic stroke
• Diazepam (____) - binds to own benzo receptors, makes ____ work better (increases affinity to its receptor) and causes hyperpolarization (Cl goes in)
○ Anti-anxiety drugs
○ Don’t pop before an exam, may be less anxious, but won’t be able to ____ on his exam questions
atrial fibrillation
vitamin K dependent clotting factors
bleeding
anxiety
chloride
drowsiness, lack of concentration
blood thinner
benzodiazepines
focus
Examples of toxic (side) effects of drugs 2
- Sildenafil (Viagra®) – “the Pfizer riser”. Male erectile dysfunction drug. TOXIC EFFECT = ____
- Propranolol (Inderal®) – ____ and ____ blocker used in treatment of hypertension, ____, arrhythmias. MAJOR SIDE EFFECTS: ____ and in some people ____
- Insulin (Humulin®) – major ____ diabetic drug. ____ blood sugar. MAJOR TOXIC EFFECT = ____.• Viagra
○ Priapism - erection that lasts for more than 4 hours - ER - can result in permanent nerve damage
• Prop - antagonist at beta receptors
○ Also works for ____
○ B2 receptors > bronchoconstriction
• Insulin
○ Hypoglycemia will kill people in dental chair - insulin shock - unconscious and cardiac arrest - get ____ into them
priapism beta 1 beta 2 angina bradycardia bronchoconstriction type 1 lowers hypoglycemia
migraines
sugar
Why take this course
• YOU NEED IT TO GRADUATE!!!!
• You are going to be licensed to prescribe and administer drugs. Local anesthetics, vasoconstrictors, analgesics, anxiolytics and antibiotics. You are expected to have a high level of expertise in these drug classes.
• Drugs being prescribed by you or other health professional can create new disease state in a patient. The new disease state is often a ____ or ____. EXAMPLES:
toxic
side effect
Examples of drugs causing new disease states 1
- Analgesics containing ____, hydrocodone, or oxycodone – produce high incidence of ____, nausea, vomiting and constipation
- Prazosin (Minipres®) – an ____ adrenergic blocking agent used in hypertension. Causes ____
- ____ (Procardia®), Verapamil (Calan®), ____ (Cardizem®)- calcium channel blockers used for hypertension, angina, arrhythmias. Cause ____. So does ____ (Dilantin®) and cyclosporine (Sandimmune®).
- ____ (Elavil®) –a tricyclic antidepressant with potent antimuscarinic activity. Causes ____.
codeine drowsiness alpha-1 postural hypertension nifedipine diltiazem gingival hyperplasia phenytoin amitriptyline xerostomia
Examples of drugs causing new disease states 1
• Opioid analgesics - side effect: addiction; tyelenol 3 - codeine, \_\_\_\_ - hydrocodone, \_\_\_\_ - oxycodone ○ Stimulate opioid receptors in CNS and periphery; the constipation is a \_\_\_\_ effect (decrease peristalsis) ○ CL-108 - vicodin like drug that's spiked with promethazine; compared with pure vico. Over 24 hours-5 days - incidience of nasusa/vom decrease by \_\_\_\_ and had analgesic effects (more likely to addictive bc you don't vom anymore) • Prazosin - \_\_\_\_ - stand up, dizzy and pass out • BP meds used in angina and cardiac arrhytmias - Ca+ channel blockers - have a unique toxicity (cause post hypotension bc vasodilate), but can cause gingival hyperplasia (gingival swollen and overgrows crowns of teeth [board question] ○ Phenotoin - treated in \_\_\_\_ also gini hyper ○ Cyclosporine - \_\_\_\_ - also results in gingi hyper (transplant patients) • Amitriptyline - blocks presyn reuptake of \_\_\_\_ and \_\_\_\_; but in periphery and CNS it also has \_\_\_\_ like effects blocks cholinergic muscarinic receptors - get atropine like side effects > dry-mouth, constipation, visual effects
vicodin percs periphery 60% vasodilation epilepsy immunosuppresent NE SE atropine
Examples of drugs causing new disease states 2
- High dose, long term (months, years) NSAIDs like ibuprofen and naproxen. Causes ____.
- Zolendronic acid (Zometa) – intravenous ____ used in certain cancers (breast) to prevent calcium resorption from bones – causes ____ of the jaw after dental extractions• Osteoarthritis - 2100 mg of NSAIDs everyday > GI ulcers and bleeds > may go to sleep with a bleed and not wake up (axanguinate)
• Breast and MM to the bone, a lot of bone resporitpon increases fractures and can increase Ca+ in the BS - use bisphosphonates
○ The ____ types used at highr doses - osteonecrosis of jaw - during extraction/implant placement, it never heals over
○ Can be minimal, and bone dies, but can be very bad (the entire maxilla on the right); major quality of life issue
GI ulcers
bisphosphonate
osteonecrosis
IV
Why take this course continued
• Drugs you prescribe may exacerbate a persons
disease state. Examples:
– Atropine – want to dry someone’s mouth. Blocks muscarinic cholinergic receptors. Unfortunately also raises intraocular pressure in patients with ____
– Patient with a history of GI ulcers – you prescribe ibuprofen for pain – patient ends up in hospital with ____
– Patient allergic to aspirin. After oral surgery procedure you prescribe ____® = oxycodone 5 mg plus aspirin 325 mg = DEATH
• Atropine - anti muscarininc blocker ○ Don't wanna give to glaucoma patients - impedes outflow of aqueous humor in the eye - jelly liquid build up in the eye - severe eye pain and perm damage to optic nerve ○ Perm charged ones - \_\_\_\_ - harder time getting into the ey chamber • Class of drug most highly associated with allergic rxns - \_\_\_\_ and \_\_\_\_ ○ Percodan at these doses are not good at post surgical dental pain, but the other component of percodan was \_\_\_\_ - the patient died (anaphylactic reaction and died)
glaucoma
GI bleed
percodan
glycopyllorate
penicillins
NSAIDs
aspirin
Why take this course continued
• Drugs you prescribe or administer may interact adversely with other drugs your patient is taking. Examples
• ____ and alcohol. Metronidazole (Flagyl®) is effective against ____ bacteria. Don’t want patient drinking ROH while on metronidazole.
Blocking - ____, Flushing, Nausea, ____ , Palpitations
• Metro - only prescribe when you're dealing with an anaerobic infection ○ Don't drink at same time ○ Not fatal • Pathway of alcohol/beer, how the body processes • Metro blocks his pathway, so you get buildup of \_\_\_\_ > side effects ○ Disulfaram/an abuse like effect > stop abuse of alcohol ○ Give \_\_\_\_ this drug, bc it does same thing as metro > gets sick when take it ○ Never dies, but feels awful • Major reason why drugs don't work - people don't \_\_\_\_ it
metronidazole
anaerobic
headache
vomiting
acetylaldehyde
alcoholics
take
Other Adverse Drug Interactions
• Metronidazole (Flagyl®) and ____ (Coumadin®) Warfarin metabolized by cytochrome P450 ____. Metronidazole inhibits the action of ____. End result may be massive bleed especially into ____.
• ____® (acetaminophen 325 mg plus butalbital 50 mg) and warfarin. Popular ____ headache drug. Barbiturates like butalbital speed up metabolism of lots of drugs. Induces ____. End result – warfarin levels drop and patient succumbs to a ____.
• Metro and warfarin - DEADLY ○ Cyto P450 - enezymes to detoxify natural compounds in our body > but also perform intial metabolic steps of drug metabolism § Don't totally inactive the drug, make more \_\_\_\_ osluble less lipid soluble more readily excreted § Major places in liver and SI, but in every organ § Warfarin processed by one isoform, and metro blocks the enzyme that processes it • Floricet and warfarin - opposite ○ Atrial fib and migraine headaches ○ Firoricent - acetam and \_\_\_\_ (NOTORIOUS FOR blocking blood levels of other drugs) ○ Now we have someone with warfarin to prevent stroke, but on fioricet, headaches get better but warfarin goes down and then you have a stroke • Drug interactions can be bad if \_\_\_\_ levels of drug and \_\_\_\_ levels of drug
warfarin
2C9
2C9
brain
fioricet
migraine
2C9
stroke
water
barbituates
increase
decrease
Other Adverse Drug Interactions
• High doses of ____ in dental local anesthetics and propranolol (Inderal). Again people taking propranolol for ____, angina, arrhythmias and migraine headaches.
Epinephrine: ____, β1+, β2+ Propranolol: β1-, β2-
End Result of Combo is pure ____ stimulation leading to hypertension and a reflex ____.
* \_\_\_\_ example * Epi - not pure vasoconstrictor - but it dialates, and with propranol with a lot fo epi, prop will block B2 vasodilation and B1 cardaic accel effect (not bad), but not epi resembles a pure a1 agonist > constriction everywhere > hypertensive > reflex bradycardia > makes situation worse
epinephrine
hypertension
alpha1
alpha1
bradycardia
pharmacodynamics
Drug Development
• Company has exclusive rights (patent) on chemical for ____ years. ____ of all drugs fail somewhere in development.
• Phase 1 - first time drugs are given to \_\_\_\_ - unless very toxic drug but benefit outweighs risk ○ Done in \_\_\_\_ people, and people without \_\_\_\_ state - look for unusually side effects and \_\_\_\_ in urine/blood, gives idea how drug is processed, and maybe a little bit of drug interactions ○ A new pain reliever for people who don't have pain - want to see how body processes it • Phase 2 - first group of people with the \_\_\_\_ ○ Intranvasal oxymetazoline > normal volunteers > not testing numbness, but measuring BP, how long to process (half lives) [this is all phase 1]; but first where drilled and filld > phase 2 study (peple with \_\_\_\_ states, need a filling/caries/post-srugical dental pain); for a statin (HMGcoA reducatse inhibite), people with high cholesterol ○ Several \_\_\_\_ people; may be diffeerent 2 reeposnes going ○ Look at \_\_\_\_ • If drug looks good and relatively safe (benefits outwiegh risks, some side effects present) > phase 3 • After all of this, submit \_\_\_\_ to FDA > can accept, can decline, or request more data • Based on all of this, develops the \_\_\_\_ (side effects, PDR, etc.)
17 90% humans normal disease metabolites disease disease 100 dose-response NDA label
Drug Development Continued
- FDA may accept, reject or request more data with regards to the NDA
- Phase 4 postmarketing surveillance. Remember during drug development process only several thousand people exposed to drug. As drug is used by tens of thousands of individuals rare ____ may become evident leading to additional warnings put on drug ____ or the drug may be ____ from the market. Some examples:• If ____ number of drug-users, the rate of side effect may not show up in that group during the trials > label may need to be updated if side effects emerge
side effects
removed
small
Examples of FDA actions caused by post-marketing surveillance
- ____ (Toradol) – highly effective analgesic for postop and kidney stone pain. FDA put a 5 day limit on its use due to a high incidence of ____ and bleeds with longer term use.
- More recently all acetaminophen/opioid combination tablets can no longer contain more than ____ mg acetaminophen because of concerns of liver toxicity.• Ketorolac - on market in early 90’s
○ Originally marketed for short-term pain (acute) - for back pain its longer (3-4 weeks)
§ Taken for logner - higehr indicidence of GI pains and ulcers
○ Opioid sparing - but has propensity to casue GI uclers and potentnt platelet effects > can lead toa GI bleed
• Narcotic combination - narcotic combined with aceto here; vico preps - 500-700 mg of aceto, but now can’t do more than 325 - don’t work as well now
ketorolac
GI ulcers
325
Drugs removed from market due to Phase 4 postmarketing surveillance
- ____ – part of the diet pill combination fen-fen. Long terms use lead to cardiac valvular damage and pulmonary hypertension
- ____ (Duract®) – an NSAID we studied for short term control of pain at PENN. Long term use lead to liver damage in some people
- Cisapride (Propulsid) – a prokinetic drug used in ____ disease. It’s use was associated with ____ (torsades de pointes).
- Terfenadine (Seldane®) – first non-____ histamine on the market. It’s use was also associated with ____ (torsades de pointes).
- Phenylpropylnolamine – an indirect ____ which was found in a lot of cold and cough preparations. Some people used it off label as a ____ aid. Its use was associated with an increased risk of ____ in young women.
- ____(Baycol) – an HMGCOA reductase inhibitor. It’s use was associated with an unusually high incidence of myalgias and rhabdomyolysis (muscle breaks down and clogs up kidney tubules).
- Rofecoxib (Vioxx®), Valdecoxib (Bextra®) – Highly selective ____ inhibitor NSAIDS whose chronic use was associated with increased risk of ____ and ____.
dexfenfluramine bromfenac GERD ventricular arrhythmias sedating ventricular arrhythmias
sympathomimetic
diet
strokes
cerivastatin
COX-2
strokes
heart attacks
Drugs removed from market due to Phase 4 postmarketing surveillance
• Pulled after FDA approveed • Dex - blcoks reupatek of \_\_\_\_ and accelerates release; taken in part of Fenfen combination; results in excessive pressure in lungs • Bromfenac - very long \_\_\_\_ ○ Raise liver enzymes, 10 day cap; and when kept on longer > liver failure • Cisapride - prokinetic (speeds movmeent of food from stomach to \_\_\_\_ - less likely reflux it up) ○ It's back now - \_\_\_\_ use - people with GERD and other things don't work > can prescribe it again • Terfen - doesn't cross \_\_\_\_ • Phenyl - poor man's version of ampheto - incrreases \_\_\_\_ ○ Ampheto-like drugs to lose weight > increase incidence of bleeding strokes in young women • All statins > \_\_\_\_ inhibiotrs > rhabdomyelsis is life threatnening (send you to renal dialysis unit); but happened more often with cerivastatin • Rofe/valdecoxib - developed for people with arthritis, tried to stop effects of \_\_\_\_, spares COX1 > increased \_\_\_\_ activity and \_\_\_\_ (coronaries)
NE lasting SI compassionate BBB NE HMGCoA reductase GI ulcers platelet vasoconstriction
Phase 4 Studies
• Results of studies after the drug is marketed can lead to additional marketing claims. i.e. For tough pain nothing OTC is stronger or lasts longer than ____, not even extra strength Tylenol®.
* If you're notactually better without proof > sued * More Advil had better effects then tyelonol (the maximum approved dose)
Advil Liquigels
Names of Drugs 1
LOOK OVER THIS SLIDE
• APAP - acetominophen ○ In europe - called paracetamol • Generic name is related to \_\_\_\_ structure of drug, decided upon by \_\_\_\_ and drug company • Major thing to speed absorption - \_\_\_\_ and \_\_\_\_ (glass of water with alka seltzer) • Ibuprofen like aspirin - \_\_\_\_
chemical FDA disintegration dissolution weak acid
Names of Drugs 2
LOOK OVER THIS SLIDE
• Classic structure of LA ○ \_\_\_\_ end, middle chain/int chain, secondary/tertiary amino end • Secondary to tertiary amino group • This is an \_\_\_\_ • \_\_\_\_ (intraoral lido bandaid) - works for soft tissue
aromatic
amide
dentipatch
Where do we get drugs
• Some totally synthesized in ____. Others totally or ____ come from natural sources.
– Bark of willow tree – ____ (aspirin precursor)
– Poppy plant – ____ and ____ (opioid analgesics). If you diacetylate morphine in lab you get ____.
– Fox glove plant – ____ and ____ (CHF drugs)
– Yew Tree – ____ (anticancer drug)
* Poppy - \_\_\_\_ - one step converts to oxycodone * Paclitaxel - useful for treating against \_\_\_\_ cancers * Digoxin/digitoxin - blocks \_\_\_\_ pump > increase force of contraction of heart; easy to send into vent arrhytmia; low \_\_\_\_ (3-4)
lab partially salicin morphine codeine heroin digoxin digitoxin paclitaxel
thebaine
breast
Na/K ATPase
TI
FDA Control of Drugs
- Rx (prescription) vs OTC (over-the-counter).
- OTC drugs can be safely taken without the guidance of a health professional. i.e. ____, acetaminophen, ibuprofen, ____ for pain. ____ (in Orajel® and Anbesol®) for toothache. PEOPLE STILL DIE FROM ____ OF THESE AGENTS.
- Acetaminophen found in a lot of products. People unintentionally overdose. Toxic metabolite is ____. N acetyl benzo quinonemine. Kills ____. Takes ____ hours to see symptoms.
- Aspirin – ____ (blood pH drops)
- Benzocaine – ____ Fe++ > Fe+++
aspirin naproxen overdoses NAPQI hepatic mitochondria 23-48 metabolic acidosis methemoglobinemia
FDA Control of Drugs
• OTC > can still overdose • Acetamen - someone has the flu (muscle aches, fever, etc) > Robutussin and then excedrin, and then feverol (all have acetomen) and then take vicadin > therapeutic overdose ○ When processed, toxic metabolic > NAPQI > kills hepatic mitochondria > turns \_\_\_\_; there is an antidote, but has to be given on first day (before any symptoms appear) • Aspirin - weak acid (higher TI) - can drop the blood \_\_\_\_ > begin to shut down organs (metabolic acidosis); shows up early > abdominal pain, vomiting, ringing in the ears • Benzocaine > MHG > overdoses of strong \_\_\_\_ drugs (oxidation make things less \_\_\_\_) > \_\_\_\_ (injectable) can also do it (has the water soluble end, benzocaine doesn't) > converts from reduced form (Fe++) to \_\_\_\_ ○ Methemo doesn't pick up O2 well, and doesn't \_\_\_\_ go; person turns blue/purple > have toruble breathing ○ Antidote drives the pathway in the other direction - \_\_\_\_ (a dye in histology)
yellow pH oxidizing electronegative prilocaine Fe+++
let
methylene blue
FDA Control of Drugs – DEA Schedules
- DEA Scheduling – based on ____ and accepted ____
- DEA Schedule I – ____ abuse potential, no acceptable medical use. ____, LSD
- DEA Schedule II – Very High abuse potential, ____ medical uses. ____, acetaminophen plus ____(Percocet®), acetaminophen plus ____ (Vicodin®), ____ (Marinol® - medical marijuana)
- Most drugs of abuse (physical depend - stop taking drug and go into withdrawal; for addicts - the whole life depends on the drug and you start doing things out of whack to get the drug)
- Nothing to do with how drug ____, but what they’re picking up in people’s pockets when busted
- DEA II is ____
abuse potential medical use highest heroin acceptable morphine oxycodone hydrocodone dronabinol
works
legal
FDA Control of Drugs – DEA Schedules
- DEA Schedule III – Less abuse potential than Schedule II, accepted medical uses. Acetaminophen with ____ (Tylenol® #1, #2, #3, #4), ____(Winstrel®) – an anabolic steroid.
- DEA Schedule IV – Less abuse potential than Schedule III, accepted medical uses. Benzodiazepines like ____ (Valium), clonazepam (Klonopin®).
- DEA Schedule V – Low abuse potential (but some), accepted medical uses. Cough syrups with low doses of ____
- Most drugs are ____ – do not have abuse potential like antihypertensive drugs, ____ lowering drugs, NSAIDs, ____ and many others .• Can refill the III
• Don’t wanna refill drugs
• ____ is weaker than hydro and oxy, that’s why it’s a III
• Some people try to balance - too stimulated with cocaine - use a ____ (alcohol/benzo)
• High students students > cough syrup > schedule V
• Write a script for DEA scheudle drug that is legal > in addition to ____ and ____ you have to put your ____ number
○ ____ letter, ____ digit number; you will apply after your dental license
codeine
stanozolol
diazepam codeine unscheduled lipid antibiotics
codeine CNS depressant signature degree DEA
two
seven
FDA Control of Drugs -Teratogenicity
- Category A – controlled studies have shown no risk to developing ____ in pregnant women. Examples: Prenatal ____, fluoride toothpaste. Only ____% of all drugs.
- Category B- ____ reproductive studies have shown no risk to developing fetus but human studies are lacking but there’s been no evidence of teratogenicity. Examples: ____, Ibuprofen in first ____ trimesters, Penicillin. ____% of all drugs• Pregnancy risk cateogires
• Looking at ability of drug to produce birth defects in a developing fetus
○ Damage that causes happens early in the pregnancy
• Limited number of cateogyr A
• Ibuprofen is different in each time of pregnancy
fetus
vitamins
0.7
animal
lidocaine
two
19
FDA Control of Drugs -Teratogenicity
- Category C- ____ studies have shown some evidence of teratogenicity but ____ studies have not been done. Or there is a relative lack of ____ studies and there is no ____ evidence in humans. Examples: ____, Bupivacaine, ____ in first two trimesters, codeine, ____. ____% of all drugs
- Category D – the drug is definitely teratogenic in ____ but it’s benefits may ____ the risks. Examples: ____ chemotherapy in a pregnant woman, ____ and ibuprofen in third trimester, diazepam (Valium®), ____. Aspirin and ibuprofen can cause more bleeding during ____, slow down ____ and cause a premature closure of the ____. ____% of all drugs
- Category X - the drug is definitely ____ and the benefits do not ____ the risks. Examples: A pregnant woman uses ____ to treat acne while pregnant. Causes a high incidence of mental ____ and blindness among other things. ____% of all drugs
animal human animal epidemiological mepivacaine aspirin hydrocodone 66
humans outweigh cancer aspirin tetracycline delivery labor patent ductus arteriosus 7
teratogenic outweight isotretenoin retardation 7
FDA Control of Drugs - Teratogenicity
• Most drugs are category ____
○ Mepivacaine - local that doesn’t ____ as much as lido; if patient has cardiovascualr issues
○ Bupivcaine - with alittle epi - soft tissue/bony anesthesia for ____ hours; complex dental procedures
• Category D - woman that’s pregnant, and has rbeat cancer and is treatable btu needs chemo/lumpectomy; take our chances, way to scheudle chemo to lessen the chance
○ Benzo - seizure disorders
○ Tetra - perm staining of ____ in developing fetus; but woman has infection and needs it
○ Aspiring/ibu - third trimester - anti-plaletlet effects, makes them bleed more and delays labor, and premature closure of ductus arterious (BV in utero, that shunts blood away from the lungs rrom the heart) - the baby can be born with ____ symptoms; if it doesn’t close upon birth (aspiring/ibuprofein via injection)
• Cateogry X
○ Isotretenoin (acutane) > ____ analog > ____, mental retardation, absorbed well right through the skin
C vasodilate 8-10 teeth respiratory distress
vitamin E
cleft palate
Some potential toxicity to fetus of teratogens
Isotrentenoi: ____, vision impairment
Tetracycline: permanent ____ discoloration
Traizolam, diazepam: ____
Aspirin, ibuprofen 3rd trimester: ____ bleeding, delayed ____, premature closure of ____
Bupivacaine: ____, respiratory ____
* Doesn't happen to every fetus, but a very high incidence with isotretenoin * Tetra bind \_\_\_\_ cation > Ca++ > lock onto ca++ in developing teeth > eruption > the Ca/tetra product becomes \_\_\_\_ and turns teeth yellow/brownish * Argument about benzos with cleft palate; triazolam is a \_\_\_\_ acting benzo (it's an X) * Bupivacine - potent LA - long acting; preferentially hits \_\_\_\_ tissue when its rapidly firing (like rapid arrhytmhia), it will block those \_\_\_\_ channels \_\_\_\_ > even when cardiac tissue is at normal rates > cause more bradycardia in fetus
mental retardation tooth cleft palate fetal labor ductus arteriosus bradycardia depression
divalent/trivalent oxidized short excitable Na+ nonpreferentially
