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Basic Science Concepts Flashcards

1
Q

Chemical structure determines

A

lipophilicity (lipid loving and can cross membranes easier, less soluble in water, and non polar)

hydrophilicity (water loving, can’t cross membranes s easy, more soluble in water, polar)

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2
Q

structure activity relationship

A

the structure of the compound and its relation to it’s activity

the functional groups in the compound (part of the chemical structure) determine the mechanisms of action and degredation

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3
Q

Explain the body’s two phase detoxification system’

A

phase 1 reactions: oxidation, hydrolysis (the body’s main way of excreting drug is renally, so drugs need to become more hydrophilic/polar)

phase 2 (conjugation) reactions: glucuronidation, sulfate conjugation

this is how the body gets non polar drugs/lipophilic/non charged drugs to be polar/hydrophilic/charged so that the metabolite can be sent to the kidney and metabolize

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4
Q

How are drugs degraded

A

oxidation (loss of electrons) & hydrolysis (water) & then photolysis (light destroys carbon bonds)

these are three mechanisms where sometimes even before a drug reaches a pts mouth, if the drug is not kept properly, it can begin to degrade

Naturally, most drugs are lipid soluble, non charged and non polar but when in the body, it wants to be in more of a hydrophilic state so that the drug can be removed from the kidney and concentrate in the urine – so it is converted through phase 1 and phase 2 reactions to a hydrophilic, polar, charged molecule

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5
Q

morphine is a full agonist at which receptor

A

a mu opioid receptor

mimics endorphins (which are endogenous)

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6
Q

naloxone is a full antagonist at which receptor

A

a mu opioid receptor

it competes with the endogenous ligand (endorphins) and even the exogenous ligand (morphine) so that it cannot act anymore

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7
Q

naloxone is a full antagonist at which receptor

A

a mu opioid receptor

it competes with the endogenous ligand (endorphins) and even the exogenous ligand (morphine) so that it cannot act anymore

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8
Q

competitive inhibition

A

when the substrate binds directly to the active site of the enzyme and competes with what’s normally supposed to be there

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9
Q

non competitive inhibition

A

when the substrate binds indirectly, to a different portion of the enzyme and causes the active site to change shape so the normal ligand is not able to fit and cause it’s action

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10
Q

CNS

A

brain, spinal cord, nerve cells/neurons

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11
Q

PNS break down

A

peripheral nervous system - somatic (voluntary, muscle) and autonomic (involuntary, heart, BP, GI) bodily functions

Autonomic nervous system communicates with internal organs and glands and there is the sympathetic (arousing) and parasympathetic (calming) division

The somatic nervous system communicates with sensory organs and voluntary muscles for the sensory (afferent nervous system- sensory input) and the motor (efferent nervous system - motor output) - the primary neurotransmitter for somatic NS is Ach, it binds to nicotinic receptors (Nn) in skeletal muscles and affects skeletal movement

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12
Q

CNS and PNS communicate to each other through

A

neurotransmitters (NTs) that pass through neurons

we dont grow new neurons, but we do grow dendrites in response to positive stress . ex: just like a muscle grows with more stress we have to keep the brain working in the elderly so the neurons/dendrites will keep being healthy

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13
Q

glial cells

A

they provide nutrition and cohesive support for the neurons life and to keep the neuron healthy

there are two types:
schwan cells and astrocytes

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14
Q

how is signal transmission between the CNS and the PNS accomplished

A

They communicate via neurotransmitters - the body’s chemical messengers (substrates/ligands). they are released from presynaptic neurons into the synaptic cleft, then they travel to post synaptic neurons or other parts of the body to exert their effect

common neurotransmitters : (Ach), epinephrine (epi)- aka adrenaline, Norepinephrine (NE) aka noradrenaline, dopamine (DA), and serotonin (5HT)

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15
Q

what is the primary NT for the somatic NS and what receptor does it bind to

A

Ach, it binds to nicotinic receptors (Nn) in skeletal muscles and affects skeletal movement specifically within the somatic nervous system (in autonomic NS they bind to muscarinic receptors)

if people can’t make muscle movements its usually because they lack the neurotransmitter or the receptor that helps to signal motor movements

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16
Q

What are the NT’s involved in the sympathetic nervous system (autonomic) vs the parasympathetic nervous system (autonomic)

A

sympathetic - fight or flight - uses NE and Epi neurotransmitters on alpha 1 and beta 1 and beta 2 adrenergic receptors in the cardiovascular and respiratory systems, and this leads to decreased urination and digestion and increased HR, BP, increased bronchodilation, and glucose production.

parasympathetic - rest and digest - Ach binds to muscarinic receptor (most drugs) throughout the body like GI system, bladder, eyes; which leads to SLUDD: salivation, lacrimation (tears), urination, diarrhea (defecation), digestion

anti-muscarinic aka anticholinergic = anti-SLUDD aka cant see, cant pee, cant spit, can’t poop

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17
Q

the location of the alpha 1 adrenergic receptor and what are examples of agonists and antagonists

A

smooth muscles
blood vessels

Agonist: vasoconstrictors - dopamine (an inotrope that raises BP to increase CO), oxymetazoline (afrin nasal spray)

Antagonist: phentolamine (nonselective for alpha 1 and alpha 2 adrenergic receptors)

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18
Q

the location of beta 1 receptors and example agonist and antagonists

A

heart

agonist - dobutamine (inotrope that increases HR and increases CO)
antagonist - metoprolol (decreases HR and decreases BP, antihypertensive that also used in HF)

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19
Q

the location of beta 2 receptors and example agonist and antagonist

A

lungs

agonist - albuterol (short acting, used for asthma and COPD, causes bronchodilation
antagonist - propranolol (This is a beta 1 and beta 2 blocker - AVOID IN COPD because it can cause bronchoconstriction and hinder breathing)

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20
Q

endorphins are

A

endogenous hormones secreted in the brain and nervous system that active the body’s opiate receptors and cause analgesia

the exogenous versions are these are opioids that bind to mu- receptors like morphine

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21
Q

pyridostigmine is a drug used for myasthenia gravis because

A

it is an acetylcholinesterase inhibitor so it allows Ach to be around longer in order to have an affect on the muscle/motor function

This is also known as a cholinergic drug or a nicotinic agonist

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22
Q

Neostigmine is a drug that is used to reverse paralytic drugs, how?

A

It reverses the non-depolarizing neuromuscular blockers that work to intentionally antagonize Ach and prevent muscle function. this drug pretty much reverses all of the neuromuscular blockers besides succinylcholine because it is a depolarizing neuromuscular blocker

This is known as a cholinergic drug or a nicotinic agonist

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23
Q

Succinylcholine MOA

A

MOA: the only depolarizing neuromuscular blocker (all others are non depolarizing) and it binds to nicotinic Ach receptors and prevents the ACh from working leading to temporary paralysis

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23
Q

Example of alpha 2 agonist and antagonist

A

An alpha 2 receptor agonist inhibits sympathetic activity and lowers blood pressure

agonist - clonidine (antihypertensive that relaxes arteries and increases blood supply to heart which then lowers BP and HR)

antagonist - yohimbine aka yohimbe (helps with erection by vasodilation

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24
Which receptor does dopamine go to
alpha 1 or beta one depending on the dose!
25
MOA of benzodiazepines
They bind to and enhance the effect of inhibitory neurotransmitter GABA - which causes anxiolytic, hypnotic, anticonvulsant, and muscle relaxant effects (including relaxing the diaphram which could lead to respiratory suppression) they shouldn't be taken with opioids because opioids can do the same thing. they both have boxed warnings for use together causing profound sedation, respiratory , coma, death.
26
Box warning for benzos and opioids
benzos shouldn't be taken with opioids because opioids can do the same thing. they both have boxed warnings for use together causing profound sedation, respiratory depression, coma, death. restrict dosages and duration, monitor patients for signs and symptoms of respiratory depression/sedation
27
True or false: since the MOA of Tylenol and opioids is different, the drugs work synergistically and there's not increased risk of respiratory depression
True. They can be taken together safely
28
pharmacokinetics is ADME
PK drug interactions occur when one drug alters the absorption, distribution, metabolism, or excretion of another drug and they can be beneficial or harmful interactions
29
what is Chelation and what kind of drugs should be separated from what due to risk of chelation
when a drug binds to polyvalent cations (+) in another compound ex: drugs like quinolones, tetracyclines, levothyroxine, and oral bisphosphates
30
Acid suppressing drugs like H2RAs, PPIs decrease the absorption of what kind of drugs
antifungals this can result in untreated infections
31
Clarithromycin does what to warfarin
Clarithromycin inhibits warfarin metabolism, which increases INR and bleeding
32
Rifampin does what to warfarin
causes warfarin to be metabolized (decreases INR and limits therapeutic action
33
probenacid blocks the renal excretion of
penicillin sometimes this can be used intentionally together if the penicillin requires high levels to cross the BBB and treat neurosyphillis
34
salicylate overdose can lead to toxicity in the urine, what can we do to compensate for this
give sodium bicarb to alkanize the urine and ionize the aspirin so that it can be excreted in urine and remain there
35
When prodrugs are taken by patients it allows for what two benefits
extend the dosing interval of the drug prevents drug abuse
36
Active metabolite of capecitabine
fluorouracil
37
true or false: clopidogrel is a prodrug
true
38
Colistimethate is a prodrug for
Colistin
39
Cortisone is a prodrug for
Cortisol
40
Famicyclovir is a prodrug for
penicycloir
41
Fosphenytoin is a prodrug for
phenytoin
42
Isavuconazonium sulfate is a prodrug for
Isavuconazole
43
Levodopa is a produg for
Dopamine
44
Lisdexamfetamine is a prodrug for
dextroamphetamine
45
Prednisone is a prodrug for
prednisolone
46
Primidone is a prodrug for
phenobarbital
47
true or false : tramadol is a prodrug
true
48
Valacyclovir is a prodrug for
acyclovir
49
Valgancyclovir is a prodrug for
Ganciclovir
50
What do we need to be careful of in patients on codeine (including tylenol #3)
if they are ultra rapid metabolizers of CYP2D6, they will have a more rapid conversion to morphine so we should NEVER USE THIS IN THOSE PATIENTS. several fatalities have occured if they are poor metabolizers, there is a risk of poor therapy, so we need to use alt. therapy
51
what is important to know about clopidogrel's metabolism and what drugs should be avoided with it
CYP2C19 inhibitors and poor metabolizers can block conversion to the active form and hinder the antiplatelet effect avoid: omeprazole and esomeprazole with clopidogrel because they are inhibitors of the enzyme use alternative antiplatelet if the patient is a CYP2C19 poor metabolizer
52
N-Acetyltransferase is an enzyme in phase 1 or 2
phase 2, changes in this enzyme can affect drugs like isoniazid another phase 2 enzyme is UGT (uridine diphosphate glucuronosyltransferase 1A1)
53
what happens when a prodrug faces an inhibited enzyme
the drug effect is diminished because its not metabolized to active form
54
what happens when multiple drugs are substrates for the same enzyme
there will be increased serum drug level and decreased metabolism rate
55
enzyme inhibition is fast, very quick onset and offset while enzyme induction takes time to onset and offset
make sure to be mindful of how the drug will impact the body when an inducer is present for the first and last 2-4 weeks
56
why do most drug interactions occur
because there are drugs that are moderate or strong CYP 3A4 inhibitors
57
List the common CYP inhibitors in drug interactions and their effects on substrates/prodrugs (G PACMAN)
G PACMAN G - grapefruit Protease inhibitors (PIs) - many are potent inhibitors, especially ritonavir (a booster for antivirals) Azole antifungals (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole, isavuconazonium) Cyclosporine, cobicistat Macrolides (clarithromycin, erythromycin, azithromycin) Amiodarone (and dronedarone) Non-DHP CCBs (diltiazem, verapamil) on substrates - they decrease the metabolism (so we should decrease the dose unless its a prodrug), and they decrease the conversion to active metabolites for prodrugs so we should consider alternate therapy. always monitor for therapeutic effect, ADRs and toxicity` INhibitors INcrease toxic effects/drug levels/ADRs because they are not being metabolized
58
whats the problem with using voriconazole for a patient taking simvastatin
simvastatin is a strong CYP 3A4 substrate and voriconazole is a strong inhibitor of CYP3a4, so the voriconazole will increase simvastatin levels to be toxic (muscles, rhabdomylosis) THESE ARE CONTRAINDICATED TOGETHER. Use rosuvastatin instead!
59
What are common cyp inducers and what is their effect on drugs. (PS PORCS)
CYP inducers increase enzyme production or activity and cause the drug to be metabolized way too fast so the therapeutic effect is decreased PS PORCS Phenytoin Smoking Phenobarbital Oxcarbazepine Rifampin (and rifabutin, rifapentine) - used in TB and combo for gram positive problems Carbamazepine (auto-inducer) St. John's Wort Increase the dose of the drug if it s not a prodrug, decrease dose if it is a prodrug because it will produce a lot of active drug and monitor therapy, use alternative drug to avoid combination INDuced = Decreased effects
60
INR goal for patient on warfarin (no mitral valve)
2.5-3.5
61
Rifampin is an inducer of which enzymes
PgP, CYP 3a4, CYP 2c9, CYp 1a2, and 2c19
62
Which enzymes is warfarin metabolized by
CYP 2C9 (major), CYP1A2, CYP 2C19, CYP3A4
63
What is the issue with a patient on warfarin and rifampin
rifampin is an inducer of PgP, CYP 3a4, CYP 2c9, CYp 1a2, and 2c19 warfarin is a substrate for CYP 2C9 (major), CYP1A2, CYP 2C19, CYP3A4. so rifampin is going to decrease warfarins effectiveness, so we need to monitor the therapy and potentially increase warfarin's dose
64
what is the pglycoprotein efflux pump and how are they affected by inhibitors or inducers
Its a "permeability glycoprotein transporter" that is located on tissue membranes to help excrete bad substances out of critical areas. Some cancer cells learn how to use these pumps to do chemo resistance so their cells can stay alive. Pgproteins in the GI tract transport metabolites of drugs into the stool to be excreted. PgPs are affected by inhibitors -- the drug that is a substrate of the PGP will have increased absorption because less drug is being effluxed, and inducers - they do too much of efflux and less drug will be absorbed
65
enterohepatic recycling
the drug is metabolized by liver but goes back into intestines via the bile acid, then it
66
example Pgp subtrates
anticoagulants - rivaroxaban**, apixaban, edoxaban, dabigatran cardiovascular drugs - digoxin*, diltiazem*, verapamil*, carvedilol, ranolazine Immunosuppresants - cyclosporine, tacrolimus, sirolimus Hepatitis C Virus (HCV) drugs - dasabuvir, ombitasvir, paritaprevir, sofosbuvir Others: atazanivir, colchicine**, dolutegravir, posaconazole, raltegravir, saxagliptin
67
Inducers of Pgp (similar as inducers for the CYP enzymes) PPORCS + others
carbamezapine, dexamethasone, phenobarbital, phenytoin, st johns wort, rifampin, tipranavir
68
Inhibitors of the Pgp transporter (similar as the CYP enzymes) PACMAN
Anti-infectives (clarithromycin, itraconazole, posaconazole) Cardiovascular drugs (amiodarone****, carvedilol, conivaptan, diltiazem**, dronedarone, quinidine, verapamil**) HIV drugs (cobicistat*, ritonavir*) Hep. C virus (HCV)- ledipasvir, paritaprevir) Others (cyclosporine, flibanserin, ticagrelor)
69
What is the Harriet Lane resource used for
its a pediatric drug information resource
70
what is guanficine used for
primary indication is ADHD and blood pressure should be taken at night because makes patients sleepy
71
which drugs can cause increased risk of rhabdomylosis
Daptomycin ,and statins so we should monitor CPK
72
Which drugs cause B12 deficiency if used long term
metformin and PPIs

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