1. Pharmacy Foundations Flashcards
Define substrate/ligand
A substance that creates a signal/produces an effect by binding to a receptor, enzyme or transporter
Define “endogenous”
Substance produced naturally by the body
Define “exogenous”
Substance produced outside the body (ie. Drugs)
Define “agonist”
A substance that binds to a receptor to initiate an action
Define “antagonist”
A substance that reduces or blocks a reaction
Define “induction”
When a substance INCREASES the metabolism of an enzyme (faster metabolism)
Define “inhibition”
When a substance decreases/blocks the metabolism of an enzyme (SLOWED metabolism)
The peripheral nervous system controls the rest of the body aside from the CNS. What are the two branches of the PNS?
Somatic nervous system
Autonomic nervous system
What is the difference between the somatic and autonomic nervous systems?
Somatic = VOLUNTARY, controls muscle movements
Autonomic = INVOLUNTARY, controls bodily functions (ie. Digestion), cardiac output and BP
What is a neurotransmitter?
The body’s chemical messengers
Released from presynaptic neuron to postsynaptic neuron/other parts of the body to create an effect
Name 5 neurotransmitters
Acetylcholine (ACh)
Epinephrine (Epi)
Norepinephrine (NE)
Dopamine (DA)
Serotonin (5-HT)
What is the primary neurotransmitter in the somatic nervous system? What is its mechanism in the somatic NS?
Acetylcholine
Binds to nicotine c receptors in skeletal muscles to cause movement
What are the two branches of the autonomic nervous system? What are they known for?
Sympathetic (“fight or flight”) - releases Epi and NE, activating the adrenergic receptors (alpha and beta) in the cardiovascular and respiratory systems. Affects BP, HR, bronchodilation.
Parasympathetic (“rest and digest”) - releases ACh that binds to muscarinic receptors, causing movement in SLUDD (salivation, lacrimation, urination, defamation, digestion)
Define SLUDD (parasympathetic nervous system)
Salivation
Lacrimation
Urination
Defecation
Digestion
(All increased w parasympathetic activation)
What is the difference between competitive and non-competitive inhibition?
Competitive - antagonist binds to SAME binding site as an endogenous substrate, preventing reaction
Non-competitive - antagonist binds at an ALLOSTERIC site that changes the shape of the active site, preventing endogenous binding
Define structure-activity relationship
When the structure of a drug affects its activity. Ie. The functional groups on a drug will affect not only its therapeutic affects but also its adverse effects
NSAIDs contain what functional group?
An acidic CARBOXYL group
What functional group is featured in Aztreonam?
One standalone LACTAM ring (thus, the class “monobactam”)
What functional groups are featured in aminoglycosides?
An AMINE group and a SUGAR (GLYCOSIDE) (thus, aminoglycoside)
What functional group is featured in levothyroxine?
T4 - so 4 IODINES
(Note, T3 is when an iodine is removed)
What is the featured functional group in tricyclic antidepressants?
Three ring structure (thus, tricyclic)
What is drug stability?
The extent which a product retains its original properties throughout its period of storage and use (SHELF LIFE)
Drug degradation can make a drug ineffective, unpalatable, or even toxic. Name 3 reactions that cause drug degradation:
Oxidation-reduction
Hydrolysis
Photolysis
What is oxidation-reduction (degradation)? What happens to a compound when it is oxidized?
When a compound is oxidized = loses electrons or reduced = gains electrons (recall OIL RIG [oxidative is lose, reduce is gain])
Oxidized compounds often have a VISIBLE COLOR change (yellow, orange, pink)
What kinds of compounds are most likely to oxidize?
Drugs with hydroxyl (-OH) groups directly bonded to a ring.
Ie. Epinephrine (catecholamines), phenylephrine (phenols), aldehydes
How is oxidation catalyzed, and how do we prevent it?
Catalyzed by light, heat, and metal ions
Prevention: light, temp, pH controls, addition of antioxidants or chelating metal agents
Describe hydrolysis and what groups are at highest risk of hydrolysis
When water causes cleavage of bonds in a molecule
Highest risk: esters, amides, lactams
What are some methods to prevent hydrolysis?
Addition of adsorbents (absorbs moisture), lyophilized powders (freeze dried), hygroscopic salt (water absorbing) and other agents for prevention of oxidation (chelating agents, temp control, pH controls, light protection)
What drugs are most prone to photolysis?
Ascorbic acid (vitamin C)
Folic acid
Nitroprusside
Phytonadione (vitamin K)
Define pharmacodynamics
The effect a DRUG has on the BODY
Define pharmacokinetics
The effect the BODY has on the DRUG
Describe additive effects of drugs at the SAME vs DIFFERENT binding sites
SAME binding site = increased AEs and direct additive effects
DIFFERENT binding sites = drugs that have similar end effects through different receptors causing additive effects (ie. Benzos enhance GABA effects, may increase risk of opioid overdose in combo w opioids)
What is drug SYNERGY?
When two drugs taken in combination have a greater effect than that the two individual effects together
Why do polyvalent cations (antacids, multivitamins, sucralfate, bile acid resins, metals, phosphate binders) need to be separated from quinolones, tetracyclines, levothyroxine and PO bisphosphonates?
CHELATION may occur, where polyvalent cations prevent quinolones, tetracyclines, levothyroxine and PO bisphosphonates from getting absorbed
Name one example of how GI acid suppression (increased pH) can decrease drug absorption?
H2RAs and PPIs decrease absorption of antifungal (ie. Itraconazole)
Ritonavir “boosting” the effects of Darunavir in HIV is an example of what PK effect?
Inhibition of metabolism to increase time of drug in circulation
Probenecid blocks the _____ ______ of penicillin, allowing for increased penicillin levels required to cross the BBB for neurosyphillis
Renal excretion
How does sodium bicarb aid in the resolution of salicylate toxicity?
Bicarb binds to salicylate and ionizes the compound, allowing it to be more hydrophilic, be retained in the urine and be excreted
Why are prodrugs used by drug manufacturers?
Increased bioavailability (prevents excessive loss during first-pass)
Prevent drug abuse (ie. Vyvanse [lisdexamfetamine] formulated so amphetamine is not released until lysine is detached only by enzymatic cleavage)
What are the major CYP inhibitors?
G PACMAN
Grapefruit
Protease inhibitors (ritonavir)
Azoles
Cyclosporine, cobicistat
Macrolides (NOT Azithromycin)
Amiodarone
Non-DHP CCBs (Diltiazem, verapamil)
What are the major CYP inducers?
PS CORPS
Phenytoin
Smoking
Carbamazepine
Oxcarbazepine
Rifampin
Phenobarbital
St. John’s Wort
What is the role of P-glycoproteins (PGPs)? What happens when PGPs are inhibited?
Efflux pumps that protects the body against foreign substances by pumping into the GI tract for excretion.
When PGPs are inhibited, drug levels INCREASE (less excretion)
What are common PGP substrates?
DOACs
Cardiovascular drugs (digoxin, non-DHP CCBs)
HCV drugs
Transplant drugs (tacro/cyclosporine)
Colchicine
What are common PGP inhibitors?
Uncommon Azoles (Itraconazole, posaconazole)
Cardiovascular drugs (Amiodarone, non-DHP. CCBs)
HCV drugs
HIV drugs (cobicistat, ritonavir)
Cyclosporine
Define enterohepatic recycling
When a drug is metabolized by the liver, dropped into the GI, reabsorbed via the small intestine and re-entering the portal vein.
Increases duration of action of the drug
What enzyme causes the interaction between amiodarone and warfarin? What is the resulting interaction?
CYP2C9 is inhibited by amiodarone, causing a decreased warfarin dose by 30-50% when amio is added to warfarin
What causes the interaction between amiodarone and digoxin? What is the resulting interaction?
Amiodarone inhibits P-gp with synergy in increased bradycardia and decreased HR. Addition of amio decreases digoxin dose by 50%
What is the interaction between digoxin and loop diuretics?
Loop diuretics decrease K+, Mg+2, Ca+2, Na+
Digoxin toxicity risk increases w decreased K and Mg levels
What enzyme causes the interaction between statins and strong CYP3A4 inhibitors? What is the resulting interaction?
CYP3A4 - causes increased CYP3A4 SUBSTRATE (statins) LEVELS from inhibition
What enzyme is warfarin a substrate of?
NOTE - This will cause changes in INR with inhibitors/inducers.
CYP2C9
What is the interaction between valproate and lamotrigine?
Valproate inhibits lamotrigine metabolism, causing INCREASED LEVELS of lamotrigine!
This can lead to SJS/TENS
How long should be waited between switching from an MAOI to a serotonergic drug? (What is the one exception?)
What is the AE of overlapping the two classes?
2 weeks between MAOIs and serotonergic drugs
*FLUOXETINE - long half life, wait 6 weeks\
Overlap = serotonin syndrome!
What is the interaction between MAOIs and NE/Epi/Dopamine?
MAOIs intrinsically increase NE/Epi/dopamine; adding more can cause hypertensive crisis
What class of foods should be avoided when on an MAOI?
Tyramine-rich foods
(Anything aged, pickled, fermented or smoked)
Ie. Cheeses, aged meats, sauerkraut, beers/wines
What enzyme does SMOKING affect? Is it an inducer or inhibitor? What kinds of drugs does it affect?
CYP1A2 INDUCER
Affects some antipsychotics, antidepressants, hypnotics, anxiolytics, caffeine, theophylline, warfarin
What drug classes have SEROTONERGIC properties and should be avoided together due to additive risk?
Antidepressants
MAOIs
Opioids
Triptans
St. John’s Wort
Buspirone, lithium
What classes of drugs have the highest BLEED RISK and thus should be avoided together to prevent additive effect?
Anticoagulants (DOACs, warfarin)
Antiplatelets (salicylates, dipyrimadole, clopidogrel/prasugrel/ticagrelor)
NSAIDs
SSRI/SNRIs
Naturals (garlic, ginger, ginko, ginseng, glucosamine, etc)
What drugs have the highest risk of HYPERKALEMIA and should be avoided together due to additive risk?
RAAS drugs (ACEi/ARBs, Entresto, MRA [spiro, eplerenon])
K-sparing diuretics (MRAs, amiloride, Triamterene)
CNIs (tacro, cyclo)
Bactrim
Canagliflozin
Drospirenone
What drug classes have the highest QTc prolongation and should not be used together due to additive affects?
Antiarrhythmics
Antimalarials
Azoles
Macrolides
Quinolones
Antidepressants (SSRIs [escitalopram/citalopram], TCAs, trazodone, mirtazapine)
Antipsychotics (1st gen, plus ziprasidone)
Antiemetics (5-HT3 antagonists [ondansetron], metoclopramide, promethazine, droperidol)
Onco meds (leuprolide, TKIs, arsenic)
Methadone
Loperamide
Donepezil
Hydroxyzine
Ranolazine
Solifenacin
What two drug classes have the highest risk for CNS depression when taken together?
Opioids + benzos
What drugs are most likely to cause ototoxicity?
Aminoglycosides
Cisplatin
IV loop diuretics
Salicylates
Vancomycin
What drugs are most likely to cause nephrotoxicity?
Antibiotics (aminoglycosides, vancomycin, amphoterecin B, polymixins)
Cisplatin
CNI
Loop diuretics
NSAIDs
Contrast dye
