Foundations 1 Flashcards
Primary NT involved in somatic nervous system
Acetylcholine (Ach)
What receptor does Ach bind to in skeletal muscles to affect muscle movement?
Nicotinic receptors
What NT does the parasympathetic nervous system release, what receptor does it bind to, and what response does the binding cause?
ACh
Muscarinic receptors (GI tract, bladder, and eyes)
SLUDD
SLUDD
Salivation, lacrimation, urination, defecation, and digestion
What are the main NTs released by the sympathetic nervous system, what receptors do these bind to, and what response occurs due to this binding?
Epinephrine and norepinephrine
Adrenergic receptors
Increased BP, HR, and bronchodilation
Where are alpha 1 receptors located?
Smooth muscles (e.g., blood vessels)
Where are beta 1 receptors located?
Heart
Where are beta 2 receptors located?
Lungs and GI tract
Antagonists binds to SAME ACTIVE SITE of receptor as the endogenous substrate —> prevents substrate from binding —> reaction
Competitive inhibition
Antagonist binds to receptor at a site other than the active site (ALLOSTERIC SITE) —> shape of active site changes —> prevents endogenous substrate from binding
Non-competitive inhibition
MUSCARINIC RECEPTOR
Endogenous substrate:
Agonist action:
Drug agonists:
Antagonist action:
Drug antagonists:
Endogenous substrate: ACh
Agonist action: Increases SLUDD
Drug agonists: Pilocarpine, bethanechol
Antagonist action: Decreases SLUDD
Drug antagonists: Atropine, oxybutynin
NICOTINIC RECEPTOR
Endogenous substrate:
Agonist action:
Drug agonists:
Antagonist action:
Drug antagonists:
Endogenous substrate: ACh
Agonist action: Increased BP, HR
Drug agonists: Nicotine
Antagonist action: Neuromuscular blockade
Drug antagonists: Neuromuscular blockers (rocuronium)
ALPHA-1 (mainly peripheral)
Endogenous substrate:
Agonist action:
Drug agonists:
Antagonist action:
Drug antagonists:
Endogenous substrate: Epi, NE
Agonist action: Smooth muscle vasoconstriction, increased BP
Drug agonists: Phenylephrine, dopamine (dose-dependent)
Antagonist action: Smooth muscle relaxation, decreased BP
Drug antagonists: Alpha 1 blockers (doxazosin, carvedilol, phentolamine)
ALPHA 2 (mainly brain; central)
Endogenous substrate:
Agonist action:
Drug agonists:
Antagonist action:
Drug antagonists:
Endogenous substrate: Epi, NE
Agonist action: Decreased release of Epi and NE, decreased BP and HR
Drug agonists: Clonidine, brimonidine (ophthalmic for glaucoma)
Antagonist action: Increased BP, HR
Drug antagonists: Ergot alkaloids, yohimbine
BETA 1 (mainly heart)
Endogenous substrate:
Agonist action:
Drug agonists:
Antagonist action:
Drug antagonists:
Endogenous substrate: Epi, NE
Agonist action: Increased myocardial contractility, CO, HR
Drug agonists: Dobutamine, isoproterenol, dopamine (dose-dependent)
Antagonist action: Decreased CO, HR
Drug antagonists: Beta blockers
BETA 2 (mainly lungs)
Endogenous substrate:
Agonist action:
Drug agonists:
Antagonist action:
Drug antagonists:
Endogenous substrate: Epi
Agonist action: Bronchodilation
Drug agonists: Albuterol, terbutaline, isoproterenol
Antagonist action: Bronchoconstriction
Drug antagonists: Non-selective beta blockers (propranolol, carvedilol)
DOPAMINE
Endogenous substrate:
Agonist action:
Drug agonists:
Antagonist action:
Drug antagonists:
Endogenous substrate: Dopamine
Agonist action: Renal, cardiac, and CNS effects
Drug agonists: Levodopa, pramipexole
Antagonist action: Renal, cardiac, and CNS effects
Drug antagonists: 1st generation antipsychotics (haloperidol) and metoclopramide
SEROTONIN
Endogenous substrate:
Agonist action:
Drug agonists:
Antagonist action:
Drug antagonists:
Endogenous substrate: Serotonin
Agonist action: Platelet, GI, and psychiatric effects
Drug agonists: Triptans (sumatriptan)
Antagonist action: Platelet, GI, and psychiatric effects
Drug antagonists: Ondansetron, 2nd generation antipsychotics (quetiapine)
ACETYLCHOLINESTERASE
Endogenous effects:
Drug examples:
Drug action:
Endogenous effects: Breaks down ACh
Drug examples: Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine)
Drug action: Blocks acetylcholinesterase —> increases ACh levels; used to treat Alzheimer’s disease
Angiotensin-converting enzyme (ACE)
Endogenous effects:
Drug examples:
Drug action:
Common uses:
Endogenous effects: Converts angiotensin I to angiotensin II (potent vasoconstrictor)
Drug examples: ACE inhibitors
Drug action: Inhibit production of angiotensin II —> decreases vasoconstriction and aldosterone secretion
Common uses: Used to treat HTN, HF, and kidney
Catechol-O-methyltransferase
Endogenous effects:
Drug examples:
Drug action:
Common uses:
Endogenous effects: Breaks down levodopa
Drug examples: COMT inhibitor (ent a sponge)
Drug action: Blocks COMT enzyme to prevent peripheral breakdown of levodopa —> increases duration of action of levodopa
Common uses: Parkinson’s disease
Cyclooxygenase (COX)
Endogenous effects:
Drug examples:
Drug action:
Common uses:
Endogenous effects: Converts arachidonic acid to prostaglandins (cause inflammation) and thromboxane A2 (causes platelet aggregation)
Drug examples: NSAIDS
Drug action: Block COX to decrease prostaglandins and thromboxane A2
Common uses: Treat pain/inflammation and decrease platelet activation/aggregation (aspirin)
Monoamine oxidase (MAO)
Endogenous effects:
Drug examples:
Drug action:
Common uses:
Endogenous effects: Breaks down catecholamines (DA, NE, Epi, 5-HT)
Drug examples: MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid, selegiline, rasagiline, methylene blue, linezolid)
Drug action: Block MAO —> increases catecholamine levels
Common uses: Depression
**Increasing catecholamines too much can cause toxicity (hypertensive crisis, serotonin syndrome)
Phosphodiesterase (PDE)
Endogenous effects:
Drug examples:
Drug action:
Common uses:
Endogenous effects: Breaks down cGMP (smooth muscle relaxant)
Drug examples: PDE-5 inhibitors (sildenafil, tadalafil)
Drug action: Competitively bind to same active site as cGMP on the PDE-5 enzyme —> prevents breakdown of cGMP and prolong smooth muscle relaxation
Common uses: Erectile dysfunction
VITAMIN K EPOXIDE REDUCTASE
Endogenous effects:
Drug examples:
Drug action:
Common uses:
Endogenous effects: Converts vitamin K to active form required for production of select clotting factors
Drug examples: Warfarin
Drug action: Blocks vitamin K epoxide reductase enzyme —> decreases production of clotting factors II, VII, IX, and X
Common uses: Treat/prevent blood clots
XANTHINE OXIDASE
Endogenous effects:
Drug examples:
Drug action:
Common uses:
Endogenous effects: Breaks down hypoxanthine and xanthine into uric acid
Drug examples: Xanthine oxidase inhibitor (allopurinol)
Drug action: Blocks xanthine oxidase —> decreases uric acid production
Common uses: Prevent gout attacks
Occurs when a drug binds to polyvalent cations (Mg++, Ca++, Fe++) in another compound (antacids or iron supplements)
Causes reduced absorption
Chelation
Name 4 drugs/drug classes that have to separated from polyvalent cations (antacids, multivitamins, sucralfate, bile acid resins, aluminum, Ca, Fe, Mg, zinc, phosphate binders)
Quinolones, tetracyclines, levothyroxine, oral bisphosphonates
What CYP450 metabolizes codeine? What happens if someone is a UM? PM?
CYP2D6; risk of toxicity; poor analgesia
What CYP450 converts clopidogrel into its active metabolite? What drugs inhibit this enzyme and should be avoided due to decreased antiplatelet effects?
Omeprazole and esomeprazole
Polymorphic phase II enzyme
N-acetyltransferase (NAT)
Acronym for common CYP3A4 inhibitors
G-PAC-MAN
Grapefruit
Protease inhibitors
Azole antifungals
Cyclosporine, cobicistat
Macrolides (not azithromycin)
Amiodarone and dronedarone
Non-DHP CCBs
CYP enzyme ___________ increase the concentration of substrate drugs and decrease the concentration of active form of prodrugs. CYP enzyme _______ do the exact opposite.
Inhibitors; inducers
Acronym for common CYP3A4 inducers
PS PORCS
Phenytoin
Smoking
Phenobarbital
Oxcarbazepine
Rifampin, rifabutin, and rifapentine
Carbamazepine
St. John’s wort
located in many tissue membranes and protect against foreign substances by moving them out of critical areas
some are located in cell membrane of Gi tract and pump drugs and their metabolites out of the body by pumping them into the gut, where they can be excreted in the stool
permeability glycoprotein pumps (P-gp)
P-gp _________ increases the absorption of drugs that are P-gp substrates (less drug is pumped into the gut). P-gp ______ do the opposite.
Inhibitors; inducers
Mechanism that increases duration of action of drugs by transporting an already metabolized drug through the bile and back to the gut –> drug gets reabsorbed in small intestine –> goes through portal vein and back to liver
enterohepatic recycling
What should you do when a patient has been taking warfarin and gets newly prescribed for amiodarone?
Decrease warfarin dose 30-50%
A patient that is taking digoxin is getting prescribed amiodarone for treatment of their afib.
What should you do and why?
Decrease digoxin dose by 50% because amiodarone causes decreased excretion of digoxin. There is also an increased risk of bradycardia.
What should you be concerned for when a patient is taking digoxin and a loop diuretic?
Increased risk of digoxin toxicity
Simvastatin and lovastatin are contraindicated with strong CYP___ _________.
3A4 inhibitors
Azole antifungals, bactrim, amiodarone, metronidazole
CYP2C9 inhibitors
CYP2C9 inducers
rifampin, St. John’s wort
What should you monitor when a patient is taking warfarin AND a CYP2C9 inhibitor/inducer?
INR
What drugs specifically include instructions that say you can NOT drink grapefruit juice with?
Amiodarone, simvastatin, lovastatin, nifedipine, tacrolimus
What drug class should be avoided with an CYP3A4 inhibitor due to increased ADRs (sedation) and can be fatal?
opioids
A patient that is taking Valproate is being newly prescribed lamotrigine.
What should you be concerned for and how can you help decrease that risk?
Valproate decreases lamotrigine metabolism, which increases the risk of serious skin reactions.
Initiate lamotrigine using the starter kit that begins with lower doses and titrate carefully every 2 weeks.
What should be done when switching between drugs with MAO inhibition or serotonergic properties?
2 week washout period
When switching between MAO inhibitors and fluoxetine, how long should wait to do so?
5 weeks
CYP2D6 inhibitors
Amiodarone, fluoxetine, paroxetine, fluvoxamine
Common CYP2D6 substrates
Codeine, meperidine, tramadol, tamoxifen
Do not exceed citalopram __ mg daily or ___ mg dialy in elderly (> 60 y/o)
40; 20
Do not exceed escitalopram __ mg daily or __ mg daily in elderly.
20; 10
What SSRI is considered safest in patients with cardiovascular disease?
Sertraline
A patient is being prescribed cisplatin. What should also be prescribed to protect the patient’s kidneys?
Amifostine (Ethyol)
Provides rapid results at the site of patient care
Point-of-care (POC) testing
Involves obtaining a drug level or other relevant labs to monitor efficacy and safety
Therapeutic drug monitoring
When this type of lab test is ordered, the types of neutrophils are analyzed.
CBC with differential
What lab values does a basic metabolic panel (BMP) analyze?
Electrolytes, glucose, renal function, and acid/base (HCO3) status
Leukocytosis
increased WBCs
Thrombocytosis
increased platelets
leukopenia
decreased WBCs
thrombocytopenia
decreased platelets
myelosuppression
decreased WBCs, RBCs, and platelets
total calcium
8.5-10.5 mg/dL
What lab value should be calculated if albumin is low?
corrected calcium
Vitamin D and thiazide diuretics can _______ calcium.
increase
What drugs can decrease calcium? (4)
Long-term heparin, loop diuretics, bisphosphonates, cinacalcet
magnesium
1.3-2.1 mEq/L
What drugs can decrease magnesium? (3)
PPIs, diuretics, amphotericin B
phosphate
2.3-4.7 mg/dL
Chronic kidney disease can _______ phosphate.
increase
potassium
3.5-5 mEq/L
What drugs can increase potassium? (10)
ACE inhibitors, ARBs, aldosterone receptor antagonists (ARAs), aliskiren, canagliflozin, cyclosporine, tacrolimus, potassium supplements, bactrim, drospirenone
Beta-2 agonists, diuretics, and insulin can ______ potassium.
decrease
sodium
135-145 mEq/L
Hypertonic saline and tolvaptan can ______ sodium.
increase
What drugs can decrease sodium? (4)
Carbamazepine, oxcarbazepine, SSRIs, and diuretics
HCO3 (venous and arterial)
Venous: 24-30 mEq/L
Arterial: 22-26 mEq/L
Topiramate can _____ bicarbonate.
decrease
blood urea nitrogen (BUN)
7-20 mg/dL
What disease states can increase BUN? (2)
renal impairment and dehydration
SCr
0.6-1.3 mg/dL
What drugs increase SCr due to impairing renal function? (11)
Aminoglycosides, amphotericin B, cisplatin, colistimethate, cyclosporine, loop diuretics, polymyxin, NSAIDs, radiocontrast dye, tacrolimus, vancomycin
anion gap
5-12 mEq/L
An elevated anion gap can suggest what disease state?
metabolic acidosis
WBCs
4000-11000 cells/mm3
Systemic steroids can ______ WBCs.
increase
What drugs can decrease WBCs? (4)
clozapine, chemotherapy, carbamazepine, immunosuppressants
Neutrophils
45-73%
Neutrophils are also called what 2 things?
polymorphonuclear cells (PMNs) or segmented neutrophils (segs)
immature neutrophils that are released from the bone marrow to fight infection
bands
What is the term used to describe elevated bands?
left shift
bands
3-5%
eosinophils
0-5%
What disease states can increase eosinophils? (3)
asthma, inflammation, parasitic infections
basophils
0-1%
What disease state can increase basophils? (1)
hypersensitivity reactions
lymphocytes
20-40%
What disease states can increase lymphocytes? (2)
viral infections, lymphoma
What disease states/drugs can decrease lymphocytes? (3)
bone marrow suppression, HIV, systemic steroids