Drugs Flashcards
Drug that exacerbates hypoglycemia and masks its adrenergic symptoms
beta-blockers
What reflects affinity of enzymes for substrates?
Km
cannot be altered by enzyme or substrate concentration
independent of Vmax
What reflects enzyme concentration
Vmax
can be changed by enzyme concentration
independent of Km
How long does it take for a drug eliminated by first-order kinetics to achieve a 95% steady state concentration?
4 to 5 half lives zero half-life = 0% elim 1 half-life = 50% elim 2 half-life = 75% elim 3 half-life = 87.5% elim 4 half-life = 93.75% elim 5 half life = 96.875% elim
List high blood flow organs.
Will lipophilic drugs be rapidly or slowly distributed to these organs?
Brain, liver, kidneys, lungs
Rapidly
List low blood flow organs.
Will lipophilic drugs be rapidly or slowly distributed to these organs?
Skeletal mm, fat, bone
Slowly
What does each part of Medicare cover? (A-D)
A - inpatient care, SNFs, hospice, homehealth
B - Physician services, labs, tests, preventive, therapies, select prescription drugs
C - All benefits and services under A and B, HMO, PPO, PFFS
D - outpatient prescription drugs
What drugs can cause serum sickness?
Type of HS rxn?
Sx?
cephalosporin (esp cefaclor), penicillin, trimethoprim-sulfamethoxazole, vaccines, antitoxins, tetracyclines, cipro.
Type III HS rxn
Sx - rash, fever, polyarthralgias or polyarthritis
What characteristics of a drug tend to trap the drug in the plasma compartment resulting in a low Volume Distribution (eg Vd = 3-5L)
High molecular weight
High plasma protein binding
High charge
Hydrophilicity
What characteristics of a drug tend to resulting in a high Volume Distribution (eg Vd = 41L)?
Low molecular weight
Avidly bind tissues
Does not bind albumin
Lipophilic
Antipsychotic side effect: subjective restlessness with inability to sit still
akathisia
Antipsychotic side effect: tremor, rigidity, bradykinesia, masked facies
Drug-induced parkinsonism
Antipsychotic side effect: sudden-onset, sustained mm contractions
Acute dystonic reaction
Antipsychotic side effect: involuntary movements (eg lip smacking, choreoathetoid movements)
Tardive dyskinesia
Antipsychotic side effect: fever, rigidity, mental status changes, autonomic instability
NMS
Fraction of administered drug that reaches the systemic circulation in a chemically unchanged form
IV vs oral?
Bioavailability (F)
IV (F=1)
Oral (F<1)
F = (area under oral curve x IV dose)/(area under IV curve x oral dose)
[substrate] at 1/2 Vmax
Km
How do K wasting drugs (loop diuretics, thiazides) contribute to digoxin toxicity?
Hypokalemia allows digoxin to inhibit the Na+-K+ ATPase more effectively
Hepatic necrosis with marked elevations of AST and ALT without concomitant elevation of alk phos or amylase is caused by OD of what?
Acetaminophen
What receptor results in influx of Ca, Na, and K outflux after binding?
Nicotinic receptors. Ach binds, then opens these ligand-gated ion channels.
Half life: how long will it take for a drug to reach 87.5% of final steady state level?
1 half-life = 50%
2 half lives = 75%
3 half lives = 87.5%
4 half lives = 93.75%
Why doesnt morphine provide good pain relief if used after buprenorphine?
Buprenorphene = partial agonist; long half life.
Morphine = full agonist
Partial agonist prevents full agonist from exerting full effects.
What is Trimethaphan and hexamethonium’s MOA?
Ganglionic blocker that blocks baroreceptor-mediated changes in HR
Dihydroergotamine is what kind of drug? Why is it contraindicated in Raynaud?
Ergot alkaloid used for migraines
Causes intense vasoconstriction so contraindicated
What type of anesthetics are prone to cause allergic reactions?
Ester-type (eg tetracaine) bc they are metabolized to para-aminobenzoic acid derivatives.
Note: Amide-type anesthetics are not metabolized to these derivatives and are less likely to cause reactions
What intracellular organelle has increased activity if a patient ODs on drugs?
Smooth ER - involved in detoxification of drugs and other toxic substances
How does quinidine cause digoxin toxicity if administered together?
Decreases clearance of digoxin –> inc serum digoxin levels
What is the risk of taking BB and non-dihydropyridine type Ca channel blockers together?
Both have additive neg effects on HR –> sinus bradycardia
Co-admin of what drugs can cause theophylline toxicity?
Theophylline is metabolized by hepatic cytochrome oxidases.
Illness, cimetidine, ciprofloxacin, macrolides, verapamil can inc serum conc
Baclofen MOA?
agonist at GABA-B receptor - effective for tx of spasticity secondary to both brain and spinal cord disease (eg MS)
Define potency of an inhaled anesthetic?
determined by the minimum conc in the brain to achieve an adequate level of anesthesia.
Potency is inversely proportional to the Minimal alveolar conc (MAC)
Minimal alveolar concentration definition?
% of anesthetic in the inspired gas mixture that renders 50% of patients unresponse to stimuli.
What CHF drug slows HR and has no effect on cardiac contractility and/or relaxation ? MOA?
Ivabradine
Slows rate of SA node firing by selective inhibition of funny sodium channels (If), prolonging the slow depol phase (phase 4)
When one hormone allows another to exert its maximal effect. (eg cortisol improves response of NE, but has no direct vasoactive properties of its own)
permissiveness
Patient on amphotericin B with premature atrial and ventricular contractions is due to what?
Renal tubular dysfunction due to amphotericin B nephrotoxicity. Hypokalemia and hypomagnesemia seen. HypoK causes U waves, premature atrial and ventricular contractions
Ptosis seen in Graves disease cannot be improved with conventional antithyroid drugs. What drug can decrease the extraocular volume?
high dose glucocorticoids since inflammatory infiltration and accumulation of GAGs are responsible
How do PPIs reduce histamine, vagal stimulation, and gastrin?
PPIs block H+/K+-ATPase proton pump, which is the final common pathway for HCL secretion (stim by Ach, histamine and gastrin)
MOA of topical capsaicin for postherpetic neuralgia?
Defunctionalizes afferent pain fibers and depletes SUBSTANCE P.
Neuropeptide Y plays a role in what, and may be found in what type of drugs?
Appetite and pain perception
Antiobesity drugs
Endorphins and dynorphins have what function?
Help with pain relief by activating u-opioid (endorphins) and k-opioid (dynorphins) receptors.
The human multidrug resistance gene codes for what? How does it function and what does it do?
P-glycoprotein
Transmembrane ATP-dependent efflux pump w/broad specificity for hydrophobic compounds.
Reduces influx of drugs into the cytosol and increases efflux from the cytosol –> prevent chemo drugs from working
MOA of gabapentin vs levetiracetam
Anticonvulsants
Gabapentin - inhibits presynaptic voltage-gated Ca channels (prevents fusion and release of NT)
Levetiracetam - disrupts vesicle fusion
What processes results in a bimodal distribution of the speed of isoniazid metabolism
Acetylation - isoniazid is metabolized by acetylation.
Some people are fast vs slow acetylators
Halogenated inhaled anesthetics (eg halothane, desflurane) has a complication of what?
metabolized by hepatic cyt P450 –> hepatocellular damage (HALOTHANE HEPATITIS)
Present with acute hepatitis days after exposure. Liver bx shows centrilobular hepatic necrosis
What diuretic, if given aggresively, can cause pulmonary edema?
Osmotic diuretics (eg mannitol) Use cautiously in high-risk patients (eg CHF or preexisting pulm edema)
MOA of rasburicase in patients with cancer?
Protects organs from rapid lysis of neoplastic cells by converting uric acid into more soluble metabolites (DEGRADES URIC ACID)
Note: allopurinol inhibits uric acid formation
Where do BB act?
Inhibit the neurotransmitter-receptor interaction in adrenergic synapses
Corticosteroids do what to:
neutrophils, lymphocytes, monocytes, basophils and eosinophils
Decreases all except neutrophils
Inc neutrophils due to demargination of neutrophils previously attached to the vessel wall
Opioid peptides are derived from what? This can be a precursor to what other proteins?
POMC - precursor to beta-endorphins (opioid), ACTH, and MSH
Intracellular signaling of sildenafil is similar to what other substance?
BNP, ANP, NO
Activate guanylyl cyclase and inc conversion of GTP to cGMP
Sildenafil dec degradation of cGMP. Inc cGMP –> inc relaxation of vascular smooth mm
What characteristic of drugs allow them to be preferentially processed by the liver into more polar compounds?
High Vd, Good penetration into CNS = high lipophilicity
What drugs target an enzyme that is IL-1 inducible that is highly expressed by inflammatory cells and undetectable in surrounding normal tissue?
COX-2 inhibitors (eg celecoxib)
Nitroprusside toxicity can result in what? Tx?
Cyanide toxicity - altered mental status, seizures, CV collapse, lactic acidosis, bight red venous blood
Tx -
Detoxifying sulfur donors (eg sodium thiosulfate)
Direct binding of cyanide (hydrocobalamin)
induction of methemoglobinemia (sodium nitrite)
Patients who have OD’d on BB should be treated with what? MOA?
Glucagon
Activates G-protein-coupled receptors –> Increases cAMP in cardiac myocytes (inc HR and contractility)
Drug metabolism:
- Dec activity of hepatic N-acetyltransferase results in what?
- Def in Thiopurine methyltransferase results in what?
- Polymorphisms of cyt p450 causes what?
- Diminished ability to metabolize drugs (eg isoniazide and sulfonamides)
- Inc drug toxicity of 6-MP
- Cyp p450 in the liver is responsible for the majority of drug metabolism. Polymorphisms results in diff phenotypes that differ in rates of metabolism. Alters tx efficacy and drug toxicity
What are the major cause of morbidity and mortality from theophylline intoxication?
Seizures
Tachyarrhythmias are another major concern
What intracellular event is responsible for the beneficial effects of nitroglycerin?
Myosin dephosphorylation
Nitrates –> NO –> activate GC –> inc cGMP –> myosin light-chain dephosphorylation –> vascular smooth mm relaxation
Differentiate efficacy vs potency
Efficacy: intrinsic ability of a drug to elicit an effect (measures max ceiling of activity)
Potency: dose of drug required to produce a given effect (affected by drug affinity for its receptor and amt of drug able to reach target tissues).
Why should all patients beginning treated with TNF-a inhibitors be evaluated for latent Tb?
TNF-a inhibitors (eg etanercept, infliximab, adalimumab)
impairs cell-mediated immunity.
TNF-a is necessary for effective sequestration of mycobacteria within granulomas.
Medication that inhibits neprilysin (metalloprotease) does what?
Prevents inactivation of bradykinin, glucagon, enkephalins, and natriuretic peptides
Drug that destroys an inflammatory mediator produced by macrophages
Infliximab - TNF a inhibitor
Note: prone to Tb reactivation bc TNFa is needed for macrophages
What causes an obese patient to have a lower steady state plasma concentration of a drug initially compared to a patient with normal BMI.
Greater volume distribution
What is a known side effect of nitric oxide overdose?
Methemoglobinemia
MOA of orlistat?
Weight loss drug
Orlistat works by inhibiting gastric and pancreatic lipases, the enzymes that break down triglycerides in the intestine. When lipase activity is blocked, triglycerides from the diet are not hydrolyzed into absorbable free fatty acids, and instead are excreted unchanged.
Decreases total cholesterol, inc HDL, dec LDL, dec triglycerides
Note: phentermine is another weight loss drug that has MOA like amphetamine
Why does taking Gemfibrozil after statins cause increase myalgia?
Gemfibrozil increased the blood concentration of most statins by partially inhibit the metabolism or glucorinidation of the statin acid byproduct.
INHIBITS CYT P450 metabolism
Compare codeine to dextromethorphan in terms of analgesia, constipation, and abuse potential
Codeine
- analgesia: increased
- Constipation: increased
- Abuse - increased
How does prednisone cause increased risk of osteoporosis?
Inhibit osteoblast function
Enhances bone resorption due to decreased calcium absorption
A drug that has rapid increase in plasma concentration initially, then increase slows down is due to what?
This drug is a rapidly redistributed drug.
At first the drug is rapidly redistributed so the plasma level falls suddenly. This is followed by normal elimination which causes the characteristic change in the slope.
MOA of baclofen?
Baclophen is an agonist for the GABAB receptors. Its beneficial effects in spasticity result from actions at spinal and supraspinal site.
MOA of neomycin?
Killing of bacteria in the gut that generate ammonia
Wiki: killing bacteria in the intestinal tract, it keeps ammonia levels low and prevents hepatic encephalopathy, especially prior to GI surgery
How can chronic use of morphine result in toxicity?
Morphine is metabolized to active metabolites that accumulate - esp problematic in kidney disease
What is magnesium trisilicate and what side effects can it cause?
Magnesium trisilicate is an inorganic compound that is used as a food additive.
It can also be used in oral pharmaceutical formulations and food products as a glidant. It is also used therapeutically as an antacid, and also for the treatment of ciprofloxacin overdose or toxic
SE: moderately severe diarrhea
