Pharmacology Flashcards
What is the primary toxicity of anthracyclines and what drug should be given to prevent this?
Doxorubin / daunorubicin
Dilated cardiomyopathy with increased use
Drug given to prevent: Dexrazoxane -> iron chelating agent
List the type 3 anti-arrhythmics and their mechanism of action.
- Sotalol
- Amiodarone
- Dofetilide / Ibutilide (“Till I Die” for -tilide in Sketchy)
Inhibit potassium K+ channels, slowing repolarization, prolonging the QT interval
How does hyperthyroidism as in Graves’ disease produce most of its symptoms? What major symptom is not accounted for by this?
T3 upregulates beta-adrenoceptors, and increased the body’s responses to catecholamines.
Exophthalmos is actually due to infiltration of retroorbital space by T lymphocytes -> increased fibroblast secretion and muscle inflammation. Most other symptoms can be blocked by beta-blockers.
For a train-of-four neurological stimulation tests, measuring muscle response after four repeat stimulations, what will be seen in the Phase I and Phase II response of succinylcholine?
These are phase I and phase II of the depolarizing blockade
Phase I - Equal reduction in each twitch -> muscles are already relatively depolarized, repeat stimulations will not produce a greater response with greater acetylcholine released into the synapse. Will be equal for the train of four.
Phase II - Membrane has repolarized, ACh receptors are available but desensitized. Not well understood, but this block functions more like a non-depolarizing blockade seen in rocuronium / tubocurarine. Each stimulation will have a reduction in response from the previous -> less acetylcholine available with each stimulation to stimulate the neuromuscular junction.
If still confused, see UWorld 1212
What patient will be particularly response to succinylcholine and can last a long time?
Patients with a plasma cholinesterase deficiency -> will need to give blood transfusion to deactivate, which contains the enzyme required.
What agent should you use in PCP pneumonia prophylaxis if CD4<200 and patient is allergic to TMP/SMX? What is the side effect of risk?
Dapsone - similar mechanism of action
Side effect: Hemolysis, especially if patient has a G6PDH deficiency
What drug is contraindicated in C1 esterase inhibitor deficiency, and what labs will be associated? Why?
C1 esterase inhibitor also inhibits kallikrein. Deficiency will lead to increased complement activation (decreased C4 levels) and increased bradykinin levels (kallikrein converts HMW kininogen to bradykinin)
-> ACE inhibitors are contraindicated in hereditary angioedema since ACE functions to degrade bradykinin.
What is the mechanism of action of leflunomide?
Inhibits pyrimidine synthesis via inhibition of dihydroorotate dehydrogenase
What is the mechanism of action of hydroxyurea?
Inhibits ribonucleotide reductase
- > inhibiting the reductase waitress
- > prevents formation of dUDP
also upregulates fetal hemoglobin levels for sickle cell treatment
What is the mechanism of action of mycophenolate?
Inhibits IMP dehydrogenase
- > inhibits guanine synthesis pathway
- > increased AMP (IMP rerouted to AMP synthesis) and decreased GMP prevents cellular proliferation
What is the mechanism of action of ouabain?
Inhibits the Na+/K+ ATPase by binding the K+ site site
Can be used as a cardiac glycoside with mechanism of action similar to digoxin
What is the treatment for cyanide poisoning?
Poisoning is mediated via binding of cytochrome c iron in the Fe+3 state
-> give sodium nitrite or amyl nitrite to cause methemoglobinemia which will compete for the cyanide
-> also give hydroxycobalamin (B12) and sodium thiosulfate as antidotes
UWorld #1415
What can happen to your nutritional state if you have excess mineral oil intake?
Used as a laxative can cause fat soluble vitamin deficiency
-> will transport fat soluble vitamins into stool by dissolving them
What is the mechanism of action of phencyclidine?
NMDA antagonist
-> dissociative agent like ketamine
Give two sympathomimetics used for uterine relaxation and their mechanism of action?
Beta 2 agonists
Terbutaline - do not disTURB
Ritodrine - I DREAM of bandcamp
What is the effect of adenosine on the heart and lungs?
It is basically parasympathetic in action overall
Heart -> increases coronary vasodilation and induces hyperpolarization of pacemaker cells by increasing K+ release
Lungs -> induces bronchospasm / bronchoconstriction. Think of this being released whenever a section of the lung is being overworked (ATP used)
Give a couple adenosine antagonists and their effects.
Theophylline and caffeine -> sympathomimetic effect
Heart -> coronary artery vasoconstriction and depolarization -> increased heart rate
Lungs -> bronchodilation
What are the side effects of concern for fibrates?
Myopathy (especially gemfibrozil in combination with statins)
Cholesterol gallstones** -> remember, fibrates are the PPARalpha modulator, so they are most likely to cause enzyme changes (unlikely cholestyramine).
Blockade of 7alpha reductase leads to decreased usage of cholesterol for bile acid synthesis (which solubilize cholesterol), and inadvertently increased excretion of pure cholesterol in bile (not used to make bile acids, thereby increasing chance of stones)
-> think of the seagull on the stack of stones.
How does cholestyramine modify your risk of gallstones?
Bile acid resin -> prevents intestinal reabsorption of bile acids. This lack of bile acids increases liver bile acid synthesis (drops your LDL by using cholesterol), but contributes to slightly increased risk of gallstones. However, it also increases gallbladder motility (decreasing risk).
-> overall, no change in the risk of gallstones #11739
What antihypertensive medication and DNA-gyrase blocking antibiotic are associated with theophylline toxicity?
Antihypertensives - calcium channel blockers (i.e. verapamil)
Antibiotic - Ciprofloxacin - think CYProfloxacin #11752
What is the name of the proteasome inhibitor used in multiple myeloma and why does it work?
Bortezomib
Used to treat cancers which produce lots of protein, especially MULTIPLE MYELOMA
- > lack of ability of cells to break down pro-apoptotic proteins which are produced in excess when they are churning out lots of proteins
- > induces apoptosis
What is a major side effect of milrinone and why? Why might it be used over dobutamine?
hypotension - more than dobutamine. This is caused by increased cAMP in arteries, causing relaxation (similar to a beta-2 effect)
Used as an inotrope when patient is on beta-blockers so dobutamine won’t work. Increases cardiac contractility by increasing cAMP via being a PDE inhibitor.
Which RNA polymerase does amatoxin inhibit? What’s the consequence?
Inhibits RNA Polymerase II -> inhibits mRNA transcription
-> consequence is severe hepatotoxicity and bloody diarrhea
What is the most important initial treatment of C. diphtheria?
Passive immunization via antitoxin -> largest effect on prognosis #1388
How does the train of four stimulation ratio results differ between phase I and phase II of succinylcholine?
1212
Phase I - depolarizing blockade. TOF ratio is 1:1. Last stimulation is = response to first stimulation, but reduced by a constant amount overall(stimulation of nerve is not highly dependent on amount of ACh in the synapse)
Phase II - non-depolarizing blockade TOF ratio is i.e. 0.3:1 (maybe 4th twitch is 30% of first twitch). (i.e. similar to vecuronium) -> muscle contractions become highly dependent on the amount of ACh required, which is reduced with each rapid contraction.
How does the y-intercept of the Lineweaver Burk plot change with increasing Vmax?
Intercept decreases (gets closer to 0)
Y axis = 1/Vmax
X axis = 1/-Km
What is the slope of the Lineweaver Burk plot?
Rise = 1/Vmax Run = 1/Km Slope = Km/Vmax
What does a rightward shift of the x axis point on a Lineweaver Burk plot mean about enzyme affinity?
1/Km is getting smaller -> Km is increasing -> affinity is decreased
How would you pharmacologically describe a drug which leads to a small maximum effect, but very little drug is required to reach this effect?
Low efficacy (similar to Vmax), high potency
Potency is inversely proportional to Km
-> competitive inhibitors decrease the potency of drugs
How do you calculate volume of distribution?
Vd = amount of drug in the body / plasma drug concentration
amount / (amount / volume) = volume
What types of drugs have the lowest volume of distribution (5-10L)?
Large / charged molecules, ones that are highly protein bound
-> stay intravascular
What types of drugs have medium Vd (20-40L)?
Small hydrophilic molecules -> stay in ECF (outside cells, do not diffuse across plasma membranes)
What effect does protein binding have on Vd?
Increasing protein binding -> decreases Vd
What is clearance equal to?
CDE
CL = Vd * ke
ke = 0.7 / t1/2
importantly: CL*Css = rate of elimination of drug
Css is plasma drug concentration
What is the full steady state equation for dosage calculations?
f(D/T) = Css*CL input = output
f = bioavailability. Aka, if bioavailability is 70%, input is only 0.7 * the dose / dosing interval
