Most beta blockers whose names start with A-M are beta-1-selective. In addition, a mnemonic to remember some of the more common beta-1 blockers is A BEAM (acebutolol, betaxolol, esmolol, atenolol, and metoprolol).
Epinephrine is an agonist of what receptors?
alpha-1 alpha-2 beta-1 beta-2
Phenazopyridine (choice E) is an analgesic with special properties that can provide pain relief in the genitourinary tract.
Norepinephrine is an agonist of what receptors?
alpha-1 alpha-2 beta-1
Cyclosporine is a fungus-derived polypeptide that complexes with cyclophilin and inhibits calcineurin.
Inhibition of calcineurin decreases production of IL-2.
Grapefruit juice dramatically increases the bioavailability of cyclosporine by inhibiting CYP3A, the same enzyme system that metabolizes cyclosporine.
Cyclosporine is indicated for the prevention of renal transplant rejection and the treatment of rheumatoid arthritis, and may be effective in patients with systemic lupus erythematosus, polymyositis, dermatomyositis, and granulomatosis with polyangiitis (Wegener’s).
Diltiazem, an example of a L-type calcium channel blocker, acts by inhibiting calcium ion influx (choice C) into vascular smooth muscle and myocardium, decreasing peripheral vascular resistance, dilating coronary arteries, and prolonging the AV node refractory period. Diltiazem is used for hypertension, chronic stable angina, and supraventricular tachycardias. Side effects include hypotension and AV block.
Acetazolamide, a carbonic anhydrase inhibitor, can cause hypokalemia, metabolic acidosis, and an alkaline urine.
Torticollis is an example of:
Acute dystonic reaction from treatment with high potency D2 receptor agonists such as haloperidol; involuntary muscle contractions
Respiratory syncytial virus (RSV) can cause serious lower respiratory tract infections in infants.
Prophylaxis is with palivizumab, which is a monoclonal antibody directed against the fusion protein of RSV. This prevents infection of the host cell.
Give the equation for half life.
The volume of distribution (Vd) is a hypothetical volume of body fluid that would be required to dissolve the total amount of drug at the same concentration that is found in the blood.
The formula t1/2 = (0.7 x Vd)/CL can be used to solve for volume of distribution if the half-life (t1/2) and clearance (CL) are known.
Drugs to increase contractility
↑ contractility: digoxin, beta agonists
Sirolimus inhibits T-lymphocyte activation and proliferation that occurs secondary to antigenic and cytokine (IL-2, IL-4, and IL-15) stimulation. Specifically, sirolimus inhibits T-cell proliferation by binding a specific serine-threonine kinase (mTOR), which is necessary for cell cycle progression. Sirolimus also inhibits antibody production. It is important to note that sirolimus has an immunosuppressant action that is different from other immunosuppressant agents, including tacrolimus and cyclosporine. Remember that one of the primarily differences between sirolimus and both tacrolimus and cyclosporine is that this drug has minimal nephrotoxicity,
Tolvaptan acts by selectively antagonizing vasopressin V2 receptors, increasing free water excretion.
Treat leishmaniasis with:
Sodium stibogluconate (antimony-containing compounds)
Maintenance dose equation
maintenance dose equation to answer this question: MD = CL x Cpss/F, where
MD = maintenance dose
CL = clearance
Cpss = plasma concentration at steady state
F = bioavailability
Mobitz type II
In Mobitz type II AV block, there are intermittent, non-conducted atrial beats not preceded by lengthening AV conduction. The PR interval remains unchanged in Mobitz type II AV block prior to a P wave that suddenly fails to conduct to the ventricles.
Efficacy is defined as the maximum effect that can be produced by a drug, regardless of dose.
Reverses the effect of heparin
Inhibits T-cell activation and proliferation by binding mTOR (a serine-threonine kinase that is instrumental in cell cycle progression)
Vincristine is a vinca alkaloid that inhibits mitosis in a cell cycle-dependent manner by blocking the formation of microtubules, thereby inhibiting neoplastic cell growth.
Vincristine is indicated for the treatment of Hodgkin and non-Hodgkin lymphoma, acute lymphoid leukemia, Ewing sarcoma, Wilms tumor, and several other types of malignancies.
Vincristine causes peripheral neuropathy.
Beta blockers and hypoglycemia
Symptoms of hypoglycemia include behavioral changes, confusion, fatigue, palpitations, tremor, anxiety, sweating, hunger, seizures, and even loss of consciousness.
Beta-adrenergic blockade may blunt or prevent some of the premonitory signs and symptoms of acute episodes of hypoglycemia mediated by the autonomic nervous system (e.g., sweats, tremor, nervousness, and tachycardia).
5-Fluorouracil (5-FU) is an antineoplastic agent and a fluorinated pyrimidine.
It is an analog of thymine in DNA (or uracil in RNA), and can impair DNA synthesis in actively proliferating cells.
Treatment for ventricular arrythmias
Lidocaine (choice C) is an antiarrhythmic agent indicated for the treatment of ventricular arrhythmias. Lidocaine has a variable effect on AV node conduction. For the most part, conduction through the AV node remains unchanged.
Procainamide (choice D) is a class IA antiarrhythmic agent indicated for the treatment of ventricular arrhythmias. It often causes AV node conduction to be slightly increased.
cytarabine, a pyrimidine analogue, (choice A) plus daunorubicin OR idarubicin is used especially for induction treatment of acute myeloid leukemia (AML). Myelosuppression, anemia and thrombocytopenia are common adverse reactions.
Kernicterus is the chronic and permanent neurologic sequelae of bilirubin-induced neurologic dysfunction (BIND). Brain regions most commonly affected include the basal ganglia and brainstem nuclei involved in oculomotor and auditory function.
Acute hyperbilirubinemia can lead to decreased alertness, hypotonia and poor feeding. Kernicterus is associated with opisthotonos, a high-pitched cry, an abnormal Moro reflex, and abnormal eye movements. Although kernicterus can occur pathologically, this condition may also occur if the mother takes sulfonamide antibiotics, such as trimethoprim-sulfamethoxazole or sulfisoxazole during the 2nd or 3rd trimester of pregnancy. Sulfonamides can displace bilirubin from its albumin-binding site, thereby increasing the serum concentration of free bilirubin available to cross the blood-brain barrier. Trimethoprim-sulfamethoxazole is not recommended for use in infants less than 2 months old. When hyperbilirubinemia occurs in an infant, the treatment of choice is to remove the bilirubin from the blood by phototherapy or exchange transfusion.
Amiodarone is a class III antiarrhythmic with class IA antiarrhythmic properties.
It blocks potassium channels, prolongs repolarization, widens QRS, and prolongs the QT interval.
It is used to treat supraventricular and ventricular tachycardia, and is also used in the management of recurring ventricular tachycardia and fibrillation.
It causes torsades de pointes, hyper/hypothyroidism, pulmonary fibrosis, bradycardia, AV block as well as corneal deposits and blue/gray skin deposits resulting in photodermatitis.
Cyclobenzaprine is a spasmolytic that is structurally related to the tricyclic antidepressants and has associated anticholinergic effects (dry mouth, impairment of urination and defecation, tachycardia) as well as sedation, confusion, and transient visual hallucinations.
Side effects: Atenolol
Atenolol is a selective beta-1-adrenergic receptor antagonist. In high doses, it can cause bradycardia and varying degrees of atrioventricular (AV) block. Additional side effects of atenolol include impotence, bradycardia, heart failure, and CNS adverse effects (sedation, seizures, sleep alterations).
Esters vs amides
An easy way to distinguish between the amides and esters are as follows: the amides have two “i’s” in their names and the esters have either one or no “i’s” in their name.
There are two classes of local anesthetics: esters and amides.
If you are allergic to one class, you will probably not be allergic to the other class.
Nephrotic syndrome is a group of symptoms including proteinuria (exceeding 3.5 grams per day), hypoalbuminemia (normal 3.2 – 5 g/dL), and high cholesterol levels (total cholesterol > 200 mg/dL). Nephrotic syndrome is caused by a variety of disorders that lead to renal damage, particularly to the basement membrane of the glomerulus. This immediately causes abnormal excretion of protein in the urine.
What is epinephrine reversal?
Epi raises BP Phentolamine decreases BP Epi again this time decreases BP
Phosphodiesterase-5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil, prevent the breakdown of cGMP.
The most common treatment for erectile dysfunction is with PDE5 inhibitors, such as sildenafil. During sexual stimulation, the release of nitric oxide (NO) is important for penile erection. NO activates guanylate cyclase, which converts GTP to cyclic guanosine monophosphate (cGMP). cGMP enhances smooth muscle relaxation in the corpus cavernosum and allows the inflow of blood and development of an erection. PDE5 inhibitors inhibit the phosphodiesterase that degrades cGMP, leading to increased levels of cGMP in the corpus cavernosum, increased smooth muscle relaxation, and increased inflow of blood. The PDE5 inhibitors cause flushing, nasal congestion, priapism and vision changes. These drugs are contraindicated for use with nitrates (nitroglycerine, isosorbide dinitrate, nitroprusside) since the combination may increase the risk of severe hypotension (synergistic effects).
Congenital syphilis occurs in infants of untreated or inadequately treated mothers with syphilis, and is transmitted through the placenta to the fetus.
Cleft palate, rhinitis, and desquamating rash are classic signs of congenital syphilis.
Penicillin is the treatment of choice in nonpenicillin-allergic patients without neurosyphilis. In penicillin-allergic patients, oral doxycycline can be used.
Direct thrombin inhibitors include:
a direct thrombin inhibitor, such as bivalirudin, argatroban, danaparoid, or fondaparinux
Important digoxin drug interaction
Loop diuretics such as furosemide, torsemide, and ethacrynic acid cause hypokalemia and hypomagnesia, both of which contribute to digoxin toxicity.
Atropine is a muscarinic receptor antagonist (choice A) used in the treatment of cholinesterase inhibitor poisoning.
Glucocorticoids and bone
Glucocorticoids also decrease intestinal calcium absorption, in part by opposing the effects of vitamin D as well as decreasing the expression of calcium channels in the duodenum. The glucocorticoids also increase renal calcium excretion by decreasing calcium reabsorption.
Mupirocin (choice E) is an antibacterial agent indicated for the topical treatment of impetigo primarily caused by Staphylococcus aureus or Streptococcus pyogenes.
Methamphetamine acts by gaining entrance to dopamine, norepinephrine, and serotonin nerve terminals, causing therelease of these neurotransmitters via the uptake carriers. Dopamine is believed to play an important role in the reward system of the brain, and is thought to be a significant factor in the reinforcing effects of stimulants. One area of the brain that is thought to be involved in this reward system is the dopaminergic projection from the ventral tegmental area of the midbrain to the nucleus accumbens of the forebrain. By comparison, cocaine blocks the reuptake of dopamine and norepinephrine, and methylenedioxymethamphetamine (MDMA) causes the release of serotonin (5-HT).
Isotretinoin (choice C) is indicated for the treatment of severe recalcitrant acne. Its non-FDA approved uses include keratinization disorders, T-cell lymphoma, and various forms of skin cancers. It can be taken safely with antacids and milk products. This agent will decrease inflammation, sebum production and Propionibacterium acnes proliferation as well as follicular hyperproliferation and abnormal desquamation.
Esmolol and acebutolol are examples of a drugs that selectively antagonize beta-1-adrenergic receptors (choice C). They are used for supraventricular tachyarrhythmias, and would not cause PSVT or xanthopsia. Side effects include bradycardia, AV block, heart failure, and asthma exacerbation.
Phentolamine is an antagonist of what receptors?
Treat benzodiazepine overdose with:
Octreotide is a synthetic somatostatin analog that binds to receptors on carcinoid tumors and inhibits the synthesis and release of tumor hormones. Octreotide is very effective in reducing the flushing and diarrhea associated with carcinoid syndrome. It has been shown to reduce the excretion of 5-HIAA and to slow the growth of carcinoid tumors. It is generally well tolerated.
Sumatriptan (choice D) is a selective serotonin1D (5-HT1D) agonist. This agent is indicated for the treatment of acute migraine attacks with or without aura. Serious adverse effect of sumatriptan include coronary vasospasm, myocardial infarction, and severe hypertension.
“Red as a beet”: Cutaneous vasodilation (flushing) occurs to dissipate heat to compensate for lost of sweating.
“Dry as a bone”: Muscarinic receptors are on sweat glands, so blockade of these receptors stops sweating (anhidrosis), causing dry skin.
“Hot as a hare”: Interference with sweating can lead to hyperthermia.
“Blind as a bat”: Blocking muscarinic receptors on the ciliary muscle prevents accommodation (causing blurry vision). Muscarinic receptors on the pupillary sphincter muscle are also blocked, causing pupillary dilation (mydriasis).
“Mad as a hatter”: Blockade of central muscarinic receptors can cause anxiety, agitation, delirium, and hallucinations. (Hallucinations can actually make people seem larger or smaller, hence the Alice in Wonderland reference.)
Other side effects: Sinus tachycardia, decreased bowel sounds, and urinary retention.
Benzodiazepines are used in the short-term management of alcohol withdrawal, panic disorder, and generalized anxiety disorder.
Benzodiazepines act by binding to the GABA-A receptor and increase the frequency of channel opening, which is a ligand-gated chloride channel.
In contrast to benzodiazepines, barbiturates increase the duration, rather than the frequency, of chloride ion channel opening. Benzodiazepine overdose can be treated with flumazenil. Note: flumazenil is ineffective for the treatment of barbiturate overdose.
Common beta-lactamase producing bacteria
Beta-lactamase producing bacteria include, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae as well as Klebsiella and Enterobacter spp.
Bleomycin (choice A) is an anticancer antibiotic and is one of the few chemotherapeutic agents that causes minimal bone marrow suppression. Its primary side effects include pulmonary fibrosis and pneumonitis. Bleomycin is used in Hodgkin lymphoma, testicular, head and neck, and skin cancers.
Tx of WPW
Regarding the treatment of WPW, antiarrhythmic agents, such as adenosine, amiodarone and verapamil, can alter the electrophysiologic mechanisms responsible for WPW, prolonging the refractory period of the conduction tissue and or the action potential.
Agents to treat bradycardia
atropine, isoproterenol, and dopamine
Treat acute angle glaucoma immediately with
Acetozolamide - will stop aqueous humor production by reducing bicarbonate
Complete heart block
In third-degree AV block there is no relationship between P waves and QRS complexes. Impulses are not transmitted through the AV node. A pacemaker develops in the ventricles, with both the atria and ventricles beating at their own rates because action potentials from the atria cannot reach the ventricles. Characteristics include a steady rhythm (usually) and very low ventricular heart rate (usually). There are no consistent PR intervals because impulses are not transmitted through the AV node. The rate for P waves (atrial depolarization) are different than the rate for R waves (first upward deflection after P wave; early ventricular depolarization).
Third-degree AV block is most commonly caused by coronary artery disease or degeneration of the cardiac conduction system with agents known to cause AV block.
Maraviroc is a CCR5 receptor antagonist
Maraviroc acts by blocking HIV gp120 attachment and preventing viral cell entry.
Common adverse reactions include hepatotoxicity and orthostatic hypotension.
Bleomycin (choice A) is an intercalating agent that complexes iron-forming reactive oxygen species and induces DNA strand breaks. It is used to treat squamous cell carcinoma, both Hodgkin and non-Hodgkin lymphoma as well as testicular carcinoma. This agent is commonly associated with the development of pulmonary fibrosis.
Prochlorperazine (choice E) is a phenothiazine derivative used primarily to control severe nausea and vomiting by blocking central dopamine receptors.
Equation for anion gap
[Na+] − ([Cl−]+[HCO3−])
Bupropion is a norepinephrine and dopamine reuptake inhibitor antidepressant.
Patients with bulimia or anorexia nervosa should not be prescribed bupropion because of the increased risk of seizures.
Bupropion causes stimulant-like effects such as tachycardia, insomnia, and weight loss.
Does not cause sexual side effects.
Also used for smoking cessation.
Adverse effects of anticholinergic agents in the elderly
Drugs with anticholinergic properties:
Can precipitate angle-closure glaucoma
Can also cause cognitive impairment and delirium in the elderly, urinary retention, constipation, dry mouth, and tachycardia
Include diphenhydramine, amitriptyline, chlorpromazine, atropine, scopolamine, oxybutynin, tolterodine, benztropine, tropicamide, and meperidine
Benign Essential Tremor
Benign essential tremor is a progressive, bilateral, largely symmetric postural tremor of the upper extremities that is not associated with other neurologic symptoms.
Benign essential tremor can be successfully treated by propranolol, a nonselective beta-antagonist, and primidone, a barbiturate analog.
Ribavirin (choice E) is used in the treatment of respiratory syncytial virus infection in infants. This is the most common cause of hospitalization for respiratory disease in the very young, probably because aerosol administration of the antiviral compound is best accomplished in a hospital setting.
Penicillamine is a chelating agent (choice B) used to chelate copper in Wilson disease and reduce excess cystine excretion in cystinuria. It is also used to treat cases of poisoning with copper, lead, arsenic, and gold, and is used in the treatment of severe rheumatoid arthritis.
Characteristics of digoxin toxicity include nausea, vomiting, diarrhea, yellow-green (most commonly) distortion, and xanthopsia (yellow halos around lights). ECG changes include decreased QT interval, increased PR interval, T-wave inversion, almost any kind of arrhythmia (including PSVT), and AV block. Factors predisposing to digoxin toxicity include renal failure (decreased drug excretion), drug interactions (verapamil, quinidine, amiodarone) and hypokalemia (K+ competes with digoxin for binding sites on the Na+/K+-ATPase; hypokalemia results in increased digoxin binding).
Treat digoxin toxicity with digoxin immune Fab.
Typical high-potency antipsychotics, such as fluphenazine and haloperidol, are more likely to cause extrapyramidal side effects (EPS).
EPS include acute dystonia, drug-induced parkinsonism, akathisia, and tardive dyskinesia.
The best way to distinguish stimulant overdose from anticholinergic overdose is the skin, which is sweaty with stimulants and dry with anticholinergics.
Drugs used to treat chronic hypertension in pregnant women include methyldopa, labetalol, nifedipine, and hydralazine (for severe hypertension).
Methyldopa is converted to α-methylnorepinephrine, which is an alpha-2-adrenergic receptor agonist. Release of α-methylnorepinephrine in the medulla leads to a decrease in sympathetic outflow, which decreases blood pressure.
Acyclovir is administered as a prodrug, which requires activation by the viral thymidine kinase and host cell kinases. Once activated, the drug inhibits the viral polymerase. It works to variable degrees with most of the Herpesviridae.
Red as a beet; Mad as a hatter; Hot as a hare; Blind as a bat; Dry as a bone.
Anticholinergic toxicity ie diphenhydramine antimuscarinic agent
Phenoxybenzamine is the only non-competitive alpha-1 blocker used therapeutically in cases of malignant hypertension and pheochromocytomas. The excessive vasodilation produced by this agent is the result of irreversible binding to the receptor, thereby decreasing the efficacy (decreased curve height) of norepinephrine
Heparin acts at multiple sites in coagulation process. It binds to antithrombin III and catalyzes the inactivation of thrombin and other clotting factors.
Heparin-induced thrombocytopenia (HIT) is the most common type of drug-induced thrombocytopenia.
Milrinone is an inotrope are indicated for the short-term IV treatment of patients with acute decompensated heart failure. It inhibits phosphodiesterase (choice B), thus increasing cAMP levels and protein kinase A activation, which increases Ca2+ influx into the cardiac cell (see figure). Milrinone can cause a variety of arrhythmias, but is not associated with nausea or xanthopsia (yellow halos around lights).
Similar to clopidogrel, ticlopidine irreversibly blocks ADP from binding platelets. Subsequently, ADP-induced expression of glycoprotein receptors is reduced, resulting in less fibrinogen binding.
Because aspirin and ticlopidine work through different mechanisms, they typically synergize. Ticlopidine may be used as a second-line agent to prevent thromboembolism or stroke. First-line therapy is typically clopidogrel in combination with aspirin because of the adverse side effects of ticlopidine. Roughly 2% of patients in clinical trials experienced neutropenia (Absolute Neutrophil Count (ANC) < 1500/mm3) or even agranulocytosis (ANC < 100/ mm3) with ticlopidine.
Give the equation for the anion gap:
[Na] - ([Cl]+[HCO3])
Cytarabine (Ara-C) (choice C) is a pyrimidine analogue that inhibits DNA polymerase. It is used for leukemias and lymphomas and is associated with the development of leukopenia, thrombocytopenia, and megaloblastic anemia.
Note: an easy way to remember beta-1 vs nonspecific beta antagonists is that antagonists that start with A through M (A-M-olol) are beta-1 specific and those that start with N through Z (N-Z-olol) are nonspecific.
Sodium thiosulfate facilitates the rhodanese-catalyzed conversion of cyanide to less toxic thiocyanate (choice C). This agent is indicated for the treatment of cyanide overdose.
Doxorubicin acts by hindering DNA replication and transcription by intercalating DNA. It also generates free radicals and inhibits topoisomerase II. Dexrazoxane can be used to decrease the incidence of doxorubicin cardiotoxicity.
A patient with cardiotoxicity secondary to doxorubicin may present with a persistently reduced voltage of the QRS complex, a prolonged systolic time interval, and a reduced ejection fraction.
Metronidazole and alcohol, why not?
Metronidazole should not be used in a patient with relapsing alcohol use disorder because the combination can cause a profound disulfiram reaction.
Nitrofurantoin (choice D) is most commonly used for the treatment and/or prophylaxis of urinary tract infections.
Triamterene (choice E) is a potassium-sparing diuretic. It inhibits sodium influx through channels in the luminal membrane of the late distal and cortical collecting tubules. Because potassium secretion is coupled with sodium entry in this area, potassium is spared.
Side Effects: Corticosteroids
Corticosteroids, such as methylprednisolone, are often associated with fluid and electrolyte imbalances such as water retention, hypernatremia, hypokalemia, and hypocalcemia, as well as hyperglycemia.
Treatment for tumor lysis syndrome
Patients who are about to receive chemotherapy for a cancer with high cell turnover rate, especially lymphomas and leukemias, should receive prophylactic oral or IV allopurinol for tumor lysis syndrome. Tumor lysis syndrome also includes hyperkalemia, hypocalcemia, and hyperphosphatemia. In addition to receiving prophylactic allopurinol, patients should receive adequate IV hydration, maintain high urine output, and alkalinize the urine with sodium bicarbonate. Febuxostat is an alternative xanthine oxidase inhibitor that can be used to treat tumor lysis syndrome.
Allopurinol is a prodrug (a suicide substrate) that is converted by the enzyme xanthine oxidase to alloxanthine (see figure). Alloxanthine inhibits xanthine oxidase, thus decreasing purine metabolism. This results in decreased uric acid formation and formation of uric acid stones.
MOA Cyclosporine and Tacrolimus
Cyclosporine (choice B) and tacrolimus (choice E) inhibit calcineurin-mediated transcription of the IL-2 gene and subsequently reduce T-cell activation. Cyclosporine and tacrolimus are limited by nephrotoxicity, whereas sirolimus has the advantage of minimal nephrotoxicity. However, sirolimus synergistically enhances cyclosporine-induced nephrotoxicity.
Mexiletine and tocainide (both are available in PO formulations) have the same mechanism of action as lidocaine (IV only).
Class 1B antiarrhythmics block fast sodium channels, shortening the action potential duration (APD); this increases the threshold for excitation and decreases the excitability of hypoxic heart muscle.
Organophosphate Poisoning (AChEi)
DUMBELSis a common mnemonic used to remember effects of AChEI poisoning:
D: Diarrhea: stimulation of GI tract smooth muscle
U: Urination: stimulation of detrusor smooth muscle
M: Miosis: contraction of pupillary sphincter muscles
B: Bronchospasm/Bradycardia: increased stimulation of bronchial smooth muscle/decreased cardiac conduction
E: Emesis/Excitation of skeletal muscle: GI stimulation/stimulation of nicotinic receptors at neuromuscular junctions (NMJ)
L: Lacrimation: Increased glandular secretion (also other secretory glands)
S: Salivation/Sweating: Increased glandular secretion/increased stimulation of sympathetic cholinergic synapses at sweat glands
Treatment is with atropine and pralidoxime (2-PAM).
Macrolide antibiotics and CYP450
Clarithromycin is a macrolide antibiotic commonly used in the treatment of upper respiratory and skin/subcutaneous infections. It is a relatively potent hepatic microsomal enzyme inhibitor of the CYP3A4 system. Since clarithromycin is likely to potentiate the effects of theophylline, it could account for this patient’s symptoms.
The half-life of a drug is clinically important because it determines the time required to reach steady-state and the dosage interval.
It takes four to five half-lives to reach steady-state.
The rule of thumb is that the plasma concentration will reach 50% in one half-life, 75% in two half-lives, 87.5% in three half-lives, etc.
How would you best treat RSV in babies?
Ribavirin - aerosol administration
Doxorubicin is an antineoplastic agent that can cause a congestive cardiomyopathy.
Cardiomyopathy/congestive heart failure is characterized by tachycardia, pulmonary rales, and a third heart sound (S3).
Doxorubicin is an antibiotic antineoplastic agent commonly used in the treatment of acute lymphocytic leukemia (ALL), acute myelogenous leukemia AML), Hodgkin lymphoma, and various solid tumors. It intercalates DNA, forms free radicals, and inhibits topoisomerase.
Metformin is a biguanide oral hypoglycemic indicated for the treatment of type 2 diabetes in conjunction with diet and exercise.
Metformin decreases hepatic glucose production and intestinal glucose absorption, and increases insulin sensitivity.
One possible adverse effect of this drug is lactic acidosis, particularly in patients with renal insufficiency. Metformin-induced lactic acidosis often is subtle and is associated with malaise, myalgias, respiratory distress, somnolence, and abdominal distress. As the acidosis becomes more severe, the patient may experience hypothermia, hypotension, and resistant bradyarrhythmias. It is recommended that use of metformin be avoided in men with creatinine higher than 1.5 mg/dL and in women with creatinine higher than 1.4 mg/dL
Lower the dose of what drug when you give allopurinol?
Azathioprine Because both operate on the de novo purine synthesis pathway
Cisplatin (choice B) is an alkylating agent indicated for the treatment of metastatic testicular and ovarian tumors in combination with other agents. This agent can cause nephrotoxicity, neurotoxicity (deafness), and mild to moderate bone marrow suppression. Amifostine, a free radical scavenger, can help prevent the nephrotoxicity.
Mobitz type I
In Mobitz type I (Wenckebach) AV block, the PR interval progressively lengthens, with the RR interval shortening before the blocked beat. In other words, there is a progressive PR interval prolongation in Mobitz type I AV block for several beats preceding a non-conducted P wave.
Drugs to reduce afterload
↓ afterload: ACEIs, ARBs, and arteriodilators (hydralazine)
Congenital toxoplasmosis can result in the development of chorioretinitis, strabismus, epilepsy, and psychomotor retardation.
Congenitally infected neonates are treated with daily pyrimethamine and sulfadiazine for 1 year.
Both of these agents act by inhibiting folic acid production.
Methamphetamine, an indirect acting sympathomimetic, is a stimulant that causes hypertension and tachycardia by inducing norepinephrine (NE) release. Methamphetamine causes the release of the mobile (nonvesicular) pool of norepinephrine, causing an increase in the synaptic concentration of NE and thus greater stimulation of postsynaptic receptors. The receptors that mediate: systemic vasoconstriction are alpha-1 adrenergic receptors increases in heart rate and inotropic state are beta-1 adrenergic receptors.
Methotrexate (choice E) is an antimetabolite and folic acid antagonistcommonly used in various neoplastic disorders, such as leukemias, lymphomas, and breast cancer. It is also used to treat rheumatoid arthritis and psoriasis. It can cause a myelosuppression that is reversible with leucovorin (folinic acid), a rescue agent.
Digoxin is a cardiac glycoside that directly inhibits Na+-K+ ATPase (see figure), leading to indirect inhibition of the Na+/Ca2+ exchanger, and causing an increase in intracellular calcium. The net effect is positive inotropy. An indirect effect of digoxin is inhibition of neuronal Na+-K+ ATPase, causing an increase in vagal activity and a decrease in heart rate. Digoxin is indicated for heart failure (increases contractility) and atrial fibrillation (increases parasympathetic stimulation to AV and SA nodes).
Because digoxin has a narrow therapeutic window, toxicity can easily develop, resulting in the development of any dysrhythmia, including paroxysmal atrial tachycardia with 2:1 block, accelerated junctional rhythm, and bidirectional ventricular tachycardia (torsades de pointes).
The incidence and severity of digoxin toxicity is greatly increased when hypokalemia is present.
Finasteride, the drug used to treat this patient, inhibits 5α-reductase, which interferes with the conversion of testosterone to 5α-dihydrotestosterone and decreases the trophic influence of DHT on the prostate. Finasteride is indicated for the treatment of symptomatic BPH and male pattern baldness.
Other agents used for BPH include alpha1-adrenergic antagonists, PDE-5 inhibitors, and antimuscarinics.
paclitaxel inhibits mitosis by preventing depolymerization of microtubules
Paclitaxel is most commonly associated with myelosuppression, alopecia, and hypersensitivity reactions.
Treat Wilson’s disease with:
Pralidoxime is an acetylcholinesterase reactivating agent (choice D) that is used in organophosphorus cholinesterase inhibitor poisoning.
Octreotide, a synthetic analog of somatostatin, decreases portal blood flow, which decreases variceal bleeding.
This agent is also used to treat acromegaly, and diarrhea in various endocrine disorders, such as carcinoid syndrome, gastrinoma, and glucagonoma.
Hydralazine decreases blood pressure by producing a peripheral vasodilating effect by relaxing vascular smooth muscle tissue. Hydralazine acts through nitric oxide to increase cGMP.
Hydralazine is most commonly used in the treatment of essential hypertension as a single agent or in combination with other medications.
Amlodipine (choice A) and felodipine are the most commonly used calcium channel blocking agents in patients who have CHF. These two medications may actually produce a small increase in myocardial contractility and cardiac output.
Tramadol (choice E) is a centrally acting synthetic analgesic compound that has action at the mu opiate receptor and may inhibit the uptake of serotonin and norepinephrine. This agent produces analgesia with little respiratory depression. It is indicated for treatment of moderate to moderately severe pain.
What is one of the primary differences between Sirolimus and Tacrolimus and Cyclosporine?
Sirolimus has minimal nephrotoxicity and neurotoxicity.
Tinea corporis or tinea circinata (body ringworm) is typically diagnosed when the patient presents with ring-shaped lesions with an advancing scaly border and central clearing, or scaly patches with a distinct border on the exposed skin surfaces or the trunk.
Treatment generally involves the use of topical antifungal agents, such as clotrimazole, miconazole, terbinafine, and butenafine.
Treatment should continue for 1 to 2 weeks after clinical clearing of the lesions.
Clomipramine is a tricyclic antidepressant that is used for obsessive-compulsive disorder. It inhibits norepinephrine and serotonin reuptake, but also blocks muscarinic, histamine H1, and alpha-1 adrenergic receptors. These last three properties contribute to the appearance of side effects. Other tricyclic antidepressants include amitriptyline, imipramine, and nortriptyline.
Blockade of muscarinic receptors causes tachycardia, dry mouth, visual disturbances, urinary retention, and constipation.
What is a rare but serious complication of metformin?
Lactic acidosis Do not use metformin in patients with renal insufficiency or heart failure
Anastrozole (choice A) is an aromatase inhibitor used to treat breast cancer. It is associated with hot flashes, thromboembolism, osteoporosis, and bone fractures.
tamsulosin and silodosin are selective alpha-1A adrenergic antagonists. They are indicated for BPH but not hypertension since they only block alpha-1A receptors, which are selective for the prostate.
Treat BPH with
alpha-1 blockers terazosin, doxazosin
Felodipine (choice A) is a dihydropyridine calcium channel blocker. It inhibits calcium ion flux into vascular smooth muscle and the myocardium. Unlike verapamil and diltiazem, which are also calcium channel blockers, it is not associated with bradycardia or AV block.
Procainamide is an example of class IA antiarrhythmic agent that decreases the slope of phase 0 of the action potential (choice E) by blocking Na+ channels. It also increases action potential duration (APD) and effective refractory period (ERP). It would not increase the risk for developing PSVT or cause xanthopsia. It causes hypotension, cardiac arrhythmias and lupus erythematous.
The drug of choice for localized cutaneous leishmaniasis is either sodium stibogluconate or meglumine antimonate.
Antimony-containing compounds are the principal medications used to treat localized cutaneous leishmaniasis, and include sodium stibogluconate and meglumine antimonate.
Second-line drugs, e.g., amphotericin B and pentamidine, are potentially more toxic, so they are used in the treatment of visceral leishmaniasis cases that are unresponsive to the antimonials.
Amphotericin B is the drug of choice for severe diffuse cutaneous and visceral leishmaniasis.
Drugs to reduce cardiac remodeling
↓ remodeling of cardiac muscle (which increases survival):ACEIs, ARBs, spironolactone, beta blockers (metoprolol, carvedilol), and hydralazine plus nitrates (Note that high doses of beta blockers can lead to acute decompensation.)
Do not administer Cipro with what other medications?
Fluoroquinolones, such as ciprofloxacin, will have a dramatic decrease in bioavailability when taken with antacids, secondary to the binding of the two medications in the intestinal tract.
Iron and calcium limit the absorption of fluoroquinolones (ciprofloxacin ); therefore, the fluoroquinolones should not be used with antacids.
In the face of heparin-induced thrombocytopenia, switch to:
Bivalirudin is a highly specific direct inhibitor of thrombin and, unlike heparin, its mechanism of action is independent of antithrombin III.
Recombinant hirudins such as bivalirudin are not inhibited by platelet factor 4 and are therefore successful in the treatment of HIT.
Ipratropium is a bronchodilator that blocks M3 muscarinic receptors in the lung. M3 receptors are coupled to Gq, which activates phospholipase C, causing the release of inositol triphosphate (IP3) and diacylglycerol (DAG) from phosphatidylinositol bisphosphate (PIP2). IP3induces the release of Ca2+ from the sarcoplasmic reticulum, leading to smooth muscle contraction. Therefore, antagonism of this receptor would lead to decreases in inositol triphosphate (IP3), intracellular Ca2+, and diacylglycerol (DAG), leading to bronchodilation.
Diazoxide is a direct acting peripheral vasodilator that decreases both systolic and diastolic blood pressure. Specifically, diazoxide opens KATPchannels on vascular smooth muscle, causing hyperpolarization and vasodilation, resulting in a decrease in peripheral vascular resistance. Opening KATP channels on pancreatic beta cells causes hyperpolarization and decreased calcium entry through voltage-gated calcium channels. As a result, diazoxide decreases insulin secretion in response to glucose.
similar mechanism as minoxidil. This agent is used for emergency hypertension and the management of hypoglycemia caused by hyperinsulinism.
Benztropine and trihexyphenidyl are antimuscarinic agents used to treat extrapyramidal side effects.
Antimuscarinic agents have anti-DUMBBelLSS properties.
Therefore, they cause constipation urinary retention, mydriasis (and blurred vision), bronchodilation, tachycardia, and dry eyes, skin, and mouth (xerostomia).
Verapamil (choice E) is a non-dihydropyridine calcium channel blockerused in the treatment of hypertension, agnina, PSVT conversion and treatment, and atrial fibrillation. Verapamil is contraindicated for use in patients with heart failure since it decreases both the rate and contractility of the heart resulting in decreased cardiac output.
Epinephrine acts on alpha-1, alpha-2, beta-1, beta-2 receptors.
Phentolamine acts as an antagonist on alpha-1 and alpha-2 receptors.
With both on board, there is unopposed activation of beta-1 and beta-2 receptors, thereby causing a decrease in BP due to the vasodilating effects of beta-2 receptors.
This is known as “epinephrine reversal.”
Fibrates (e.g., gemfibrozil, fenofibrate, and clofibrate) lower triglycerides by approximately 35-50% and increase HDL-c by 5- 20%.
Fibrates activate proliferator-activated receptor-α (PPARα) and increase the expression of lipoprotein lipases.
Adverse affects include gallstones and muscle toxicity.
Treatment for atrial fibrillation
The primary goals of drug therapy for patients with AF are to maintain sinus rhythm, avoid risk of complications (i.e. stroke), and minimize symptoms. Warfarin represents the cornerstone of anticoagulant therapy for AF patients at moderate to high risk of thromboembolic events. Although not commonly used as a first-line therapy for the treatment of atrial fibrillation, digoxin is an acceptable treatment option. It acts by decreasing conduction through the atrioventricular node.
Beta blockers, such as esmolol and metoprolol, and calcium channel blockers, such as verapamil and diltiazem, are generally considered to be the treatment of choice for atrial fibrillation in patients without evidence of heart failure.
Do not use Metformin in patients with:
Metformin should not be used in patients with renal insufficiency, heart failure, conditions predisposing to hypoxemia, or lactic acidosis.
Pilocarpine is an example of a cholinomimetic drug that stimulates muscarinic cholinergic receptors (choice D). It decreases heart rate by decreasing AV conduction velocity and would not cause PSVT or xanthopsia. Common side effects include diaphoresis, flushing, rhinitis, and dizziness
Indomethacin and kidneys
Indomethacin, an NSAID, can precipitate acute renal failure (ARF), also known as acute kidney disease (AKD). The NSAIDs increase the risk of renal damage, especially in the ischemia-sensitive papillae. Nonspecific cyclooxygenase inhibitors, such as indomethacin, reduce prostaglandin synthesis, leading to decreased renal perfusion and potentially renal ischemia. Remember, PGE2, a potent vasodilator, is especially important in prevention of such ischemia. Healthy kidneys are resistant to NSAID-induced damage, apparently because they have adequate reserve of blood flow and prostaglandin synthesis. Kidneys that are overstressed, as in this patient, in diabetics, or in many other conditions, lack this reserve, and are at significant risk for NSAID-induced damage. Therefore, NSAID use may result in papillary necrosis of the kidney.
1st gen cephalosporin Avoid in patients with penicillin allergy
Treatment of AV heart block
Atropine (choice A) is an anticholinergic agent that has been used in the treatment of atrioventricular heart block to increase conduction through the AV node when increased vagal tone is a major factor in the conduction defect.
digoxin toxicity does NOT cause hypokalemia; however, hypokalemia can lead to the development of digoxin toxicity.
Treatment for serum sickness
Common signs and symptoms of serum sickness include fever, cutaneous eruptions, lymphadenopathy, and arthralgias. Arthralgias occur in approximately two-thirds of patients. The joints most commonly involved include the metacarpophalangeal joints, knees, wrists, ankles, and shoulders. Erythema multiforme may also appear in severe cases. The reaction is generally delayed for 5 to 10 days after initial exposure, because it takes that long for the generation of specific IgG antibodies. Treatment measures include, withdrawal of the causative agent, symptomatic treatment (antihistamines for urticaria), and glucocorticoids. Due to the severity of the signs and symptoms in this patient, oral prednisone and diphenhydramine should be administered. The glucocorticoid prednisonewill treat the arthralgias and the skin rash, and the diphenhydramine will alleviate the urticaria.
Zafirlukast (choice F) is an orally active LTD4 leukotriene receptor antagonist. It can prevent bronchospasms caused by exercise, aspirin, and antigens; it is not used for acute asthmatic attacks. Montelukast is another member of this “-lukast” class.
Therapy for AML
Standard induction therapygenerally involves either a four-drug regimen of vincristine, prednisone, anthracycline (daunorubicin or doxorubicin), and cyclophosphamide or L -asparaginase or a five-drug regimen of vincristine, prednisone, anthracycline, cyclophosphamide, and L-asparaginase. Both of these regimens are generally administered over the course of 4-6 weeks and obtains a complete remission in approximately 65-85% of all patients.
Scopolamine or tropicamide can cause acute angle glaucoma because:
they are anticholinergic agents that dilate the pupil, like walking into a dark room.
Cyclophosphamide is an alkylating agent that acts through DNA crosslinking.
Cyclophosphamide is used to treat Hodgkin and non-Hodgkin lymphoma and breast and ovarian cancer.
Side effects include bone marrow suppression, hemorrhagic cystitis (treat with mesna), and hepatotoxicity.
Selectively antagonizes vasopressin V2 receptors, increasing free water excretion
Dinoprostone is an analog of:
Prostaglandin E2 use to soften the cervix causing dilation and uterine contractions
Dopamine DA2 receptors
DA2 receptors are coupled to Gi proteins, which inhibit adenylate cyclase and decrease cAMP production when stimulated.
Blockade of DA2 receptors will, therefore, produce the opposite results and increase cAMP production.
Vecuronium is a nondepolarizing skeletal muscle relaxant that competitively blocks the nicotinic acetylcholine (ACh) receptor.
Its effect can be reversed by an acetylcholinesterase inhibitor such as neostigmine because the increased levels of ACh will compete with vecuronium at the receptor.
Succinylcholine is an irreversible ACh blocker.
Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome (choice C) is a rare, but potentially fatalsyndrome that usually occurs within 10 days of starting neuroleptic therapy. Clinical manifestations include fever, encephalopathy, muscle rigidity, dystonia, diaphoresis, tachycardia, and labile blood pressure. Treatment is with dantrolene or with dopamine agonists such as bromocriptine.
Dystonia is an acute extrapyramidal side effect that can be a consequence of neuroleptic therapy, usually within the first few days of therapy. It is a movement disorder characterized by repeated, sustained involuntary muscle contractions as well as abnormal postures of the trunk, face and/or extremities.
Dystonia tends to occur more frequently in children and young adults, and occurs in males more often than females.
Treatment is with anticholinergic drugs (e.g., benztropine), botulinum toxin, or diazepam.
Ceflacor and serum sickness
Serum sickness is a type III hypersensitivity reaction that is commonly caused by a reaction to certain drugs. Key features of serum sickness are rash, fever, and polyarthralgias or polyarthritis, which begin one to two weeks after exposure to the responsible agent. Patients are often extremely ill during the febrile stage, but serum sickness is self-limited and once the responsible drug is discontinued, the prognosis is excellent.
In serum sickness, it is suggested that the drug acts as a hapten, which binds to serum or cell-bound proteins. This drug-protein complex is recognized as being foreign to the body and induces the serum sickness. Medications commonly associated with the development of this condition include cephalosporins (especially cefaclor), penicillins, trimethoprim-sulfamethoxazole, vaccines, antitoxins, hormones from other species, tetracyclines captopril, and ciprofloxacin. In children, cefaclor is 15 times more likely to cause serum sickness than other cephalosporins or amoxicillin.
The second-generation H1 receptor antagonists (cetirizine, loratadine, desloratadine, and fexofenadine) are far less sedating because they do not penetrate the blood-brain barrier or have anticholinergic properties. Therefore, these second-generation agents are often the drugs of choice for the treatment of allergic disorders.
Tricyclic antidepressants block the reuptake of norepinephrine and serotonin.
They also have anticholinergic actions (xerostomia, urinary retention), cause sedation and QT prolongation.
What is a complication of TCA ia amitriptyline overdose?
Lethal arrhythmia (cardiotoxicities, convulsions, coma)
Benzodiazepines bind what kind of channel in the CNS?
Tacrolimus (choice E) is also nephrotoxic, is metabolized by CYP3A, and inhibits IL-2 transcription through a calcineurin-dependent mechanism. However, tacrolimus specifically binds the immunophilin FK506-binding protein rather than cyclophilin. Tacrolimus is a soil fungus-derived macrolide that is indicated for kidney, heart, and liver transplant rejection prophylaxis. Common adverse effects seen with tacrolimus include tremor, hypertension, infection, and renal impairment. Serious reactions include thrombocytopenia, leukopenia, neutropenia, immunosuppression, nephrotoxicity, neurotoxicity, seizures, and opportunistic infections.
Etoposide (choice B) is a topoisomerase inhibitor used to treat testicular cancer, small cell lung carcinoma, and leukemia. Common side effects of etoposide include propensities to infection and bleeding caused by myelosuppression, mucositis/stomatitis, alopecia, and rash.
Buspirone is a nonbenzodiazepine anxiolytic agent that is generally nonsedating, is not associated with tolerance or dependence, does not interact with benzodiazepine receptors or alcohol, has no abuse potential, and does not cause sexual dysfunction. Many physicians who treat patients with GAD start them on benzodiazepines (which act quickly) and then switch them to buspirone (which takes about 2 weeks to work) or more commonly the selective serotonin reuptake inhibitors, such as fluoxetine.
a 5-HT 1Apartial agonist
Salmeterol is a long-acting β2 agonist (LABA), which acts by increasing levels of cAMP. β2 agonists can be divided into two classes of agents: short-acting (SABA) and long-acting (LABA).
SABA: Fast-onset, short-acting “rescue” inhalers, drugs of choice for quick relief of acute asthma symptoms, lasts 3-4 hours; albuterol, metaproterenol, terbutaline, pirbuterol
LABA: Longer-acting inhalers for prophylaxis, lasts at least 12 hours, slower onset, recommended to be used with inhaled steroids; salmeterol, formoterol
All β receptors are coupled to Gs and adenylate cyclase, thus βreceptor stimulation leads to increases in cAMP. Increases in cAMP lead to relaxation of bronchial smooth muscle.
Metoclopramide is a dopamine antagonist that is used as an antiemetic in the prevention of chemotherapy-induced nausea and vomiting and to promote gastrointestinal motility in patients with gastroparesis. It is also used in the treatment of gastroesophageal reflux disease (GERD) in patients unresponsive to other therapies. Specifically, this agent antagonizes central and peripheral dopamine receptors and stimulates upper gastrointestinal tract motility.
Rifampin inhibits bacterial and mycobacterial RNA synthesis by binding to the beta-subunit of DNA-dependent RNA polymerase, thereby inhibiting the binding of the enzyme to DNA and blocking RNA transcription.
Rifampin is a safe drug that is used principally for the treatment of active tuberculosis and meningococcal prophylaxis.
Tizanidine (choice E) is an agonist of alpha-2 adrenergic receptors in the central nervous system and increases presynaptic inhibition of motor neurons. Therefore, it can be used to treat spasticity in ALS patients. However, tizanidine does not prolong survival in ALS.
Drugs that cause constipation
Medications associated with the development of constipation include opioid analgesics (e.g., codeine, hydrocodone, oxycodone, and morphine), calcium channel blockers, anticholinergics, tricyclic antidepressants, and antipsychotics. Other factors or conditions associated with constipation include hypercalcemia, hypothyroidism, Parkinson disease, diabetes mellitus, and diseases of the colon (e.g., stricture, cancer, anal fissure, proctitis).
ACE inhibitors block the formation of angiotensin II, which is a potent vasoconstrictor and a negative feedback mediator for renin activity.
The ACE inhibitors are associated with the development of angioedema, a dry, “hacking” cough, and hyperkalemia.
Metoclopramide (choice C) is used for chemotherapy-related nausea and vomiting and is also a prokinetic agent indicated for the treatment of GERD and diabetic gastroparesis
Side effects Verapimil
Congestive heart failure (CHF) is characterized by fatigue, peripheral edema, S3 heart sounds, and by exertional and nocturnal dyspnea.
Verapamil has strong negative inotropic effects, which can exacerbate a patient’s underlying heart failure.
Improvement of patient survival has been documented with diuretics, beta blockers, ACE inhibitors, ARBs, hydralazine plus nitrates, and aldosterone antagonists.
elderly patients and those with a past history of myocardial infarction are more prone to developing heart failure symptoms when given a medication with negative inotropic effects, such as verapamil and beta-blockers.
ACE inhibitors prevent bradykinin degradation and angiotensin II formation.
ACE inhibitors can cause electrolyte imbalances such as hyperkalemia and mild hyponatremia by decreasing the secretion of aldosterone.
The primary therapeutic goals of the treatment of secondary hyperparathyroidism are to decrease the levels of PTH and phosphorus in the blood. In patients with chronic kidney disease who are on dialysis, a decrease in PTH is associated with a positive impact on bone-specific alkaline phosphatase (BALP), bone turnover, and bone fibrosis. Cinacalcet is a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor (CaSR) on chief cells of the parathyroid gland to extracellular calcium. This causes a reduction in PTH.
Cinacalcet is indicated for the management of secondary hyperparathyroidism in patients with chronic kidney disease (and parathyroid level, iPTH >300 pg/mL) and for the treatment of hypercalcemia in patients with parathyroid carcinoma.
Dantrolene (choice B) prevents the release of calcium from the sarcoplasmic reticulum of skeletal muscle by blocking ryanodine receptors. Thus, anesthesiologists use this medication to treat malignant hyperthermia associated with the concomitant use of succinylcholine and halothane. It is also used to treat neuroleptic malignant syndrome.
Prazosin is a competitive alpha-1 receptor blocker used in treatment of hypertension because of its vasodilatory effect,
atrial fibrillation (AF), which is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with subsequent decline of atrial function. On the ECG, there is replacement of consistent P waves by fibrillatory waves that vary in size, shape, and timing, associated with an irregular, frequently rapid ventricular response (irregularly, irregular).
Pentoxifylline (choice E) lowers blood viscosity and improves erythrocyte flexibility. It is indicated for the treatment of intermittent claudication, and is generally well tolerated with few side effects; however, it has been associated with the development of dyspnea and mild hypotension.
Sulfa drugs include
celecoxib, sulfonylureas, sulfamethoxazole, sulfasalazine, and thiazide diuretics
Drugs to reduce preload
↓ preload: diuretics (loops and thiazides), angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and venodilators (nitrates)
MOA Docusate sodium
Docusate is an anionic surfactant (i.e., a surface-active agent) that reduces the surface tension at the oil-water interface of the feces, allowing water and lipids to penetrate the stool.
Docusate helps to hydrate and soften the fecal material, facilitating natural defecation. This agent is classified as a stool softener.
G6PD deficient individuals should not be administered:
Sulfa drugs, including TMP-SMX Heinz bodies in red cells –> denatured Hgb
Azithromycin and Clarithromycin are examples of:
Macrolides Use to treat mycoplasma pneumonia - lack a cell wall
Lithium is used for the treatment of bipolar affective disorder as are carbamazepine and valproic acid.
Lithium can inhibit thyroid function, which should be monitored by measuring thyroid-stimulating hormone (TSH) every 6-12 months of therapy.
Lithium has a very narrow therapeutic index (LD50/ED50),
Alteplase is a serine protease that binds to fibrin protein threads of a thrombus and converts the enmeshed plasminogen to plasmin, causing local fibrinolysis. It produces a limited conversion of plasminogen in the absence of fibrin, thereby producing a limited systemic effect.
Glyburide is a sulfonylurea used in the treatment of type 2 diabetes mellitus. It stimulates the pancreas to release insulin. In high doses, it can cause hypoglycemia.
Cisplatin (choice D) is a platinum compound that forms metabolites that bind and crosslink DNA strands. Cisplatin is less likely to cause myelosuppression compared to other anticancer drugs; however, is one of the most emetogenic compounds available. It also causes nephrotoxicity, neuropathy, ototoxicity, and optic neuritis.
Digoxin inhibits Na+/K+-ATPase, which moves 2 K+ into cardiac myocytes for every 3 Na+ out. In the image below, the mechanism of digoxin is shown on the left. By blocking the Na+/K+-ATPase, more Na+ will increase intracellularly, thus slowing the Na+/Ca2+ antiporter. This leads to the accumulation of intracellular Ca2+, thus increasing contractility (inotropy). Digoxin also increase increases vagal tone, causing decreased conduction through sinoatrial (SA) and atrioventricular (AV) nodes.
Flutamide (choice C) is an androgen receptor blocker, which inhibits testosterone-induced prostatic DNA synthesis and thus is used to treat prostate cancer. Common side effects include hepatotoxicity, gynecomastia, loss of libido, impotence, galactorrhea, and myelosuppression.
Hyperkalemia is a potentially life-threatening complication of succinylcholine. Succinylcholine is a depolarizing skeletal muscle relaxant. It acts by binding to and stimulating nicotinic acetylcholine receptors (Nm) at skeletal muscle motor end plates. Nm receptors are ligand-gated cation channels that allow Na+ in and K+ out of the cell.
In addition to hyperkalemia, this agent is associated with malignant hyperthermia, prolonged paralysis, respiratory depression, cardiac arrhythmias, rhabdomyolysis, and myoglobinemia.
Hyperkalemia and burn patients
Patients with burns and extensive soft tissue injury are at greater risk for hyperkalemia because the tissue damage leads to a loss of potassium into the circulation. Because succinylcholine causes prolonged muscle depolarization, the muscle can release substantial amounts of K+. Therefore, succinylcholine should be either avoided or used with extreme caution in such patients.
Hyperkalemia on EKG looks like
In hyperkalemia, the ECG usually first shows tall, peaked T waves, then prolongation of the PR interval, then absent P waves with widened QRS complexes, and finally ventricular tachycardia/ventricular fibrillation.
Colchicine is one of the drugs that can be used to treat acute attacks of gout.
Colchicine acts by inhibiting microtubule formation, which prevents leukocyte migration and phagocytosis and thus leads to a reduction in inflammation.
Warfarin and Clarithromycin
Clarithromycin, like other macrolides, binds to the 50S ribosomal subunit, thereby blocking bacterial protein synthesis.
The macrolides potentiate warfarin’s effects by inhibiting its metabolism via hepatic isozyme CYP3A4.
When warfarin is administered with clarithromycin, the decreased metabolism of warfarin can cause bleeding.
Warfarin increases prothrombin time (PT) and international normalized ratio (INR) because it interferes with the synthesis of the vitamin K-dependent clotting factors of the liver (II, VII, IX, and X) and therefore necessitates regular monitoring of the PT.
PT vs PTT
Here is a summary to differentiate PT from aPTT:
The prothrombin time (PT), which is affected by warfarin, measures factors I (fibrinogen), II (prothrombin), V, VII, and X. The PT is a measure of the extrinsic pathway of coagulation.
The activated partial thromboplastin time (aPTT), which is affected by the heparins, measures the intrinsic pathway and common pathway.
MOA Botulism toxin
Botulinum toxin blocks neuromuscular conduction by binding to protein sites on motor nerve terminals, entering nerve terminals via endocytosis, and inhibiting the release of acetylcholine (ACh) thereby reducing local skeletal muscle activity. Different subtypes of the toxin cleave different SNARE proteins, which are essential to the successful docking and release of acetylcholine from vesicles located within nerve endings. Examples of SNARE proteins are SNAP-25, synaptobrevin, and syntaxin. After intramuscular injection, botulinum toxin produces partial chemical denervation of the muscle, resulting in a localized reduction in muscle activity.
Side effects: Metoclopramide
Pseudoparkinsonism is a condition that commonly occurs in individuals taking medications that block the action of dopamine in the CNS.
Pseudoparkinsonism can be produced by dopamine antagonists, such as metoclopramide.
Metoclopramide is a prokinetic agent indicated for the treatment of resistant cases of gastroesophageal reflux disease (GERD) and diabetic gastroparesis.
Pseudoparkinsonism is a condition that commonly occurs in individuals taking medications that block the action of dopamine in the CNS. Pseudoparkinsonism, as the name implies, is a condition in which the patient’s symptomatology is similar to that seen in patients with Parkinson disease. Common signs and symptoms include mask-like facies, drooling, tremors, pill rolling motion, cogwheel rigidity, and shuffling gait. This condition is commonly seen in individuals taking dopamine receptor antagonists such as antipsychotic medications and metoclopramide.
Doxepin (choice A) is approved for use in the topical treatment of eczematous dermatitis (atopic dermatitis, eczema, or lichen simplex chronicus).
Foscarnet (choice C) is approved for use in immunosuppressed patients suffering from cytomegalovirus infections. It inhibits the viral DNA polymerase by mimicking the pyrophosphate portion of nucleoside triphosphates.
Causes of metabolic acidosis
There are many causes of high-anion gap metabolic acidosis. The mnemonic for remembering these causes is MUDPILES: Methanol, Uremia, Diabetic ketoacidosis, Paraldehyde, Propylene glycol or Phenformin, Iron tablets or Isoniazid (INH), Lactic acidosis, Ethylene glycol, Salicylates.
Urge incontinence is characterized by involuntary leakage accompanied by urgency. It is at least partly caused by detrusor hyperactivity.. Inflammatory conditions or neurogenic disorders (including those seen in diabetes) of the bladder are commonly associated with urge incontinence.
Oxybutynin inhibits detrusor muscle contraction by blocking muscarinic receptors and by exerting a direct antispasmotic effect. Other antimuscarinics used include: tolterodine, darifenacin, solifenacin, fesoterodine, and trospium. Potential adverse side effects include dry mouth, blurred vision, tachycardia, constipation, facial flushing, and drowsiness. Antimuscarinics are contraindicated in narrow-angle glaucoma and should be used with caution in the elderly.
Risedronate is a bisphosphonate indicated as a first line therapy for the treatment and prevention of osteoporosis.
The bisphosphonates are the safest and best tolerated agents for the treatment of osteoporosis and are associated with a reduced risk of non-vertebral fractures.
Bethanechol is a choline-like compound that stimulates muscarinic receptors, leading to contraction of the detrusor muscle. This agent is indicated for the treatment of urinary retention,
In a pediatric patient with a cyanotic congenital heart lesion, a patent ductus arteriosus (PDA) may be lifesaving.
Alprostadil, a PGE1 analog, can maintain the PDA.
In a typical PDA, closure can be achieved with prostaglandin synthesis inhibitors such as indomethacin or through surgical intervention.
The patent ductus arteriosus (PDA) is a direct communication between the aorta and pulmonary artery due to the continued patency of the ductus arteriosus after birth. It is associated with prematurity and congenital rubella infections. Clinical findings include machinery murmur, late cyanosis, and congestive heart failure. Eisenmenger syndrome may develop as a complication. When this condition occurs (withoutconcomitant transposition of the great vessels) it is treated with NSAIDS, such as indomethacin.
Prazosin is a competitive alpha-1 receptor blocker used in treatment of hypertension because of its vasodilatory effect,
Macrolides such as azithromycin are used to treat atypical “walking” pneumonia caused by M. pneumoniae.
Macrolides inhibit the translocation of peptidyl-tRNA from the acceptor site to the donor site of the 50S subunit.
Trihexyphenidyl and benztropine are muscarinic antagonists that are used as adjunctive therapy in Parkinson disease (PD). Antimuscarinics are most useful in treating tremor, and are less efficacious in treating bradykinesia and rigidity. It is thought that motor symptoms of PD result from an imbalance of dopamine and acetylcholine in the striatum, and therefore treatment is directed at increasing dopaminergic tone and decreasing cholinergic tone.
Trihexyphenidyl also blocks muscarinic receptors in the autonomic nervous system (see figure). It blocks parasympathetic tone by antagonizing muscarinic receptors on end organs and also blocks muscarinic receptors on sweat glands, which receive postganglionic sympathetic cholinergic innervation.
Felodipine is a calcium channel blocking agent associated with hypotension, reflex tachycardia, peripheral edema, and dizziness.
Thiazides and gout
Thiazide diuretics, such as hydrochlorothiazide, can cause drug-induced gout due to a decreased elimination of uric acid.
Gout is characterized by hyperuricemia, and pain and inflammation, most commonly in the first metatarsophalangeal joint.
Factors that lead to gout include acute alcohol intoxication, overindulgence of foods high in purines, rapid weight loss, dehydration, trauma, and medications (e.g., thiazide or loop diuretics, allopurinol, uricosuric agents, low-dose aspirin).
Phenytoin or fosphenytoin can be used for long-term seizure control or if the patient continues to have seizures after initial treatment with benzodiazepines.
Ethosuximide (choice B) is indicated for the treatment and prevention of absence seizures.
Carbamazepine (choice A) is indicated for the long-term treatment and prevention of tonic-clonic, focal, and complex partial seizures.
Valproic acid (choice E) is indicated for the treatment and prevention of tonic-clonic, myoclonic, absence, and absence seizures.
way to remember the p450 inhibitors is with the mnemonic PICK EGS (INHIBITORS): Protease inhibitors, Isoniazid, Cimetidine, Erythromycin, Grape fruit juice, Sulfonamides.
These drugs can cause a decrease in the metabolism of other agents such as warfarin, increasing their blood levels and subsequently their systemic effects.
Buspirone is an anxiolytic that is a serotonin 5-HT1A partial agonist. It is also moderate antagonist at dopamine receptors. It is used in the long-term treatment of generalized anxiety disorder and is known to cause serotonin syndrome, extrapyramidal symptoms, and impaired concentration.
Drugs that cause SIADH
SIADH is associated with impaired water excretion as well as hyponatremia and hypoosmolality secondary to inappropriate secretion of ADH.
Drugs that can cause SIADH include antidepressants (SSRIs, tricyclics, MAOIs), antipsychotics, anticonvulsants, and antineoplastics.
Thiazides vs ACEi’s
thiazides cause hypokalemia by increasing potassium excretion in contrast to the ACE inhibitors that decrease potassium excretion.
Drugs that prolong the QT interval
Drugs known to prolong the QT interval (or cause hypokalemia and/or hypomagnesemia) are contraindicated for use in patients with long QT syndrome. These agents include quinidine, procainamide, sotalol, amiodarone, disopyramide, dofetilide, phenothiazines, and tricyclic antidepressants. Procainamide increases AP duration, increases effective refractory period, and increases the QT interval. Procainamide causes SLE, QT prolongation, torsades de pointes, hypotension, and flushing.
Adenosine (choice A) is an unclassified antiarrhythmic medication with a half-life of < 10 seconds. It can slow both SA and AV nodal activity, as well as prolong the AV nodal refractory period. Its mechanism of action involves the activation of adenosine receptors and the reduction of the level of cAMP. It is not contraindicated in the treatment of patients with long QT syndrome. It is used for treatment of PSVT conversion and in cardiac stress testing.
ACEi’s and Acute Renal Failure
The ACE inhibitors, such as captopril, lisinopril, and ramipril, decrease total peripheral resistance, which reduces blood pressure; this contributes to risk of prerenal failure. Dilation of efferent arterioles decreases glomerular capillary pressure, which decreases glomerular filtration rate (GFR). ACE inhibitors prevent efferent renal arteriolar constriction out of proportion to their effect on the afferent arteriole, so GFR decreases. The decreased GFR, leads to elevated serum creatinine level. Administration of ACE-inhibitors in hypotensive patients increases risk of acute kidney disease (AKD); this patient’s rapid development of high serum creatinine implicates AKD. Additionally, patients with renovascular disease (which this patient may have because he had an MI, implying atherosclerosis) are especially susceptible to ARF with the addition of an ACE inhibitor.
Thiazolidinediones, such as pioglitazone and rosiglitazone, are antidiabetic agents that increase insulin sensitivity through a variety of mechanisms, resulting in decreased hepatic gluconeogenesis and increased insulin-dependent muscle glucose uptake. These agents bind to peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as skeletal muscle, adipose tissue and the liver. The activation of PPAR-gamma receptors regulates the transcription of insulin-responsive genes that are involved in the control of glucose production, transport, and utilization. This results in enhanced tissue sensitivity to insulin. As a drug class, the thiazolidinediones are contraindicated for use in patients with New York Heart Association (NYHA) Class III or IV heart failure because of worsening heart failure symptoms, fluid retention leading to peripheral edema, and the promotion of weight gain.
Glipizide and Glyburide
Glipizide and glyburide are sulfonylurea oral hypoglycemic agents that stimulate the secretion of insulin from the pancreatic beta cells (choice E). It should be noted that the sulfonylureas have been shown to increase the risk for cardiovascular events.
GLP-1 receptor agonists (choice B), such as exenatide, stimulate glucose-dependent insulin secretion by pancreatic beta cells, slowing gastric emptying as well as decreasing inappropriately elevated glucagon secretion.
The COX-2 inhibitor celecoxib would be effective for pain management and would not cause as much gastrointestinal irritation, however, it is contraindicated in this in patients with sulfonamide allergies and his family history of coronary disease.
Mupirocin (choice E) is an antibacterial agent indicated for the topical treatment of impetigo primarily caused by Staphylococcus aureus or Streptococcus pyogenes.
Neuroleptic Malignant Syndrome
NMS is a potentially fatal condition most commonly associated with typical antipsychotic medications as well as abrupt withdrawal of dopamine agonists. Clinical characteristics of NMS include hyperpyrexia, muscle rigidity, altered mental status, myoglobinuria, and evidence of autonomic instability (tachycardia, diaphoresis, irregular pulse or blood pressure, and cardiac arrhythmias). Laboratory studies often show a creatine kinase (CK) > 1000 IU/L (and can be as high as 100,000 IU/L). The AST, ALT, and LDH are all generally mildly elevated (as seen in this patient).
Haloperidol, chlorpromazine, and fluphenazine are typical antipsychotics that act by blocking dopamine D2 receptors. They are associated with the development of NMSas well as acute extrapyramidal symptoms (parkinsonism, dystonia, akathisia) and tardive dyskinesia.
NMS can be treated with immediate withdrawal of the offending drug and other treatment measures are primarily supportive and directed toward controlling the rigidity and hyperthermia and preventing complications. Antipyretics and cooling methods can be used to reduce hyperthermia. Fluid resuscitation and alkalization of urine can help prevent acute renal failure and increase excretion of muscle breakdown products. Dantrolene, amantadine, and bromocriptine have all been used for the treatment of NMS.
D2 receptor blockers
Haloperidol, chlorpromazine, and fluphenazine are typical antipsychotics that act by blocking dopamine D2 receptors
Metformin vs. Sulfonureas in renal dysfx
Glimepiride is a second-generation sulfonylurea that undergoes hepatic clearance and is safer to use in patients with renal dysfunction than metformin.
Sulfonylureas are indicated in patients with type 2 diabetes when their diabetes cannot be controlled with metformin, diet and exercise alone.
Metformin should not be used in patients with renal insufficiency, heart failure, conditions predisposing to hypoxemia, or lactic acidosis.
Treatment for hypertriglyceridemia
Three classes of medications are used to manage major elevations in triglycerides: fibric acid derivatives, niacin, and omega-3 fatty acids. Statins are often given concomitantly, although they are not as effective in lowering triglycerides.
Niacin decreases hepatic VLDL and LDL production, inhibits adipose tissue lipolysis, increases lipoprotein lipase activity, and prevents (to some degree) hepatic triglyceride esterification. High dose niacin can decrease triglyceride levels by at least 40% and can raise HDL-c levels by 40% or more. It can also significantly lower LDL-c levels.
Niacin side effects
Facial flushing is the most common side effect associated with niacin and occurs in almost 90% of patients. This symptom is the primary reason for patient noncompliance.
Aspirin can be used to alleviate the severity and duration of the flushing symptom associated with niacin therapy.
Paclitaxel inhibits mitosis by binding tubulin and preventing degradation of microtubules. This agent is used in the treatment of ovarian cancer, breast cancer, and non-small cell lung cancer. Bone marrow suppression, alopecia, and hypersensitivity reactions are the most common toxic effects seen with paclitaxel.
Etoposide is a topoisomerase inhibitor used in the treatment of testicular cancer, small cell lung carcinoma, and acute myelogenous leukemia. Myelosuppression is the dose-limiting toxicity associated with this agent.
Cytarabine is an antineoplastic used for acute myelogenous leukemia (AML).
Its mechanism of action is to inhibit DNA polymerase.
Cytarabine causes anemia, leukopenia, thrombocytopenia, and megaloblastosis.