Pharmacology

Naloxone

-short acting opioid receptor antagonist and creates affinity to mu receptors (mediate opioid induced bradycardia and respiratory depression) -treats ACUTE opioid overdose that leads to sedation with respiratory suppression, miosis(constriction of pupil), decreased bowel sounds. Naloxone is a potent opiate antagonist that is used intravenously for treatment of life-threatening overdose. It is not active when taken in its oral/sublingual form, so it is often delivered in a combined tablet with buprenorphine in order to prevent the drug from abused by being injected intravenously.

Steady-state equilibrium

-this state is reached at approximately 4-5 half-lives. -Half-life can be quickly calculated by using the rounded equation: T1/2 = (0.7xVd)/CL

Niacin (Vitamin B3)

-used to lower triglyceride levels and raise HDL levels. -Its major side effect is cutaneous flushing, usually of the face and arms. -Flushing may be accompanied by pruritus, mediated by prostaglandins. -Decreases the secretion of VLDL by hepatocytes and preventing lipolysis in adipose tissue. Niacin is a lipid-lowering medication that has a very common adverse effect of facial and upper body flushing. This flushing is a direct result of prostaglandin release. To prevent this common and uncomfortable effect, patients can take acetylsalicylic acid to inhibit prostaglandin synthesis.

Cyproheptadine ($)

-used to treat Serotonergic overdose that leads to serotonin syndrome: AMS, mydriases, sympathetic hyperactivity, hyperreflexia/clonus

Lidocaine (Class 1B)

-weakly blocks sodium channels and preferentially slows depolarization in ischemic tissue. -binds to inactivated sodium channels and rapidly dissociates -The most common adverse effects involve the central nervous system (CNS)

SGLT2 and renal hyperfiltration

-will cause reduction in GFR hyperfiltration

Opiates MOA

1) Opiate agonists exert analgesic and other effects via binding to mu opioid receptors Binding causes decreased release of neurotransmitters such as Ach, NE, Glutamate, substance P and serotonin (via Ca channels) 2) Hyperpolarizes postsynaptic membranes to prevent response to painful neurotransmitters

Interferons

1. Alpha -treats hepatitis B and C infections -treats malignant melanoma and hairy cell leukemia -treats Kaposi sarcoma caused by HHV8 -treats condyloma accuminata caused by HPV -treats renal cell carcinoma 2. Beta -treats multiple sclerosis 3. Gamma -treats chronic granulomatous disease (CGD) -Glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antihumoral properties. *Immunomodulatory cytokines -Side effects: Flu-like symptoms, depression, neutropenia, myopathy

TMP/SMX MOA

1. Block DHFR -TMP (bacteria) -MTX (humans) -Pyrimethamine (protozoa) 2. Competes with PABA to inhibit dihydropteroate synthetase -Sulfamethoxazole

Dopamine agonist

1. Bromocriptine = Ergot compounds 2. Pramipexoles and Ropinrole = Nonergot compounds

Etanercept

-Mechanism: fusion protein (receptor for TNF-α + IgG1 Fc), produced by recombinant DNA. -Etanercept is reduces the activity of TNF alpha by acting as a soluble receptor decoy protein --keeps TNF alpha away from TNF alpha receptor -used when methotrexate therapy fails alone -Use: rheumatoid arthritis, psoriasis, ankylosing spondylitis

Tamoxifen

-SERM -Antagonist on breast tissue via inhibiting estrogen effects on breast tissue; used to treat and prevent recurrence of ER-positive breast cancer --Estrogen or progesterone receptor positive -It acts as a partial agonist on the endometrium, resulting in an increased risk of endometrial hyperplasia, polyps, and cancer. -prevents osteoporosis -reduce risk of gynecomastia in males

Cyanide poisoning

-cherry red skin color, AMS, seizure, cardiovascular collapse, lactic acidosis and bright red venous blood -via nitroprusside infusion *Tx (3): 1.Hydrocycobalamin (Vit B12 precursor) -via direct binding of cyanide ions 2. Sodium nitrate -induction of methemglobinemia 3. Sodium thiosulfate -detoxifying sulfur donors

highly active antiretroviral therapy (HAART)

-commonly associated with body fat redistribution -subcutaneous lipoatrophy involving face and extremities is associated with NRTI (zidovudine and stavudine) and protease inhibitors -central fat accumulation occurs with any HAART regimen

Alcohol withdrawal

-considered in hospital pt's who develop tremulousness, agitation and elevated pulse and blood pressure within 48 hrs following admission. -Benzodiazepines act as substitute for the effects of alcohol and GABA receptors, preventing alcohol withdrawal from occurring

Hydralazine

-first-line therapy for hypertension in pregnancy. -It is also known to cause drug-induced lupus, which may present as myalgias, arthralgias, lymphadenopathy, purpura, erythema nodosum, fever, and positive anti-histone antibodies

MOA of immunosuppressants

1. Calcineurin is a protein phosphatase that is essential in the activation of IL-2, which promotes the growth and differentiation of T cells (Cyclosporin(binds cyclophilin) and Tacrolimus(binds FK506) MOA is inhibiting calcineurin activation) -increase risk of nephrotoxicity 2. Sirolimus (mTOR inhibitor) binds to FKBP in the cytoplasm forming a complex that inhibits mTOR -inhibition of mTOR signaling blocks IL-2 signal transduction and cell cycle progression and lymphocyte proliferation -can lead to pancytopenia but not nephrotoxic The most common induction therapy for anti-rejection after organ transplantation is a combination of prednisone, mycophenalate mofetil and a calcineurin inhibitor. (e.g., cyclosporin or tacrolimus).

Cocaine & blockers of catecholamine neurotransmitter release

1. Cocaine -inhibit presynaptic reuptake of norepi, DA and serotonin -will have light responsive mydriasis -potent vasoconstrictor that can cause MI and atrophy of nasal mucosa and septum 2. Metyrosine -blocks rate limiting step of catecholamine synthesis (tyrosine hydroxylase) 3. Reserpine (no longer in use) -block monoamine entry into presynaptic vesicles resulting in sympatholytic effects 4. COMT -found in brain and liver -Entacapone and tolcapone are COMT inhibitors used to prolong the effects of levodopa tx in parkinson's

Insulin synthesis and secretion

2 peptide chains (A and B) connected by 2 disulfide bonds precursor = preproinsulin- made form ribosomes and enters ER of Beta cells, cleaved to form proinsulin transported with C chain to Golgi to be vesicilizedanti

Cephalosporins

A. Generation 1--gram + and also PEcK (Proteus mirablisi, E. coli, Klebsiella) -Cefazolin & Cephalexin B. Generation 2--gram + and also HENS PEcKS (H. influenza, Enterobacter, Neisseira, Serratia, Proteus mirablisi, E. coli, Klebsiella) -ceFAclor, ceFOXitin, ceFURoxime, and cefoTEtan -"2nd graders wear FAke FOX FUR to TEa parties" C. Generation 3--serious gram negative infections Ceftriaxone--gonorrhea and meningitis Ceftazidime--Pseudomonas D. Generation 4--Cefepime, both gram + and serious gram negative infections SE = disulfiram-like reaction with EtOH; hypersensitivity rxn (10% of those allergic to penicillin will get this) *mechanism of resistance via structural change in penicillin binding proteins

Beta-Lactamase inhibitors

"CAST -Clavulanic acid -Avibactam -Sulbactam -Tazobactam *Given with amoxicillin expands amoxicillin's spectrum of activity to include strains of Beta-lactamase synthesizing bacteria that are resistant to amoxicillin alone *Amoxicillin has greater oral bioavailability

Carbapenems

"DIME" Doripenem Imipenem Meropenem Ertapenem *always given with cilastatin ( inhibitor of dehydropeptidase I) to decrease inactivation of drug in renal tubules -adverse effects = GI distress, seizures and rash

Metronidazole

-free radical metabolites disrupt bacterial DNA (bactericidal) -coverage of polymicrobial anaerobic infections (e.g. intra-abdominal infections) Side Effects: Concurrent ingestion of alcohol results in a disulfiram-like reaction (flushing, tachycardia, palpitations, nausea, vomiting Treats: -Entamoeba histolytica -Giardia -vaginitis and cervicitis caused by Trichomonas -bacterial vaginosis caused by Gardnerella -substitute for amoxicillin in the triple therapy for Helicobacter pylori infection in penecillin-allergic patients -anaerobic bacteria (e.g. Bacteroides, Prevotella, Fusobacterium, Clostridium -pseudomembraneous colitis caused by Clostridium difficile Metronidazole is a commonly used drug that interacts with bacterial DNA causing cell death. It is used for the treatment of trichomoniasis, pseudomembranous colitis, amebiasis, giardiasis, H. pylori, and Gardnerella vaginosis. Commonly tested adverse reactions are metallic taste, disulfiram-like reaction (make sure patient avoids alcohol), and dark urine.

Arsenic Poisoning

-garlic odor via insecticides and contaminated water source *Tx:Dimerecaprol (chelating agent)

Sulfonylureas

-glipizide, glyburide, glimepiride -stimulate insulin release from pancreatic beta cells, by inhibiting beta cell potassium ATP channels -side effects are hypoglycemia and weight gain

loratidine, cetirizine (2nd generation antihistamines)

-have minimal side effects -less lipophilic, do not cross BBB and not sedating

1st generation antihistamines

-ie. Diphenhydramine, Chlorpheniramine, Promethazine, Hydroxyzine -can cause significant side effects due to blockade of cholinergic(can cause blurring of vision via effects on ocular ciliary muscles), alpha-adrenergic, and sertonergic pathways *avoided in older patients with cognitive/functional impairments

Direct-acting antiviral agents (DAA)

-inhibit viral replication and assembly *ledipasvir, simeprevir and sofosbuvir

Aminoglycosides (GNATS)

-irreverisble inhibitors of 30s ribosomal subunit -bactericidal -coupled with cell wall active drugs (beta-lactams, vancomysin) ototoxicity, Renal toxicity(via Proximal Tubule), neruomucular blockade and teratogen, Can't take with PCN at all! - gentamicin, neomycin, amikacin, tobramycin and streptomycin --neomycin and paromomycin active in GI tract --streptomycin trats franciella and yersinia pestis -inhibit genetic code reading and protein synthesis by binding to the prokaryotic 30s ribosomal subunit *mechanism of resistance via bacterial transferases enzymes inactivate the drug by acetylation, phosphorylation or adenylation

Methadone

-is a Potent long acting opioid agonist used in the maintenance treatment of opioid use disorder -its prolong affects suppress withdrawal symptoms and cravings

Celecoxib

-is a selective COX-2 inhibitor that provides anti-inflammatory benefits without interfering with the physiological functions of COX-1 -relieve pain with lower risk of bleeding and gastric ulceration than nonselective NSAIDS -Selective COX-2 inhibition is associated with an increased incidence of thrombosis

Haloperidol

-is a typical antipsychotic. -Hyperprolactinemia causing lactation is a common side-effect due to its dopamine antagonist effects. -cna treat delirium when nonpharmalogical interventions are ineffective

Donepezil, rivastigmine and galantamine

-is an acetylcholinesterase inhibitor used particularly for Alzheimer's disease. -It blocks the metabolism of acetylcholine at the synapse. *Also causes enhanced PNS tone that can lead to bradycardia, AV blocks and syncope -Catabolism is the breakdown of complex molecules while anabolism is the synthesis of complex molecules

Propofol

-lipophilic GABA agonist that reduces airway resistance disadvantage is vasodilation-->hypotension -Used for sedation in ICU, rapid anesthesia induction, short procedures. Less postoperative nausea than thiopental. Potentiates GABA-A

Oseltamivir

-neuraminidase inhibitor that prevent the release of newly formed virions from infected host cells and impairs penetration of mucous secretion that overlie the resp. epithelium -Tx for Influenza A & B

Varenicline

-partial agonist of nicotinic acetylcholine receptors -Smoking cessation

Direct Oral Anticoagulants (DOACs) vs Warfarin

-rivaroxaban is a DOACs and is unaffected by dietary changes, and does not require monitoring -warfarin is a Vitamin K antagonist

ACE inhibitors

"PRIL" Captopril, Enalapril, Afosiopril -Antihypertensive. Blocks ACE in lungs from converting angiotensin I to angiotensin II preferentially constricts the efferent arteriole, there by maintaining the GFR, can lead to GFR reduction (powerful vasoconstrictor). BUT, "BLANK" will cause efferent vasodilation(BAD in bilateral renal artery stenosis) *COUGH VIA ACCUMULATION OF BRADYKININ, SUBSTANCE P OR PROSTAGLANDINS -Decreases BP, Enhancement of adrenal aldosterone secretion, Sodium and fluid loss. Check BP before giving (hypotension) , can cause significant first-dose hypotension in pt's with volume depletion or heart failure *Orthostatic Hypotension -Contraindicated in pregnancy, bilateral renal artery stenosis, CHF

Physostigmine

-Anticholinesterse inhibitor - increases ACh -Used in anticholinergic toxicity (Its mechanism is to prevent the hydrolysis of acetylcholine by acetylcholinesterase at the transmitted sites of acetylcholine. This inhibition enhances the effect of acetylcholine, making it useful for the treatment of cholinergic disorders and myasthenia gravis) -Crosses the blood-brain barrier (CNS) -used to treat anticholinergic overdose(atropine overdose) that leads to agitated delirium with sympathetic hyperactivity, mydriasis, dry skin/mucous membranes, urinary retention

Tetracycline

-Bacteriostatic (inhibit translation) -Bind to 30S and prevent attachment of aminoacyl-tRNA, there fore inhibiting protein synthesis -Limited CNS penetration -Doxycycline is fecally eliminated and can be used in patients with renal failure. -Do not take tetracyclines with milk (Ca2+), antacids (Ca2+ or Mg2+), or iron-containing preparations because divalent cations inhibit drugs absorption in the gut *Adverse effects: -Gl distress (esophagitis) -discoloration of teeth (children) -inhibition of bone growth in children, -photosensitivity -Contraindicated in pregnancy *mechanism of resistance = decrease uptake or increase efflux out of bacterial cells by plasmid-encoded transport pumps.

Lithium

-Bipolar disorder is treated with a mood stabilizer such as lithium. -Lithium also acts as an ADH antagonist and can cause nephrogenic diabetes insipidus, which commonly presents with polyuria, dilute urine, and intense thirst

Clindamycin

-Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic. -Anaerobic infections (e.g., Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections. Also effective against invasive group A streptococcal infection. -Treats anaerobic infections above the diaphragm vs. metronidazole (anaerobic infections below diaphragm) -Toxicity: pseudomembranous colitis (C. difficile -overgrowth), fever, diarrhea

Chloramphenicol

-Blocks peptidyltransferase at 50S ribosomal subunit. -Bacteriostatic. -Use: Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and Rocky Mountain spotted fever (Rickettsia rickettsii). Limited use owing to toxicities but often still used in developing countries because of low cost. -Toxicity: anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase). -Resistance: plasmid-encoded acetyltransferase inactivates the drug.

PCP intoxication

-MOA: NMDA antagonist -Belligerence, impulsivity, fever, psychomotor agitation, analgesia, vertical and horizontal nystagmus, tachycardia, homicidality, psychosis, delirium, seizures. Treatment: benzodiazepines, rapid-acting antipsychotic PCP intoxication causes impulsiveness, psychosis, violent behavior, hypertension, tachycardia, and agitation. Another KEY association with PCP intoxication on test day is nystagmus (horizontal, vertical, or rotary).

Antichloinergics

Acute dystonic manifestations are treated with anticholinergics such as diphenhydramine or benztropine, that counteract the loss of dopamine with acetylcholine excess via M1 receptor blockers.

Common Antiemetics meds

Acute phase is mediated via serotonin Delayed phase is mediated via substance P that activates neurokinin-1

Salicylate intoxication ($)

After an acute salicylate overdose patients typically present to the hospital with a mixed Primary respiratory alkalosis and anion gap metabolic acidosis. Prolonged exposure to high doses of salicylates leads to depression of the medulla, with central respiratory depression and circulatory collapse. Respiratory failure is the usual cause of death. Tx: Sodium bicarbonate -conversion to the lipophobic ionized salicylate, that traps much of the compound in the blood stream and increases its urinary excretion

Bisphosphonates

Alendorate and risendorate -MOA: inhibit osteoclast-mediated bone resorption via attaching to hydroxyapatite binding sites on bony surfaces, especially surfaces undergoing active resorption -side effects: --osteonecrosis of the jaw Bisphosphonates are the most appropriate management option for osteoporosis. Osteoporosis is suspected in women above the age of 65 with non-traumatic fractures of the distal extremities or vertebral compression fractures. Bisphosphonates work to reduce fracture risk via the decrease of osteoclastic bone resorption.

Amiodarone

Amiodarone is a potassium channel blocker (class III antiarrhythmic), prolonging the action potential. Amiodarone use is associated with pulmonary fibrosis. Thus, pulmonary function should be assessed regularly and TSH levels Hypo or hyper or destructive

Amphotericin B and Flucytosine

Amphotericin B (right side of image): -amphotericin and nystatin bind ergosterol to form holes in the fungal cell membrane -amphotericin treats severe systemic fungal infections -amphotericin toxicity results from non-selective binding to mammalian cholesterol membranes -intrathecal administration of amphotericin to treat fungal CNS infections Side Effects: -hypotension, headache, fever, chills, and thrombophlebitis are immediate infusion-related toxicities & NEPHROTOXICITY -Type 1 RTA via cumulative toxicity-->hypokalemia can cause weakness and arrhtmias -can cause hypomagnesemia (due to renal magnesium wasting) Flucytosine (left side of image): -cytosine deaminase in fungal cells converts flucytosine (a fluorinated cytosine) into 5-fluorouracil (5-FU) -flucytosine halts fungal DNA and RNA synthesis *flucytosine and amphotericin combo treats cryptococcal meningitis Nystatin (outside window): -same mechanism of action as amphotericin B -treats Candida infections (candidiasis) -topical nystatin treats mucocutaneous candidiasis (e.g. vaginal candidiasis) -oral nystatin rinse treats oropharyngeal candidiasis

Drug-induced lupus

Anti-histone antibodies Having lupus is Mega "SHIPP-E" Methyldopa Sulfonamides Hydralazine Isoniazid Procainamide Phenytoin Etanercept

Clopidogrel

Antiplatelet -blocks release of ADP into circulation that inhibits activation of other platelets

Organophosphate poisoning/Cholinesterase inhibitor poisoning ($)

DUMBBELSS: Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle, Lacrimation, Sweating, and Salivation. -Essentially makes you very LEAKY. -Caused by Parathion and Organophosphates. Tx with Atropine (Competitive inhibitor, does not block excitation to skeletal muscle because skeletal muscle has NM not NN receptors) and Pralidoxime (regenerates AChE)

Glucocorticoids

Decreased pro-inflammatory cytokine (IL-1, interferon gamma) production, increase anti inflammatory cytokine (Il-10) production and impaired migration of leukocytes (neutrophils) to sites of inflammation

essential tremor (ET)

First-line treatments for "BLANK" include the anticonvulsant primidone and the beta-blocker propranolol. Both medications decrease the amplitude of the tremors, which can improve someone's ability to perform tasks. Primidone, a phenobarbital analog, may cause increased sedation and emotional disinhibition. Someone who has both hypertension and ET may benefit from use of beta-blocker therapy if he or she is not at risk for symptomatic bradycardia with use.

Conivaptan (-Vaptan)

In hyponatremic SIADH patients requiring medical therapy, the drug of choice is a vasopressin receptor antagonist such as conivaptan

Indapamide

Indapamide is a thiazide diuretic. It has the same mechanism as chlorthalidone. One notable difference is that indapamide does not seem to cause hyperlipidemia.

Alemtuzumab target

CD52 antigen (CLL or MS)

SGLT2 inhibitors

Canagliflozin Dapagliflozin

Deferoxamine

Chelator: bacterial product; chelates iron very avidly, aluminum less so -should be given to pt's receiving chronic RBC transfusions -prevents iron-induced cardiotoxicity and CHF from developing

Bosentan

MOA: Competitively inhibits endothilin-1 receptors thus decreasing pulmonary vascular resistance. (Endothelin vasoconstricts). Clinical Use: Pulmonary HTN Toxicity: Hepatotoxicity (Monitor LFTs)

Trastuzumab

Monoclonal for Breast cancer with HER2(tyrosine kinase receptor) -prevents activation of tyrosine kinase receptor

Etoposide

Prevents Topoisomerase II from sealing the double-stranded DNA breaks it has made

Mifepristone

Progesterone, initially produced by the corpus luteum of the ovary, is required to support the endometrium and sustain pregnancy. "BLANK" antagonizes the intracellular progesterone receptor, and thus leads to breakdown of the endometrium and detachment of the developing blastocyst. It also removes the inhibition of progesterone on the uterine muscle, leading to uterine contractions and causing expulsion of the endometrium.

Azathioprine Metabolism

Reduced function of xanthine oxidase or thiopurine methyltransferase causes increased levels of 6-MP leading to increased immunosuppression and risk of toxicity

Photosensitivity drugs

Sulfonamides, Amiodarone, Tetracyclines, 5-FU SAT For a Photo

TMP/SMX

TMP: Block DHFR SMX: Competes with PABA to inhibit dihydropteroate synthetase Side effects: -Pancytopenia -Megaloblastic anemia -Teratogen in 1st trimester -Sulfa allergy -Hemolytic anemia in G6PD def -Steven-Johnson syndrome -Type 4 RTA-->hyperkalemia -Photosensitivity -Kerniterus in neonate (last month of pregnancy) -sulfa displace albumin and warfarin(increasing its effects) -inhibition of P450 -drug induced lups Treats: 1. UTI 2. Acute prostatitis 3. Nocardia 4. Pneumocystis jirovecii 5. Prophylaxis against Toxoplasmosis gondii

Drugs that cause hyperglycemia

Tacrolimus, Protease inhibitors, Niacin, HCTZ, Corticosteroids These People Need Hard Candies

Abacavir (NRTI)

Usage: HIV Contraindication: allergy, test positive for "HLA-B*57:01"

Red Man Syndrome

What might happen if you infuse vancomycin too fast? -non allergic drug reaction

irreversible inhibition

active site is made unavailable for prolonged period of time or enzyme is permanently altered -DECREASES Vmax

Toxic Alcohols

all increase the osmolar gap Fomepizole is a competitive inhibitor of alochol dehydrogenase, ethanol - prevents further breakdown of the ethylene glycol Sodium bicarbonate help alleviate the acidosis hemodialysis might be required

Tamulosin

an alpha-1 antagonist. It is commonly used in the treatment of BPH.

Bleomycin

an anti-cancer drug known to have pulmonary fibrosis as a major side effect

Colestipol, together with cholestyramine and colesevelam

are bile acid sequestrants primarily used for isolated increases in low-density lipoproteins (LDL). These drugs bind to bile causing an increase in hepatic synthesis of bile acids from cholesterol. The adverse effects of these drugs are mostly gastrointestinal in nature (constipation, bloating, abdominal pain, elevated liver enzymes, flatulence, and heartburn). They also impair the absorption of fat-soluble vitamins (A, D, E, K)

Amphetamines

are central nervous system (CNS) stimulants. Patients with methamphetamine intoxication present with signs and symptoms of stimulation: agitation, increased alertness, bruxism (grinding teeth), euphoria, diaphoresis, mydriasis (dilated pupils), confusion, anorexia, tachycardia, hypertension, and fever.

Cholinomimetics

are indicated in non-obstructive urinary retention (atonic bladder), parayltic ileus, and glaucoma. their side effects include nausea, vomitting, abdominal cramps, diarrhea, dyspnea and INCREASED SECRETIONS (lacrimation, sweating, and salvation). If you just think of Cholinergic agnonists as increasing fluid secretions- things can make sense.

Class 1A antiarrhythmics (Quinidine, Procainamide & Disopyramide)

are sodium channel-blocking agents that depress phase 0 depolarization. They also prolong repolarization due to moderate potassium channel-blocking activity, increasing action potential duration in cardiac myocytes.

Chlorthalidone and Metolazone

are thiazide diuretic. It inhibits the Na+/Cl- transporter in the distal convoluted tubule. Thiazide diuretics commonly cause hypokalemia, hypercalcemia, hyperglycemia, hyperlipidemia, and hyperuricemia.

Bioavailability

area under the oral curve divided by area under the IV curve Bioavaialability = FRACTION of administered drug that reaches systemic circulation in a chemically changed form F = (area under oral curve * IV dose) / (area under IV curve * oral dose) What factors affect oral bioavailability -gastric acidity & motility -capability of drug to be absorbed by gut -presence of material such as food or other drugs in gut -first-pass metabolism by liver

Anastrozole

aromatase inhibitor - Blocks the conversion to active estrogen/androgen/corticosteroid/mineralcorticoid to reduce cell growth in breast, prostate and/or adrenal cancer. -These agents are approved for post-menopausal women and are not-fda approved for men with breast cancer.

Opioids i.e oxy, morphine, methadone, heroin, Peres, happy pills

attach themselves to the opioid receptors, mimicking the endogenous opioids within the brain. Patients experience analgesia due to the interruption of the transmission of the pain signal from the peripheral nerve to the CNS. In addition, the opioid triggers the release of dopamine, causing a sense of euphoria. Patients present with a decreased respiratory rate, decreased oxygenation and increased carbon dioxide, miotic pupils, decreased gastrointestinal function (fewer bowel sounds), and depressed mental status. Severe hypoxia and decreased respiratory drive can lead to acidosis and cardiac arrest. Opioid withdrawal will present with agitation, diaphoresis, mydriasis, and increased gastrointestinal motility (diarrhea and/or vomiting).

Antibiotics that inhibit cell wall synthesis

beta-lactams/ penicillin vancomycin fosfomycin Cephalosporins (ie cefuroxime)

Cyclosporine

binds to cyclophilins inhibiting calcineurin -used to suppress organ rejection after transplant surgeries. This drug can cause nephrotoxicity, hirsutism, and gingival hyperplasia.

Combination oral contraceptives

contain both estrogen (eg, ​ethinyl estradiol) and progesterone (progestin). Estrogen decreases the secretion of follicle stimulating hormone (FSH), and progesterone suppresses the surge of luteinizing hormone (LH); these effects result in inhibition of ovulation. In addition, progestins promote viscous cervical mucus, which deters sperm penetration, and they inhibit endometrial proliferation. Combination oral contraceptives reduce the risk of ovarian and endometrial cancer. The mechanism is thought to be a decrease in the number of lifetime ovulations a woman has, which decreases the amount of cumulative tissue disruption and repair that occurs with ovulation (an environment ripe for malignant transformation).

Beers Criteria

developed to identify drugs requiring caution in geriatric patients. Common drugs to avoid include anticholinergics (eg. First-generation antihistamines), alpha blockers, tricyclic antidepressants, benzodiazepines (and other sedating medications), antipsychotics, most anti arrhythmic, and skeletal relaxants.

Motion sickness presents with

dizziness, nausea, and vomiting that only occurs while a patient is in motion. Look for complaints of symptoms on boats, public transportation, and long car rides. A test favorite scenario is a child who is getting sick in the morning on the way to school with no other symptoms (motion sickness on the school bus). Motion sickness can be prevented with scopolamine, a muscarinic antagonist.

Siladenafil ($)

drug of choice for erectile dysfunction; it inhibits phosphodiesterase-5, thus increasing cGMP to promote erection

TNF-alpha inhibitors

etanercept adalimumab infliximab certolizumab -impairs cell mediated immunity -all patients begining treatment with with "BLANK" should be evaluated for latent TB.

Azoles

ie. Clotrimazole, fluconazole, isavuconazole, itraconazole, ketoconazole, miconazole, voriconazole. Inhibit fungal sterol (ergosterol) synthesis by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol. Side effects: Testosterone synthesis inhibition (gynecomastia, especially with ketoconazole), liver dysfunction (inhibits cytochrome P-450).

NSAIDs

ie. Diclofenac, Naproxen, ibuprofen and indomethacin -reversibly inhibit COX-1 and COX-2

Corticosteroid side effects

increased neutrophil via demarginantion

Pioglitazone

increases the sensitivity of tissues to insulin by increasing the transcription of insulin responsive genes. It can cause weight gain, edema, hepatotoxicity, and cardiovascular toxicity.

Paclitaxel

is a cytotoxic agent in the taxane category. The taxanes (docetaxel is the other to remember) act by binding to cellular beta tubulin, stabilizing it and preventing disassembly of microtubules. This has the effect of arresting the cell in mitosis. is useful for treatment of metastatic ovarian, breast, lung, GI, genitourinary, and head and neck cancers. It is also used in the treatment of Kaposi sarcoma, a malignant skin disorder associated with infection with human herpes virus-8. In the U.S., Kaposi sarcoma is seen primarily in AIDS patients and presents with violaceous plaques. The primary adverse effects of taxanes are neutropenia and neuropathy.

Mannitol

is a diuretic that is used in trauma to reduce intracranial pressure and cerebral edema. Signs of elevated intracranial pressure are papilledema, dilated pupils, and Cushing's triad (hypertension, bradycardia, and irregular breathing).

Leucovorin

is a folic acid analogue that is given as an adjunct therapy to enhance the chemotherapeutic activity of 5-fluorouracil (5-FU). 5-FU is a commonly prescribed chemotherapy agent used in the treatment of colorectal cancer.

Atropine

is a muscarinic antagonist that competitively inhibits acetylcholine receptors. Atropine is clinically useful to treat sinus bradycardia. Atropine toxicity results in dilated pupils (blurred vision), dry flushed skin, confusion, nausea, and dizziness.

Propanolol

is a nonselective beta blocker and may cause bronchospasm through its antagonist activity at beta-2 receptors Treats essential tremor

Ketorolac

is a nonsteroidal anti-inflammatory drug (NSAID) that is commonly administered parenterally/IV for post-operative pain.

Buprenorphine

is a partial opioid receptor agonist that binds with high affinity but has low intrinsic activity. -less likely to cause respiratory depression and mortality in overdose compared to methadone -In pt's on long-term opioid therapy, buprenorphine can displace other opioids and precipitate withdrawal.

5-Flurouracil (5-FU)

is a thymidylate synthetase inhibitor that disrupts DNA synthesis and repair. It is used to treat solid organ cancers especially colorectal cancer. The most important adverse effect of 5-FU is myelosuppression. It is often given with leucovorin to enhance its activity.

opioid overdose

is characterized by altered level of consciousness, pinpoint pupils, and central respiratory depression. Pt's are expected to have acute respiratory acidosis (low pH, high PaCO2) due to hypoventilation. Serum bicarbonate is typically near normal as there is not time for metabolic compensation in the acute setting. -TX is Naloxone Opiate intoxication produces a typical triad of pupillary constriction, respiratory depression, and coma. Naloxone is a competitive antagonist at the opioid receptor. This is used to decrease the potency of the drug, making sure that the amount of drug needed to achieve the maximally effective concentration is increased.

Inhibition of adenosine diphosphate receptors

is the mechanism of action of the anti-platelet drugs clopidogrel, ticlopidine, and prasugrel. Ticlopidine is associated with neutropenia and can place patients at risk of developing severe infections and sepsis.

Hypericum (St. John's Wort)

is used for mild to moderate depression and is probably the most tested herbal supplement. It induces the cytochrome P450 metabolism and can decrease the efficacy of other drugs subject to the CYP system that are given along with it.

Enoxaparin

low molecular weight heparin and binds and activates antithrombin 3. AT3 binds to factor Xa and stops factor Xa from converting prothrombin into thrombin. -preferred therapy, with patients transitioned to unfractionated heparin at term

antiarrhythmic

minus 1A

Gylcopyrrolate

muscarinic receptor antagonist

Patiromer therpy

nonabsorbable cation exchange resin used to treat hyperkalemia -binds to colonic potassium in exchange for calcium, trapping potassium with the resin where it is then excreted in the feces.

Naltrexone

opioid antagonist that is a first -line pharmacotherapy for moderate-to-severe alcohol use disorder, and works by preventing the reinforcing effects for alcohol use -Opioid Overdose

Diphenoxylate

opioid antidiarrheal that binds to mu opiate receptors in the gut to slow motility

Sevelamer

phosphate binder, decreases phosphate levels in GI tract for dialysis (CKD) -non-absorbable anion-exchange resin that binds intestinal phosphate to reduce absorption

Gemfibrozil (Fibrate)

reduce TG (X2) cholesterol solubility and promote gallstone formation by reducing bile acid synthesis via cholesterol 7-alpha-hydroxylase.

alpha 1 selective antagonist

reduces arteriolar resistance and increases venous capacitance, causing reflex tachycardia and may cause postural hypotension.

Arteriovenous concentration gradient

reflects the overall tissue solubility of an anesthetic. Anesthetic with high tissue solubility are characterized by large arteriovenous concentration gradients and slower onsets of action.

Clomiphine

selective estrogen receptor modulator, inhibits negative feedback on gonadotropins (FSH and LH) used to treat anovulation in the setting of PCOS *causes Hot flashes -SERM's --tamoxifen --Clomiphene --raloxifene

Pyridoxine (Vitamin B6)

should be taken by patients who are taking isoniazid to help prevent peripheral neuropathy

Penicillin

structurally similar to D-alanine- D-alanine, inhibit transpeptidase by binding covalently to it active site -result in failed synthesis of the bacterial peptidoglycan cell wall

competitive inhibition

substance that resembles the normal substrate competes with the substrate for the active site -INCREASES Km = lower affinity of enzyme for its substrate *Competitive inhibitors Cross each other, where as noncompetitive inhibitors do not *Kompetitve inhibitors increase Km

Effects of Desmopressin therapy

synthetic analog of vasopressin

Interleukin-2

treatment of renal cell carcinoma

Imantinib

tyrosine kinase inhibitor, binds to fusion protein bcr-abl (constitutively active cytoplasmic tyrosine kinase) and prevents activity, effective against chronic myeloid leukemia

A well-known side effect of anesthesia is

urinary retention. This can be treated with muscarinic receptor agonists to stimulate the parasympathetic nervous system. Bethanechol, a muscarinic receptor agonist, is the primary drug used in urinary retention caused by anesthesia. By stimulating the muscarinic receptors in the bladder, this drug stimulates the micturition reflex and causes contraction of the smooth muscles of the bladder.

Malignant hyperthermia

via inhalation anesthetics and/or succinylcholine to genetically susceptible individuals -causes unregulated passage of calcium from the sarcoplasmic reticulum into the intracellular space-->hypercarbia, hyperthermia and acidosis

Monoclonal Antibodies (mAbs)

-blocks deleterious receptor interactions or triggering cytotoxic immune response -no eliminated hepatically or renally

Metformin

-can have weight loss

Catopril

ACE-inhibitors, such as captopril, have been shown to improve survival in post-MI patients due to their ability to reduce the detrimental remodelling process of the heart that occurs after a myocardial infarction.

Infliximab

"Inflicts pain on TNFalpha" Really very similar to Etanercept, but this actually binds TNF alpha itself Chimeric aby that binds TNFa-->inhibits binding of TNFa with its receptor-->decreased other cytokines released-->anti-inflammation Uses = autoimmune diseases (RA, IBD, etc) SE = increased infection susceptibility (antidrug anitbodies can develop against them, that can block it interaction with TNF-alpha, preventing drug from functioning and leading to more rapid drug clearance) *Before starting infliximab on a person with rheumatoid arthritis, one needs to rule out latent tuberculosis infection.*

Protease inhibitors

"Navir tease a protease" MOA: stops cleavage of HIV polypeptide into functional parts, thus preventing maturation of new viruses Clinical use: HIV POL gene codes for production of HIV enzymes (e.g. protease) Toxicity: -hyperglycemia, GI intolerance, lipodystrophy (buffalo hump); nephropathy, hematuria (indinavir) -Ritonavir inhibits P450 enzymes *simeprevir

Common antibiotic resistance mechanisms

*Carbapenems are treatment of choice for ESBL-producing organisms

train of four stimulation

- 4 successive 200 microsecond stimuli in 2 seconds (2 Hz) - twitches progressively fade as non-depolarizing muscle relaxant block increases - the ratio of the responses to the 1st and 4th twitches is a sensitive indicator of non-depolarizing muscle paralysis

lead poisoning

- Increase intake of calcium and iron for the prevention of lead poisoning. - Chelation therapy using CANA2 EDTA

Acetaminophen (Tylenol)

- an analgesic and antipyretic agent that reversibly inhibits COX enzymes (primarily in the central nervous system) -it lacks anti-inflammatory properties due to its weak inhibition of cocks in peripheral tissues

Thiazolidinediones (TZDs)($)

- are peroxisome proliferator-activated receptor gamma (PPARy) agonists causing increase peripheral insulin sensitivity (Increase uptake and utilization of glucose by the peripheral tissues; insulin sensitizers) -(eg pioglitazone) can cause fluid retention, leading to peripheral edema and weight gain. The excess fluid can potentially exacerbate underlying CHF

Alpha-glucosidase inhibitors

-Acrabose -decreases starch and disaccharide absorption in the gut.

Rituximab

-Anti-CD20 antibody that is used in treating symptomatic follicular lymphoma

Pyridostigmine (rid of MG)

-Anticholinesterse - increases ACh -Increases muscle strength -Used in myasthenia gravis (long acting) -Does not penetrate CNS

Amylin Analog

-Pramlintide -Amylin is secreted by the pancreas along with insulin and helps regulate glucose absorption by slowing down gastric emptying

Fluoroquinolones

-Ciprofloxacin, Levofloxacin, Moxifloxacin Resp FQ: Levo and Moxi -treat community acquired pneumonia -treat atypical "walking" pneumonia caused by Mycoplasma pneumoniae -treat atypical "walking" pneumonia caused by Legionella pneumophila -Inhibit bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. Bactericidal. Must not be taken with antacids. Treats: -Gram-negative rods of urinary and GI tracts (including Pseudomonas), Neisseria, *Cipro and Levo treat UTIs via pseudomonas -pyelonephritis -acute pancreatitis -treat gram negative bacterial causes of gastroenteritis (e.g. Shigella, Salmonella, E. coli, Campylobacter -treats gram negative osteomyelitis -treat anthrax caused by Bacillus anthracis Toxicity: -GI upset, superinfections, skin rashes, headache, dizziness. -Contraindicated in pregnant women, nursing mothers, and children < 18 years old due to possible damage to cartilage. -prolong QT interval. -Can cause tendonitis or tendon rupture in people > 60 years old and in patients taking prednisone. -Resistance: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.

Fenoldopam

-Dopamine D1 receptor agonist(G-alpha S)—coronary, peripheral, renal, and splanchnic vasodilation. -Decrease BP, increase natriuresis and renal perfusion. -Hypertensive Emergency TX, esp if pt w/ renal insufficiency

Incretin Mimetics

-Exenatide -has properties similar to glucagon-like-peptide-1

Rasburicase

-Exogenous Urate oxidase that oxidizes uric acid to allantoin for excretion. -Given w/ chemotherapy to avoid tumor lysis syndrome

Medications that increase methadone effect

-Fluconazole, voriconazole, ketoconazoole -Ciprofloxacin, clarithromycin -Cimetidine -Fluvoxamine *CY3A4 inhibitors

Etomidate

-GABA agonist most hemodynamically neutral -can lead to adrenocoritcal suppression -used for anesthesia induction to provide sedation and amnesia -NO ANELGESIC EFFECTS

Budesonide

-Glucocorticoid w/ potent anti-inflammatory activity -Corticosteroids reduce COX-2 expression and decrease the synthesis of arachidonic acid via phospholipase A2 inhibition -reduces inflammation by binding to a cystolic receptor-->translocating into the nucleus and inhibiting pro-inflammatory transcription factors (NFKappa-Beta)

Antifungal targets

-Griseofulvin(Echinocandin) --inhibit synthesis of the polysaccharide glucan, an essential component of the fungal cell wall -Flucytosine -Caspofungin -Amphotericin B & Nystatin bind ergosterol -Azoles inhibit synthesis of ergosterol

Vancomycin

-Inhibits cell wall peptidoglycan formation by binding D-alanine- D-alanine in bacterial pantapeptide peptidoglycan subunits, that prevents transpeptidase from binding to the pentapeptide, thereby inhibitng cell wall cross-linking portion of cell wall precursors. Not susceptible to β-lactamases. -Gram-positive bugs only—serious, multidrug-resistant organisms, including MRSA, S. epidermidis, sensitive Enteroccocus species, and Clostridium difficile (oral dose for pseudomembranous colitis). -Well tolerated in general—but NOT trouble free. Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing—red man syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate) and DRESS syndrome -Resistance occurs in bacteria via amino acid modification of D-ala D-ala to D-alanine- D-lactate. "if you LACk a D-alas (dollars) you cant ride the VAN (vancomycin)."

Ketamine

-NMDA antagonist -can be used for anesthesia induction. -the side effects of increased catecholamine release (bronchodilation) are often exploited in patients with bronchospasm

Phentolamine

-Nonselective α-blocker --> vasodilation -reversible -Give to patients on MAO inhibitors who eat tyramine containing foods -Toxicity: orthostatic hypotension, reflex tachycardia

Phenoxybenzamine

-Nonselective α-blocker = alpha 1 & 2 -Irreversible -Used preoperatively for pheochromocytoma to prevent catecholamine (hypertensive) crisis -Toxicity: orthostatic hypotension, reflex tachycardia

Antidiarrheal agents

-Opioid agonists --Loperamide does not cross BBB -Bulk forming agents -Bismuth subsalicylate -Octreotide Bile acid sequesterants(chloestyramine)

Linezolid

-Oxazolidinone -Inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex. -bacteriostatic -Gram-positive species including MRSA and VRE (Vancomycin Resistant Bacterial). -Toxicity: Bone marrow suppression (especially thrombocytopenia), peripheral neuropathy, serotonin syndrome. -Resistance: Point mutation of ribosomal RNA.

Sulfonamides

-Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine -Inhibit folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase. *Hyperkalemia is a common adverse effect of TMP/SMX via trimethoprim-induced blockade of the sodium channels in the collecting duct -Bacteriostatic (bactericidal when combined with trimethoprim). (Dapsone, used to treat lepromatous leprosy, is a closely related drug that also inhibits folate synthesis.) -Gram-positives, gram-negatives, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI. -Toxicity: Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g., warfarin). -displace warfarin from plasma proteins, thus increasing the anticoagulation effects. (TMP/SMX increases PT by inhibiting the metabolism of warfarin. Both TMP/SMX and warfarin require the P-450 enzyme system, specifically CYP2C9, for metabolism. Since the two drugs compete for binding sites at the CYP2C9 enzymes, neither is able to be metabolized at their normal rates. The displacement of warfarin from the binding sites means that there is an increase in active warfarin in the body, resulting in an increased PT. The higher concentration of free warfarin increases the anticoagulation effects, prolonging the prothrombin time and increasing the INR.) -Resistance: Altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or increased PABA synthesis.

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

-These drugs inhibit DPP-4 from breaking down incretins. -Incretins are responsible for increasing glucose dependent insulin secretion from pancreatic beta cells and decreasing gastric emptying. -Sitagliptin and saxagliptin are examples of DPP-4 inhibitors.

Lithium Toxicity

-Tremor, hypothyroidism, polyuria (causes nephrogenic diabetes insipidus), teratogenesis. -Causes Ebstein anomaly in newborn if taken by pregnant mother. -Narrow therapeutic window requires close monitoring of serum levels. -Almost exclusively excreted by kidneys; most is reabsorbed at PCT with Na+. Thiazide use is implicated in lithium toxicity in bipolar patients.

Serotonin Syndrome ($)

-With any drug that increases 5-HT (e.g., MAO inhibitors, SSRI/SNRIs, TCAs) hyperthermia, confusion, myoclonus, cardiovascular instability, flushing, diarrhea, seizures. -Treatment: cyproheptadine (5-HT2 receptor antagonist).

Methotrexate

-a dihydrofolate reductase inhibitor that decreases THF levels (Increase in Dihydrofolate polyglutamate= intermediate DHF) -inhibits growth of rapidly dividing cells - commonly causes macrocytic anemia in patients if used in 1st trimester of pregnancy *used to treat ectopic pregnancies TX is Leucovorin a folinic acid analog, that does not require the action of dihydrofolate reductase is commonly used to deter the bone marrow suppression caused by this drug *Side effects: -stomatitis (oral lesions) -bone marrow suppression -liver function abnormalities -hepatotoxicity and pulmonary fibrosis

Aspirin (NSAID)

-acetylsalicylic acid -Is a non-steroidal anti-inflammatory drug that irreversibly inhibits COX 1 & 2 enzymes via acetylation -blocks release of TXA2 into circulation that inhibits activation of other platelets

Theophylline intoxication

-adenosine receptor antagonist and indirect adrenergic agent -seizures are the major cause of morbidity and mortality -tachyarrhythmias are the other major concern

Metoclopramide

-anti-emetic drug. It works by blocking dopamine receptors and can have extrapyramidal side effects

Ipratropium

-anticholinergic bronchodilator, that blocks acetylcholine at muscarinic receptors -derivative of atropine -prevents bronchoconstriction and treat Obstructive lung disease and asthma

Flumazenil

-antidote for benzodiazepines -is a benzodiazepine receptor antagonist, decreasing the potency -It can reverse the sedative effects of benzodiazepines related to overdose and procedural sedation with normal vital signs and slurred speech with ataxia.

Benzodiazepines

-bind GABA A receptors, resulting in an increased frequency of chloride channel opening in the presence of GABA. Indications for prescribing include short-term treatment of anxiety disorders, status epilepticus and alcohol withdrawal syndrome. -TX is Flumazenil

Ganciclovir, Valganciclovir, Foscarnet, Cidofovir

1. Ganciclovir -hemorrhages and infiltrates of CMV retinitis -converted to ganciclovir monophosphate by a virus encoded kinase (UL97) 2. Valganciclovir - has better oral bioavailability *ganciclovir and valganciclovir are associated with bone marrow suppression 3. Foscarnet -does not require phosphorylation by the viral kinase - active against ganciclovir or acyclovir resistant HSV, CMV, VZV -may induce renal insufficiency and hypocalcemia, hypomagnesmia, hypokalemia, induce seizure 4.Cidofovir -does not require phosphorylation by the viral kinase - active against acyclovir or ganciclovir resistant HSV, CMV, VZV -is nephrotoxic, leading to proteinuria, azotemia, and metabolic acidosis *cidofovir and foscarnet directly inhibit viral DNA polymerase *probenecid prevents excretion and increases plasma concentrations of many different drugs (e.g. penicillins, methotrexate, NSAIDs)

General Anesthesia

1. Inhaled -desirable effects in CNS -Decrease CO -Increase ICP -Decrease GFR and renal plasma flow -Increase renal vascular resistance

Maraviroc, fusion inhibitors, integrase inhibitors

1. Integrase inhibitors -Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase. -can cause rhabdomyolsis 2. Fusion inhibitors Enfuvirtide -Binds gp41, inhibiting viral entry Enfuvirtide inhibits fusion. 3. Maraviroc -Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120. Maraviroc inhibits docking *gag structural gene codes for virion core proteins (e.g. p24, p7) *env structural gene encodes viral envelope proteins for infiltration (e.g. gp41, gp120)

LAME and "Buy AT 30 and CCEL at 50"

1. Organisms not covered by cephalosporins (LAME) -Listeria Monocytogenes -Atypical pneumonia (chlamydia and mycoplasma) -MRSA -Enterococci 2. "buy AT 30 & CCEL at 50" -30s ribosome --Aminoglycosides --Tetracylcine (Doxycycline) -50s ribosomes --Chloramphenicol --Clindamycin --Erythromycin (Macrolide) --Linezolid

Antihyperlipidemic medications

1. Statins 2. Ezetimibe 3. Bile acid sequestrants 4. Niacin 5. Fibrates 6. Fish oil/omega-3 fatty acids

Antihyperlipidemic Agents ($$$)

1. Statins (3x decrease in LDL, 1x decrease in TG and ^ HDL-HMG-CoA reductase inhibitors(*RATE-LIMITING STEP), decreases production of mevalonate. *Primary and Secondary prevention of cardiovascular events 2. Ezetimibe (2x decrease in LDL variable HDL and TG) prevents cholesterol absorption at SI brush border. 3. Fibrates (3x decrease in TG, 1x decerease in LDL and ^ in HDL) decrease in hepatic VLDL and up-regulates LPL --> ^ TG clearance. Activates PPAR-alpha to induce HDL synthesis. ADE myopathy, cholesterol gallstones (vi inhibition of 7-alpha reductase) 4. Niacin (2x decrease in LDL and HDL and 1x decrease in TG) inhibits lipolysis (HSL) in adipose tissue reduce hepatic VLDL synthesis. 5. PCSK9 inhibitors (3x decrease in LDL, 1 x decrease in TG and ^ in HDL) in activation of LDL receptors degradation --> increasing the amount of LDL removed from blood. 6. Bile acid Sequestrants/binding resins -increase hepatic cholesterol and bile acid synthesis

Medications for weight loss

1. Sympathomimetic amines -phentermine, diethylopropion, benzphentamine -MOA: stimulate CAS 2. Orlistat -MOA: intestinal lipase inhibitor 3. Buproprion/naltrexone -MOA: CAS (antidepressent +opioid antagonist)

Drugs for neuropathic pain

1. TCA 2. Anticonvulsants 3. Opioids 4. Caspaicin (Topical) -depletes substance P -excessive activation of TRPV1 5. Lidocaine (Topical)

Finasteride

5-alpha reductase inhibitor -and inhibits the conversion of testosterone to dihydrostestosterone acts on epithelial components of the prostate gland Tx: BPH and androgenetic alopecia

DRESS syndrome

=drug reaction with eosinophilia and systemic symptoms (internal organ issues) Reactin occuring 2-8 weeks after drug exposure. ASSOCIATED DRUGS: phenytoin, carbamazepine, allopurinal, sulfonamides, antibiotics. SX: fever, generalized LAD, facial edema, diffuse morbilliforn skin rash

NRTIs

Abacavir Didanosine Emtricitabine Lamivudine Stavudine Tenofovir Zidovudine -Competitively inhibit nucleotide binding to reverses transcriptase and incorporate into viral DNA strand causing termination of chain (lack a 3' OH group). -All need to be phosphorylated to be active. -Tenofovir is a nuceloTide; the others are nucleosides. --can cause damage to the proximal tubule -Abacavir hypersensitivity is associated with the HLA-B 57:01 allele -ZDV can be used for general prophylaxis and during pregnancy to decrease risk of fetal transmission. --can cause myelosuppression, agranulocytosis, and anemia Megaloblastic anemia is a well-known complication of zidovudine (ZDV). Look for low hemoglobin and an increased mean corpuscular volume above 100 fL. Patients can complain of weakness and dizziness. Signs of anemia on physical examination can include new-onset palpitations and conjunctival or skin pallor. Have you dined (vudine) with my nuclear (nucleosides) family?

Acetozolamide

Acetozolamide acts at the proximal convoluted tubule and inhibits bicarbonate formation, which can lead to type 2 RTA

Phases of drug trials

Asks if the drug can "*SWIM*" on its own: Safe?: uses small number of *healthy* volunteers to test toxicity, pharmacology, safety (20-100 people) Works?: uses small number of *diseased* volunteers to see if the drug works on that disease, what ADEs there are, dosing optimization (1000-300 people) Improves?: uses larger population in an RTC to see if the drug improves outcomes vs. placebo (300-3000 people) Markets well?: post-market surveillance to monitor for long-term ADEs A clinical trial is conducted to establish the safety and efficacy of a particular drug before allowing it to be marketed and used by the public. It is generally divided into four phases: phase 1 aims to establish a drug's safe dosing range; phase 2 checks the effectiveness and safety of a drug by conducting a study on a larger number of subjects; phase 3 is a randomized controlled multicenter trial that assesses a drug's effectiveness when compared with the treatment of choice; and phase 4 is a post-marketing safety surveillance after a drug receives permission to be sold. Phase 0 is considered "microdosing" and newly added.

Immunosuppressant inhibition of purine synthesis

Azathioprine/6-MP-->pancytopenia

Macrolides ("ACE")

Azithromycin, Clarithromycin, and Erythromycin are all examples of what type of antibiotic? -inhibit 50s ribosomal subunit, inhibiting translocation -inhibit P450 -bacteriostatic -Symptoms: --increase GI motility(MOTILIN AGONIST), via acting as an agonist on motilin receptors --acute choleastatic hep A --Prolong QT interval

Monobactams

Aztreonam - narrow-spectrum drug for infections by gram-negative aerobic bacilli(pseudomonas); may be used by people allergic to penicillin

Abciximab

Blocks glycoprotein IIa/IIIb receptor to decrease platelet binding to fibrinogen -administered during angioplasty in patients with acute coronary syndrome "IIb times IIIa equals abSIXmab"

NNRTIs

Delavirdine Efavirenz Nevirapine -Bind to reverse transcriptase at site different from NRTIs. -Do not require phosphorylation to be active or compete with nucleotides.

Rocuronium ($)

Derivatives of curare paralyze skeletal muscle for the purposes of inducing anesthesia in the surgical patient. These agents act by competitively antagonizing post-synaptic acetylcholine receptors, Nondepolarizing NMJ blocker

Anticholinergic Toxicity

Dry mouth, decreased peristalsis, mydriasis (or prolonged pupil dilation), non reactive pupils, hot dry skin, hyperpyrexia without sweat, tachycardia, agitation, unstable vital signs, delirium, seizure, repetitive motor movements. Causes: - anticholingeric drugs (ie: atropine) - jimson weed (gardener's pupil, due to plant alkaloids)

Cytochrome P450

Drugs commonly affected: -Antiepileptics -Theophylline -Warfarin *Inducer cyclophosphamide Inducers: Most chronic alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs Inhibitors: SICKFACES.COM (when I Am drinking Grapefruit juice)

Tricyclic Antidepressants (TCAs)

Drugs that inhibit the reuptake of norepinephrine and serotonin by the presynaptic neurons in the central nervous system, increasing the amount of time they are available to the postsynaptic receptors. Muscarinic blockage leads to anticholinergic effects such as blurred vision, dry mouth, tachycardia, urinary retention, and constipation. *Caution in elderly

Cetuximab target

EGFR (Stage 4 colorectal cancer, head and neck cancer)

Ethacrynic Acid

Ethacrynic acid is a loop diuretic that does not contain a typical sulfa moiety, unlike other diuretics. Loop diuretics inhibit the Na+/K+/2Cl- transporter in the thick ascending loop of Henle. The common side effects that you should know include hypokalemia, hypocalcemia, and alkalosis. Loop diuretics can also be ototoxic, ethacrynic acid being the most potent in this area.

misoprostol

Gastric damage and bleeding are common adverse effects seen with chronic nonsteroidal anti-inflammatory drug (NSAID) use. Patients present with abdominal pain, fatigue, tachycardia, and the presence of occult blood in the stool. Gastrointestinal bleeding can be prevented with a medication that stimulates prostaglandin receptors on gastric parietal cells, the prostaglandin analog "BLANK" being the prototypical drug. *also causes uterine contractions

Arteriolar vasodilators

Hydralazine Minoxidil -lower blood pressure vis decreasing SVR-->that leads to reflex SNS activation: --increase HR, CO, and contractility --stimulate RAAS and results in sodium and fluid retention with peripheral edema

Minimal Alveolar Concentration (MAC)

Inversely proportional to the potency of inhalation anesthetics, the lower the MAC the more potent the anesthetic -Inhaled anesthetic = Renders 50% of subjects unresponsive painful/noxious stimulant [skin incision] -Examples: --Nitric oxide [N2O] has ↓ solubility in blood and ↓ lipid solubility = Fast induction and low potency --Halothane = ↑ Lipid and blood solubility, high potency and slow induction

Ledipasvir

NS5A inhibitor -in HCV that prevents replication and assembly of the mature viral proteins

methylphenidate

Patients with narcolepsy present with excessive daytime sleepiness and cataplexy (sudden total collapse). The most appropriate management is with "BLANK" , a central nervous system stimulant that works via inhibition of reuptake of norepinephrine and dopamine.

alpha-adrenergic agonist

Phenylephrine -vasoconstriction and effective decongestants *Tachyphlaxis = declning effect after a few days -overuse can cause negative feedback, resulting in decreased norepinephrine synthesis and release from nerve endings, which diminishes their effect (eg removal of normal vasoconstrictive effect and vasodilation occurs)

Sofosbuvir

RNA polymerase inhibitor -Nucleotide/non-nucleoside RNA polymerase inhibitor

Ranitidine (idines)

Ranitidine, cimetidine, nizatidine, and famotidine are H2-receptor antagonists that function to decrease gastric acidity -tx for Peptic ulcer disease

Potassium sparing diuretics

Spironolactone Eplerenone Amiloride Triamterene

Terbinafine, Griseofulvin, Echinocandins

Terbinafine -Inhibits the fungal enzyme squalene epoxidase. -Dermatophytoses (especially onychomycosis—fungal infection of finger or toe nails). -GI upset, headaches, hepatotoxicity, taste disturbance. Griseofulvin -Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing tissues (eg. nails) -Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm). -Teratogenic, carcinogenic, confusion, headaches, disulfram-like reaction, increase cytochrome p-450 and warfarin metabolism. Echinocandins -Anidulafungin, caspofungin, micafungin. -Inhibit cell wall synthesis by inhibiting synthesis of beta-glucan. -Treats Invasive aspergillosis, Candida. -Side effect: GI upset, flushing (by histamine release).

Griseofulvin

The most common presentation of tinea capitis is enlarging single or multiple patches of scaling with hair loss, with or without erythema. "BLANK" is the mainstay of treatment for this condition, and works by binding to mitotic spindles in fungal cells, disrupting mitosis. or can treat with terbinafine

Therapeutic Index (TITE)

Therapeutic Index = TD50/ED50 -Higher TI = safer drugs -Lower TI = require monitoring --Warfarin, Theophylline, Digoxin, Lithium --"Warning, These Drugs are Lethal!" *Potency = EC50 -Decrease in EC50 = Increased potency = lower amount of drug needed

toxicity - methanol, ethylene glycol (antifreeze)

Treatment: fomepizole -a competitive inhibitor of alcohol dehydrogenase

Carbamezapine

Tx of trigeminal neuralgia -MOA; reduces the ability of sodium channels to recover from inactivation -can cause aplastic anemia and SIADH -P450 inducer

Bevacizumab target

VEGF (Colorectal Cancer, renal cell carcinoma, non-small cell lung cancer

Zero-order kinetics vs first-order kinetics

Zero-order: -PEA = Phenytoin, Ethanol, Aspirin -Capacity-limited elimination -Constant amount First-order: -Flow-dependent elimination -Constant fraction

Efavirenz

a non-nucleoside reverse transcriptase inhibitor (NNRTI). It does not incorporate itself into viral DNA *may cause SJS and toxic epidermal necrolysis -Other NNRTIs include efavirenz, delavirdine, nevirapine, and rilpivirine.

Edrophonium

a short-acting acetylcholinesterase inhibitor used in the diagnosis of myasthenia gravis. Edrophonium is a short-acting acetylcholinesterase inhibitor that is used in the so-called "Tensilon test" to diagnose myasthenia gravis. The brief but dramatic improvement in muscle strength after administration of this drug confirms the diagnosis of MG and increases the probability of responding to treatment with pyridostigmine or neostigmine (longer acting AChE inhibitors).

Succinylcholine ($$)

can cause significant potassium release and life-threatening arrhythmias in pt's at high risk for hyperkalemia, including those with burns , myopathies, crash injuries, and denervating injuries or disease. MOA:Depolarizing Acetylcholine agonist at the NMJ (nicotinic acetychholine receptors) and causes fasciculations before flaccid paralysis *Depolarizing blocker -Rapidly hydrolyzed by plasma pseudochlinesterase *Def. in this -esertase leads to prolonged neuromuscular paralysis s/p drug administration

CDK4/6 inhibitors

can inhibit cellulare replication in other rapidly dividing cells such as the hematologic cells in bone marrow (neutropenia, anemia or thrombocytopenia)

LSD intoxication

causes an expanded experience of senses (radiant colors, visual hallucinations, echoing of sounds), delusions, dilated pupils, fever, tachycardia, hypertension, diaphoresis, paranoia, dry mouth, and sleeplessness. An intoxicated patient may state s/he can see music and hear colors.

Ezetimibe

cholesterol absorption inhibitor via blockin NPC1L1 transporter protein

Antipsychotics

work by blocking D2 receptors (G-alpha i) in the mesolimbic dopamine pathway. -Dystonia (involuntary, repetitive muscle contractions) is associated with dopamine (D2) antagonist use -Dopamine-2 receptor blockade in the tuberoinfundibular pathway can result in galactorrhea and amenorrhea