Pharm (Gen Principles) Flashcards
Alprostadil
a prostaglandin E1 analog used to maintain the patent ductus arteriosus (PDA) in congenital heart defects such as tetralogy of flow and pulmonary atresia; key effect of delivering blood to the lungs
Indomethacin
a NSAID that inhibits cyclooxygenase (COX) and decreases prostaglandin formation; used to close the patent ductus arteriosus (PDA) if remains open after birth
treatment for a gastrinoma
Octreotide (somatostatin) - inhibits gastrin release; high does PPI’s (omeprazole, lansoprazole, pantoprazole) or surgical excision
Octreotide
treatment for a gastrinoma; Zollinger-Ellison syndrome; gastrin secreting tumor; somatostatin analog; also used for bleeding varcies (slows blood flow); used in carcinoid syndrome (receptors are on most carcinoid tumors); acromegaly (inhibits GH)
Which antibiotic can be used to treat gastroparesis (as seen in diabetes) and why?
Erythromycin - because it binds to motilin receptors in the stomach, intestine and colon; promotes motility in the fasting state
Drug of choice for Ascites Tx
remove fluid from the body:
diet - sodium restriction
**Spironolactone - K+ sparing diuretic that blocks aldosterone at the distal tubule
large volume paracentesis
Infectious complication of ascites
Spontaneous Bacterial Peritonitis (SBP) - ascitic fluid infections; usually E. coli and Klebsiella (gram negatives); fever, abdominal pain, and increased PMNs; tx with Cefotaxime (3rd generation cephaloporins)
Penicillamine
copper chelator used in Wilson’s Disease; accumulation of copper due to ATP7B defect
Treatment for H. pylori
triple therapy:
PPI
Clarithromycin
Amoxicillin/Metronidazole
Antiacids
OTC use for GERD symptoms:
Sodium Bicarbonate
Calcium carbonate
Aluminum hydroxide
Magnesium hydroxide
Aluminum hydroxide
OTC use for GERD symptoms; no bloating to alkalosis (no C02 by product); can cause constipation (aluminum = decreased GI motor activity); bind phosphate in the gut (can be used in renal failure to lower P03 levels); can cause HYPOphosphatemia leading to muscle weakness; can cause aluminum toxicity in renal failure pt
Drugs at risk for poor absorption w/ the use of antiacids
**Tetracycline
Fluoroquinolones
Isonizid
Iron supplements
Histamine (H2) blockers
Fanotidine
Ranitidine
Nizatidine
Cimetidine
block H2 receptors on parietal cells; can cause **confusion (elderly - can block CNS receptors)
Cimetidine
one of the 1st histamine (H2) blocker; potent P450 inhibitor; anti-androgen: gynecomastia, impotence and PRL release; crosses BBB can cause confusion and headaches and reduces creatinine excretion
Proton Pump Inhibitors (PPI’s)
Omeprazole
Pantoprazole
Lansoprazole
Esomeprazole
inhibit H+/K+ pump on parietal cells; increased rates of **C. Diff infections (loss of protective barrier) and Pneumonia (more pathogens in upper resp); can lead to malabsorption (hypomagnesium, decreased Ca2+, B12 def, iron and vit C)
Bismuth Salicylate
Pepto-Bismol; coats ulcers/erosions; most effective in H. pylori ulcers; another use b/c salicylate inhibits PGEs and cane used in diarrheal illnesses; blackens the stool (can be confused w/ melena)
Sodium polystyrene sulfonate
Kayexalate (trade name) an osmotic laxative that binds K+ in the gut, can also be used for hyperkalemia
Lactulose
an osmotic laxative that is a synthetic disaccharide also used in hyperammonemia (traps NH4 and is excreted in the stool)
Ondansetron
5-HT3 receptor antagonist used in vomiting; blocks 5-HT receptors found in vomiting center in the medulla; commonly used in pt receiving chemo; side effects of headache and constipation
Metoclopramide
Reglan; D2 receptor antagonist used in gastroparesis (diabetic gastroparesis); activated chemoreceptor trigger zone so has effect as anti-emetic as well and can be used w/ migraines; whenever you block dopamine watch for Parkinson-like symptoms (movement symptoms - fear consequence of long term use - tardive dyskinesia - irreversible); contraindicated in epilepsy (lowers seizure threshold), pts w/ Parkinson and also bowel obstructions (stimulates GI motility)
Isoniazid tx for latent TB infection
can be directly hepatotoxic causing acute mild dysfunction in pt and frank hepatitis (fever, anorexia and nausea)
Cephalosporin resistant organisms
Class III anti arrhythmic drugs
amiodarone, sotalol, dofetilide
predominately blocks K+ chs and inhibit the outward K+ currents during phase 3 prolonging repolarization and total AP duration
beta blocker withdrawal syndrome
prolonged beta blockers leads to up regulation of beta-adrenergic receptors and increased sensitivity to circulating catecholamines, causing enhanced beta response on abrupt beta blocker cessation
Fenoldopam
selective peripheral dopamine-1 receptor agonist; causes vasodilation of systemic and renal arterioles to lower BP while also increasing renal perfusion, urine output and natriuresis; useful tx for HTN emergency in pts w renal insufficiency
Hydralazine
direct arteriolar vasodilator; often used in HTN emergency; associated w reflex sympathetic activation resulting in increased in HR and contractility
Phenylephrine
alpha-adrenergic agonist that causes an increase in SVR due to arterial vasoconstriction; used in pts w hypotension or shock and is contraindicated in HTN emergency
RAAS and anti-HTN agents
Chronic digitoxin toxicity
presents w nonspecific GI and neurological symptoms; changes in color vision are particularly associated w digoxin OD; life-threatening ventricular arrhythmias are the most serious complication
Fenofibrate therapy MOA
fibrates lower triglyceride levels by activating peroxisome proliferator-activated receptor alpha, which leads to decreased hepatic VLDL production and increased lipoprotein lipase activity; fish oil supplements containing high concentrations of omega-3 FAs lower triglycerides by decreasing production of VLDL and apolipoprotein B
Statin induced myopathy
statin inhibit RLS via competitive inhibition of HMG-CoA reductase leads to enhanced hepatic LDL receptor recycling and increased LDL clearance from the circulation; statin-induced myopathy (elevated creatine kinase) is the most common complication
Statin induced myopathy
statin inhibit RLS via competitive inhibition of HMG-CoA reductase leads to enhanced hepatic LDL receptor recycling and increased LDL clearance from the circulation; statin-induced myopathy (elevated creatine kinase) is the most common complication but also watch for liver injury by checking LFT before initiating tx
Clonidine induced orthostatic syncope
an antiHTN agent stimulates central alpha-2adrenergic receptor causing a decrease in presynaptic release of NE and a decrease in sympathetic outflow; prevents normal baroreceptor-mediated increase in PVR and HR during standing which can cause orthostatic syncope
Niacin tx for hyperlipidemia
increases HDL levels and decreases LDL levels and triglycerides; niacin causes cutaneous flushing which is mediated by prostaglandins and can be diminished by pretreatment w aspirin
Major side effects of amiodarone
class III anti-arrhythmic used in a-fib; 40% iodine by weight amIODarone can cause HYPOthyroidism due to decreased production of thyroid hormone; order serum TSH before starting a pt on this tx
Digoxin
only cardiac glycoside approved for chronic HF; reversible inhibition of Na/K+ ATPase; K+ cannot enter (hyperkalemia) and Na+ can’t leave; increase in intracellular Na+ prevents Ca2+ from leaving the cell via Na+/Ca2+ exchanger; build up of Ca2+ leads to cardiac contractility and increased LV systolic fxn;
chronic digoxin use may cause “scooped” concave ST segments on ECG
presents w nonspecific GI and neurological symptoms; changes in color vision (xanthopsia - objects appearing yellow) are particularly associated w digoxin OD
Dobutamine
beta adrenergic agonist w predominant activity on beta-1 receptors; causes increase in HR and cardiac contractility leading to an increase in myocardial O2 consumption
Digoxin MOA
reversible inhibition of Na/K+ ATPase; K+ cannot enter (hyperkalemia) and Na+ can’t leave; increase in intracellular Na+ prevents Ca2+ from leaving the cell via Na+/Ca2+ exchanger; build up of Ca2+ leads to cardiac contractility and increased LV systolic fxn
Side effects of statins
HMG-CoA reductase inhibitors (statins) are muscle and liver toxicity; hepatic enzymes should be checked prior to initiating therapy and repeated if symptoms of hepatic injury occur
Tx for beta blocker OD
should be treated w glucagon; increases HR and contractility independent of adrenergic receptors; activates the Gs,AC, cAMP pathway resulting in calcium release from intracellular stores and increased SA firing
Dobutamine MOA
Beta 1 agonist; increased cAMP and intracellular [Ca2+] leading to increased myocardial contractility
examples of tachyphylaxis
activation of adrenergic receptors in arrestin binding and receptor internalization; this effect is responsible for the tolerance effect seen w alpha-adrenergic (decongestants) and beta-adrenergic (bronchodilators) agonists
effects of bisphosphonates
alendronate, risedronate
medication induced esophagitis is a common adverse effect of bisphosphonates; they are also associated w increased risk of osteonecrosis of the jaw and atypical femoral fractures
pharmacokinetic differences between neonatal patients and adults
neonates have a higher proportion of body water compared to adults; this can result in lower [water-soluble drugs] if they are administered at the same weight-based dosage as given to adult pts
Beers criteria
the Beer’s criteria identify drugs that should be used w caution in geriatric pts; common drugs to avoid include anticholinergics (1st-gen antihistamines - diphenhydramine)
antiplatelet therapy
GI mucosal injury and bleeding are the most common side effects of aspirin; these are primarily due to COX-1 inhibition which results in impaired PGE-dependent GI mucosal defense and decreased platelet aggregation
Drug allergy
drugs and their metabolites can act as happens that bind to a carrier protein to form antigens that generate an immunologic response; type 1 hypersensitivity is IgE-mediated and involves a sensitization phase and a repeat exposure phase; clinical manifestation include urticarial rash, wheezing, and anaphylaxis
serum drug levels and half life
the half-life of a drug is the time required to lower its concentration by 50%; vD refers to how well the drug distributes into tissues compared to plasma; the higher the vD the greater the drug distributes; drug concentration = drug dose/vD
statin-associated myopathy
the risk of severe myopathy are increased when statins are given concurrently w vibrates (particularly gemfibrozil), which impair the hepatic clearance of statins and lead to excessive blood levels
maintenance dose
clearance determines the dose rate required to maintain a given steady-state plasma concentration
Amiodarone effects on digoxin
amiodarone increases digoxin blood levels via inhibition of P-glycoprotein transmembrane efflux transporters in the intestine to cause increased digoxin absorption, and in the kidneys to cause decreased digoxin excretion; therefore a dose reduction of digoxin is needed when coadministered w amiodarone
causes of low volume of distribution (vD)
characteristics of a drug such as high molecular weight, high plasma protein binding, high charge and hydrophilicity tend to trap the drug in the plasma compartment resulting in a low vD (3-5L)
chelation drug interactions
tetracyclines interact w polyvalent cations (Fe2+,Ca2+,Al3+, Mg2+) to form non absorbable chelate complexes in the GI tract; this can lead to significantly decreased drug absorption and therapeutic affect; fluoroquinolones and thyroxine are also susceptible to chelation
log dose-response curves
the changes in the log dose-response curve for the effect of a reversible competitive antagonist added to a full agonist are:
1) a parallel shift to the R due to increase in the ED50
2) no change in the maximum effect (Emax)
*competitive = change ED50 = shift R; noncompetitive = change Emax = shift down
Linezolid and serotonin syndrome
serotonin syndrome is characterized by a triad of autonomic instability, altered mental status, and neuromuscular irritability; it may develop when a monoamine oxidase inhibitor (MAOI) antidepressant or a non-antidepressant with MAOI activity (linezolid) is combined w serotonin meds
acetaminophen poisoning pathogenesis
excessive acetaminophen use causes toxicity through its metabolite N-acetyl-p-benzoquinone imine, which disrupts hepatocyte mitochondrial function and induces oxidative injury throughout the liver; the resulting hepatocellular liver injury markedly elevates ALT (>1000 U/L)
acetylation
isoniazid is metabolized by acetylation; the speed a pt is able to acetylate drugs depends on whether they are genetically “fast” or “slow” acetylators; the presence of fast and slow acetylators within the same population results in a bimodal distribution of the speed of isoniazid metabolism; slow acetylators are at increased risk of adverse side effects
Folinic acid (leucovorin)
Folinic acid (leucovorin) can reverse the toxicity of methotrexate in the non-cancerous cells in the GI mucosa and bone marrow if administered in the appropriate times leucovorin serves as a reduced form of folic acid that does not require the action of dihydrofolate reductase (DHF reductase)
metformin clearance
metformin is excreted unchanged by the kidney; pts w significant renal insufficiency due to HF or CKD are at increased risk of toxicity (ex: lactic acidosis)
limitations of drugs needed to pass the BBB
P-glycoprotein is an efflux pump found on brain capillary endothelial cells (BBB) that inhibits a wide range of substrates from entering the brain; inhibition of p-glycoprotein can improve drug delivery to the CNS
mesna
hemorrhagic cystitis during therapy w cyclophosphamide or ifosfamide is caused by urinary excretion of the toxic metabolite acrolein; it can be prevented by aggressive hydration, bladder irrigation and admin of *mesna (a sulfhydryl compound that bonds acrolein in the urine)
monoclonal antibody (mAbs) clearance
monoclonal antibodies (mAbs) are not eliminated by hepatic or renal clearance; therefore, no dose adjustment is necessary w impaired hepatic/renal function or use of cytochrome P450 inducers or inhibitors
cytochrome P450 polymorphism
cytochrome P450 enzymes found in the liver are responsible for the majority of drug metabolism; polymorphism occurring in the genes coding for these enzymes result in various phenotypes that differ in their rates of metabolism; individual differences in phenotype alter tx efficacy and drug toxicity
anesthetic multi-compartment drug metabolism
following IV admin, a highly lipophilic drug will be rapidly distributed to organs w high blood flow (ex: brain, liver, kidneys, lungs); the drug is then redistributed to tissues w relatively lower blood flow (ex: skeletal muscle, fat, bone); this accounts for the short duration of action of many commonly used anesthetics such as propofol
dose-response curves interpretation
efficacy is a measurement of the maximum pharmacodynamic effect achievable w a drug; potency refers to the dose of drug that is required to produce a given effect; drugs that bind their receptors w a higher affinity or are better able to gain access to their target tissues will have greater potency (lower ED50)
antiemetic drugs
zero-order and first-order kinetics
1st-order kinetics, a constant fraction of drug is metabolized per unit of time, so the amount metabolized changes based on the serum concentration; in zero-order kinetics, a constant amount of drug is metabolized per unit of time, independent of serum levels
physostigmine
a cholinesterase inhibitor w a tertiary ammonium structure that can reverse both the central and peripheral nervous system symptoms of anticholinergic toxicity
antibody-drug conjugates
antibody-drug conjugates improve drug efficacy and minimize toxicity by allowing conventional chemotherapeutic agents to selectively target and kill cancer cells while sparing healthy cells (targeted delivery)
tx of toxoplasmosis
congenital toxoplasmosis is tx w sulfadiazine plus pyrimethamine; these medications work synergistically to inhibit formation of THF a necessary cofactor in purine nucleotide synthesis
rifampin moa in TB tx
inhibit bacterial DNA-dependent RNA polymerase; decreases RNA production; also turns bodily fluids orange
Pyridostigmine
drug used in myasthenia gravis; inhibits acetylcholinesterase (Ache) enzymes from breaking down the ACh
TB Drugs
“RIPE ONGO”
Rifampin - Orange secretions
Isoniazide - Neuropathy
Pyrazinamide - Gout
Ethambutol - Optic neuritis
Ethambutol
can cause optic neuropathy that results in color blindness, central scotoma, and decreased visual acuity; this adverse side effect may be reversed w discontinuation of the drug
