Drugs - First Aid 2014 Flashcards
What do these drugs do and what are their side effects? Lispro, Aspart, Glulisine
Insulin, rapid acting. Binds insulin receptor (Tyrosine kinase activity).
Liver: increased glucose stored as glycogen
Muscle: increased glycogen, protein synthesis; increased K+ uptake.
Fat: increased TG storage.
For DM1, DM2, GDM (post prandial control).
Toxicity: Hypoglycemia, rare hypersensitivity reactions
Which are the long acting insulin drugs?
Glargine, Detemir. Used for DM1, DM2, GDM (basal level control).
What does metformin do and what is its side effects?
Buguanide class. Decrease gluconeogenesis, increased glycolysis, and increased peripheral glucose uptake (insulin sensitivity).
First line therapy in DM2. Can be used in patients without islet function.
Causes GI upset; most serious adverse effect is lactic acidosis (cant use in renal failure)
What do tolubatmide and chlorpropamide do?
First generation Sulfonylureas. Close K+ channel in Beta cell membrane so cell depolarizes and causes insulin release. Stimulates release of endogenous insulin in type 2 DM. Requires some islet function so cant use in DM1. Risk of hypoglycemia when there is renal failure. Has disulfram like side effects.
What do glyburide, glimepiride, and glipizide do?
Second generation Sulfonylureas. Close K+ channel in Beta cell membrane so cell depolarizes and causes insulin release. Stimulates release of endogenous insulin in type 2 DM. Requires some islet function so cant use in DM1. Risk of hypoglycemia when there is renal failure. Hypoglycemia side effects.
What do Pioglitazone and rosiglitazone do?
Glitazones/Thiazolidinediones. Increased insulin sensitivity in peripheral tissue. Binds to PPAR-gamma nuclear transcription regulator (this activates genes for regulating fatty acid storage and glucose metabolism. Increases insulin sensitivty. Also increased adiponectin). Used as monotherapy in type 2 DM or combined with above agents. Side effects: weight gain, edema, hepatoxicity, heart failure. From fluid retention.
What do acarbose and miglitol do?
Alpha-glucosidase inhibitors. Inhibit intestinal brush-border alpha-glucosidases. Delayed sugar hydrolysis and glucose absorption resulting in decreased postprandial hyperglycemia. Used as monotherapy in type 2 DM or in combination with other agents. Side effects include GI disturbances.
What does pramlintide do?
Amylin analog. Decreases gastric emptying and decreases glucagon. Type 1 and type 2 DM. Side effects: hypoglycemia, nausea, diarrhea.
What does exenatide and liraglutide do?
GLP-1 analogs. Increased insulin and decreased glucagon release. Type 2 DM. Nausea, vomiting, pancreatitis.
What do linagliptin, saxagliptin, and sitagliptin do?
DPP-4 inhibitors. (DPP-4 breaks down GLP-1) Increased insulin and decreased glucagon release. Type 2 DM. Mild urinary or respiratory infections.
What do propylthiouracil and methimazole do?
They block thyroid peroxidase, inhibiting the oxidation of iodide and the organification (coupling) to iodine. Inhibition of thyroid hormone synthesis. Propylthiouracil also blocks 5’-deiodinase, which decreases peripheral conversion of T4 to T3. Used for hypoerthroidism. PTU blocks peripheral conversion and is used in pregnancy. Side effects: skin rash, agranulocytosis, aplastic anemia, hepatotoxicity (propylthiouracil). Methimazole is a possible teratogen (aplastia cutis).
What do levothyroxine and triiodothyronine do?
Thyroxine replacements. Used for hypothyroidism and myxedema. Side effects: Tachycardia, heat intolerance, tremors, arrhythmias.
What is somatostatin (octreotide) used for?
Acromegaly, carcinoid, gastrinoma, glucagonoma, esphageal varices
What is oxytocin used for?
Stimulates labor, uterine contractions, milk let-down; controls uterine hemorrhage.
What is ADH used for?
central DI, but not nephrogenic.
What is demeclocycline used for?
Is an ADH antagonist and is used for SIADH. Side effects: nephrogenic DI, photosensitivity, abnormalities of bone and teeth.
What are glucocorticoids do?
Examples: Hydrocortisone, prednisone, triamcinolone, dexamethasone, beclomethasone, fludrocortisone (mineralocorticoid and glucocorticoid activity).
metabolic, catabolic, anti-inflammatory, and immunosuppressive effects mediated by interaction with glucocorticoid response elements and inhibition of transcription factors such as NFkB. Used for Addison disease, inflammation, immune suppression, and asthma. Side effects: iatrogenic Cushing syndrome- buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis (treat with bisphosphonates), adrenocortical atrophy, peptic ulcers, diabetes (if chronic). Adrenal insufficiency when drug stopped abruptly after chronic use (from inhibition of ACTH).
What are cimetidine, ranitidine, famotidine, nizatidine?
H2 blockers. Reversible block of histamine H2-receptors and decreases H+ secretion by parietal cells.
Clinical use: peptic ulcer, gastritis, mild esophageal reflux
Toxicity: cimetidine is a potent inhibitor of cytochrome P-450. Antiandrogenic effects (prolactin release, gynecomastia, impotence, decreased libido in males). Crosses blood brain barrier (confusion, dizziness, headaches). Cimetadine and ranitidine decrease renal excretion of creatinine.
What are omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole?
Irreversibly inhibit H+/K+ ATPase in stomach parietal cells.
Clinical use: peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome.
Toxicity: increased risk of C. difficile infection, pneumonia. Hip fractures, decreased serum Mg+2 with long term use.
What are Bismuth, sucralfate?
Bind to ulcer base, providing physical protection and allowing HCO3- secretion to reestablish pH gradient in the mucous layer.
Clinical use: increases ulcer healing, fixes traveler’s diarrhea, and for constipation.
Increases motility.
What is misoprostol?
A PGE1 analog. Increased production and secretion of gastric mucous barrier. Decreased acid production.
Clinical use: prevention of NSAID induced peptic ulcers (NSAIDs block PGE1 production); maintenance of a PDA. Also used to induce labor (ripens cervix)
Toxicity: Diarrhea. Contraindicated in women of childbearing potential (abortifacient).
What is octreotide?
Long-acting somatostatin analog.
Clinical use: acute variceal bleeds, acromegaly, VIPoma, and carcinoid tumors.
Toxicity: nausea, cramps, steatorrhea.
What do antacids do?
Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying.
All can cause hypokalemia.
Overuse can also cause the following problems.
What is Aluminum hydroxide?
It’s an antacid that causes constipation and hypophosphatemia; proximal muscle weakness, osteodystrophy, seizures.
What is Calcium carbonate?
Antacid. Causes hypercalcemia, rebound acid increase, constipation. Can chelate and decrease effectiveness of other drugs (e.g. tetracycline)
What is Magnesium hydroxide?
Antacid. Causes diarrhea, hyporeflexia, hypotension, cardiac arrest.
Think magnesium and diarrhea. Magnesium salts will do this in general.
What are magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose?
Provides osmotic load to draw water out. Lactulose also treats hepatic encephalopathy since gut flora degrade it into metabolites (lactic acid and acetic acid) that promote nitrogen excretion as NH4+.
Clinical use: constipation
Toxicity: diarrhea, dehydration; may be abused by bulimacs.
What is infliximab?
monoclonal antibody to TNFalpha.
Clinical use: Crohn disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis.
Toxicity: infection (including reactivation of latent TB), fever, hypotension
What is sulfasalazine?
A combination of sulfapyridine (anti-bacterial) and 5-aminosalicylic acid (anti-inflammatory). Activated by colonic bacteria.
Clinical use: Ulcerative colitis, Crohn disease
Toxicity: Malaise, nausea, sulfonamide toxicity, reversible oligospermia.
What is ondansetron?
It is a 5-HT3 antagonist; decreased vagal stimulation. Powerful central-acting antiemetic.
Clinical use: Control vomiting postoperatively and in patients undergoing cancer chemotherapy.
Toxicity: Headache, constipation.
Note: all -etron drugs are serotonin antagonists useful for anti-emetic purposes. e.g. granisetron and dolasetron.
What is metoclopramide?
It is a D2 receptor antagonist. Increased resting tone, contractility, LES tone, motility. Does not influence colon transport time.
Clinical use: diabetic and post-surgery gastrparesis, antiemetic.
Toxicity: increased parkinsonian effects. Restlessness, drowsiness, fatigue, depression, nausea, diarrhea. Drug interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel obstruction or Parkinson disease (D1-receptor blockade)
Note: another prokinetic drug is erythromycin (that’s why it has GI mobility side effects!)
What are the alpha-agonist glaucoma drugs?
Epinephrine (alpha-1): Decreased aqueous humor synthesis via vasoconstriction.
Toxicity: Mydriasis and do not use in closed angle glaucoma.
Brimonidine (alpha-2): Decreased aqueous humor synthesis (inhibit cAMP production and thus less secretion).
Toxicity: Blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, ocular pruritis.
What is the general principle for Glaucoma drugs?
decrease IOP by decreasing amount of of aqueous humor. (by inhibiting synthesis/secretion or increasing drainage).
What are the beta-blocker glaucoma drugs?
Timolol, betaxolol, carteolol.
Decreased aqueous humor synthesis.
Toxicity: no pupillary or vision changes.
What are the diuretics used for glaucoma drugs?
Acetazolamide. Decreased aqueous humor synthesis via inhibition of carbonic anhydrase.
Toxicity: no pupillary or vision changes.
What are the cholinomimetics glaucoma drugs?
Direct: pilocarpine, carbachol. Increased outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork. Toxicity: miosis, and cyclospasm (contraction of ciliary muscle).
Use pilocarpine in emergencies- very effective at opening meshwork into canal of Schlemm.
Indirect: physostigmine (reversible), echothiophate (irreversible).
What are the prostaglandin glaucoma drugs?
Latanoprost (PGF2alpha).
Toxicity: darkens color of iris (browning).
What are morphine, fentanyl, codeine, loperamide, methadone, meperidine, dextromethorphan, diphenoxylate?
Opioid analgesics.
Act as agonists at opioid receptors (mu = morphine, delta = enkephaline, kappa = dynorphin) to modulate synaptic transmission - open K+ channels, close Ca+2 channels. Decreased synaptic transmission.
Inhibit release of ACh, norepinephrine, 5-HT, glutamate, substance P.
Clinical use: pain, cough suppression (dextromethorphan), diarrhea (loperamide and diphenoxylate), acute pulmonary edema, maintenance programs for heroin addicts (methadone).
Toxicity: addiction, respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression with other drugs.
Tolerance does not develop to miosis and constipation.
Toxicity treated with naloxone or naltrexone (opioid receptor antagonist).
What is butorphanol?
Mu-opioid receptor partial agonist and kappa-opioid receptor agonist; produces analgesia.
Clinical use: severe pain (migraine, labor, etc). Causes less respiratory depression than full opioid agonists.
Toxicity: can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition for opioid receptors). Overdose not easily reversed with naloxone.
What is tramadol?
Very weak opioid agonist; also inhibits serotonin and norepinephrine reuptake (works on multiple neurotransmitters).
Clinical use: chronic pain
Toxicity: similar to opioids. Decreases seizure threshold. Serotonin syndrome.
What is ethosuximide used for?
Treating generalized absence seizures.
Mech: blacks thalamic T-type Ca+2 channels.
Side effects: EFGHIJ
Ethosouximide causes Fatigue, GI distress, Headache, Itching, Stevens-Johnson syndrome
What are benzodiazepines used for in epilepsy? And which ones?
Diazepam, Lorazepam. Used for first-line acute generalized status epilepticus. Increases GABA-A action.
Side effects: Sedation, tolerance, dependence, respiratory depression.
(Also for eclampsia seizures, but 1st line is MgSO4).
What is phenytoin used for?
First line in generalized tonic-clonic and prophylaxis in status epilepticus. Also used for partial simple and complex seizures.
Increased Na+ channel inactivation zero-order kinetics.
Side effects: nystagmus, diplopia, ataxia, sedation, gingival hyperplasia, hirsutism, peripheral neuropathy (from B6 deficiency), megaloblastic anemia, teratogenesis (fetal hydantoin syndrome), SLE-like syndrome, induction of cytochrome P450, lymphadenopathy, Stevens-Johnson syndrome, osteopenia.
Fosphenytoin for parenteral use.
FLOG MASSH
What are carbamazepines used for in seizures?
First line for partial simple and complex seizures and generalized tonic-clonic seizures.
Increased sodium channel inactivation.
Side effects: diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis, induction of cytochrome P450, SIADH, Stevens-Johnson syndrome.
What does valproic acid do for epilepsy?
First line for generalized tonic-clonic. Otherwise used for partial simple and complex seizures and generalized absence. Increased sodium channel inactivation and increased GABA concentration by inhibiting GABA transaminase.
Side effects: GI distress, rare but fatal hepatotoxicity (measure LFTs), neural tube defects in fetus (spina bifida), tremor, weight gain, contraindicated in pregnancy.
Also for myoclonic seizures and bipolar disorder.
What does gabapentin for epilepsy?
Used for partial simple and complex seizures and generalized tonic-clonic seizures. Primarily inhibits high-voltage-activated Ca+2 channels; designed as GABA analog.
Side effects: sedation, ataxia.
Also used for peripheral neuropathy, postherpetic neuralgia, migraine prophylaxis, bipolar disorder.
What does phenobarbital do for epilepsy?
Used for partial simple and complex seizures and generalized tonic-clonic seizures.
Increased GABA-A action.
Side effects: sedation, tolerance, dependence, induction of cytochrome P450, cardiorespiratory depression.
1st line in neonates.
What does topiramate do in epilepsy?
Used for partial simple and complex seizures and generalized tonic-clonic seizures.
Blocks sodium channels, increased GABA action.
Side effects: sedation, mental dulling, kidney stones, weight loss.
Also used for migraine prevention.
What does lamotrigine in epilepsy?
Used for partial simple and complex seizures and generalized tonic-clonic and absence seizures.
Blocks voltage-gated sodium channels.
Side effects: Stevens-Johnson syndrome.
What does levetiracetam do in epilepsy?
Used for partial simple and complex seizures and generalized tonic-clonic seizures.
Unknown mech; may modulate GABA and glutamate and release.
What does tiagabine do in epilepsy?
Used in partial simple and complex seizures.
Increased GABA by inhibiting re-uptake.
What does vigabatrin do in epilepsy?
Used in partial simple and complex seizures.
Increased GABA by irreversibly inhibiting GABA transaminase.
What is Stevens-Johnson syndrome?
Prodrome of malaise and fever followed by rapid onset of erythematous/purpuric macules (oral, ocular, genital). Skin lesions progress to epidermal necrosis and sloughing.
What are the inducers of cytochrome P-450?
Inducers: Chronic alcohol use Modafinil St. John's wort Phenytoin Phenobarbital Nevirapine Rifampin Griseofulvin Carbamazepine
Mnemonic: chronic alcohol Mona steals phen-phen and never refuses greasy carbs.
What are the inhibitors of the cytochrome P-450 system?
Inhibitors: Acute alcohol abuse Gemfibrozil Ciprofloxacin Isoniazid Grapefruit juice Quinidine Amiodarone Ketoconazole (all azoles: fluconazole, itraconazole, voriconazole) Macrolides Sulfonamides Cimetidine Ritonavir
A cute gentleman Cipped iced Grapefruit juice quickly and kept munching on soft cinammon rolls
What are the sulfa drugs?
Probenecid, Furosemide, Acetazolamide, Celecoxib, Thiazides, Sulfonamide antibiotics, Sulfasalazine, Sulfonylureas.
Patients with sulfa allergies may develop:
fever, urinary tract infection, Stevens-Johnson syndrome, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives).
What are the common barbiturates and what do you they?
Phenobarbital, pentobarbital, thiopental, secobarbital.
Facilitate GABA-A action by increased duration of Cl- channel opening thus decreasing neuron firing (barbidurates increase duration). Contraindicated in porphyria.
Clinical USE: Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental).
Toxicity: respiratory and CV depression (can be fatal); CNS depression (can be exacerbated by EtOH use); dependence; drug interactions (induces cytochrome P-450). Overdose treatment is supportive (assist respiration and maintain BP).
What are the common benzodiazepines and what do they do?
Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chloridazepoxide, alprazolam.
Facilitate GABA-a action by increased frequency of Cl- channel opening. Decreases REM sleep. Most have long half-lives and active metabolites (exceptions: triazolam, oxazepam, and midazolam are short acting -> higher addictive potential).
Clinical USE: Anxiety, spasticity, status epilepticus (lorazepam and diazepam), detoxification (especially alcohol withdrawal-DTs), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxation), hypnotic (insomnia).
Toxicity: Dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than with barbiturates. Treat overdose with flumazenil (competitive antagonist at GABA benzo receptor).
Frenzodiazepines increased frequency. Benzos, barbs, and EtOH all bind GABA-a receptor
What are the Nonbenzodiazepine hypnotics and what do they do?
Zolpidem (Ambien), Zaleplon, esZopiclone. All ZZZs put you to sleep.
Act via the BZ1 subtype of GABA receptor. Effects reversed by flumazenil (competitive antagonist at GABA benzo receptor).
Clinical USE: Insomnia.
Toxicity: Ataxia, headaches, confusion. Short duration because of rapid metabolism by liver enzymes. Unlike older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic effects. Decreased dependence risk than benzodiazepines.
What are the inhaled anesthetics and what do they do?
Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide.
Mechanism unknown
Effects: myocardial depression, respiratory depression, nausea/emesis, increased cerebral blood flow (decreased cerebral metabolic demand).
Toxicity: Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), expansion of trapped gas in a body cavity (nitrous oxide).
Malignant hyperthermia: rare, life-threatening hereditary condition in which inhaled anesthetics (except nitrous oxide) and succinylcholine induce fever and severe muscle contractions.
Tx: dantrolene.
How do barbiturates act as IV anesthetics?
Thiopental-high potency, high lipid solubility, rapid entry into brain. Used for induction of anesthesia and short surgical procedures. Effect terminated by rapid redistribution into tissue (i.e. skeletal muscle) and fat. Decreased cerebral blood flow.
How do benzodiazepines act as IV anesthetics?
Midazolam most common drug used for endoscopy; used adjunctively with gaseous anesthetics and narcotics. May cause severe postoperative respiratory depression, decreased BP (treat overdose with flumazenil), and anterograde amnesia.
How does Arylcyclohexylamines/Ketamine work as an IV anesthetic?
PCP analog that act as dissociative anesthetics. Block NDMA receptors (non-competitive antagonist of glutamate binding). CV stimulants. Cause disorientation, hallucination, and bad dreams. Increased cerebral blood flow.
How do Opioids work as IV anesthetic?
Morphine, fentanyl used with other CNS depressants during general anesthesia.
How do Propofol work as IV anesthetic?
Used for sedation in ICU, rapid anesthesia induction, and short procedures. Less postoperative nausea than thiopental. Potentiates GABA-A.
What are the local anesthetics esters?
Esters - procaine, cocaine, tetracaine
What are the local anesthetics amides?
lidocaine, mepivacine, bupivacaine, (amides have two I’s in them)
What are the mechanism of local anesthetics and what do they do?
Mechanism: Block Na+ channels by binding to specific receptors on inner portion of channel. Preferentially bind to activated Na+ channels, so most effective in rapidly firing neurons. Tertiary amine local anesthetics penetrate membrane in uncharged form, then bind to ion chanels as charged form.
Principle: can be given with vasoconstrictors (usually epinephrine) to enhance local action - decreased bleeding, increased anesthesia by decreased systemic concentration.
In infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate membrane effectively -> need more anesthetic.
Order of nerve blockade: small-diameter fibers > large diameter. Myelinated fibers > unmyelinated fibers. Overall, size factor predominates over myelination such that small myelinated fibers > small unmyelinated fibers > large myelinated fibers > large unmyelinated fibers.
Order of loss: 1. pain 2. temperature 3. touch 4. pressure.
Clinical use: minor surgical procedures, spinal anesthesia. If allergic to esters, give amides.
Toxicity: CNS excitation, severe CV toxicity (bupivacaine), hypertension, hypotension, and arrhythmias (cocaine).
What are Neuromuscular blocking drugs used for?
Used for muscle paralysis in surgery or mechanical ventilation. Selective for motor (vs. autonomic) nicotinic receptor.
What are the depolarizing neuromuscular blocking drugs and what do they do?
Succinylcholine - strong Ach receptor agonist; produces sustained depolarization and prevents muscle contraction.
Reversal blockade:
Phase 1 (prolonged depolarization): no antidote. Block potentiated by cholinesterase inhibitors.
Phase 2 (repolarized but blocked; ACh receptors are available, but desensitized): antidote consists of cholinesterase inhibitors.
Complications include hypercalcemia, hyperkalemia, and malignant hyperthermia.
What are the nondepolarizing neuromuscular blocking drugs and what do they do?
Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium - competitive antagonists - compete with ACh for receptors.
Reversal of blockade: neostigmine (must be given with atropine to prevent muscarinic effects such as bradycardia), edrophonium, and other cholinesterase inhibitors.
What is dantrolene and what does it do?
prevents the release of Ca+2 from the sarcoplasmic reticulum of skeletal muscle.
Clinical use: used to treat malignant hyperthermia and neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).
What are the dopamine agonists?
Bromocriptine (ergot), pramipexole, ropinirole (non-ergot); non-ergots are preferred.
What are the drugs that increase dopamine release?
Amantadine (may increase dopamine release); also used as an antiviral against influenza A and rubella; toxicity = ataxia.
L-dopa/carbidopa (converted to dopamine in CNS). Carbidopa is a peripheral decarboxylase inhibitor.
What drugs prevent dopamine breakdown?
Selegiline (selective MAO type B inhibitor); entacopone, tolcapone (COMT inhibitors- prevent L-dopa degradation -> increased dopamine availability)
What drugs curb excess cholinerigc activity? In the context of Parkinson’s.
Benztropine (antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia.
How does L-dopa/carbidopa?
increased level of dopamine in brain. Unlike dopamine, L-dopa can cross blood-brain barrier and is converted by dopa decarboxylase in the CNS to dopamine. Carbidopa, a peripheral decarboxylase inhibitor, is given with L-dopa to increase the bioavailabity of L-dopa in the brain and to limit peripheral side effects.
Clinical use: Parkinson disease.
Toxicity: arrhythmias from increased peripheral formation of catecholamines. Long-term use can lead to dyskinesia following administration (on-off phenomonen), akinesia between doses.
What does selegiline do?
Selectively inhibits MAO-B, which preferentially metabolizes dopamine over norepinephrine and 5-HT, thereby increased availability of dopamine.
Clinical use: adjunctive agent to L-dopa in treatment of Parkinson disease.
Toxicity: may enhance adverse effects of L-dopa.
How does memantine work in the context of Alzheimer?
NDMA receptor antagonist; help prevent excitotoxicity (mediated by Ca+2 )
Toxicity: dizziness, confusion, hallucinations.
From wiki: The drug belongs to a class of drugs called NMDA receptor antagonists, which reduce certain types of brain activity by binding to NMDA receptors on brain cells and blocking the activity of the neurotransmitter glutamate. At normal levels, glutamate aids in memory and learning, but if levels are too high, glutamate appears to overstimulate nerve cells, killing them through excitotoxicity.
What do donepezil, galantamine, and rivastigmine do?
They are AChE inhibitors and are used for Alzheimer.
Toxicity: nausea, dizziness, insomnia.
What are the huntington drugs?
Neurotransmitter changes in Huntington disease: decreased GABA, decreased ACh, increased dopamine.
Tx:
Tetrabenazine and reserpine: inhibit vesicular monoamine transporter (VMAT); limit dopamine vesicle packaging and release.
Halperidol-dopamine receptor antagonist.
What does sumatriptan do?
It’s a 5-HT-1B/1D agonist. Inhibits trigeminal nerve activation; prevents vasoactive peptide release (can result in vasodilation and headaches); induces vasoconstriction. Half-life <2 hours.
Clinical USE: acute migraine, cluster headache attacks.
Toxicity: coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina), mild tingling.
How do you treat metal toxicity? Think about Arsenic, Mercury, Lead, Copper, and Iron
Dimercaprol - Arsenic, Mercury, Lead
Pencillamine - copper toxicity, (also gold, arsenic, lead)
CaNA2 - EDTA - lead poisoning
Dimercaptosuccinic acid - lead poisoning
Deferoxamine/Deferasirox - acute iron poisoning and overload
How do calcium channel blockers work? Toxicity?
BLock voltage-dependent L-type Calcium channels of cardiac/smooth muscle, thereby reducing contractility
Toxicity: cardiac depression, AV block, peripheral edema, flushing, dizziness, hyperprolactinemia, constipation.
What are the Ca channel blockers for vessels?
Vascular smooth muscle: amlodipine = nifedipine > diltiazem > verapamil
Except for Nimodipine the Dihydropyridines are used for hypertension, angina (including Prinzmetal), and Raynaud’s
Nimodipine used for Subarachnoid hemorrhage (prevents cerebral vasospasm).
What are the Ca channel blockers for heart muscle?
Heart- verapamil > diltiazem > amlodipine = nifedipine
Non-dihydropyridine used for hypertension, angina, atrial fib/flutter.
How does hydralazine used for and toxicity?
increases cGMP -> smooth muscle relaxation -> Vasodilates arterioles more than veins. Reduces afterload.
Clinical use: severe hypertension, CHF. First-line therapy for hypertension in pregnancy, with methyldopa. Frequently co-administered with a Beta-blocker to prevent reflex tachycardia.
Toxicity: compensatory tachycardia (contraindicated in angina/CAD), fluid retention, nausea, headache, angina. Lupus-like syndrome.
What drugs for hypertensive emergency?
nitroprusside, nicardipine, clevidipine, labetalol, and fenoldopam,
How does nitroprusside work?
short acting; increased cGMP via direct release of NO. can cause cyanide toxicity.
How does fenoldopam work?
Dopamine D1 receptor agonist - coronary, peripheral, renal, and splanchnic vasodilation. Decreased BP and Increased natriuresis.
What does nitroglycerin, isosorbide dinitrate do and toxicity?
Vasodilate by increased NO in vascular smooth muscle by increased cGMP and smooth muscle relaxation. Dilates veins more than arteries so decreased preload.
Clinical use: Angina, acute coronary syndrome, pulm edema.
Toxicity: Reflex tachycardia (treat with Beta blockers), hypotension, flushing, headache. Monday disease is due to loss of tolerance over the weekend such that these toxic symptoms occur on Monday with tachycardia, dizziness, and headache on re-exposure.
What does HMG-CoA reductase do and what are the drugs/uses/toxicity?
Lovastatin, pravastatin, simvastatin, atorvastatin, rosuvastatin.
Inhibit conversion of HMG-CoA to mevalonate, a cholesterol precursor.
Decreases LDL the most with slight decrease in TGs and slight increase in HDL.
Toxicity: Hepatotoxicity (increased LFTs), rhabdomyolysis (esp when used with fibrates and niacin).
What does Niacin do/uses/toxicity?
Vitamin B3. It inhibits lipolysis in adipose tissues and reduces hepatic VLDL synthesis.
Decreases LDL and increases HDL and slightly decreases TG.
Toxicity: Red, flushed face, which is decreased by aspirin or long-term use. Hyperglycemia (aconthosis nigricans). Hyperuricemia (exacerbates gout).
What do bile acid resins do/uses/toxicity?
Cholestyramine, colestipol, colesevelam
Decreased LDL and slightly increased HDL/TGs.
Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more (thus increasing LDL receptors and taking LDL into the liver from the blood).
Toxicity: Patients hate it - tastes bad, causes GI discomfort, decreased absorption of fat soluble vitamins.
What do cholesterol absorption blockers do/uses/toxicity?
Ezetimibe
Decreased LDL and no effect on HDL/TGs.
Prevent cholesterol absorption at small intestine brush border.
Rare increased LFTs, diarrhea.
What do fibrates do/uses/toxicity?
Gemifibrozil, clofibrate, bezafibrate, fenofibrate
Bigg decrease in TGs and decrease in TGs and increase in HDL.
Upregulate LPL -> increased TG clearance.
Activates PPAR-alpha to induce HDL synthesis.
Toxicity: Myositis (increased risk with concurrent statins), hepatotoxicity (increased LFTs), cholesterol gall stones (suppresses cholesterol 7alpha-hydroxylase, especially with concurrent bile acid resins).
What do cardiac glycosides do, uses, toxicity?
Digoxin (75% bioavailabiity, 20-40% protein bound). Long half life at 40 hrs by urine.
Direct inhibition of Na/K ATPase leads to indirect inhibition of Na/Ca exchanger/antiport.
Increased Ca+2 leads to positive inotropy. Stimulates vagus nerve leading to decreased HR.
Uses: CHF (increased contractility); atrial fib (decreased conduction at AV node and depression of SA node).
Toxicity: Cholinergic - nausea, vomiting, diarrhea, blurry yellow vision (think Van Gogh).
ECG - increased PR interval, decreased QT, ST scooping, T-wave inversion, arrhythmia, AV block.
Can lead to hyperkalemia, which indicates poor prognosis.
Factors predisposing to toxicity - renal failure (decreased excretion), hypokalemia (permissive for digoxin binding at K+-binding site on Na/K ATPase), verapamil, amiodarone, quinidine (decreased digoxin clearance; displaces digoxin from tissue binding site).
Antidote: slowly normalize K+, cardiac pacer, anti-digoxin Fab fragments, Mg+2.
How do Class 1 anti-arrythmics do in general?
Slow conduction in depolarized cells, decrease slope of phase 0 depolarization and increase threshold for firing in abnormal pacemaker cells. State dependent: affects most frequently depolarizing cells
Hyperkalemia increases toxicity because it leaves cells partially depolarized and so more sodium channels will be inactivated. Putting a Class 1 on top of this will make the situation even worse.
How do Class 1A work, uses, toxicity?
Disopyramide, Quinidine, Procainamide,
Double Quarter Pounder.
Increases AP duration, Increases effective refractory period, increases QT interval.
Uses: Atrial/ventricular arrhythmias, especially re-entrant and ectopic SVT and VT.
Toxicity: heart failure (disopyramide), Cinchonism (headache, tinnitus with quinidine), reversible SLE-like syndrome (procainamide), thrombocytopenia, torsades de pointes due to increased QT interval.
How do Class 1B work, uses, toxicity?
Lidocaine, Phenytoin, Mexiletine
Lettuce, Pickles, Mayo
Decreased AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue.
Uses: Acute ventricular arrhythmias (especially post MI), digitalis-induced arrhythmias.
1B is Best for post-MI.
Toxicity: CNS stimulation/depression, CV depression.
How do Class 1C work, uses, toxicity?
Flecainide, Propafenone
Fries with that Please.
Significantly prolongs refractory period in AV node. Minimal effect on AP duration.
Uses: SVTs, including A-fib, Last resort in refractory ventricular tachycardias.
Toxicity: proarrhythmic, especially post MI (contraindicated). IC is Contraindicated post MI in structural and ischemic heart tissue.
How do class II blockers work, uses, toxicity?
Metoprolo, propranolol, esmolol, atenolol, timolol, carvedilol.
Decrease SA/AV nodal activity by decreased cAMP, decreased Ca+2 activity. Suppresses abnormal pacemakers by decreased slope 4.
AV node particularly sensitive. Increased PR interval. Esmolol very short acting.
Uses: SVT, slowing ventricular rate during atrial fibrillation and atrial flutter.
Toxicity: Impotence, exacerbation of COPD and asthma, CV effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alterations). May mask signs of hypoglycemia. Metoprolol can cause dyslipidemia. Propranolol can exacerbate vasospasm in Prinzmetal angina.
Contraindicated in cocaine users (risk of unopposed alpha-adrenergic receptor agonist activity). Treat overdose with glucagon.
How do Class III work, uses, toxicity?
Amiodarone, Ibutilide, Dofetilide, Sotalol. AIDS
K+ channel blockers
Increased AP duration, increased effective refractory period. Used when other anti-arrhythmics fail. Increased QT interval.
Uses: Atrial Fib, atrial flutter, ventricular tachycardia (amiodarone, sotalol).
Toxicity: Sotalol - torsades de pointes, excessive Beta blockade.
Ibutilide - torsades de pointes.
Amiodarone - pulmonary fibrosis, hepatoxicity, hypothyroidism/hyperthyroidism (amiodarone is 40% iodine by weight), corneal deposits, skin deposits (blue/grey) resulting in photodermatitis, neurologic defects, constipation, CV effects (bradycardia, heart block, CHF).
Must check PFTs, LFTs, TFTs, when using amiodarone. Amiodarone has class I, II, III, IV effects and alters lipid membrane.
How do Class IV work, uses, toxicity?
Verapamil, diltiazem.
Calcium channel blockers.
Decreased conduction velocity, increased effective refractory period, increased PR interval.
Uses: Prevention of nodal arrhythmias (e.g. SVT), rate control in atrial fib.
Toxicity: Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression). Verapamil has gingival hyperplasia.
What does adenosine do?
Increased K+ out of cells -> hyperpolarizing cells and decreasing Calcium current. Can be used for slowing HR in nodal cells.
Drug of choice in diagnosing/abolishing SVT. Very short acting (15 seconds).
Adverse effects include flushing, hypotension, chest pain. Effects blocked by theophylline and caffeine.
What does Mg+2 doo
Effective in torsades de pointes and digoxin toxicity.
What are the H1 first-gen/reversible blockers and what do they do?
Reversible inhibitors of H1 histamine receptors
Diphenhydramine, dimenhydrinate, chlorpheniramine.
Names contain en/ine or en/ate
Uses: allergy, motion sickness, sleep aid.
Toxicity: Sedation, antimuscarinic, anti-alpha-adrenergic.
What are the 2nd generation H1 blockers and what do they do?
Loratadine, fexofenadine, desloratadine, cetirizine.
Names usually end in “adine”.
Uses: allergy.
Toxicity: far less sedating than 1st generation because of decreased entry into CNS.
What are the expectorants and how do they work?
Guaifenesin - Expectorant: thins respiratory secretions; does not suppress cough reflex.
N-acetylcysteine - Mucolytic: can loosen mucous plugs in CF patients. Also used as an antidote for acetaminophen overdose.
What does Dextromethorphan do?
Antitussive (suppresses cough by antagonizing NMDA glutamate receptors). Synthetic codeine analog. Has mild opioid effect when used in excess. Naloxone can be given for overdose. Mild abuse potential.
What do psudoephedrine, phenylephrine do and what are its uses?
Sympathomimetic alpha-agonistic nonprescription nasal decongestants.
Use: Reduce hyperemia, edema, and nasal congestion. open obstructed eustachian tubes. Pseudoephedrine also illicitly used to make methamphetamine.
Toxicity: hypertension. can also cause CNS stimulation/anxiety (psuedophedrine).
What are the B2 agonists and how do they work? list 3
Albuterol - relaxes bronchial smooth muscle (Beta-2). Use during acute exacerbation.
Salmeterol, formoterol - long-acting agents for prophylaxis. Adverse effects are tremor and arrhythmia.
What are the methylxanthines and what do they do?
Theophylline - likely causes bronchodilation by inhibiting phosphodiesterase -> increases cAMP levels due to decreased cAMP hydrolysis.
Usage limited because of narrow therapeutic index (cardiotoxicity, neurotoxicity); metabolised by cytochrome P-450.
Blocks actions of adenosine.
What are the muscarinic antagonists and what do they do? list 2.
Ipratropium - competitive block of muscarinic receptors, preventing bronchoconstriction. Also used for COPD, as is tiotropium, a long-acting muscarinic antagonist.
What are the corticosteroids and what do they do?
Beclomethasone, fluticasone - inhibit the synthesis of virtually all cytokines. Inactivate NF-kB, the TF that induces the production of TNF-alpha and other inflammatory agents. 1st line therapy for chronic asthma.
What are the anti-leukotrienes and what do they do?
Montelukast, zafirlukast - block leukotriene receptors. Especially good for aspiring induced asthma.
Zileuton - a 5-lipoxygenase pathway inhibitor. Blocks conversion of arachidonic acid to leukotrienes.
What is omalizumab and what does it do?
Monoclonal anti-IgE antibody. Binds mostly unbound serum IgE and blocks binding to FceRI. Used in allergic asthma resistant to inhaled steroids and long-acting B2 agonists.
What does methacoline do?
Muscarinic receptor agonist. Used in bronchial provocation challange to help diagnose asthma.
What does Bosentan do?
Used to treat pulmonary arterial hypertension. Competitively antagonizes endothelin-1 receptors, decreased pulmonary vascular resistance.
What inhibits lipoxygenase?
Zileuton
What inhibits LTC4, LTD4, LTE4?
Zafirlukast, montelukast. Receptor antagonists
What is the function of LTB4 vs LTC4/LTD4/LTE4?
LTB4: Neutrophil chemotaxis (neutrophils arive B4 others)
LTC4/LTD4/LTE4: Increased bronchial tone, vasoconstriction, contraction of smooth muscle, and increased vascular permeability.
What does Prostacyclin do (PGI2)?
Decreases platelet aggregation, vascular tone, bronchial tone, uterine tone.
Platelet Gathering Inhibitor (mnemonic)
What do PGE2/PGF2alpha do?
Increased uterine tone and decreased bronchial tone
What does thromboxane do?
Increased platelet aggregation, vascular tone, and bronchial tone.
What does aspirin do and side effects?
Irreversibly inhibits COX1/COX2 by covalent acetylation. Decreased TXA2 and prostaglandins and increased bleeding time until new platelets are produced (about 7 days). No effect on PT/PTT. Type of NSAID.
With increasing doses you get, decreased platelet aggregation, antipyretic/analgesic, and antiinflammatory actions (in order of increasing dosage)
Toxicity: gastric ulceration, tinnitus (CNVIII). Chronic use can lead to acute renal failure, interstitial nephritis, and upper GI bleeding. Risk of Reye syndrome in children treated with aspirin for viral infection. Also stimulates respiratory centers, causing hyperventilation and respiratory alkalosis.
What are common NSAIDs and what do they do/toxicity?
Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac.
Reversibly inhibit COX1/COX2.
Antipyretic, analgesic, anti-inflammatory. Indomethacin used to close a PDA.
Toxicity: interstitial nephritis, gastric ulcer (PGs protect gastric mucosa), renal ischemia (PGs vasodilate afferent arteriole).
What do COX2 inhibitors do and what are they used for/toxicity?
Reversible inhibition of COX2. Blocks pain/inflammation but spares platelet function (TXA2 dependent on COX1).
Use: Rheumatoid arthritis, osteoarthritis; patients with gastric ulcers.
Toxicity: increased risk of thrombosis. Sulfa allergy.
What is Acetominophen used for/toxicity?
Reversibly inhibits COX, mostly in CNS. Inactivated peripherally.
Use: antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome in children with viral infection.
Toxicity: overdose produces hepatic necrosis; acetominophen metabolite (NAPQI) depletes glutathione and forms toxic tissue adducts in liver. N-acetylcysteine is antidote - regenerates glutathione.
What are bisphosphonates used for?
Alendronate, other -dronates.
Mechanism: Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity (and induces apoptosis).
Use: Osteoporosis, hypercalcemia, Paget disease of bone.
Toxicity: Corrosive esophagitis (patients are advised to take with water and remain upright for 30 minutes), osteonecrosis of the jaw.
What are the chronic gout drugs?
Allopurinol: inhibits xanthin oxidase, decreases xanthine to uric acid. Also used for tumor lysis syndrome. You see increase in azothioprine and 6-MP (before xanthine oxidase). Don’t give salicylates because they depress uric acid clearance.
Febuxostat: inhibits xanthine oxidase.
Probenecid: Inhibits reabsorption of uric acid in PCT (also inhibits secretion of penicillin).
What are the acute gout drugs?
NSAID: naproxen, indomethacin.
Glucocorticoids: oral/intra-articular
Colchicine: binds and stabilizes tubulin to inhibit microtubule polymerization, impairing leukocyte chemotaxis and degranulation. Acute and prophylactic value. GI side effects.
What do the TNF-alpha inhibitors do/toxicity?
Etanercept: fusion protein of TNF-alpha receptor + IgG1 FC. Decoy receptor.
Use: RA, psoriasis, ankylosing spondylitis.
Inflixamab/adalimumab - anti-TNF-alpha monoclonal antibody.
Use: IBD, RA, psoriasis, ankylosing spondylitis.
All TNF-alpha inhibitors predispose to an infection, including re-activation of TB, since TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes.
What does Leuprolide do/toxicity?
Mechanism: GnRH analog with agonist properties when used in pulsatile function; antagonist properties when used in continuous function (downregulates GnRH receptor in pituitary leading to decreased FSH/LH).
Use: infertility (pulsatile), prostate cancer (continuous - use with flutamide), uterine fibroids (continuous), precocious puberty (continuous)
Toxicity: antiandrogen, nausea, vomiting
Leuprolide in Lieu of GnRH
what do the estrogens do/use/toxicty?
Ethinyl estradiol, DES, mestranol
Binds estrogen receptors
Use: hypogonadism or ovarian failure, menstrual abnormalities, HRT postmenopausal women; use in men with androgen-dependent prostate cancer
Toxicity: increased risk of endometrial cancer, bleeding in postmenopausal women, clear cell adenocarcinoma of vagina in females exposed to DES in utero, increased risk of thrombi. Contraindications- ER positive breast cancer or history of DVTs.
What is clomiphene used for?
SERM.
Antagonist at estrogen receptors in hypothalamus. Prevents normal feedback inhibition and increased release of LH/FSH from pituitary, which stimulates ovulation.
Used to treat infertility due to anovulation (PCOS).
Toxicity: may cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, and visual disturbances.
What is Tamoxifen used for?
Antagonist on breast tissue; agonist at uterus, bone;
Associated with endometrial cancer and thromboembolic events.
Primarily used to treat and prevent recurrence of ER positive breast cancer.
What is raloxifene used for?
Agonist on bone; antagonist at uterus.
Causes decreased resorption of bone and so is used to treat osteoporosis.
Toxicity: increased risk of thromboembolic events.
What is hormone replacement therapy?
Used for relief or prevention of menopausal symptoms(e.g. hot flashes, vaginal atrophy) and osteoporosis (it increases estrogen and decreases osteoclast activity)
Unopposed estrogen replacement therapy (ERT) increases the risk of endometrial cancer, so progesterone is added.
Possible increased CV risk.
What are anastrozole/exemestane?
Aromatase inhibitors used in postmenopausal women with breast cancer. Decreases estrogen production.
What are progestins used for?
Bind progesterone receptors, decreases growth and increased vascularization of endometrium.
Use: used in oral contraceptives and in treatment of endometrial cancer and abnormal uterine bleeding.
What is MIfepristone used for? it’s other name?
RU-486.
Competitive inhibitor of progestins at progesterone receptors.
Use: termination of pregnancy. Administered with misoprostol (PGE1).
Toxicity: heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain
what is oral contraception?
Estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge means no LH surge and no ovulation.
Progestins cause thickening of the cervical mucus, thereby limiting access of sperm to uterus. Progestins also inhibit endometrial proliferation, thus making endometrium less suitable for the implantation of embryo.
Contraindications: smokers > 35 yrs old (increased risk of CV events), patients with history of thromboembolism and stroke or history of estrogen-dependent tumor.
What is terbutaline used for?
B2-agonist that relaxes the uterus; used to decrease contraction frequency in women during labor.
What is danazol used for?
Synthetic androgen that acts as partial agonist at androgen receptors.
Use: Endometriosis and hereditary angioedema.
Toxicity: weight gain, edema, acne, hirsuitism, masculinization, decreased HDL levels, hepatotoxicity.
From wiki:
Danazol exhibits hypoestrogenic, hyperandrogenic effects that cause atrophy of the endometrium, which can alleviate the symptoms of endometriosis.
Danazol prevents ovulation by suppressing the increase of luteinizing hormone during the middle of the menstrual cycle.[4][5] Danazol inhibits ovarian steroidogenesis resulting in decreased secretion of estradiol and may increase androgens. Danazol displaces testosterone from sex hormone-binding globulin (SHBG), displacing it and increasing serum testosterone levels.[4] Danazol also directly stimulates androgen and progesterone receptors.[4]
What is testosterone/mehtyltestosterone used for?
Agonist at androgen receptors
Use: treats hypogonadism and promotes development of secondary sex characteristics; stimulation of anabolism to promote recovery after burn or injury.
Toxicity: causes masculinization in females; decreased intratesticular testosterone in males by inhibiting release of LH (via neg feedback) and resultant gonadal atrophy. Premature closure of epiphyseal plates. Increased LDL and decreased HDL.
What is finasteride used for?
5-alpha reductase inhibitor (decreased conversion of testosterone to DHT).
Used in BPH. Also promotes hair growth-used to treat male pattern baldness.
To prevent male pattern hair loss, give a drug that will encourage female breast growth.
What is flutamide used for?
A nonsteroidal competitive inhibitor of androgens at the testosterone receptor.
Used in prostate carcinoma
What is ketoconazole used for?
Inhibits steroid synthesis (inhibits 17,20 desmolase)
Uses: Ketaconazole and spironolactone are used in the treatment of PCOS to prevent hirsutism. Both have side effects of gynecomastia and amenorrhea.
what is spironolactone used for?
Inhibits steroid binding, 17-alpha hydroxylase, and 17,20 desmolase
Uses: Ketaconazole and spironolactone are used in the treatment of PCOS to prevent hirsutism. Both have side effects of gynecomastia and amenorrhea.
What is tamsulosin used for?
alpha-1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for alpha1A,D receptors (found on prostate) vs. vascular alpha1B receptors.
What are sildenafil, vardenafil used for?
Inhibit phosphodiesterase 5, causing increased cGMP, smooth muscle relaxation in the corpus cavernosum, increased blood flow, and penile erection.
SildaneFIL and vardenaFIL fill the penis.
Use: treatment of erectile dysfunction.
Toxicity: headache, flushing, dyspepsia, impaired blue green color vision.
Risk of life threatening hypotension in patients taking nitrates.
“Hot and sweaty” but then Headache, Heartburn, and Hypotension. All the Hs.
What is Penicillin G,V, mechanism, use and toxicity?
Penicillin G (IV/IM forms), penicillin V (oral). Prototype B-lactam antibiotics.
Mechanism: bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan. Activate autolytic enzymes.
Use: mostly used for gram-pos organisms (S. pneumoniae, S. pyogenes, Actinomyces). Also used for N. meningitidis and T pallidum. Bactericidal for gram-pos cocci, gram-positive rods, gram-negative cocci, and sphirochetes. Penicillinase sensitive.
Toxicity: hypersensitivity reactions, hemolytic anemia.
Resistance: pencillinase in bacteria (a type of B-lactamase) cleaves B-lactam ring.
What is ampicillin, amoxicillin, mechanism, use, toxicity, and resistance?
Amino penicillins, penicillinase-sensitive penicillins.
Mechanism: Same as penicillin. Wider spectrum; penicillinase sensitive. Also combine with clavulanic acid to protect against B-lactamase.
Use: Extended spectrum penicillin - Haemophilus influenzae, E. coli, Listeria Monocytogenes, Proteus, Salmonella, Shigella, enterococci. HELPSS mnemonic.
Toxicity: Hypersensitivty reactions; rash; pseudomembranous colitis.
Mechanism of Resistance: Penicillinase in bacteria (a type of B-lactamase) cleaves B-lactam ring.
What is oxacillin, nafcillin, dicloxacillin? mech, use, toxicity
Pencillinase-resistance penicillins
Mech: same as penicillin. Narrow spectrum; pencillinase resistant because bulky R group blocks access of B-lactamase to B lactam ring.
Use: Staph aureus (except MRSA; resistant because of altered penicillin-binding protein target site). Use NAFcillin for staph.
Toxicity: Hypersensitivity reactions, interstitial nephritis.
What are ticarcillin, piperacillin? mechanism, use, toxicity?
Anti-pseudomonals.
Mechanism: same as penicillin, extended spectrum.
Use: Pseudomonas spp. and gram-neg rods; susceptible to penicillinase; use with B-lactamase inhibitors.
Toxicity: hypersensitivity reactions.
What are the B-lactamase inhibitors?
CAST.
Include clavulanic acid, sulbactam, tazobactam. Often added to penicillin antibiotics to protect the antibiotic from destruction by B-lactamase (penicillinase).
What is the mechanism of cephalosporins? Toxicity?
B-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.
Organisms typically not covered by cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci. Exception: ceftaroline covers MRSA.
Toxicity: Hypersensitivity reactions, vitamin K deficiency.
Low cross-reactivity with penicillins. Increased nephrotoxicity of aminoglycosides.
What are cefazolin, cephalexin?
1st generation cephalosporins
Gram positive cocci: Proteus mirabilis, E. Coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections. PEcK.
What are cefoxitin, cefaclor, cefuroxime?
2nd generation cephalosporins.
Gram-positive cocci: Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens.
HEN PEcKS.
What are ceftriaxone, cefotaxime, ceftazidime?
3rd generation cephalosporins.
Serious gram-negative infections resistant to other B-lactams.
Ceftriaxone: meningitis and gonorrhea.
Ceftazidime: Pseudomonas.
What is cefepime?
4th generation cephalosporin
Increased activity against Pseudomonas and gram-positive organisms.
