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190 Cards in this Set
- Front
- Back
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Phenobarbital
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A barbiturate
Side effect: induces cyp P450 (acts on PXR and CAR receptors). |
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Phenytoin
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Antepileptic
Side effects: -Long-term therapy can cause folate deficiency. -Is an inducer of P450 (CAR receptor) PK: Has zero-order kinetics (constant amount of drug is eliminated per unit time). |
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Rifampin
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ONLY antibiotic that has pharmacokinetic evidence that it substantially lowers steroid levels. (estradiol needs to be hydrolyzed by intestinal bacteria for proper reabsorption that is part of the enterohepatic circulation).
Side effect: An inducer of P450 (PXR receptor). Hence, should not be given with oral contraceptives. |
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Carbamazepine
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An antiepileptic
Side effect: an inducer of P450 (specifically cyp3A4). |
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Cimetidine
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H2 receptor antagonist.
Clinical use: to inhibit gastric acid secretion. MOA: reduce intracellular cAMP. Side effect: -inhibitor of P450. -antagonizes androgen receptors resulting in gynecomastia and reduced sperm count in men; galactorrhea in women. -can cross placenta causing harmful effects to fetus. |
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Ketoconazole
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Anti-fungal
Side effect: inhibitor of P450. |
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Erythromycin
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Macrolide antibiotic
Side effect: inhibitor of P450. (don't use with theophylline). |
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Chloramphenicol
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antibiotic
Side effects: -inhibitor of P450. -can cause oxidative stress on RBCs |
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Warfarin
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Coumarin Anticoagulant
MOA: Vit. K epoxide reductase inhibitor (affecting II, VII, IX, X, protein C, protein S) Clinical use: -Patients with afib >48 hrs. -Used to prevent progression or recurrence of acute DVT or pulmonary embolism. -prosthetic valves. PK: has a narrow TI->use PT to monitor levels. Toxicity: -hemorrhage -cutaneous necrosis d/t reduced activity of protein C -crosses placenta (category X) -Drug-induced hypoprothrombinemia Antidote: Vit K IV or oral. SNPs: -CYP2C9 (metabolizes S-warfarin) polymorphism->give smaller dose. -VKORC1 (gene encodes for epoxide reductase) polymorphism->give larger dose. Contraindications: Sulfonamides can displace warfarin from albumin, increasing toxicity. |
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Acetaminophen
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Analgesic and Antipyretic
Toxicity: -5% metabolized by CYP2E1 to NAPQI (normally detoxified by glutathione). Antidote: N-acetylcysteine (can also be used in CF b/c it breaks disulfide bonds in mucus, making it easier to cough out). |
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N-acetylcysteine (NAC)
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MOA: supplies cysteine as a precursor for increased glutathione production.
Clinical use: -Acetaminophen toxicity -Cystic fibrosis (breaks disulfide bonds in mucus) |
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Acetylcholine
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Direct acting, cholinergic agonist
Synthesis: in cytoplasm, via ChAT (acetyl CoA+choline). Acetyl CoA is made in the mitochondria. Choline is transported from ECF into nerve terminal via CHT1 (sodium symporter). This is the rate-limiting step. It then goes into vesicles via VAChT (H+ antiporter) Small doses: -transient drop in BP d/t vasodilation accompanied by reflex tachycardia Large doses: -bradycardia and decreased conduction velocity through the AV node in addition to causing hypotension and vasodilation. Clinical use: -rapid miosis after delivery of lens in cataract surgery (decreasing pupillary diameter decreases aqueous humor outflow, thus decreasing stress in anterior chamber). -same for keratoplasty, iridectomy, and other anterior segment surgery where rapid miosis is required. |
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Bethanechol
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Direct acting cholinergic agonist
-strong muscarinic activity (little nicotinic) -not metabolized by AChE Uses: -atony of the urinary bladder that occurred postoperatively or postpartum. Side effects: -general parasympathomimetic like sweating, flushing, salivation, hypotension, nausea, diarrhea, bronchospasm, abdominal pain. |
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Carbachol
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Direct acting cholinergic agonist
-acts on both muscarinic and nicotinic. -not really metabolized by AChE Uses: -miosis during ocular surgery (reducing intraocular pressure). |
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Methacholine
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Direct acting cholinergic agonist
-not metabolized by pseudocholinesterases and metabolized at a slower rate via AChE compared to ACh. -acts mainly on muscarinic Uses: -asthma stress test for non-clinically apparent asthma |
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Muscarine
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Natural Alkaloid
-acts exclusively on muscarinic receptors. |
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Arecoline
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Natural Alkaloid
-acts on both muscarinic and nicotinic |
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Pilocarpine
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Natural Alkaloid
-acts on mainly muscarinic Uses: -sialagogue (induces salivation) and miotic agent. -2nd line for open-angle glaucoma and management of closed-angle glaucoma. Side effects: -can cross BBB->sweating and salivation |
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Nicotine
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Ganglion stimulant (nicotinic agonist)
Low dose: -sympathetic heart effects (increases HR and BP) -parasympathetic GI and urinary effects (nausea, vomiting, diarrhea, urination, salivation, increased bronchial secretions) High doses: -prolonged depolarization results in ganglionic blockade and NMJ blockade Acute Toxicity: -BP and HR falls (unlike in low doses!) -death occurs via respiratory paralysis. Uses: for smoking cessation therapy |
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Edrophonium
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Anticholinesterase inhibitor (simple alcohol)
Uses: -diagnosis of myasthenia gravis (diagnosis not therapy). -reverse the block by non-depolarizing NMJ blocker like curare |
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Physostigmine
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Anticholinesterase inhibitor (Carbamate)
Uses: -Glaucoma (b/c it can cross BBB) -Atropine overdose Contraindications: -Do not use with TCA b/c it can make cardiac conduction depression worse. Toxicity: -since it can cross BBB, one might get convulsions. |
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Neostigmine
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Anticholinesterase inhibitor (Carbamate)
Uses: -postoperative neurogenic illeus -urinary retention -myasthenia gravis -mainly used to reverse the effects of non-depolarizing NMJ blockers after surgery. |
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Pyridostigmine
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Anticholinesterase inhibitor (Carbamate)
Uses: -primary treatment for myasthenia gravis. |
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Echothiophate
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Anticholinesterase inhibitor (Organophosphate)
Uses: -chronic open-angle glaucoma -subacute or chronic angle-closure glaucoma after iridectomy |
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Malathion
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Anticholinesterase inhibitor (Organophosphate)
Uses: -insectide -not harmful to humans b/c we can metabolize it (unlike parathion). |
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Parathion
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Anticholinestrase inhibitor (Organophosphate)
Uses: -insectide, but harmful to humans (we cannot metabolize it, malathion we can) Antidote: Pralidoxime (reactivates inhibited AChE)+atropine |
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Tabun, Sarin, Soman
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Anticholinesterase inhibitor (Nerve agents)
Uses: -in war,-cause death via respiratory paralysis |
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Tacrine, Donepezil, Rivastigmine, Galantamine
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orally active AChE inhibitor
Uses: Alzheimer's disease (b/c cholinergic activity is reduced in this disease) |
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Pralidoxime
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-used as antidote for organophosphate poisoning. Works by reactivating inhibited AChEs.
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Atropine
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Muscarinic antagonist
Actions: -mydriasis, cycloplegia -can lead to tachycardia since the heart is predominantly parasympathetic. -blocks salivary, sweat, and lacrimal glands. Toxicity: -Atropine flush (cutaneous vasodilation) Uses: -antispasmodic -antisialogogue -bradycardia or AV-block or excess vagal tone -OD on cholinergic drugs -antidote for Amanita mushroom poisoning. |
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Scopolamine
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Muscarinic antagonist
-administered transdermally Uses: -motion sickness -to induce mydriasis or cycloplegia such as in iridocyclitis. Side effect: -blocks short-term memory Low dose: -produces sedation (in contrast to atropine) High dose: -excitation |
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Ipratropium
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Muscarinic antagonist
-administered by pressurized aerosol Uses: -prevents bronchoconstriction in COPD -can be used in asthma, but beta-2 agonists are usually preferred for acute attack, unless the patient has COPD. |
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Tiotropium
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Muscarinic antagonist
Uses -superior efficacy in treatment of COPD compared to ipratropium -NOT FDA approved for asthma |
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Homatropine, Cyclopentolate, Tropicamide
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Muscarinic antagonists
Uses: -produce mydriasis and cycloplegia -preferred over atropine b/c of shorter duration |
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Benzotropine, Trihexylphenidyl
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Muscarinic antagonists
-can cross BBB Uses: -Parkinsonism and the extrapyramidal effects of antipsychotic drugs. (b/c there is an imbalance of ACh and dopamine in the brain with the former being too high). |
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Glycopyrrolate
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Muscarinic antagonist
Uses: -used orally to inhibit GI motility -used parenterally to prevent bradycardia during surgical procedures |
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Tolterodine
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Muscarinic antagonist
Uses -treat for overactive bladder |
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Hexamethonium, Mecamylamine, Trimethaphan
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Ganglion blocker (nicotinic antagonists)
-d/t many side effects, have been replaced by superior antihypertensive agents. |
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Tubocurarine
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Non-depolarizing NM blocker
MOA: -compete with ACh for binding to nicotinic receptor. Uses: -given IV for anesthesia during surgery to relax muscles. Side effects: -may cause histamine release. |
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Succinylcholine
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Depolarizing NM blocker
MOA: -binds to nicotinic receptors and stimulates them. Initially results in disorganized muscular contraction. Eventually, flaccid paralysis results. PK: Given via IV, extremely short duration (5-10 mins). Uses: -rapid endotracheal intubation -ECT (electro-convulsive therapy) Side effects: -malignant hyperthermia (b/c excessive release of calcium from SR increases heat production due to increase in muscle tone) Antidote: -Dantrolene which blocks release of calcium from SR. |
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Hemichlonium
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ACh synthesis inhibitor
MOA: -blocks the CHT1 sodium-choline symporter, blocking uptake of choline. |
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Vesamicol
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ACh Storage inhibitor
MOA: -blocks the ACh-H+ antiporter that puts ACh into vesicles. |
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Botulinum Toxin
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ACh release inhibitor
-produced by Clostridium Botulinum MOA: -prevents fusion of synaptic vesicle with the axon terminal membrane, inhibiting ACh exocytosis. Uses: -injected locally into muscles to treat torticollis, achalasia, strabismus, blepharospasm, and other focal dystonias. |
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Epinephrine
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Endogenous catecholamine
Low doses: -beta effects (vasodilation) dominate -moderate increase in systolic BP -diastolic BP falls -MAP remains relatively the same, so there is no reflex by baroreceptors. High doses -alpha effects (vasoconstriction) dominate. -systolic rises greater than diastolic. As the response dies, the MAP might drop below normal before returning to baseline. |
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Norepinephrine
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Catecholamine
Actions: -vasoconstriction via alpha-1 -both systolic and diastolic BPs rise -effects via beta-1 are masked by reflex bradycardia Low dose: -do not cause vasodilation (unlike Epi) Uses: -used in shock, but not as good as dopamine since dopamine doesn't decrease blood flow to kidney. |
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Dopamine
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Catecholamine
Low dose: -vasodilation via D1 on renal, mesenteric, and coronary beds. -this increases GFR and Na+ secretion. High dose: -positive intropic effect on heart via beta-1 -also causes release of NE from nerve terminals, which contributes more the effects on the heart -increases SBP and pulse pressure, but does not affect DBP. Higher doses: -activates alpha-1 receptors leading to vasoconstriction. Uses: -best drug for shock |
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Fenoldopam
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D1 agonist
Action: -causes peripheral vasodilation Uses: -in-hospital, short-term management of severe hypertension. PK: -should be given via IV not bolus dose. |
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Isoproterenol
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Beta agonist
Actions -increases stimulation of heart (beta-1) -vasodilation of skeletal muscle (beta-2) -increases SBP slightly, but it greatly decreases MAP and DBP. -less hyperglycemia than epinephrine b/c of insulin stimulation via beta receptors. Uses -rarely for asthma -sometimes in stimulating the heart in emergencies |
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Dobutamine
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selective beta-1 agonist
-racemic mixture, but results in a predominantly beta-1 agonistic activity. Uses: -increases CO without increasing HR or oxygen demand. Hence, can be used in heart failure. |
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Terbutaline
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Beta-2 agonist
PK: -not a substrate for COMT->longer duration -given orally, by inhalation, or SC Uses: -bronchodilator -reduces premature uterine contractions. |
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Albuterol (Salbutamol)
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Selective beta-2 agonist
Uses -for asthma via inhalation |
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Salmeterol
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Selective beta-2 agonist
Uses -asthma, but it has a slow onset of action, so not for acute attacks. -while the effect is delayed, the duration is 12 hours. |
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Formoterol
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Beta-2 agonist
Uses -asthma, long acting like Salmeterol |
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Phenylephrine
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selective alpha-1 agonist
Actions -raises both SBP and DBP -no direct effect on heart, but induces reflex bradycardia. Uses: -nasal decongestant -mydriatic -increase BP and terminate episodes of SVT MOA: -decrease resistance to airflow by decreasing volume in the nasal mucosa by vasoconstricting venous capacitance vessels via alpha-1. |
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Clonidine
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selective partial alpha-2 agonist
MOA: -can act on alpha-2 receptors in the CNS, hence are called centrally acting antihypertensives. Action -if given IV, causes transient rise in BP followed by more prolonged drop in BP. -if given orally, there is no hypertensive response seen. Side effects: -rebound hypertension if stopped suddenly |
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Methyldopa
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selective alpha2 agonist (centrally acting antihypertensive)
MOA: -like Clonidine, causes reduced sympathetic outflow, leading to reduced TPR and BP. Uses: -drug of choice for treatment of hypertension during pregnancy. Side effects: -sedation -impaired mental concentration -hemolytic anemia is less than 1% -can cause transient elevation of hepatic transanimases (hepatitis). -rebound hypertension if drug is stopped suddenly |
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Brimonidine
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Selective alpha-2 agonist
Uses: -reduces intraocular pressure in glaucoma by reducing aqueous humor production and increases uveoscleral flow. |
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Amphetamine
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Releasing agents
MOA: -displaces endogenous catecholamines from storage vesicles. -weak inhibitor of MAO -blocks catecholamine reuptake -can increase BP via alpha-1 agonist action and beta-1 stimulatory effects on heart Uses: -treat depression, fatigue, narcolepsy, and to suppress appetite. |
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Methylphenidate
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structural analogue of amphetamine
Uses: -treats ADHD in children |
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Tyramine
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Releasing agent
-found in ripe cheese and Chianti wine -normally oxidized by MAO Contraindications: -if patient is taking MAO inhibitors or TCAs, patient should avoid above products or can get Tyramine toxicity. |
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Cocaine
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Uptake inhibitor
MOA: -blocks DAT (dopamine transporter) -higher concentrations block SERT (serotonin transporter) and NET (NE transporter) -by inhibiting dopamine uptake into the neurons of the pleasure centers (limbic system), it produces intense euphoria. Uses -anesthetic (blocks local Na+ channels) |
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Atomoxetine
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Uptake inhibitor
MOA: -inhibits NET (NE transporter) Uses: -ADHD |
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Ephedrine
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Mixed-action adrenergic agonist
MOA: -stimualtes alpha and beta -releases NE from nerve endings -poor substrate of MAO and COMT -penetrates CNS Actions: -increases SBP and DBP by vasoconstriction and cardiac stimulation. -prophylactically in treatment of chronic asthma (slow onset bronchodilation) Uses: -myasthenia gravis (synergistic effect with AChEI) -nasal decongestant -asthma -raise BP in hypotensive patients Side effects: -life threatening cardiovascular reactions |
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Pseudoephedrine
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Mixed action adrenergic agonist
Uses: -nasal decongestant -found in combination with H1 antagonists |
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Phenoxybenzamine
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Non-selective alpha antagonist
-also blocks H1, muscarinic, and serotonin receptors Uses: -unsuccessful in maintaining low BP in hypertension and is NO longer used for this purposed. -pheochromocytoma Side effects: -postural hypotension -nasal stuffiness -inhibit ejaculation -contraindicated in patients with decreased coronary perfusion |
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Phentolamine
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Non-selective alpha antagonist
-also blocks serotonin receptors. -agonist at muscarinic, H1, and H2 receptors. Uses: -pheochromocytoma -prevention of dermal necrosis after extravasation of NE -stimulant overdose -cocaine-induced acute coronary syndrome -hypertensive crisis with sudden withdrawal of sympatholytic drugs Effects of Epi reversal -blocks alpha effects of Epi, but not beta, hence BP goes down. Effects of NE reversal -no reversal since NE has minimal beta effects. |
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Prazosin
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alpha-1 antagonist
Actions: -relaxes both arterial and venous smooth muscle (avoids reflex tachycardia). -decreases LDL and TAGs, while increasing HDLs. Uses: -hypertension Side effect: -orthostatic hypotension |
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Terazosin and Doxazosin
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alpha-1 antagonists
-longer half-life than prazosin Uses: -hypertension and BPH Side effect: -orthostatic hypotension |
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Tamsulosin
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selective alpha-1A antagonists
-avoids the orthostatic hypotension that you see with other alpha-1 antagonists. Uses: -BPH because alpha-1A mainly acts on genitourinary muscle |
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Yohimbine
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selective alpha-2 antagonists
-used in the past to treat erectile dysfunction, but PDEI have replaced it. Uses: -to reverse the antihypertensive effects of alpha-2 agonists like clonidine and methyldopa. |
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Propranolol
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non-selective beta blocker
Actions -negative inotropic and chromotropic -TPR increases d/t block of beta-2 -reduces renin release -decreased glycogenolysis and glucagon secretion. Contraindications -asthma patients -diabetic patients (can give but needs to be extra careful since the tachycardia is masked after insulin injection) -Prinzmetal angina Uses: -Hypertension -Glaucoma (decreases secretion of aqueous humor from ciliary body by not changing pupil size or accomodation like cholinergic drugs) -prophylaxis of Migraine (blocks vasodilation of arterioles in head) -Hyperthyroidism -Angina pectoris (decrease O2 requirement of heart) -Atrial fibrillation -prophylaxis against MI after first one -performance anxiety -essential tremor Side effects: -bronchoconstriction -sedation, dizziness, lethargy -should be gradually withdrawn in CAD patients to avoid acute tachycardia. |
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Nadolol
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non-selective beta blocker
Uses: -long term management of angina pectoris. -hypertension |
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Timolol
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non-selective beta antagonist
Uses: -hypertension -prophylaxis of migraines -open angle glaucoma (decreases aqueous humor production) |
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Atenolol and Metoprolol
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beta-1 selective antagonists
Uses: -hypertensive patients with impaired pulmonary function. -diabetic hypertensive patients receiving insulin or oral hypoglycemic agents. -prophylaxis of MI -angina pectoris |
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Esmolol
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beta-1 selective antagonists
-ultra short acting -given IV Uses: -SVT -arrhythmias associated with thyrotoxicosis. -perioperative hypertension -MI |
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Labetalol
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competitive antagonist at beta and alpha-1 receptors.
MOA: -relaxation of smooth muscle (alpha-1 block) -fall in BP (beta block) -vasodilation (intrinsic beta-2 agonist) Uses: -hypertension Side effects: -orthostatic hypotension -hepatic injury |
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Carvedilol
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combined beta and alpha-1 blocker
-also has antioxidant properties Uses: -hypertension and CHF |
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Pindolol
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partial beta agonist
-possess intrinsic sympathomimetic activity (ISA) Uses: -preferred as antihypertensive agents in patients with diminished cardiac reserve or a propensity for bradycardia. |
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alpha-methyltyrosine (metyrosine)
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competitive inhibitor of tyrosine hydroxylase
MOA: -reduces NE and Epi levels Uses: -adjuvant to alpha blockers for management of pheochromocytoma. |
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Reserpine
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Irreversible inhibitor of VMAT
MOA: -NE can't go inside vesicle and is degraded by MAO in cytoplasm. Uses: -hypertensive patients will show a gradual decrease in BP. |
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Guanethidine
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Inhibitor of NE storage
MOA: -displaces NE from vesicle leading to gradual depletion. -also disrupts AP that trigger release of NE from nerve terminal. Uses: -hypertension Side effects: -orthostatic hyptension -interferes with male sexual function |
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Histamine
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-Found in granules of mast cells and basophils
-found in ECl cells of the fundus of stomach. Receptors: H1 - found in endothelium, smooth muscle cells, and nerve endings. Act via Gq. H2 - found in gastric mucosa, cardiac muscle cells, and some immune cells. Act via Gs. H3 - histaminergic neurons. H4 - leukocytes in bone marrow and blood. Actions: -Vasodilation via H1 and H2 -H1 decreases contractility of heart -H2 increases contractility of heart -increased capillary permeability via H1-->urticaria (hives) -Triple response (if injected intradermally) - red spot (vasodilation)+flare (stimulation of axon reflexes)+wheal (edema) -bronchoconstriction via H1 -contraction of intestinal smooth muscle via H1 -pain and itching via H1 -gastric acid secretion via H2 Toxicity: -flushing, hypotension, tachycardia, headache, wheals, bronchoconstriction, GI upset Contraindications: -asthmatics, patients with active ulcer disease or GI bleeding. |
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Cromolyn and Nedocromil
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Release inhibitors
MOA: -reduce the degranulation of mast cells Note: Beta-2 agonists can also inhibit histamine release. |
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H1 receptor antagonists (inverse agonists)
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First generation:
chlorpheniramine, dimenhydrinate, diphenhydramine, doxylamine, promethazine, meclizine, hydroxyzine Second generation: -Terfenadine and astemizole (discontinued d/t torsades de pointes side effect) -fexofenadine, loratadine, cetirizine Actions: -first generation also bind to cholinergic, alpha-adrenergic, serotinergic, and local anesthetic receptor sites. Uses: -Allergic conditions (but Epi still #1 for systemic anaphylaxis) -motion sickness and nausea (only first generation and not as good as scopolamine) -somnifacients Side effects: -Sedation (less common in 2nd generation) -dry mouth (d/t anticholinergic effects) Toxicity: -hallucinations, excitement, ataxia, and convulsions. |
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H2 receptor antagonists
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Cimetidine, Ranitidine, Famotidine, Nizatidine
Action: -inhibit gastric acid secretion Uses: -Peptic ulcers, acute stress ulcers -GERD Side effects: -headache, dizziness, diarrhea, muscular pain -rapid IV infusion may cause bradycardia and hypotension |
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Serotonin (5-HT)
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-most found in ECl cells in GI tract
-in raphe nuclei of brain stem -found in platelets in blood Actions: -increased GI motility via 5-HT2 -increased ACh release via 5-HT4 -vaso and veno constriction via 5-HT2 -platelet aggregation via 5-HT2A -vomiting reflex via 5-HT3 -pain and itch via 5-HT3 |
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Sumatriptan, Zolmitriptan
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5-HT 1D/1B Agonists (Triptans)
Uses: -1st line for migraine headache (via vasoconstriction and by inhibiting susbtance P and neurokinin A) -other drugs used for migraine prophylaxis include beta blockers, amitriptyline, valproic acid, topirimate, CCBs Contraindications: -patients with CAD (b/c of vasoconstriction) |
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Metoclopramide
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5-HT4 agonist
Actions: -facilitates ACh release -antagonizes 5-HT3-->suppression of inhibitory interneurons -activates 5-HT4-->stimulation of excitatory neurons -antidopaminergic Uses: -antinauseant and antiemetic (central antidopaminergic) -prokinetic (peripheral D2 antidopaminergic) Side effects: -somnolence, nervousness, and dystonic reactions. -extrapyramidal symptoms like tardive dyskinesia |
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Cisapride
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5-HT4 agonist
Side effects: -prolongs QT interval -VT, torsades de pointes No longer used |
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Cyproheptadine
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5-HT2 antagonist
-also has potent H1 blocking actions Uses: -allergic rhinitis, vasomotor rhinitis -allergic conjunctivitis -cold urticaria -dermatographism -serotonin syndrome (which is due to overstimulation of 5-HT1A and 5-HT2) and results in hyperthermia, muscle rigidity, and myoclonus |
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Odansetron, Granisetron
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5-HT3 antagonist
Uses: -antiemetic |
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Ergot Alkaloids
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Ergotamine, Dihydroergotamine, Bromocriptine, Cabergoline, Ergonovine, Methylergonovine
MOA: -agonist, partial agonist, and antagonist actions at alpha and 5-HT -agonist and partial agonist actions at dopamine receptors Uses: -Migraine (not analgesic for anything else except this) -Hyperprolactinemia (Cabergoline > Bromocriptine b/c dopamine inhibits prolactin secretion) -Postpartum hemorrhage (uterus is very sensitive to ergot, so only use to prevent bleeding AFTER delivery not before) - usually oxytocin is better, but if it doesn't work, use ergonovine or methylergonovine. -diagnosis of Prinzmetal angina (Ergonovine provokes coronary artery spasm) |
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Dinoprostone
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PGE2 derivative
Uses: -ripens the cervix at term before induction of labor with oxytocin. -abortifacient (2nd trimester), alternative to carbopost tromethamine -management of benign hydatiform mole PK: -administered via vaginal insert, vaginal suppository, and cervical gel. |
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Carboprost tromethamine
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15-methyl-PGF-2alpha derivative
Uses: -abortifacient (2nd trimester), alternative to dinoprostone -control of postpartum hemorrhage which has not responded to ergonovine or oxytocin PK: -given IM |
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Misoprostol
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PGE1 derivative
FDA: -not approved for obstetric indications -approved for reducing risk of NSAID-associated gastric ulcers. Uses: -abortifacient used with mifepristone and methotrexate -prevention of peptic ulcers -cervical ripenening -management of postpartum hemorrhage PK: -IV or oral |
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Alprostadil
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PGE1 derivative
Uses: -used to maintain PDA in infants with TGV -used in treatment of impotence |
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Prostacyclin
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PGI2 derivative
Actions: -lowers peripheral, pulmonary, and coronary resistance Uses: -prevent platelet aggregation in dialysis machines. -pulmonary hypertension |
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Latanoprost
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PGF2 alpha derivative
Uses: -gold standard for glaucoma (increases outflow of aqueous humor, reducing intraocular pressure) |
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Zileuton
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5-lipoxygenase inhibitor
Uses: -asthma |
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Zafirlukast, Montelukast
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-prevents binding of LTD4 to receptor
Uses: -asthma |
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Thiazide diuretics
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Chlorthalidone, Hydrochlorothiazide, Metolazone
MOA: -inhibits the NCCT on the distal tubule Uses: -Hypertension -Heart failure -Hypercalciuria (promotes Ca2+ absorption) -Diabetes insipidus (by causing more sodium deficit, it induces more thirst, leading the body to correct itself more) -premenstrual edema Side effects: -magnesuria (magnesium is not reabsorbed but calcium is) -hypokalemia, hyponatremia, hypovolemia, hyperuricemia, hypercalcemia -hyperglycemia (reduces insulin secretion, decreasing glucose tolerance) -hyperlipidemia (increases LDL) -hypersensitivity (photosensitivity or dermatitis) |
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Loop diuretics
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Furosemide, Torsemide, Ethacrynic acid
MOA: -inhibit NKCC2 at TAL. -distal nephron segments compensate by absorbing Na+ and excreting K+-->hypokalemia -diminishes lumen positive potential-->hypocalcemia and hypomagnesia -hypochloremic metabolic alkalosis (d/t hypokalemia) Side effects: -Ototoxicity (mostly ethacrynic acid) -hyperuricemia (b/c uric acid competes with sodium for absorption) -acute hypovolemia -Hypokalemia, hypomagnesia, hypocalcemia Uses: -acute pulmonary edema associated with heart failure and hepatic/renal disease. -hypertension |
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Spirinolactone, Eplerenone
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Potassium sparing diuretics - Aldosterone antagonists
MOA: -antagonize aldosterone at the late distal tubule and cortical collecting tubule. PK: -both given orally -spirinolactone has a slower onset Side effects: -gastric upset and ulcers (b/c spirinolactone may induce gastritis and diarrhea) -Antiandrogenic effects (spirinolactone can also antagonize androgen receptors leading gynecomastia, impotence, hirsuitism, deeping of the voice) -Hyperkalemia and hyponatremia -hyperchloremic metabolic acidosis (b/c H+ secretion is inhibited along with K+) -CNS effects (lethargy, ataxia, confusion, and headache) Uses: -offset hypokalemia caused by other diuretics -heart failure (to treat refractory edema) -hypertension -primary hyperaldosteronism -edema (associated with hyperaldosteronism) |
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Amiloride, Triamterene
|
Potassium sparing diuretics - ENaC inhibitors
MOA: -inhibit ENaC in late distal tubule and collecting duct. K+ secretion is also inhibited since that is coupled with Na+ reabsorption via ROMK. Uses: -offset hypokalemia from other diuretics -heart failure -hypertension PK: -both are primary eliminated via renal excretion Side effects: -Hyperkalemia -Hyponatremia -Triamterene is associated with reduced glucose tolerance, photosensitivity, interstitial nephritis, and renal stones. |
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Acetazolamide
|
Carbonic anhydrase inhibitor
Uses: -Glaucoma -Mountain sickness -Metabolic alkalosis -Epilepsy (retards abnormal excessive discharge) MOA: -inhibit carbonic anhydrase in the proximal tubule both intracellularly and extracellularly. This inhibits the reabsorption of bicarbonate. -it also indirectly inhibits Na/K pump b/c the H+ provided to generate the ATP is not there. Hence, there is slight reduction in Na+ reabsorption. Side effects: -Metabolic acidosis -Hypokalemia and slight Hyponatremia -renal stones (b/c of phosphaturia and hypercalciuria, calcium and phosphate can't be reabsorbed properly since bicarbonate neutralizes lumen positive potential) -malaise, fatigue, drowsiness, paresthesias following large doses |
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Mannitol
|
Osmotic diuretic
Uses: -increase urine flow in patients with ARF -reduce ICP and treatment of cerebral edema -promote excretion of toxic substances MOA: -increase urinary excretion of all electrolytes everywhere in the nephron. -they do this by extracting intracellular water, expanding the extracellular volume, decreasing blood viscosity, and inhibit renin release. PK: -must be administered IV Side effects: -Extracellular volume expansion and hyponatremia -headache, nausea, vomiting -dehydration Contraindications: -patients with active cranial bleeding |
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Conivaptan
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ADH antagonist
MOA: -inhibits the V1 and V2 receptors that bind to ADH in the collecting tubule. Use: -hyponatremia -SIADH -heart failure (only if benefits outweigh risks since safety is not well established) PK: -must be administered IV -inhibits CYP3A4 Side effects: -Nephrogenic diabetes inspidus -infusion site reactions -atrial fibrillation, GI, and electrolyte disturbances. Contraindications: -hypovolemic hyponatremia (i.e. can treat euvolemic or hypervolemic only) -renal failure |
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Stage 1 hypertension 1st line drugs
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thiazide diuretics, ACEI, ARB, or CCBs
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2nd line antihypertensives
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alpha1- blockers, direct renin inhibitors, loop diuretics, central alpha2 agonists, peripheral adrenergic antagonists, and direct vasodilators
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LV dysfunction, what is 1st and 2nd antihypertensive drugs?
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1st line:
diuretic with ACEI; then add beta-blocker 2nd line: ARB or aldosterone antagonist |
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post-MI, what is 1st line and 2nd line antihypertensive drugs?
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1st line:
beta-blocker; then add ACEI or ARB 2nd line: aldosterone antagonist |
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coronary disease, what is 1st line and 2nd line antihypertensive drugs?
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1st line:
beta blocker; then add ACEI or ARB 2nd line: CCB, diuretic |
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diabetes mellitus, what is 1st line and 2nd line antihypertensive drugs?
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1st line:
ACEI or ARB 2nd line: diuretic; then beta blocker and CCB |
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chronic kidney disease, what is 1st line antihypertensive drugs?
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1st line:
ACEI or ARB |
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recurrent stroke prevention, what is 1st line antihypertensive drug?
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1st line:
diuretic with ACEI or ARB |
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Captopril, Enalapril, Lisinopril
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ACE inhibitors
MOA: -block conversion of angiotensin I to angiotensin II. This also attenuates aldosterone secretion resulting in slight hyperkalemia. -decrease GFR via decreased vasoconstriction of efferent arteriole. -block the degradation of bradykinin and stimulate the secretion of other vasodilating substances such as PGE2 and prostacyclin. PK: -all once-daily dosing except captopril which is usually 2-3 times per day. Side effects: -Hypotension (since they inhibit vasoconstriction) -Hyperkalemia (d/t aldosterone attenuation) -ARF (if bilateral renal stenosis, the other kidney can't compensate for the decrease in GFR) -dry cough (d/t increase in bradykinin levels) -Angioedema -altered sense of taste, skin rashes, drug fever Contraindications: -Pregnancy (causes congenital malformations in fetus) -bilateral renal artery stenosis -hyperkalemia Use: -1st line agents in primary hypertension caused by unilateral renal artery stenosis. -hypertension with diabetes -heart failure -24h after MI |
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Losartan, Valsartan
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Angiotensin receptor blockers (ARBs)
MOA: -block angiotensin type I receptor. Unlike ACEIs, they do not inhibit breakdown of bradykinin. Side effects: -lowest incidence of side effects compared to other antihhypertensives -hypotension, hyperkalemia -ARF (in bilateral renal artery stenosis) -Angioedema Contraindicaitons: -Pregnancy -bilateral renal artery stenosis -hyperkalemia |
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Aliskiren
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direct renin inhibitor
MOA: -blocks renin Use: -hypertension (only as alternative therapy) PK: -half life about 24 hrs and dose is daily Side effects: -low side effects like ARBs -hypotension, hyperkalemia -ARF -Angioedema Contraindications: -Pregnancy -bilateral renal artery stenosis -hyperkalemia |
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Verapamil
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Non-dihydropyridine CCB
MOA: -block L-type Ca2+ channels on vascular smooth muscle, cardiac myocytes, and cardiac nodal tissue. -non-dihydropyridines have more selectivity for cardiac muscle than vascular smooth muscle Use: -angina and arrhythmias PK: -orally administered Side effects: -Cardiac conduction abnormalities (bradycardia, AV block, and heart failure) -other effects (anorexia, nausea, peripheral edema, and hypotension) -Constipation Contraindications: -bradycardia, conduction defects, heart failure |
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Diltiazem
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non-dihydropyridine CCB
Uses: -hypertension, angina, arrhythmias MOA: -blocks L-type calcium channels -an intermediate between dihydropyridines and non-dihydropyridines. Hence, it has both cardiac depressant and vasodilation effects, so its reflex tachycardia is not as bad. PK: -orally administered Side effects: -constipation -bradycardia, AV block, and heart failure Contraindications: -bradycardia, conduction defects, heart failure |
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Nifedipine, Amlodopine, Nicardipine, Felodopine
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dihydropyridine CCB
MOA: -blocks L-type calcium channels -more selective for vascular smooth muscle than cardiac muscle, hence results in a reflex tachycardia Uses: -hypertension (primarily), angina, arrhythmias -Nifedipine: can also be used as a tocolytic Side effects: -reflex tachycardia -dizziness, flushing, headache, gingival hyperplasia, and peripheral edema Contraindications: -bradycardia, conduction defects, heart failure |
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Hydralazine, Minoxidil
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Direct vasodilators
-all patients receiving these drugs should receive a beta-blocker and a diuretic to attenuate the effects of the reflex tachycardia and sodium retention. MOA: -Minoxidil is a K+ channel opener that results in hyperpolarization of vascular smooth muscle -hydralazine is less potent and has an uncertain mechanism, but increases cGMP--> SM relaxation of arteriolar> veins. Uses: -hypertension and severe heart failure -hydralazine is first-line in treatment of hypertension in pregnancy along with methyldopa PK: -both are orally active -IV hydralazine in preeclampsia/eclampsia Side effects for hydralazine: -hypotension, reflex tachycardia -sodium and water retention -reversible lupus-like syndrome -dermatitis, drug fever, peripheral neuropathy, hepatitis, vascular headaches, nausea, flushing Side effects of Minoxidil: -Hypotension -reflex tachycardia -renin release and Na+ retention (more dramatic than hydralazine - use loop diuretic and beta blocker to combat this) -reversible trichosis on face, arms, back, and chest. |
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Bosentan
|
Endothelin receptor antagonist
MOA: -blocks the endothelin receptors (ETA > ETB ) located on vascular smooth muscle. This results in vasodilation. Uses: pulmonary hypertension PK: -strong inducer of CYP2C9 and 3A4 Side effects: -edema, headache -spermatogenesis inhibition -respiratory tract infection Contraindications: -pregnancy (category X drug) |
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treatment of hypertensive emergencies
|
1. Lower BP by no more than 25% (within min to 1 hr). Appropriate 100-110 mmHg (DBP)
2. if stable, followed by further reduction towards goal of 160/100 mmHg (SBP/DBP) within 2-6 h and gradual reduction to normal over next 8-24 hr. |
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Sodium nitroprusside
|
Antihypertensive
MOA: -dilates both arterial and venous via guanyl cyclase. This results in net reduction of TPR. Uses: -drug of choice for hypertensive emergencies. -heart failure -controlled hypotension PK: -reduces BP <2 min -broken down to cyanide -->cyanide toxicity -aqueous solution in sensitive to light and must be made up directly before each administration and covered with opaque oil. Side effects: -hypotension -reflex tachycardia -goose bumps, abdominal cramping, nausea, vomiting, headache, muscle twitching, sweating. -cyanide toxicity (treat with sodium thiosulfate) |
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Nitroglycerin
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Vaso/Veno dilator
MOA: -activates guanyl cyclase, resulting in relaxation of both arterial and venous smooth muscles. Uses: -management of hypertensive emergencies -acute decompensated heart failure -controlled hypotension PK: -reduces BP in 5-10 mins -duration of action: 5-10 mins Side effects: -hypotension -reflex tachycardia -methemoglobinemia (oxygen curve shifts to left), tolerance |
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Digoxin
|
Cardiac glycoside
MOA: -positive inotrope and negative chromotrope -inhibits Na/K pump, impairing Na/Ca2+ exchanger to pump calcium out. This results in increased intracellular calcium. -it decreases automaticity d/t increase in vagal tone and decrease in SNS activity. -prolongation of ERP and decreased conduction velocity in AV nodal tissue. -baroreceptor sensitization (sustained elevation of plasma NE, renin, etc.) PK: -half life is 36-40 hrs Side effects: -Cardiac arrhythmias, atrial tachycardias, and AV block -GI (anorexia, nausea, and vomiting) -CNS (headache, fatigue, confusion, blurred or yellow vision, alteration of color perception, halo on dark objects) Contraindications: -hypokalemia (potassium decreases affinity of Na/K pump to digoxin, so hypokalemia leads to toxicity of it) -hypercalcemia (this would just be helping digoxin since it already increases calcium) -hypomagnesia (sensitizes the heart to digoxin-induced arrhythmias) -bradyarrhythmias -uncontrolled hypertension -diastolic or RHF Drug and disease interactions: -quinidine, amiodarone, verapamil, and NSAIDs compete with digoxin binding sites and depress renal clearance of digoxin (increases toxicity). -diuretics (can cause hypokalemia which can lead to toxicity) -hypothyroidism (less thyroid hormone means less metabolism means increased toxicity) -hyperthyroidism (leads to increased metabolism of digoxin) -renal failure (will lead to increased toxicity) Treatment of toxicity: -withdraw the drug -adjust electrolytes -treat VT with lidocaine or Mg2+ -digibind or digoxine immune fab (antibodies to digoxin) |
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Inamrinone, Milrinone
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Phosphodiesterase (PDE) III inhibitors
MOA: -inhibit myocardial PDE, resulting in an increase in cAMP levels. Increased cAMP produces positive inotropic, arterial and venous vasodilating effects. Use: -short-term for intractable heart failure -long term therapy shows increased mortality PK: -given IV Side effects: -arrhythmia -hypotension -thrombocytopenia |
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glucagon
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MOA:
-stimulates adenyl cyclase-->increases cAMP-->positive inotropic and chronotropic -produces the same effects as beta-agonist without the need to bind to beta receptors. Uses: -beta blocker overdosage |
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quinidine, procainamide, disopyramide
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Class IA Antiarrhythmics (Na+ channel blockers)
MOA: -block Na+ channels that are responsible for Phase 0 depolarization, hence reducing slope of Phase 4 and automaticity of SA node. -these drugs also block K+ channels in phase 3, resulting in a longer ERP (reflected as QT elongation). -Anticholinergic activity (Disopyramide>Quinidine>Procainamide) Uses: -afib, SVT, VT PK: -quinidine is an inhibitor of CYP2D6, 3A4, and P-glycoprotein -procainamide can be acetylated to NAPA, which has class III activity and prolongs ERP and AP. Side effects: -tachycardia, dry mouth, urinary retention, blurred vision, and constipation. -quinidine: cinchronism (headache, tinnitus, psychosis, blurred vision); thrombocytopenic purpura, hemolytic anemia, nausea, vomiting, diarrhea -Procainamide: reversible lupus-like syndrome, GI tolerance, VT, depression, hallucinations, psychosis -Dispyramide: negative inotropic effects, hypotension and cardiac failure w/o pre-existing myocardial dysfunction. Contraindications: -complete heart block, prolonged QT interval, torsades de pointes, incomplete heart block, uncompensated heart failure, myocarditis, and severe myocardial damage |
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Lidocaine, Mexilitine, Tocainide
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Class IB Antiarrhythmics (Na+ blockers)
Uses: -acute VT -digitalis-induced VT MOA: --block Na+ channels that are responsible for Phase 0 depolarization, hence reducing slope of Phase 4 and automaticity of SA node. -exert only at fast heart rates (not normal rhythm), cause slight reduction in ERP by promoting K+ efflux. PK: -Lidocaine can only be given IV d/t extensive first-pass metabolism Side effects: -Lidocaine: has wide TI, but effects can include dizziness, sedation, slurred speech, blurred vision, paresthesia, muscle twitching, confusion, nausea, vomiting, seizures, psychosis, sinus arrest, convulsions, and coma. -Mexilitine: cns and gi effects -Tocainide: hematological and pulmonary toxicities. |
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flecainide, propafenone
|
Class IC Antiarrhythmics
Use: -life-threatening SVT and VT -prevention of paroxysmal afib -maintenance of normal sinus rhythm in afib patients. MOA: -block Na+ channels that are responsible for Phase 0 depolarization, hence reducing slope of Phase 4 and automaticity of SA node. -work at all heart rates, making them the most potent of all class I drugs. Side effects: -Flecainide: blurred vision, dizziness, dyspnea, headache, tremor, nausea, makes heart failure worse (d/t negative inotropic), conduction disturbances, life-threatening VTs. -Propafenone: dizziness, fatigue, bronchospasm (d/t slight beta blocking effect), headache, taste disturbances, GI upset, AV block, conduction disturbances Contraindications: -post-MI |
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Class II Antiarrhytmics
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Esmolol, Metoprolol, Propranolol
Uses: -supraventricular arrhythmias (atrial flutter, afib, AV nodal re-entrant tachycardia). MOA: -decreases cAMP and Calcium currents -HR is slowed, PR is lengthened, and repolarization is prologed. Side effects: -metoprolol can cause dyslipidemia Toxicity: -treat with glucagon |
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Amiodarone, Dofetilide, Sotalol
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Class III antiarrhythmics (K+ blockers)
Uses: -Amiodarone: severe SVT and VTs. -Dofetilide: maintenance of normal sinus rhythm in patients with chronic afib/aflutter. -Sotalol: life-threatening ventricular arrhythmias. Maintenance of sinus rhythm in patients with afib/aflutter. MOA: -by blocking K+ channels in phase 3, AP duration is prolonged, ERP is increased, QT interval is prolonged. -Amiodarone: shows class I-IV blocking, so decreases slope of phase 4 and conduction velocity. -Dofetilide: potent K+ channel blocker. -Sotalol: has potent non-selective class II activity. PK: -amiodarone: can be taken IV or orally. Requires loading dose b/c half life is long and effect takes 6 weeks to achieve. Side effects: -amiodarone: tremor, ataxia, paresthesia, GI disturbances, bradycardia, AV block, hyper/hypo thyroidism, interstitial pulmonary fibrosis, arrhythmias, liver toxicities, photosensitivity, blue-gray skin discoloration and hypotension (IV only). -Dofetilide: headache, dizziness. VT and torsades de pointes can also occur. -Sotalol: weakness, dizziness, and fatigue. Contraindications: -Amiodarone: bradycardia, SA or AV nodal block, severe hypotension, severe respiratory failure. |
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Class IV antiarrhythmics
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Diltiazem, Verapamil
Use: -SVT, reduction of ventricular rate in afib and aflutter. MOA: -decrease rate of phase 4 depolarization, thus decrease the rate of automaticity, slow conduction velocity, and prolong ERP. -HR is slowed and PR is prolonged. |
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Adenosine
|
Use:
-drug of choice for acute SVT MOA: -increases K+ conductance, thereby inhibiting SA nodal, atrial, and AV nodal conduction. -net result is decreased conduction velocity, prolongation of ERP, and decreased automaticity of AV node. PK: -short half life, hence use IV Side effects: -flushing, headache, chest pain, excessive AV or SA nodal inhibition. -bronchoconstriction |
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Magnesium
|
Use:
-torsades de pointes -digitalis-induced arrhythmias -prophylaxis of arrhythmias in acute MI MOA: -magnesium is required for Na/K pump to function properly. Hence, it inhibits calcium entry and promotes pumping out calcium via Na/Ca2+ exchanger. -works exactly opposite to digoxin. |
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Isosorbide dinitrate and mononitrate
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Nitrates (also includes nitroglycerin and sodium nitroprusside)
MOA: -NO activates guanyl cyclase-->GTP-->cGMP-->inhibits entry of Calcium into the cell, thereby reducing intracellular Ca2+ concentrations-->smooth muscle relaxation. -also activates K+ channels that leads to hyperpolarization. -cGMP-dependent kinase also activates myosin light chain phosphatase. Actions -venodilation more than vasodilation-->decreased preload-->decreased oxygen demand by heart. PK: -tolerance: vessels become desensitized to the vasodilating effects (use a daily nitrate-free interval of 10-12 h to avoid, use in day, then stop at night using a patch). -isosorbide drugs have longer half life than nitroglycerin and are more useful in long-term management and prophylaxis of angina. -unlike other nitrates, this can survive first-pass metabolism and has almost 100% bioavailability. Side effects: -hypotension -reflex tachycardia (d/t vasodilation) -headache (d/t cerebral vasodilation) -facial flushing Contraindications: -sildenafil (b/c it also increases cGMP like nitrates). Too much cGMP can lead to impaired coronary perfusion. |
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Ranolazine
|
Na+ channel blocker
Use: -last line for angina patients MOA: -blocks inward late Na+ currents in cardiomyocytes. This promotes calcium pumping via Na/Ca2+ exchanger, reducing intracellular calcium. Actions: -improved coronary blood flow -fatty acid oxidation Side effects: -QT prolongation -nausea, vomiting, dizziness, constipation Contraindications: -long QT |
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Aspirin
|
Cyclooxygenase inhibitor
MOA: -inhibits TXA2 synthesis by irreversible acetylation of the enzyme COX. -platelets are anuclear and can't synthesize another COX, hence it takes 10 days for new platelets to be made. Uses: -cerebral ischemia -reduce recurrent MI -decrease mortality in post-MI patients |
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Clopidogrel and Ticlopidine
|
ADP Receptor blockers
Uses: -cerebrovascular, cardiovascular, and peripheral vascualr disease -reduce rate of stroke, MI, and acute coronary syndrome MOA: -irreversibly inhibit P2Y12, one of the two subtypes of ADP receptors on the platelet surface. As a result, platelet aggregation is stopped. PK: -Clopidogrel - has to be converted to its active form by CYP2C19, hence the patient must not be a CYP2C19 poor metabolizer. Side effect: -ticlopidine: neutropenia -thrombocytopenic purpura -both drugs inhibit P450 -clopidogrel - has less side effects Contraindications: -cyp2c19 poor metabolizers -omeprazole (b/c its a cyp2c19 inhibitor) |
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Dipyridamole, Cilostazol
|
Phosphodiesterase inhibitors
MOA: -dipyridamole: coronary vasodilator, increases cAMP by inhibiting phosphodiesterase and/or by blocking adenosine uptake. -Cilostazol: PDE inhibitor, promotes vasodilation and inhibition of platelet aggregation. Uses: -Dipyridamole: as an adjunct to warfarin to prevent post-operative thromboembolic complications. -Cilostazol: intermittent claudication. |
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Abciximab, Eptifibatide, Tirofiban
|
Gp IIb/IIIa receptor antagonist
Abciximab: -monoclonal antibody against Gp IIb/IIIa receptor. Eptifibatide: -cyclic peptide reversible antagonist of the Gp IIb/IIIa Tirofiban: -reversible antagonist of the Gp IIb/IIIa Uses: -coronary syndromes PK: given parenterally |
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|
Heparin
|
Anticoagulant
UFH (unfractionated heparin): -heparin activates antithrombin III-->inhibits II, VII, IX-XII -monitor using aPTT (monitors II, V, VIII-XII, and fibrinogen) Uses: -venous thrombosis, pulmonary embolism -unstable angina or acute MI Side effects: -bleeding -hypersensitivity reactions -heparin-induced thrombocytopenia: Type I is mild, Type II is systemic that occurs with UFH. (treat with direct thrombin inhibitor or fondaparinux) - it caused by antibodies that recognize UFH and platelet factor 4. -mild elevations of liver enzymes -osteoporosis (UWH for long time) Antidote: -protamine sulfate LMWH (low molecular weight heparin): -includes Enoxaparin, Dalteparin, Tinzaparin -inhibit activated factor X, but not much II (thrombin) like UFH does. -longer halflife and bioavailability than UFH -only needs to be monitored in renal insufficiency, obesity, and pregnancy. |
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|
Fondaparinux
|
selective Xa inhibitor
MOA: -inhibits Xa, with neglible antithrombin activity Uses: -DVT, pulmonary embolism. PK: -once daily SC injection |
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|
Lepirudin
|
Direct thrombin inhibitor
MOA: -can inhibit both II and IIa Uses: -HIT Contraindications: -renal insufficiency (b/c no antidote exists for toxicity) PK: -given IV and monitored with aPTT |
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|
Bivalirudin
|
direct thrombin inhibitor
MOA: -bivalent inhibitor of thrombin PK: -given IV and monitored by aPTT |
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|
Argatroban
|
direct thrombin inhibitor
Use: -prophylaxis or treatment in patients with HIT. -HIT that are getting percutaneous coronary intervention (PCI) PK: -given IV, monitored via aPTT |
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|
Streptokinase
|
Thrombolytic
MOA: -produced by beta-hemolytic strep, converts plasminogen to plasmin. -also catalyzes the degradation of fibrinogen, V, and VII. Uses: -acute MI -acute pulmonary embolism |
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|
Urokinase, Anistreplase
|
Thrombolytic
MOA: -converts plasminogen to plasmin. Uses: -pulmonary emboli |
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|
Alteplase, Reteplase, Tenecteplase
|
Recombinant t-PA (tissue plasminogen activators)
MOA: -t-PA usually converts bound plasminogen (to fibrin) to plasmin. Free plasminogen has a less affinity for it. Uses: -Alteplase: acute MI, acute ischemic stroke -Reteplase: acute MI -Tenecteplase: acute MI PK: -Alteplase: half life is 3-6 mins -Reteplase: half life is 14-18 mins, so given as double bolus -Tenecteplase: half life is 20-24 mins, so single IV dose. |
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|
Aminocaproic acid
|
plasminogen activation inhibitors
MOA: -competitive inhibitor of plasminogen activation. Uses: -hemophilia -reverses fibrinolytic therapy -postsurgical GI bleeding -postprostatectomy bleeding -bladder hemorrhage secondary to radiation and drug-induced cystitis Side effects: -intravascular thrombosis -hypotension -myopathy -abdominal discomfort -diarrhea -nasal stuffiness |
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|
Protamine sulfate
|
Heparin antagonist
MOA: -positively charged binds to negatively charged heparin and inhibits it. Uses: -life-threatening hemorrhage -heparin excess (esp. UFH) - inactive against fondaparinux PK: given IV Side effects: -hypersensitivity, dyspnea, flushing, bradycardia, hypotension |
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|
Vitamin K
|
Uses:
-hypoproteinemia of the newborn (elevates clotting factors back to normal) -for mothers who are receiving anticonvulsants prior to delivery. -vitamin K deficiency -drug-induced hypothrombinemia PK: -IV or oral b/c bioavailability SC is erratic |
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|
Atorvastatin, Fluvastatin, Lovastatin, Pravastatin, Rosuvastatin, Simvastatin
|
HMG CoA reductase inhibitors (statins)
MOA: -competitively inhibit HMG-CoA reductase, inhibiting cholesterol synthesis. -this results in upregulation of LDL receptors and increased clearance of LDL from the blood. Other actions: -reduce inflammation -decrease platelet aggregation -improve endothelial function -decrease plasma levels of CRP PK: -Rosuvastatin and atorvastatin are the most powerful ones. -Lovastatin and simvastatin are prodrugs. Uses: -most effective drugs for lowering LDL -type IIa hypercholesterolemia Contraindications: -women who are pregnant or lactating Side effects: -elevation of aminotransferases (liver enzymes) -myopathy and rhabdomyolysis |
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Niacin (Nicotinic acid)
|
Antihyperlipidemic
Action: -most effective agent for increasing HDL and the only agent to reduce Lp(a) -also decreases VLDL, LDL MOA: -via Gi, inhibits cAMP in adipocytes, inhibiting HSL, reducing transport of FFAs to liver and decreasing hepatic TAG synthesis. -this also reduces VLDL synthesis and consequentially LDL. -it also increases LPL activity, promoting clearance of chylomicrons, VLDLs, and TAGs. Side effects: -cutaneous flush, pruritus, dry skin, acanthosis nigricans -hepatotoxicity and hyperglycemia -elevates uric acid levels -->gout -insulin resistance |
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|
Gemfibrozil, Fenofibrate
|
Fibrates
Action: -lower VLDL and increase HDL MOA: -activate PPAR-alpha (peroxisome proliferator-activated receptor) -this results in increased LPL expression, decreased TAGs, decreased expression of apoCIII, and increased hepatic oxidation of fatty acids. Uses: -hypertryglyceridemias where VLDL predominates and in dysbetalipoproteinemia. Side effect: -myositis -lithiasis (increase biliary cholesterol excretion) |
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|
Cholestyramine, Colestipol, Colesevelam
|
Bile-acid resins
MOA: -bind to anionic bile acids in intestinal lumen and prevent their reabsorption. Uses: -used with statins or niacin to increase LDL secretion. -drugs of choice for children and women who are or are planning to become pregnant. Side effects: -bloating, cramping, nausea -constipation |
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|
Ezetimibe
|
Cholesterol absorption inhibitors
Action: -lower LDL, small increases in HDL, mild decrease in TAGs MOA: -selective inhibitor of NPCIL1 in jejunal enterocytes, which takes cholesterol from the lumen. -reduced delivery of cholesterol to liver leads to upregulation of LDL receptors and increased clearance of LDL. -complementary to statins (these drugs inhibit reabsorption of cholesterol, increasing synthesis while statins inhibit synthesis, increasing reabsorption) Vytorin -is a statin and ezetimibe (inhibiting both synthesis and reabsorption) Side effects: -reversible impaired hepatic function -myositis |
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Lovaza, EPA, DHA
|
omega-3 fatty acids
MOA: -decrease plasma TAGs and increase fatty acid oxidation in the liver. -might increase LDL as they decrease TAGs |
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Codeine
|
requires CYP2D6 conversion to morphine.
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|
6-mercaptopurine and azathiopurine
|
anticancer drug
-metabolized by TPMT via methylation for inactivation. -patients with TPMT receive 1/10 of the dose. Toxicity: -myelosupression |
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Gefitinib
|
Tyrosine kinase inhibitor of EGFR
Uses: -NSCLC |
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Iron
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Uses:
-iron deficiency PK: -ferrous iron is most efficiently absorbed orally (ferrous sulfate, ferrous gluconate, ferrous fumarate). -parental iron is only for patients unable to absorb oral iron or with chronic anemia (iron dextran, sodium ferric gluconate complex, and iron sucrose) Side effects: -nausea, epigastric discomfort, abdominal cramps, constipation, diarrhea Acute iron toxicity: -necrotizing gastroenteritis, vomiting, abdominal pain, bloody diarrhea (treat with deferoxamine - iron chelator) Chronic iron toxicity: -hemochromatosis (when excess iron is deposited in organs) - treat with deferoxamine or deferasirox. -chronic iron overload in the absence of anemia is most effectively treated with phlebotomy. |
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Filgrastim and Sargramostin
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Myeloid growth factors
Filgrastim: -G-CSF stimulator (granulocyte) Sargramostin -GM-CSF stimulator (granulocyte monocyte) Uses: -accelerate recovery of neutrophils after cancer therapy. -other neutropenia. G-CSF toxicity -bone pain GM-CSF toxicity: -fever, arthralgias, and capillary damage |
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Interleukin-11
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Megakaryocyte growth factor
Uses: -thrombocytopenia after chemotherapy |
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Hydroxyurea
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MOA:
-increases HbF levels, thus diluting HbS levels in sickle cell anemia. Toxicity: -bone marrow suppression and cutaneous vasculitis. Uses: -sickle cell anemia -CML, polycythemia vera |
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Dexamethasone, fluticasone, budesonide, flunisolide, beclomethasone, prednisone, hydrocortisone
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Corticosteroids
MOA: -inhibit phospholipase A2 -->decreases arachidonic acid -->decreased cyclooxygenase --> decrease PGs and LTs. -also increase beta receptor sensitivity in respiratory tract. -bind to intracellular receptors and activate GRE (glucocorticoid response elements), that results in the synthesis of substances that inhibit inflammation and allergy. Use: -1st line in pediatric cases -patients not responding to beta2 agonists Side effects: -oropharyngeal candidiasis -mild growth retardation IV steroids: -prednisone and hydrocortisone -these are used in status asthmaticus Surface active: -beclomethasone, dexamethasone, fluticasone, flunisolide, budesonide -these are 1st line inhalational agents for moderate to severe asthma |
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Omalizumab
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Anti-IgE antibody
MOA: -binds to IgE on mast cells and prevents degranulation. Uses: -prophylactically for asthma PK: -administered IV Side effects: -anaphylaxis in 1-2/1000 |
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Ethinyl estradiol and mestranol
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Oral contraceptives
PK: -ethinyl estradiol: active as long as it can be hydrolyzed by intestinal bacteria (use of broad-spectrum antibiotics may decrease efficacy) -mestranol: must be converted by liver to ethinyl estradiol |
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Levonorgestrel and norgestrel
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Progestins (part of contraceptives)
-1st generation -have highest androgenic activity MOA: -suppress LH and FSH release. -progestin also thickens cervical mucus, preventing sperm penetration Uses: -reduce risk of endometrial cancer -reduce risk of ovarian cancer -improve regulation of menstruation -relief of benign breast disease -prevention of ovarian cysts -reduce risk of PID -improvement in acne control Side effects: -nausea, bloating, breakthrough bleeding -headache (if migraine, discontinue use) -insulin resistance (competes with insulin for binding to TRK) -Hirsutism (b/c of androgenic activity) -Melasma (hyperpigmentation d/t estrogen stimulation of melanocytes) -Amenorrhea -Dyslipidemia (low dose have no significant effect on LDL or HDL) -cardiovascular disease (estrogens increase hepatic production of factor VII, factor X, and fibrinogen-->thromboembolism) -Carcinogenicity (while they reduce endometrial and ovarian, they might induce other cancers) -Depression Contraindications: -Absolute: thromboembolic disease, stroke, CAD, breast carcinoma, estrogen-dependent neoplasm, pregnancy, smoking (>15 cigarettes per day and older >35), hepatic tumors, active liver disease -Relative: diabetes, smoking (<15 cigarettes per day at any age), hypertension, migraine, fibroid tumors, breast-feeding |
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Norethindrone
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Progestin (part of contraceptives)
-2nd generation -lower androgenic activity MOA: -suppress LH and FSH release. -progestin also thickens cervical mucus, preventing sperm penetration Uses: -reduce risk of endometrial cancer -reduce risk of ovarian cancer -improve regulation of menstruation -relief of benign breast disease -prevention of ovarian cysts -reduce risk of PID -improvement in acne control Side effects: -nausea, bloating, breakthrough bleeding -headache (if migraine, discontinue use) -insulin resistance (competes with insulin for binding to TRK) -Hirsutism (b/c of androgenic activity) -Melasma (hyperpigmentation d/t estrogen stimulation of melanocytes) -Amenorrhea -Dyslipidemia (low dose have no significant effect on LDL or HDL) -cardiovascular disease (estrogens increase hepatic production of factor VII, factor X, and fibrinogen-->thromboembolism) -Carcinogenicity (while they reduce endometrial and ovarian, they might induce other cancers) -Depression Contraindications: -Absolute: thromboembolic disease, stroke, CAD, breast carcinoma, estrogen-dependent neoplasm, pregnancy, smoking (>15 cigarettes per day and older >35), hepatic tumors, active liver disease -Relative: diabetes, smoking (<15 cigarettes per day at any age), hypertension, migraine, fibroid tumors, breast-feeding |
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desogestrel and norgestimate
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Progestin (part of contraceptives)
-3rd generation -lower androgenic activity than 2nd generation MOA: -suppress LH and FSH release. -progestin also thickens cervical mucus, preventing sperm penetration Uses: -reduce risk of endometrial cancer -reduce risk of ovarian cancer -improve regulation of menstruation -relief of benign breast disease -prevention of ovarian cysts -reduce risk of PID -improvement in acne control Side effects: -nausea, bloating, breakthrough bleeding -headache (if migraine, discontinue use) -insulin resistance (competes with insulin for binding to TRK) -Hirsutism (b/c of androgenic activity) -Melasma (hyperpigmentation d/t estrogen stimulation of melanocytes) -Amenorrhea -Dyslipidemia (low dose have no significant effect on LDL or HDL) -cardiovascular disease (estrogens increase hepatic production of factor VII, factor X, and fibrinogen-->thromboembolism) -Carcinogenicity (while they reduce endometrial and ovarian, they might induce other cancers) -Depression Contraindications: -Absolute: thromboembolic disease, stroke, CAD, breast carcinoma, estrogen-dependent neoplasm, pregnancy, smoking (>15 cigarettes per day and older >35), hepatic tumors, active liver disease -Relative: diabetes, smoking (<15 cigarettes per day at any age), hypertension, migraine, fibroid tumors, breast-feeding |
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dospirenone
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Progestin (part of contraceptives)
-4th generation -antiandrogenic MOA: -suppress LH and FSH release. -progestin also thickens cervical mucus, preventing sperm penetration Uses: -reduce risk of endometrial cancer -reduce risk of ovarian cancer -improve regulation of menstruation -relief of benign breast disease -prevention of ovarian cysts -reduce risk of PID -improvement in acne control Side effects: -nausea, bloating, breakthrough bleeding -headache (if migraine, discontinue use) -insulin resistance (competes with insulin for binding to TRK) -Hirsutism (b/c of androgenic activity) -Melasma (hyperpigmentation d/t estrogen stimulation of melanocytes) -Amenorrhea -Dyslipidemia (low dose have no significant effect on LDL or HDL) -cardiovascular disease (estrogens increase hepatic production of factor VII, factor X, and fibrinogen-->thromboembolism) -Carcinogenicity (while they reduce endometrial and ovarian, they might induce other cancers) -Depression Contraindications: -Absolute: thromboembolic disease, stroke, CAD, breast carcinoma, estrogen-dependent neoplasm, pregnancy, smoking (>15 cigarettes per day and older >35), hepatic tumors, active liver disease -Relative: diabetes, smoking (<15 cigarettes per day at any age), hypertension, migraine, fibroid tumors, breast-feeding |
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Minipils (progestin-only pill)
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Contraceptive
-contain norethindrone or norgestrel Benefits: -have not shown any risk of thromboembolic disease like estrogen-containing contraceptives have -decreased dysmenorrhea, decreased menstrual blood loss, and decreased premenstrual syndrome symptoms. MOA: -thickening of cervical mucus PK: -taken every day |
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Contraceptive patch (Ortho-Evra)
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transdermal patch that contains ethinyl estradiol and a progestin
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Contraceptive ring (NuvaRing)
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transvaginal delivery system that delivers ethinyl estradiol and a progestin
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Depo-Provera
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Contraceptive
-contains DMPA (depot medroxyprogesterone acetate) Side effects: -greater chance of menstrual irregularities and weight gain compared to combined oral contraceptives. -significant loss of bone mineral density |
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Subdermal progestin implants (Implanon)
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-implant containing progestin placed under the arm for 3 years.
-good for women who have adverse reactions to estrogen-related drugs or contraindications. |
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Mirena (IUS)
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Levonorgestrel-releasing Intrauterine system
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Nonoxynol-9
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Spermicide
MOA: -surfactant that destroys the cell membranes of sperm |
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Plan B and Next Choice
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-contain two tablets of levonorgestrel to be taken within 72 hrs after unprotected intercourse.
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Plan B One-Step
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-contains one tablet of levonorgestrel to be taken within 72 hrs after unprotected intercourse.
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Ella (ulipristal acetate)
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Progesterone antagonist
-single tablet is taken within 5 days after unprotected intercourse. |
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Oxytocin
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Peptide hormone
MOA: -activates phospholipase C via GPCRs. -increases PG synthesis which further stimulates uterine contractions. Uses: -labor induction -postpartum hemorrhage (if this is ineffective, ergonovine or methylergonovine may be used) -oxytocin challenge test (fetal heart rate should go down, if it is delayed, then can mean fetal hypoxia and warrant cesarian delivery). -induction of abortion PK: -IV (for labor induction) -IM (control of postpartum bleeding) -nasal spray (promote milk ejection) Side effects: -inadvertent activation of vasopressin receptors (SIADH symptoms) -abnormal uterine contractions. -bolus injections can cause hypotension (hence give IV in dilute solutions). Contraindications: -fetal distress, prematurity, cephalopelvic disproportion, uterine rupture |
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Magnesium sulfate
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Uterine relaxants (Tocolytics)
Uses: -primary purpose is to delay delivery for 48 hours to allow glucocorticoids to accelerate maturation of fetal lungs. MOA: -Magnesium sulfate: primary tocolytic agent. It inhibits APs, uncoupling excitation-contraction in myometrial cells. Side effects: -flushing, nausea, headache, drowsiness, and blurred vision -mother should be monitored for toxic effects (respiratory depression, cardiac arrest). -can cross placenta and lead to motor depression of the neonate |
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Indomethacin
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Uterine relaxants (Tocolytics)
MOA: -prostaglandin inhibitor Use: -close PDA -delay preterm (<37 wks) labor PK: -orally or rectally Side effects: -similar efficacy to terbutaline -oligohydramnios (b/c they decrease renal blood flow if used for more than 48 hrs) Contraindications: -if after 32 weeks gestation b/c can cause premature closure of PDA. |
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Atosiban
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Competitive antagonist at oxytocin receptors
MOA: -decreases and stops uterine contractions. -analog of oxytocin |
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N-acetyltransferase 2
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Enzyme that acetylation:
-isoniazid -hydralazine -procainamide -sulfonamides Autosomal recessive mutation results in less acetylation. |
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Theophylline, Aminophylline
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Methylxanthines
MOA: -inhibit PDE and block adenosine receptors Action: -bronchodilator PK: -narrow TI (not a safe drug) Side effects: -CNS (tremors, seizures, insomnia) -arrhythmias Antidote: -beta-blockers for toxicity |
