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85 Cards in this Set
- Front
- Back
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DMSO (dimethyl sulfoxide)
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enhances percutaneous absorption of many drugs (controversial due to toxicity)
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cimetidine
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anti-ulcer drug
potent inhibitor of drug metabolism (CYPs), leading to potentially toxic levels of drugs in the blood |
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phenobarbital
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induces P450IIB, results in faster drug metabolism (need to give more drug for same effect)
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probenecid
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competitively inhibits tubular secretion of penicillin to prolong the duration of its effects
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penicillin
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antibiotic, secretion can be inhibited by probenecid
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NET (norepinephrine transporter)
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takes norepinephrine back into the synaptic terminal (also transports DA and E)
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Cocaine
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inhibits NET
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MAO (monoamine oxidase)
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degrades NE on mitochondrial surface
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OCT (organic cation transporters)
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takes up NE into other cells, where it can be metabolized by COMT
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COMT (Catechol-o-methyltransferase)
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cytoplasmic enzyme for metabolizing NE, most of the NE and E released by the adrenal medulla is metabolized in the liver
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alpha 1 receptors
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↑Gq = ↑PLC = ↓PIP2 = DAG/IP3 = ↑PKC/(↑Ca=↑PK)
equal E and NE affinity Blood vessels (smooth muscle) - vasoconstriction found in blood vessels in Skin, constrict during sympathetic inn to redirect blood to muscles |
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alpha 2 receptors
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↑Gi = ↓AC = ↓cAMP = ↓PKA
equal E and NE affinity nerve terminals (presynaptic inhibitory response) - decreased NE release vascular smooth muscles (less imp than a1) - vasoconstriction |
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Beta 1 receptors
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↑Gs = ↑AC = ↑cAMP = ↑PKA
equal E and NE affinity Heart - increased force and HR |
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Beta 2 receptors
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↑Gs = ↑AC = ↑cAMP = ↑PKA
affinity E>>NE smooth muscle (vascular, bronchial, GI) - relaxation found in blood vessels in skeletal muscles, dilate during sympathetic inn to receive increased blood supply |
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bethanechol
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muscarinic agonist (parasympathomimetic)
resistant to all cholinesterases stimulant of GI tract and bladder relatively specific for M3, few CV effects |
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muscarine
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muscarinic agonist
(parasympathomimetic) increased gut motility, gland secretion, etc toxic: from poisonous mushrooms |
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pilocarpine
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muscarinic agonist
(parasympathomimetic) increased gut motility, gland secretion, etc tx: glaucoma (reduce pressure), xerostomia (dry mouth) |
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nicotine
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nicotinic agonist
sympathetic & parasympathetic actions causes release of E from adrenal medulla with CV effects; stimulates chemoreceptors in aortic bodies; can desensitize its receptors |
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physostigmine
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anticholinesterase - binds to Ach but hydrolysis is much slower
nicotinic and muscarinic effects parasympathomimetic at ANS: miosis, ↓HR, ↑GI motility, ↑glands block after prolonged exposure |
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neostigmine
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anticholinesterase - binds to Ach but hydrolysis is much slower
nicotinic and muscarinic effects parasympathomimetic at ANS: miosis, ↓HR, ↑GI motility, ↑glands skeletal muscle: increased contraction block after prolonged exposure tx: atony of GI tract and bladder |
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atropine
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muscarinic antagonist (competitive)
parasympatholytic - effects in order with increasing dose: decreased salivation and sweating, pupil dilation, ↑HR, ↓mictrurition; ↓gut motility, ↓ GI acid NO CNS EFFECT tx: parkinsons, bronchodilator, pupil dilation, reduce nasal secretion, overactive bladder |
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scopolomine
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muscarinic antagonist (competitive)
parasympatholytmuscarinic antagonist (competitive) parasympatholytic - effects in order with increasing dose: decreased salivation and sweating, pupil dilation, ↑HR, ↓mictrurition; ↓gut motility, ↓GI acid CAUSES DROWSINESS tx: parkinsons, motion sickness prev, bronchodilator, pupil dilation, reduce nasal secretion, overactive bladder |
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hexamethonium
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nicotinic antagonist
blocks the open ion channel in the nicotinic receptor on the autonomic gangila (not skeletal) - blocks symp and parasymp ganglia transmission |
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epinephrine
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nonspecific adrenergic agonist
sympathomimetic ↓ blood to skin (alpha) ↑ blood to skeletal (B2), brain, heart ↑ heart force, ↑ HR - B1 bronchodilation (B2) ↓ GI muscle tone (A and B2) ↓ uterine muscle tone (B2) |
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routes of administration of epinephrine
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given IM or SC or nebulized
ineffective orally (degraded by COMT and MAO) |
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norepinephrine
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more specific than epinephrine - no B2 stimulation (potent A and B1 cardio effects) - different effects on the vasculature
↑ BP (diastolic) |
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phenylephrine
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alpha 1 agonist
(looks like epinephrine but missing a hydroxyl) |
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clonidine
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alpha 2 agonist
1) works in CNS on postsynaptic alpha-2 receptors to reduce sympathetic outflow 2) binds to presynaptic alpha-2 receptors to decrease NE release and inhibit NE input to vasculature anti-HTN |
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brimonidine
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alpha 2 agonist
tx: glaucoma, ↑ production of aqueous humor |
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isoproterenol
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nonselective B agonist
↑ HR, ↑ Force ↓ BP (B receptor vasodilation) administered like epinephrine metabolized by COMT, poor substrate for MAO |
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terbutaline
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B2 agonist
brochodilation without CV effects less susceptible to COMT breakdown |
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albuterol
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B2 agonist
brochodilation without CV effects less susceptible to COMT breakdown |
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cocaine
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inhibits NET
indirect sympathomimetic amine (indirectly acts to buildup NE) |
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tyramine
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indirectly acting sympathomimetic
dopamine without 3-OH causes hypertensive crisis false transmitter - taken up into storage granule, converted by DBH, released without physiological effects - also reverses NE transport into huge NE release when taking MAOIs |
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amphetamine
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indirectly acting sympathomimetic
alternate substrate for NET effective orally, long duration of action tachyphylaxis: repeated doses given at short intervals, smaller response pumped into synaptic terminal or passes thru membrane, degrades proton gradient needed by VMAT, NE not take into storage vesicle so ir leaks out (also reverses rate of transport) |
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ephedrine
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directly and indirectly acting sympathomimetic
alpha and beta agonist - releases NE can be nebulized and inhaled |
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pharmocological effects of sympathomimetic drugs (and therapeutic uses)
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vasoconstriction (A1) - tx hypotension, nasal congestion, reduce spread of local anesthetic
pupillary dilation (A1) - ophthalmic procedures vasodilation (A2) - clonidine (HTN) Smooth muscle relaxation (B2) - tx COPD, Asthma |
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phenoxybenzamine
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nonspecific alpha-antagonist, noncompetitive
sympathomimetic cardiac stimulation (baroreceptor reflex due to ↓TPR), ↑NE release in heart orthostatic hypotension - no vasoconstriction in response to increased sympathetic firing when standing epinephrine reversal - depressor responses |
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phentolamine
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nonspecific alpha-antagonist, noncompetitive
sympathomimetic cardiac stimulation (baroreceptor reflex due to ↓TPR), ↑NE release in heart parasympathetic ↑GI (cause?) histamine release (vasodilation) |
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prazosin
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alpha 1 antagonist
↓ BP 95% bound to plasma protein NO ↑HR - avoid baroreceptor reflex |
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yohimbine
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alpha-2 antagonist
competitive, opposite of clonidine, similar to reserpine ↑ sympathetic outflow from CNS, ↑BP and ↑HR by 1) blocking postsynaptic A2 receptors and 3) blocking A2 receptors in vasomotor center |
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B receptor antagonists - important function
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Cardiovascular disease treatment!!
↓ HR, ↓ contractility ↓ BP in HTN (due to ↓CO) bronchoconstriction in 1st generations |
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propranolol
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nonselective (first generation) B receptor antagonist
in tx CVD, also see bronchoconstriction side effects lipid soluble, quickly absorbed and metabolized |
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timolol
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nonselective (first generation) B receptor antagonist
short acting in tx CVD, also see bronchoconstriction side effects lipid soluble, quickly absorbed and metabolized |
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pindolol
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nonselective (first generation) B receptor antagonist
nonselective (first generation) B receptor antagonist partial agonist - weak effect blocks NE/E binding in tx CVD, also see bronchoconstriction side effects lipid soluble, quickly absorbed and metabolized |
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atenolol
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B1 selective (second generation) antagonist
CVD tx without bronchial effects more water soluble, longer half-life |
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carvedilol
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third generation beta blocker (includes extra mechanism of action)
alpha 1 |
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methyldopa
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alpha 2 agonist (like clonidine)
competes with dopa for enzyme, false transmitter, anti-HTN effects |
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reserpine
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irreversible blocker of VMAT, blocks NE uptake into vesicles
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imipramine
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inhibits NET
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clinical uses of sympatholytic (adrenergic blocking) drugs
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- HTN (prazosin, methyldopa, B blockers)
- exertional angina - B blockers - CHF - A-antagonists (↓BP, ↓Force), B-blockers (pure and vasodilatory) - arrythmia - B-blockers - pheochromocytoma - tumor of chromaffin (phenoxybenzamine) - glaucoma - timolol (↓production of aqueous humor) |
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chlorpheniramine (chlortrimeton)
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first generation H1 antihistamine - sedating
metabolized by CYP450 |
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cetirizine (zyrtec)
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second generatiion H1 antihistamine - non-sedating
excreted largely unchanged in urine |
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cyclizine (Marezine)
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first generation H1 antihistamine - sedating
metabolized by CYP450 |
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Desloratidine (Clarinex)
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second generatiion H1 antihistamine - non-sedating
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Dimenhydrinate (Dramamine)
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first generation H1 antihistamine - sedating
metabolized by CYP450 |
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Diphenhydramine (Benadryl)
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first generation H1 antihistamine - sedating
metabolized by CYP450 |
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Fexofenadine (Allegra)
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second generation H1 antihistamine - non-sedating
excreted largely unchanged in feces (and kidney) |
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Loraditine (Claritin)
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second generatiion H1 antihistamine - non-sedating
metabolized by CYP450 to desloratidine (clarinex) |
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Mecyclizine (Antivert, Bonine)
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first generation H1 antihistamine - sedating
metabolized by CYP450 |
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Promethazine (Phenergan)
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first generation H1 antihistamine - sedating
metabolized by CYP450 |
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H1 antihistamines mechanism of action
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combine with and stabilize the inactive form of the H1 receptor, shifting equilibrium to the inactive state
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H1 antihistamines pharmocological properties (first and second generation)
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- inhibit rapid vasodilator effects of histamine (H1) - still get slow H2 vasodilation
- prevent increased capillary permeability - prevent pain and itch caused by histamine on peripheral nerves |
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H1 antihistamines pharmocological properties (first generation only)
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- CNS depression - drowsiness (cross BBB)
- prevent motion sickness by muscarinic blocking |
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Therapeutic uses of H1 antihistamines
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- allergy - seasonal rhinitis, conjunctivitis
- limited use in asthma (leukotrienes also play a role) - allergic drug reactions - common cold - little effect except drying - motion sickness (1st gen) |
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Side effects of H1 antihistaminics
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- sedation (1st gen)
- dry mouth, urinary retention, other muscarinic blocking effects (1st gen) - prolongation of QT interval, tachycardia |
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H2 Receptor blocker
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tx: peptic ulcers, GERD, stress ulcers
inhibits basal (nocturnal) acid secretion minor side effects: headache, etc |
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cimetidine (Tagamet)
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H2 receptor blocker
inhibits CYPs (drug interaction) |
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ranitidine (Zantac)
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H2 receptor blocker
tx: peptic ulcer disease |
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famotidine (Pepcid)
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H2 receptor blocker
tx: peptic ulcer disease |
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histamine involvement in GI acid secretion
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stimulates pareital cells through H2 receptors
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eicosanoids
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COX products such as prostaglandins (PG), prostacyclin, thromboxane (TX) and lipogenase products (leukotrienes)
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eicosanoid synthesis
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Arachadonic Acid (essential) stored in membranes
eicos synthesized when needed (not stored) by releasing AA from membrane (rate limiting step) |
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cyclooxygenase (PG endoperoxide)
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microsomal enzyme
COX 1 - ubiquitous, constitutively expressed, homeostasis COX 2 - inducible, rapidly produced and degraded after exposure to cytokines |
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PGI1 (prostacyclin)
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- potent vasodilator
- induces hypotension - helpful in maintaining normal vascular tone - anti-aggregation in platelets - inhibits gastric acid secretion synthesized in vascular tissues by prostacyclin tissues half life = 3 min spontaneously degrades to biologically inactive compound, also B-oxidized and into urine |
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TXA2 (thromboxane)
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induces platelet aggregation, powerful vasoconstrictor
synthesized in lung and platelets by thromboxane synthase half life = 30 seconds spontaneously degrades to biologically inactive compound, also B-oxidized and into urine |
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PGE2
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- PGE2 - inhibits gastric acid secretion but also causes contraction (cramps)
synthesized in most tissues enzymatically and non-enzymatically cleared in a singly pass through pulmonary circulation |
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lipoxygenases
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cytosolic enzymes, insert oxygen to make HPETE
5-LO - WBCs - most important, initiates leukotriene synthesis 12-LO - platelets 15-LO - macrophage, epithelium |
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LTB4
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generated by LTA4 hydrolase (ubuquitous - often found in cells lacking 5-LO)
most important source: neutrophil metabolized by omega-oxidation |
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LTC4
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- powerful vasoconstrictor
- edema formation addition of glutathione to LTA4 by LTC4 synthase equally important biological activity as LTD4 converted to LTD4 for metabolism |
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LTD4
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- powerful vasoconstrictor
- edema formation rapidly converted from LTC4 in many tissues by g-glutamyl transpeptidase equally important biological activity as LTC4 converted to inactive LTE4 for excretion |
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Mechanism of action of PG and leukotrienes
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intracellular second messengers
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leukotriene effects on the cardiovascular system
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- vasoconstriction especially in coronary and pulmonary circulations
- induces hypotention due to secondary effects in volume depletion and decreased coronary blood flow (capillary leakage and edema) |
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misoprostol
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PGE1 analog
- protects GI mucosa by inhibiting acid secretion and increasing blood flow - approved for mid-trimester abortions |
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PGF2a
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- required for induction of labor
synthesized in most tissues enzymatically and non-enzymatically cleared in a singly pass through pulmonary circulation |
