Download - Baby-Katzung-Second-Shifting-Reviewer.pdf
-
Page 1 of 13
#PharMasaya
4.0-02January 21, 2014
Baby Katzung(2nd Shifting Reviewer)"Realize that if you have time to whine and complain about something, then you have the
time to do something about it." Anthony J. D'Angelo
WALKTHROUGH
MAJOR DRUG CLASS Notes on the major drug class above (if any)DRUGSUBCLASS
Notes on the drug subclass on the left side DRUG
o Specific informationDRUG Specific information
LECTURER FAVORITE QUESTIONSLOYOLA Basic physiology, mechanism of actionALABASTRO Emphasized parts in pharmacokinetics, clinical uses, toxicityFILARCA Clinical uses, toxicityDIMAANO Clinical uses, toxicity, contraindicationsTORRES Drug of choice, toxicities (Di halata. Hahahaha.)
SECOND SHIFTINGGASTROINTESTINAL PHARMACOLOGY
ACID-PEPTIC DISEASES
ANTACIDS Given 1 hour after meals Short-acting (1-2 hours) Cautions: renal insufficiency Interactions: affect drug absorption by binding to other drugs or altering
intragastric pHSODIUMBICARBONATE
HCL CO2 + NaCl NaHCO3: renal insufficiencymetabolic alkalosis CO2: gastric distention, belching NaCl: heart failure, hypertension, renal insufficiency
fluid retentionMAGNESIUMHYDROXIDE +ALUMINUMHYDROXIDE
MgCl2: osmotic diarrhea AlCl3: constipation No gas formation no belching
ALGINATE Reacts with HCl forms protective viscous foam Clinical uses: heartburn, GERD
H2 RECEPTOR ANTAGONISTS ("tidine") Highly selective competitive antagonist at parietal cell H2 receptor Extremely safe (few adverse effects) Pharmacokinetics: long-acting (6-10 hours), given BID Clinical uses: prophylaxis of heartburn, PUD, stress-related gastritis No CYP450 interactions: famotidine, nizatidineCIMETIDINE Toxicity: mental status changes, gynecomastia, impotence,
galactorrhea, bradycardia, hypotension Interactions: CYP1A2, CYP2C9, CYP2D6, CYP3A4
RANITIDINE Less affinity to CYP450 than cimetidineFAMOTIDINE blood ethanolNIZATIDINE Little first-pass metabolism
~100% bioavailability
PROTON PUMP INHIBITORS ("prazole") Substituted benzoimidazoles, inactive prodrugs Active metabolite: sulfonamide cation irreversibly inactivates proton
pump (H+/K+-ATPase) Given BID on empty stomach to absorption Formulated as acid-resistant enteric-coated tablets or capsules Concentrated in parietal cell canaliculi (site of action) by Henderson-
Hasselbach trapping Short t1/2 (1.5 hours), long-acting (24 hours) DOC for acid-peptic diseases
o GERD and Barrett esophagus
o Triple therapy in H. pylori-associated peptic ulcers (10-14 dayregimen of PPI + clarithromycin + amoxicillin/metronidazole)
o NSAID-associated ulcerso Gastrinomas and hypersecretion
Toxicity: B12 and electrolyte absorption, risk of nosocomial infections,hypergastrinemia
OMEPRAZOLE Formulated as non-enteric-coated powder
MUCOSAL PROTECTANTSSUCRALFATE Reacts with water or acid forms viscous paste
Negatively-charged sucrose sulfate binds to positively-charged proteins on ulcers
Alternative to acid-inhibitory therapies (less risk ofnosocomial infections)
Cautions: renal insufficiencyMISOPROSTOL PGE1 analog stimulates mucus and HCO3 secretion,
acid DOC for NSAID-induced ulcers Toxicity: diarrhea, abdominal pain, abortifacient
BISMUTHSUBSALICYLATE
Coats ulcers and erosions Binds enterotoxins Clinical uses: traveler's diarrhea, H. pylori (second-line) Toxicity: harmless black stool, encephalopathy,
salicylate toxicity
GASTROPROKINETIC AGENTS Selectively stimulate gut motor function LES pressure (useful in GERD) GI emptying (useful in gastroparesis, post-vagotomy/antrectomy)
CHOLINERGICAGENTS
BETHANECHOLo Stimulates M3 receptors on GIT smooth muscle and
at myenteric plexus synapses NEOSTIGMINE
o Clinical uses: Ogilvie syndrome (acute colonicpseudo-obstruction)
D2 RECEPTORANTAGONISTS
Clinical uses: GERD, gastroparesis, antiemetic,postpartum lactation
METOCLOPRAMIDEo Toxicity: extrapyramidal symptoms
DOMPERIDONEo Promotes postpartum lactationo Toxicity: hyperprolactinemia
MACROLIDES
ERYTHROMYCINo Stimulates motilin receptors and facilitates MMCo Clinical uses: pre-endoscopy evacuation of blood in
patients with UGIB
CONSTIPATION
LAXATIVES Clinical uses: colonic evacuation in constipated patientsBULK-FORMINGLAXATIVES
Indigestible hydrophilic colloids Form emollient gel colonic distention, hyperperistalsis Bacterial digestion of fiber bloating, flatulence PSYLLIUM, METHYLCELLULOSE
STOOLSURFACTANTS
Given PO or rectally Minimize straining DOCUSATE
o Commonly prescribed stool surfactant MINERAL OIL
o Lubricates feces and retards water absorptiono Clinical uses: fecal impaction in children and
-
#PharMasaya :P Page 2 of 13
Baby Katzung (Finals Reviewer)
debilitated adultso Aspiration lipid pneumonitiso Prolonged use: vitamin malabsorption
OSMOTICLAXATIVES
NON-ABSORBABLE SUGARS OR SALTSo Clinical uses: treatment of acute constipation,
prevention of chronic constipation BALANCED POLYETHYLENE GLYCOL MAGNESIUM HYDROXIDE (MILK OF MAGNESIA)
o Most commonly used osmotic laxativeo Prolonged use: hypermagnesemia in renal
insufficiency LACTULOSE
o DOC for hepatic encephalopathyo Metabolized by bacteria flatus, cramps
MAGNESIUM CITRATE AND SODIUM PHOSPHATEo Purgativeso Toxicity: hypovolemia, electrolyte fluctuations
BALANCED POLYETHYLENE GLYCOLo Lavage solution of PEG and electroyteso Clinical uses: pre-endoscopy colonic cleansing
STIMULANTLAXATIVES
Direct ENS stimulation + colonic electrolyte and fluidsecretion colonic movement
ANTHRAQUINONE DERIVATIVES (ALOE, SENNA,CASCARA)o Chronic use: melanosis coli
DIPHENYLMETHANE DERIVATIVES (BISACODYL)o Clinical uses: acute and chronic constipation, pre-
endoscopy cleansingCHLORIDECHANNELACTIVATORS
Stimulate type 2 Cl- channels in small intestine Cl-
secretion GI motility, transit time LUBIPROSTONE
o Prostanoic acid derivativeOPIOIDRECEPTORANTAGONISTS
Inhibit GIT -opioid receptors METHYLNALTREXONE
o Opioid-induced constipation ALVIMOPAN
o Post-bowel resection ileus5-HT4RECEPTORAGONISTS
Stimulate 5-HT4 receptors in submucosal plexus TEGASEROD
o High affinity partial agonisto Withdrawn due to risk of CV events
CISAPRIDEo Partial agonisto Inhibits hERG QT prolongation
PRUCALOPRIDEo High affinity agonisto Clinical uses: chronic constipation in women
PROKINETICBENZAMIDES
ITOPRIDEo Inhibits D2 receptors and acetylcholinesteraseo gastric emptying time
GUANYLATECYCLASE CAGONISTS
LINACLOTIDEo Binds to guanylate cyclase C receptor on enterocyte
luminal surface CFTR activation fluidsecretion
DIARRHEA
ANTIDIARRHEALS Clinical uses: mild to moderate acute diarrhea Cautions: bloody diarrhea, hyperthermia, systemic toxicityOPIOIDAGONISTS
Inhibit presynaptic cholinergic neurons in entericplexuses colonic transit time, mass movement
No analgesic property LOPERAMIDE
o No CNS entry DIPHENOXYLATE
o CNS effects
o Prolonged use: dependence (combined withatropine to discourage dependence)
BILE-SALTSEQUESTRANTS
fecal excretion of bile acids Toxicity: bloating, flatulence, constipation, fat
malabsorption COLESEVELAM
o No drug interactions OTHERS (COLESTIPOL, CHOLESTYRAMINE)
SOMATOSTATINANALOGS
OCTREOTIDEo Inhibits GIT hormone and neurotransmitter
secretion antimotility effecto Clinical uses: diarrhea 2 to hypersecretion, post-
vagotomy, dumping syndrome, VIPomao Toxicity: steatorrhea (2 to impaired pancreatic
secretion), alterations in GI motility, acutecholecystitis, hyperglycemia
OTHERS BISMUTH KAOLIN (ATTAPULGITE) AND PECTIN
o Absorb bacteria, toxins, fluids stool liquidityo Clinical uses: acute diarrhea
IRRITABLE BOWEL SYNDROME
ANTISPASMODICS DICYCLOMINE, HYOSCYAMINE
o Inhibit muscarinic cholinergic receptors
5-HT3 RECEPTOR ANTAGONISTS ("setron") 5-HT3 receptor blockade in enteric terminals motilityALOSETRON IBS with predominant diarrhea in women
Toxicity: GI toxicity, constipation, ischemic colitis
5-HT4 RECEPTOR AGONISTSTEGASEROD IBS with predominant constipation in women
CHLORIDE CHANNEL ACTIVATORSLUBIPROSTONE IBS with predominant constipation in women
NAUSEA AND VOMITING
5-HT3 RECEPTOR ANTAGONISTS ("setron") ONDANSETRON, GRANISETRON, DOLASETRON, PALONOSETRON
o Potent antiemetic properties Peripheral 5-HT3 blockade in extrinsic intestinal neurons Central 5-HT3 blockade in chemoreceptor trigger zone
o Clinical uses: post-operative and post-radiation N/Vo DOC for acute chemotherapy-induced N/V (CINV)o Not used in delayed CINVo Toxicity: headache, dizziness, constipation
PALONOSETRON Newer IV agent Higher affinity to 5-HT3 receptor Long-acting (t1/2: 40 hours)
DOLASETRON QT prolongation
CORTICOSTEROIDS WITH ANTIEMETIC ACTIVITY DEXAMETHASONE, METHYLPREDNISONE
o Enhance efficacy of 5-HT3 receptor antagonistso Clinical uses: prevention of acute and delayed CINV
NEUROKININ (NK1) RECEPTOR ANTAGONISTSAPREPITANT Central blockade in area postrema
Metabolized by CYP3A4 Combined with 5-HT3 receptor antagonists and steroids Clinical uses: acute and delayed CINV
-
#PharMasaya :P Page 3 of 13
Baby Katzung (Finals Reviewer)
DOPAMINERGIC ANTAGONISTS Toxicity: mental status changes, extrapyramidal symptomsPHENOTHIAZINES PROMETHAZINE, PROCHLORPERAZINE,
THIETHYLPERAZINEo Potent antiemetic and sedative activity
BUTYROPHENONES DROPERIDOLo Clinical uses: post-operative N/Vo Toxicity: extrapyramidal symptoms,
hypotension, QT prolongationPROKINETICS TRIMETHOBENZAMIDE, METOCLOPRAMIDE
ANTICHOLINERGIC H1 ANTIHISTAMINES Weak antiemetic activity Clinical uses: motion sicknessSCOPOLAMINE DOC for motion sicknessDIPHENHYDRAMINE Potent sedativeMECLIZINE Minimal anticholinergic and sedating effects
DOC for vertigo
BENZODIAZEPINESLORAZEPAM,DIAZPEAM
Given pre-chemotherapy to reduce anticipatory vomiting
CANNABINOIDS ("nabi")DRONABINOL THC analog
Clinical uses: antiemetic, appetite stimulant Interactions: phenothiazines (synergistic effect,
attenuates adverse effects of both) Toxicity: sedation, euphoria, dysphoria, hallucination,
ANS effects
INFLAMMATORY BOWEL DISEASE
AMINOSALICYLATES (5-ASA) 5-aminosalicylic acid Inhibits COX, nuclear factor-B, lymphocyte function Pharmacokinetics: rapidly absorbed from proximal small intestine, N-
acetylated to inactive metabolite in GIT epithelium and liver DOC for mild to moderate IBDAZOCOMPOUNDS("salazine")
5-ASA bound by azo bond (N=N) to inert compound or toanother 5-ASA molecule
SULFASALAZINEo 5-ASA + sulfapyridine
BALSALAZIDEo 5-ASA + 4-aminobenzoyl--alanine
OLSALAZINEo 2 molecules of 5-ASA
MESALAMINECOMPOUNDS
PENTASAo Small intestine
ASACOL, APRISOo Distal ileum, proximal colon
LIALDAo Colon
ROWASA (enema), CANASA (suppository)o Rectum, sigmoid colon
GLUCOCORTICOIDSPREDNISONE Most commonly usedHYDROCORTISONE Topical treatment of active IBD in rectum and
sigmoid colonBUDESONIDE Potent synthetic analog of prednisolone
High affinity glucocorticoid receptor agonist
ANTIMETABOLITES Clinical uses: induction and maintenance of remission in ulcerative colitis
and Crohn's disease Toxicity: myelosuppression (leukopenia, anemia)AZATHIOPRINE Nonenzymatically converted to 6-MP inhibits purine
metabolism and DNA synthesis T-lymphocyte apoptosis Toxicity: N/V, hepatotoxicity Pre-therapy monitoring: TPMT activity Interactions: allopurinol (severe leukopenia)
METHOTREXATE Inhibits dihydrofolate reductase
ANTI-TNF MONOCLONAL ANTIBODIES High affinity to TNF- prevent binding of TNF- to receptor Clinical uses: treatment of acute and chronic moderate to severe Crohn's
disease and ulcerative colitis Toxicity: infection, reactivation of latent TB, antibody formationINFLIXIMAB Chimeric mouse-human
Acute adverse infusion reactionsADALIMUMAB Fully humanizedCERTOLIZUMAB Pegylated Fab fragment
ANTI-INTEGRINNATALIZUMAB Humanized IgG4 monoclonal antibody
Blocks integrin prevents IgG binding to vascularadhesion molecules
Clinical uses: moderate to severe Crohn's disease (ifother therapies fail)
EXOCRINE PANCREATIC INSUFFICIENCY
PANCREATIC ENZYME SUPPLEMENTS Toxicity: mucositis, hyperuricosuria, renal stonesPANCRELIPASE Greater lipolytic (X12) and proteolytic (X4) activity
compared to PANCREATIN Creon: most common
GALLSTONES
URSODIOL (URSODEOXYCHOLIC ACID) hepatic cholesterol secretion cholesterol content of bile Clinical uses: dissolution of small gallstones, symptomatic gallbladder
disease, prevention of gallstones liver function deviations and improves liver histology in biliary cirrhosis
ESOPHAGEAL VARICES
HEMOSTATIC AGENTSOCTREOTIDE portal blood flow variceal pressure
Initial hemostasisARGININEVASOPRESSIN
Splanchnic arterial vasoconstriction portal venouspressure
Toxicity: CVS effects (hypertension, ischemia,hyponatremia, pulmonary edema), GIT effects (nausea,abdominal cramps, diarrhea)
TERLIPRESSINo Fewer adverse effects
NONSELECTIVEBETA BLOCKERS
PROPRANOLOL, NADOLOLo portal inflow and portal venous pressureo 2 blockade: splanchnic vasoconstriction
ALCOHOL PHARMACOLOGY
ALCOHOLSETHANOL Water-soluble, rapidly absorbed in GIT in fasting state,
peaks in blood in 30 minutes, 90% oxidized in liver
-
#PharMasaya :P Page 4 of 13
Baby Katzung (Finals Reviewer)
Alcohol dehydrogenaseo Primary metabolic pathway of alcoholo Converts alcohol to acetaldehyde
Microsomal ethanol oxidizing systemo Utilizes NADPH as cofactoro Low affinity for alcoholo Significantly active at BAC of >100 mg/dL
Aldehyde dehydrogenaseo Oxidizes acetaldehyde to acetate (further degraded
to CO2 + water) Acute: sedation, anxiolysis, intoxication, memory loss,
myocardial contractility, vasodilation, hypothermia Chronic: liver disease (fatty liver, alcoholic hepatitis,
cirrhosis), chronic pancreatitis, CNS effects (dependence,Wernicke-Korsakoff), CVS effects (heart failure,arrhythmia, hypertension, coronary diseases), endocrineeffects (steroid imbalance), fetal alcohol syndrome
Interactions: acetaminophen (hepatotoxicity), CNSdepressants (additive depression)
METHANOL Metabolized by alcohol dehydrogenase Metabolites: formaldehyde, formic acid, CO2 Toxicity: "snowstorm" vision, formalin breath, sudden
cessation of respiration Management: respiratory support, hemodialysis,
alkalinization, ethanol and fomepizoleETHYLENEGLYCOL
Metabolized to toxic aldehydes and oxalates Same management in methanol poisoning
ANTI-ALCOHOLISM AGENTSDISULFIRAM Alcohol dehydrogenase inhibitor
Provokes severe discomfort (flushing, N/V, sweating,hypotension) after consuming alcohol
Interactions: alcohol-containing medicationsNALTREXONE Long-acting opioid receptor antagonist at -opioid
receptors Interactions: disulfiram (hepatotoxicity), opioids
(withdrawal syndrome)ACAMPROSATE NMDA antagonist
GABAA receptor activator Contraindications: renal impairment Toxicity: N/V, vomiting, rashes
FOMEPIZOLE Alcohol dehydrogenase inhibitor DOC for methanol or ethylene glycol poisoning
OTHERS ONDANSETRON, TOPIRAMATE, BACLOFENo craving in chronic alcoholism
RIMONABANTo CB1 receptor antagonisto Suppresses alcohol-related behaviors
CENTRAL NEUROTRANSMITTERS
AMINO ACIDSEXCITATORY GLUTAMATE
o Taken up via vesicular glutamate transporter (VgluT)o Released by Ca2+-mediated exocytosiso Converted by glutamine synthetase to glutamine
(then converted to glutamine by glutaminase)o Receptors
Ionotropic AMPA: permeable to Na+ and K+
Kainic acid: expressed in hippocampus,cerebellum, spinal cord
NMDA: present in all CNS neurons,involved in long-term potentiation
Metabotropic (G protein-coupled) Group I: postsynaptic Group II: presynaptic
INHIBITORY GAMMA-AMINOBUTYRIC ACID (GABA)o Present in CNS in GABA-releasing interneuronso Types
GABAA Ionotropic Fast component of inhibitory potentials Activators: MUSCIMOL Inhibitors: PICROTOXIN, BICUCULLINE
GABAB Metabotropic (G protein-coupled) Slow component of inhibitory potentials Either inhibit Ca2+ channels or activate K+
channels Activators: BACLOFEN Inhibitors: 2-OH SACLOFEN
GLYCINEo Interneurons in spinal cord and brainstemo Inhibitors: STRYCHININE (potent spinal cord
proconvulsant)
SEDATIVE-HYPNOTICS
BENZODIAZEPINES ("zep", "zepam", "zolam") 7-membered heterocyclic ring with carboxamide group Electronegative substituent at 7 position confers sedative-hypnotic activity Bind to benzodiazepine site of GABAA receptor frequency of channel-opening events Cross placenta and breastmilk Biotransformation: microsomal oxidation (phase I) catalyzed by CYP3A4
conjugation (phase II) to glucuronides Toxicity: tolerance and dependence, anterograde amnesia,
cardiorespiratory depressionANXIOLYTICS All are long-acting except alprazolam and oxazepam
(short-acting) Desmethyldiazepam
o Active metabolite of chlordiazepoxide,clorazepate, and diazepam
ALPRAZOLAM CHLORDIAZEPOXIDE, CLORAZEPATE
o Used in alcohol withdrawal CLONAZEPAM
o No active metaboliteo Used in epilepsy
DIAZEPAMo Used in epilepsy, alcohol withdrawal, and
muscle relaxationo Alternative DOC for status epilepticus
OXAZEPAMo Short-acting and no active metaboliteo Used in alcohol withdrawal
HYPNOTICS ESTAZOLAM, FLURAZEPAM, QUAZEPAM,TEMAZEPAM, TRIAZOLAMo Used in sleep disorders
MIDAZOLAMo Conscious sedation
ANXIOLYTIC-HYPNOTIC
LORAZEPAMo Intermediate-actingo Used in delirium tremenso DOC for status epilepticus
TRIAZOLES Triazole ring at 1,2 position Transformed to alpha-hydroxy metabolites Short-acting ALPRAZOLAM
o Used in panic attacks TRIAZOLAM
o Used in sleep disorders
-
#PharMasaya :P Page 5 of 13
Baby Katzung (Finals Reviewer)
Rapidly-absorbed: CLONed Dad, Father, Tatay (clonazepam, diazepam,flurazepam, triazolam)
Active metabolites: FACT MD (flurazepam, alprazolam, chlordiazepoxide,triazolam, midazolam, diazepam)
No active metabolites: CLOT (clonazepam, lorazepam, oxazepam,temazepam)
Short-acting: TRI MO (triazoles, midazolam, oxazepam)Intermediate-acting: LET (lorazepam, temazepam, estazolam)Long-acting: everything else
BENZODIAZEPINE SUBTYPE Generally rapid-acting Metabolized by CYP3A4 Clinical uses: sleep disorders (insomnia)ZALEPLON Short-acting
Hydroxylation, oxidation (no active metabolite) REM and latency of sleep risk of tolerance
ZOLPIDEM Ultra-short-acting Aldehyde dehydrogenase (no active metabolite) latency of sleep Lowest risk of withdrawal symptoms
ESZOPICLONE Intermediate-acting total sleep time No rebound insomnia
BENZODIAZEPINE ANTAGONISTFLUMAZENIL 1,4-benzodiazepine derivative
Competitive antagonist of benzodiazepines andbenzodiazepine subtype
High affinity to benzodiazepine site on GABAA receptor Rapid-acting (t1/2: ~1 hour) sedation may recur Clinical uses: BZ-induced CNS depression Toxicity: severe abstinence syndrome Interactions: tricyclics (seizures, arrhythmias)
NON-BENZODIAZEPINES
BUSPIRONE
Selective anxiolytic Partial 5-HT1A agonist with affinity to D2 receptors No depressant, anticonvulsant, relaxant properties Active metabolite: 1-(2-pyrimidyl)-piperazine Clinical uses: generalized anxiety state (not for panic
disorders) Less risk of dependence and rebound anxiety
BARBITURATES ("barbital") Bind to allosteric site on GABAA receptor duration of channel-opening events Clinical uses: sedation, hypnosis, anesthesia, anticonvulsant Toxicity: cardiorespiratory depression Contraindications: porphyria, hepatic and renal impairmentTHIOPENTAL Ultra-short-acting, very lipid-soluble (can enter CNS)SECOBARBITAL Short-acting (t1/2: 18 hours)PENTOBARBITAL Intermediate-acting (t1/2: 48 hours)PHENOBARBITAL Long-acting (t1/2: 4-5 days)
MELATONIN RECEPTOR AGONISTSRAMELTEON MT1 and MT2 receptor agonist
Metabolized by CYP1A2 Clinical uses: maintenance of circadian rhythm, reduces
latency of sleep No rebound effects or withdrawal symptoms Cautions: hypertension and diabetes Contraindications: hepatic impairment Toxicity: mental status changes (dizziness, somnolence),
hyperprolactinemia
OTHER ANXIOLYTICS AND HYPNOTICSANTIHISTAMINES Marked sedation
Long t1/2ANTIDEPRESSANTS TRICYCLICS, MIRTAZAPINE, TRAZODONEBETA BLOCKERS Clinical uses: management of physiologic
components of anxiety (tachycardia, palpitations,tremors, sweating)
No CNS depression and addiction
ANTIEPILEPTICSPARTIAL AND GENERALIZED TONIC-CLONIC SEIZURES
ANTI-MAXIMAL ELECTROSHOCK CLASS
SODIUM CHANNEL BLOCKERS Blocks voltage-gated Na+ channels (VGNC) high-frequency neuronal
firing (no effect on physiologic firing)HYDANTOINS PHENYTOIN
o Alters Na+, K+, and Ca2+ conductanceo glutamate releaseo Exhibits non-linear kineticso High protein binding (99%)o Toxicity: gingival hyperplasia, hirsutism
FOSPHENYTOINo Prodrug of phenytoin
TRICYCLICS("zepine")
CARBAMAZEPINEo DOC for complex partial seizureso Active metabolite: carbamazepine-10,11 epoxideo Toxicity: CNS effects (diplopia, ataxia),
hyponatremia OXCARBAZEPINE
o Active metabolite: 10-hydroxy metaboliteMISCELLANEOUS ZONISAMIDE
o Blocks VGNC and T-type Ca2+ channelso Toxicity: renal stones
LACOSAMIDEo Enhances slow inactivation of VGNCo Binds to CRMP-2 neuronal growth
RUFINAMIDEo Clinical uses: Lennox-Gastaut syndrome
(childhood-onset epilepsy)
POTASSIUM CHANNEL AGONISTSRETIGABINE K+ channel opening hyperexcitability
Toxicity: CNS effects (dizziness, somnolence, confusion,blurred vision, dysarthria)
GABA AGONISTSBENZODIAZEPINES DIAZEPAM
LORAZEPAMo Longer-acting than diazepamo DOC for status epilepticus
BARBITURATES PHENOBARBITALo inhibitory and excitatory transmissiono DOC for seizure in infants, also used in febrile
seizures PRIMIDONE
o Active metabolites: phenobarbital,phenylethylmalonamide (PEMA)
GABA ANALOGS("gaba")
VIGABATRINo Irreversibly inhibits GABA aminotransferase GABA degradation GABA levels
o DOC for infantile spasms (West syndrome)o Toxicity: drowsiness, dizzinesso Prolonged use: visual field defectso Contraindications: psychosis
-
#PharMasaya :P Page 6 of 13
Baby Katzung (Finals Reviewer)
GABAPENTINo Enters CNS via L-amino acid transportero Modifies release of GABAo Clinical uses: dystonia, migraine
PREGABALINo Clinical uses: fibromyalgia
TIAGABINEo Inhibits GABA uptake in neurons and gliao Prolongs inhibitory action of synaptically-
released GABAo Toxicity: cognitive slowing
PLEIOTROPICS Multiple mechanisms of action Clinical uses: partial seizuresLAMOTRIGINE Suppresses sustained rapid firing
Voltage- and use-dependent inactivation of Na+
channels Inhibits voltage-gated N and P/Q Ca2+ channels Bipolar disorder Toxicity: skin rash
LEVETIRACETAM Binds to synaptic vesicular protein SV2A glutamateFELBAMATE Use-dependent block of NR1-2B NMDA receptor
Blocks strychnine-insensitive glycine site on NMDA complexTOPIRAMATE AMPA receptor antagonist
ABSENCE SEIZURESANTI-PENTYLENETETRAZOL CLASS
CALCIUM CURRENT INHIBITORS T-type Ca2+ current in thalamic neurons Clinical uses: absence seizuresSUCCINIMIDES ETHOSUXIMIDE
o DOC for absence seizuresMISCELLANEOUS VALPROIC ACID
o K+ channel agonisto Blocks voltage-gated Na+ channelo Blocks NMDA receptor-mediated excitationo Facilitates glutamic acid decarboxylase
GABA synthesiso High protein bindingo Displaces phenytoin from plasma proteinso DOC for Lennox-Gastaut syndromeo Second line for absence seizureso Toxicity: hepatotoxicity, spina bifida
OXAZOLIDINEDIONES TRIMETHADIONEo seizure thresholdo Active metabolite: dimethadioneo Toxicity: sedation
OTHER ANTIEPILEPTICS
CARBONIC ANHYDRASEINHIBITORS
ACETAZOLAMIDEo Produces mild acidosis in the brain
anticonvulsant effectHORMONES PROGESTERONE
PARKINSON'S DISEASE
DOPAMINE PRECURSORSLEVODOPA(L-DOPA)
Enters CNS via L-amino acid transporter Decarboxylated to dopamine Extracerebral metabolism only 1-3% enters CNS Metabolites: homovanillic acid (HVA),
dihydroxyphenylacetic acid (DOPAC) Toxicity: GIT effects (N/V, anorexia), CVS effects
(arrhythmias, hypotension), dyskinesias
Prolonged use: fluctuations in responseo Wearing-off reaction: timing-relatedo On-off phenomenon: characterized by "off" periods of
akinesia with "on"periods of dyskinesia, non-timing-related
Interactions: MAOA inhibitors (hypertensive crisis)CARBIDOPA Peripheral dopa decarboxylase inhibitor
L-dopa metabolism available L-dopa for CNSSINEMET LEVODOPA + CARBIDOPASTALEVO LEVODOPA + CARBIDOPA + ENTACAPONE
DOPAMINE RECEPTOR AGONISTS Monotherapy in younger patients No toxic metabolites incidence of fluctuations Toxicity: GIT effects (N/V, anorexia), dyskinesias, mental disturbancesERGOTDERIVATIVES
BROMOCRIPTINEo D2 agonist
PERGOLIDEo D1 and D2 agonisto "on" periods in fluctuatorso Toxicity: cardiac valvulopathies
NON-ERGOTDERIVATIVES
PRAMIPEXOLEo D3 agonist
ROPINIROLEo D2 agonisto Metabolized by CYP1A2
APOMORPHINEo Pharmacokinetics: SQ route, rapid absorptiono Clinical uses: temporary relief (rescue) from "off"
periods of akinesiao Toxicity: persistent nauseao Pre-therapy: trimethobenzamanide (anti-nausea)
SELECTIVE MONOAMINE OXIDASE B INHIBITORS ("giline") Clinical uses: mild parkinsonism or children with parkinsonism Interactions: L-dopa or tyramine (hypertensive crisis), SSRI or tricyclic
antidepressants (serotonin syndrome) Contraindications: analgesics, OTC cold medicationsSELEGILINE Inhibits MAOA at high doses
on-off or wearing-off fluctuations Metabolites: desmethylselegiline (neuroprotective),
amphetamines (causes adverse effects)RASAGILINE Early symptomatic treatment of Parkinson
CATECHOL-O-METHYLTRANSFERASE INHIBITORS ("capone") Clinical uses: severe parkinsonism or on-off phenomenonENTACAPONE Peripheral COMT inhibitor
No CNS entryTOLCAPONE Central and peripheral COMT inhibitor
Capable of CNS entry Longer-acting, more potent Toxicity: hepatotoxicity ( liver enzymes)
OTHER ANTIPARKINSONIANSAMANTADINE Potentiates dopaminergic functions
Inhibits adenosine effects at adenosine A2A receptors disinhibition of D2 receptor function
iatrogenic dyskinesias Toxicity: mental status changes, livedo reticularis,
peripheral edemaANTICHOLINERGICAGENTS
BENZTROPIN, BIPERIDEN, ORPHENADRINE,PROCYCLIDINE, TRIHEXYPHENIDYLo Muscarinic receptor antagonists in basal gangliao tremors and rigidityo Little effect on bradykinesia
-
#PharMasaya :P Page 7 of 13
Baby Katzung (Finals Reviewer)
THERAPY FOR NON-MOTOR MANIFESTATIONS OF PARKINSONRIVASTIGMINE, MEMANTINE, DONEPEZIL Cognitive decline (dementia)ANTIDEPRESSANTS, ANXIOLYTICS Affective disordersMODAFINIL Excessive daytime sleepiness
DEPRESSION AND ANXIETY DISORDERS
SELECTIVE SEROTONIN REUPTAKE INHIBITORS Highly selective SERT blockade Little effect on NET and adrenoceptors All protein-bound and highly lipophilic Potent CYP2D6 inhibitors: fluoxetine, paroxetine Clinical uses: generalized anxiety, post-traumatic stress, OCD, panic, bulimia First-line therapy for depression Interactions: MAOI (serotonin syndrome), tricyclic antidepressants (toxicity)CITALOPRAM Significant improvement in anxiety symptomsESCITALOPRAM Most potent SSRIFLUOXETINE Longest half-life
Toxicity: weight lossFLUVOXAMINE Highest bioavailability
Clinical uses: OCD, panic disorder Most drug interactions
PAROXETINE Anticholinergic effects Highest volume of distribution Toxicity: weight gain, cardiac septal defects
SERTRALINE Nausea
SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS Moderately selective SERT and NET blockade serotoninergic and
noradrenergic effects Clinical uses: major depression, generalized anxiety, neuropathies,
fibromyalgia Interactions: MAOI, tricyclic antidepressantsDULOXETINE HepatotoxicityMILNACIPRAN Highest bioavailability
Shortest t1/2VENLAFAXINE Weak NET inhibitor
Lowest protein binding antidepressant Cardiotoxicity
TRICYCLIC ANTIDEPRESSANTS ("triptyline", "ipramine") Oldest antidepressants Mixed/variable SERT and NET blockade Clinical uses: depression unresponsive to other antidepressants, pain
conditions, enuresis, migraine Toxicity: anticholinergic effects, blockade (orthostatic hypotension), H1
antagonism (weight gain, sedation), discontinuation syndrome Interactions: benztropin, diphenhydramine, antihypertensivesAMITRIPTYLINE Prototype tricyclic antidepressantMORE AFFINITY TO SERT CLOMIPRAMINE
o Sexual effects IMIPRAMINE
o Shortest t1/2MORE AFFINITY TO NET DESIPRAMINE, NORTRIPTYLINE
o No active metaboliteso Wide therapeutic window
5-HT2A RECEPTOR ANTAGONISTS ("zodone") Inhibit 5-HT2A receptor Little effect on NET, weak-moderate presynaptic blocker, modest H1
receptor antagonistNEFAZODONE Weak SERT and NET inhibitor
Potent CYP3A4 inhibitor Toxicity: hepatotoxicity Interactions: triazolam and simvastatin ( levels of both)
TRAZODONE Weak selective SERT inhibitor More bioavailable Clinical uses: hypnosis Toxicity: sedation, priapism Interactions: ritonavir and ketoconazole ( trazodone)
Exception to the rule: vilazodone is classified as an SSRI.
TETRACYCLIC AND UNICYCLIC ANTIDEPRESSANTS Least associated with sexual side effects: bupropion, mirtazapineAMOXAPINE NET > SERT inhibition
Shortest t1/2 Toxicity: parkinsonism
BUPROPION NE and DA activity Biphasic elimination Toxicity: agitation, insomnia, anorexia, seizures Interactions: cyclophosphamide, desipramine, MAOI
MAPROTILINE Interactions: fluoxetine (additive anticholinergic andantihistaminic effects)
MIRTAZAPINE NE and 5-HT release H1 receptor antagonist Toxicity: sedation
MONOAMINE OXIDASE INHIBITORS Block MAOA and MAOB Toxicity: orthostatic hypotension, weight gain, amphetamine-like effects,
discontinuation syndrome Interactions: SSRI (serotonin syndrome), tyramine (hypertensive crisis)IRREVERSIBLENONSELECTIVEINHIBITORS
PHENELZINEo Toxicity: sexual side effects, sedation
TRANYLCYPROMINESELECTIVE MAOAINHIBITORS
SELEGILINE
OTHERS ISOCARBOXAZID, MOCLOBEMIDE
PSYCHOTIC DISORDERS
TYPICAL ANTIPSYCHOTICS Primarily block D2 receptors but can also block , muscarinic, H1, and 5-HT2 Clinical uses: schizophrenia, Tourette syndrome Toxicity: parkinsonism (2 to dopamine antagonism)PHENOTHIAZINES("azine")
ALIPHATIC (CHLORPROMAZINE)o 1 = 5-HT2A > D2 > D1o Toxicity: orthostatic hypotension, impaired
ejaculation, lens deposits PIPERIDINES (THIORIDAZINE)
o Toxicity: cardiotoxicity, retinal deposits PIPERAZINES (FLUPHENAZINE)
o Toxicity: risk of tardive dyskinesiaBUTYROPHENONES("peridol")
HALOPERIDOLo High potency among typical antipsychoticso D2 > 1 > D4 > 5-HT2A > D1 > H1o Toxicity: severe extrapyramidal symptoms,
cardiotoxicity (torsades)DIBENZOXAPINES LOXAPINE
THIOXANTHENE THIOTHIXENEo Less risk of tardive dyskinesiaDIHYDROINDOLONES MOLINDONE
ATYPICAL ANTIPSYCHOTICS Clinical uses: manic phase of bipolar affective disorderCLOZAPINE Advantages: suicidal tendencies
Disadvantages: agranulocytosis, seizure threshold,diabetes mellitus
High affinity to M1 anticholinergic effects High affinity to 1 orthostatic hypotension High affinity to 5-HT weight gain
-
#PharMasaya :P Page 8 of 13
Baby Katzung (Finals Reviewer)
RISPERIDONE Shortest peak time (1-1.5 hours) Moderate affinity to D2 extrapyramidal symptoms
OLANZAPINE Highest volume of distribution (10-20 L/kg)QUETIAPINE High affinity to 1 and H1 sedation
Lowest affinity to M1ZIPRASIDONE Highest protein binding (>99%)
Advantages: least weight gain (low affinity to 5-HT2) Disadvantages: QT prolongation
ARIPIPRAZOLE Advantages: no hyperprolactinemiaMISCELLANEOUS PIMOZIDE
BIPOLAR DISORDERS
MOOD STABILIZERS Inhibit inositol monophosphate (rate-limiting enzyme in inositol recycling)LITHIUM Classic mood stabilizer
Inhibits IP and glycogen synthase kinase-3 Narrow therapeutic window Long-term risk of hypothyroidism Clinical uses: manic phase of bipolar disorder,
schizoaffective disorder, unipolar depression Toxicity: ECG changes, dermatologic effects (acne,
rashes), hypothyroid and hyperparathyroid state,teratogenic effects (septal and valve defects), GITeffects (anorexia, N/V, diarrhea), granulocytosis,cognitive tremors, nephrogenic diabetes insipidus
CARBAMAZEPINE Monotherapeutic alternative to lithium Prophylaxis and treatment of bipolar disorder
VALPROIC ACID Inhibits IP and GSK-3 Anti-manic effect Initial treatment and maintenance of bipolar disorder
GENERAL ANESTHESIA
INHALATION ANESTHETICS Meyer-Overton principle: nonspecific interactions with lipid matrix of
neuronal membrane ion flux neuronal activity Minimal alveolar concentration (MAC)
o MAC potencyo Minimum concentration resulting in immobility in 50% of patients even
with surgical stimulus or incisiono Additive in nature (used in balanced anesthesia)o Elderly or CNS depressants (opioids, sedative-hypnotics) lower MAC
Factors DIRECTLY related to uptakeo Anesthetic concentration in inspired air
anesthetic concentration in gas mixture faster inductiono Pulmonary ventilation
Hyperventilation uptake Factors INVERSELY related to uptake
o Solubility Index: blood-gas partition coefficient Low solubility or blood-gas partition coefficient rapid onset
and recoveryo Pulmonary blood flow
pulmonary blood flow faster induction of anesthesiao Arteriovenous concentration gradient
AV gradient faster equilibration Route of elimination: lungs (primary), liver Toxicity: hepatotoxicity, nephrotoxicity, malignant hyperthermiaLOW-SOLUBILITY NITROUS OXIDE
o Least potent inhaled anesthetic (MAC: 100%)o Lowest brain-blood partition coefficient (1.1)o Not metabolized
DESFLURANEo Highest blood-gas partition coefficient (0.42)o Brain-blood partition coefficient: 1.3o MAC: 6-7%
o Least metabolized among fluranesHALOTHANE High-solubility
Oxidized to trifluoroacetic acid and chlorotrifluoro-ethyl free radical halothane-induced hepatitis
OTHERS SEVOFLURANE, ENFLURANE, METHOXYFLURANEo Metabolized to fluoride ions nephrotoxicity
INTRAVENOUS ANESTHETICS Clinical uses: rapid induction of general anesthesia, ICU sedation,
maintenance of anesthesia Organ level effects: cerebral vasoconstriction CBF and ICP, CMRO2,
cardiorespiratory depressionBARBITURATES THIOPENTAL, METHOHEXITALPROPOFOL Potentiates Cl- current mediated through GABAA
receptor complex Relatively short context-sensitive t1/2 even with
prolonged infusion up to 8 hours DOC for induction and maintenance of anesthesia
BENZODIAZEPINES MIDAZOLAMo Rapid onset, short context-sensitive t1/2o DOC for "conscious" sedationo Preoperative medication (anxiolysis,
anterograde amnesia)ANALGESICS KETAMINE
o Blocks glutamate effects on NMDA receptoro Lowest protein binding among IV anestheticso Clinical uses: dissociative anesthesia (eyes
wide open with slow nystagmic gaze)o Causes psychotomimetic effects (emergence
reactions: vivid dreams, hallucinations)o Minimal respiratory depression
FENTANYLo Opioid analgesico Clinical uses: neurolept anesthesia (combined
with droperidol and nitrous oxide)o Toxicity: chest wall rigidity
ETOMIDATE GABA potentiator Short context-sensitive t1/2 Minimal hemodynamic effects Toxicity: adrenocortical suppression (inhibits 11-
hydroxylase)DEXMEDETOMIDINE Highly-selective 2 agonist
Stimulates 2 receptors in locus ceruleushypnosis
LOCAL AND REGIONAL ANESTHESIA
LOCAL ANESTHETICS Goal: localized analgesia Block voltage-gated Na+ channels (in active or inactive state but not in
rested state) but can also act on other ion channels (K+, Ca2+), enzymes, andreceptors (NMDA, G protein, 5-HT3, NK1)
Structure: lipophilic (aromatic) ring + intermediate chain (ester or amide) +ionizable group (tertiary amine)
Non-ionized (non-protonated) form: biologically active form Routes: parenteral, topical (transdermal, transmucosal) Pharmacokinetics
o More vascular site rapid absorptiono Vasoconstrictors (epinephrine) blood flow less systemic
absorption and toxic effects, better uptakeo Smaller and more lipophilic local anesthetics faster interactiono Metabolism: plasma butyrylcholinesterase (esters), hepatic amidase
(amides) Factors affecting local block
o Preferential blockade of small-diameter fibers (type B and C),myelinated fast-firing fibers (type C) over large-diameter (type A) ormotor fibers
-
#PharMasaya :P Page 9 of 13
Baby Katzung (Finals Reviewer)
o Motor fibers blocked first in large mixed nerve trunkso Sensory fibers blocked first in extremities
Clinical uses: local infiltration, blockade of peripheral nerves, regionalanesthesia (Bier block, short surgical procedures)
Toxicity: CNS effects (dizziness, sensory disturbances, nystagmus),neurotoxicity, tachyphylaxis, allergic reaction (2 to PABA from esters)
AMINOESTERS(one i)
COCAINEo First local anesthetico Restricted to topical anesthesia of EENTo Vasoconstrictory property bleedingo Toxicity: adrenergic effects from NET blockade
(vasoconstriction, hypertension, arrhythmia) BENZOCAINE CHLOROPROCAINE
AMINOAMIDES(two I's)
ARTICAINEo Dental anesthetic
BUPIVACAINEo DOC for regional spinal anesthesia, also used in
epidural infusions for labor analgesia and post-operative pain control
o Toxicity: cardiotoxicity (antidote: lipid emulsion) LIDOCAINE
o Intermediate-acting anesthetico Reference standard agent of local anestheticso Toxicity: transient neurologic syndrome (sudden
transient pain or dysthesia) PRILOCAINE
o Spinal anesthetico Highest clearance systemic toxicityo Metabolized to o-toluidinemethemoglobinemia
ROPIVACAINEo Same clinical uses as bupivacaine but less
cardiotoxic
BIOLOGIC TOXINSMARINETOXINS
TETRODOTOXIN (puffer fish), SAXITOXIN (dinoflagellates)o Bind externally to "ready" state of Na+ channels
conductionOTHERS BATRACHOTOXIN (frogs), CIGUATOXIN (moray eel)
o Bind internally to receptors in Na+ channel Na+ influx persistent depolarization
SKELETAL MUSCLE RELAXANTS
NONDEPOLARIZING NEUROMUSCULAR BLOCKERS Reversed by acetylcholinesterase inhibitors (neostigmine, pyridostigmine)ISOQUINOLINEDERIVATIVES("curium")
d-TUBOCURARINEo Prototype neuromuscular blockero Paralyzes small muscles before large muscles
(abdominal, paraspinous, diaphragm) ATRACURIUM, CISATRACURIUM
o Spontaneous chemodegradation (Hofmannelimination) into laudanosine and quarternary acid
MIVACURIUMo Shortest-acting nondepolarizing blockero Competitively inhibits acetylcholine at NM receptoro Blocks prejunctional Na+ channelso Rapidly cleared by plasma cholinesterase
STEROIDDERIVATIVES("curonium")
PANCURONIUMo Long-actingo Most potent nondepolarizing blocker
INTERMEDIATE-ACTING (ROCURONIUM, VECURONIUM)o ROCURONIUM: fastest-onset nondepolarizing
blocker (60-120 seconds), reversed by sugammadex
DEPOLARIZING NEUROMUSCULAR BLOCKERSSUXAMETHONIUM(SUCCINYLCHOLINE)
2 acetylcholine molecules linked together Extremely short duration of action (5-10 minutes) Hydrolyzed by plasma cholinesterase Pharmacodynamics
o Phase I block: fasciculation and flaccidparalysis, augmented by cholinesteraseinhibitors
o Early phase II block: desensitizationo Late phase II block: reversed by cholinesterase
inhibitors DOC for procedures requiring short-term
relaxation (intubation, electroconvulsive therapy) Toxicity: malignant hyperthermia, cardiac effects,
hyperkalemia, IOP, GI regurgitation, myalgias
SPASMOLYTICSDIAZEPAM tonic output of -motor neuronsBACLOFEN GABA analog
Activates GABAB receptors K+ conductancehyperpolarization presynaptic inhibition
Inhibits release of excitatory neurotransmitters in CNS andsubstance P in spinal cord (analgesic effect)
TIZANIDINE 2 adrenoceptor agonist (similar to clonidine but has lessantihypertensive property)
Reinforces presynaptic and postsynaptic inhibition inspinal cord
DANTROLENE Binds to ryanodine receptor RyR1 (in skeletal muscle) Ca2+ release from SER
DOC for malignant hyperthermiaOTHERS PROGABIDE
o GABAA and GABAB agonist GLYCINE (endogenous inhibitory neurotransmitter) IDROCILAMIDE, RILUZOLE
o Clinical uses: amyotrophic lateral sclerosis BOTULINUM TOXIN
o Clinical uses: ophthalmology, relief of local spasm,aging-associated wrinkles, generalized spasm ofcerebral palsy
ANALGESIA AND INFLAMMATION
OPIOIDS Organ level effects: analgesia (, , ), euphoria (), sedation and
respiratory depression (), cough suppression, miosis, truncal rigidity, N/V,hyperthermia () or hypothermia (), bradycardia (except in meperidine),hypotension, constipation, urinary retention, peripheral effects (prolongedlabor, neuroendocrine effects, pruritus, lymphocyte proliferation)
ENDOGENOUSPEPTIDES
ENDORPHINS ( AGONISTS)o Precursor: preproopiomelanocortin (POMC)o Present in CNSo Pain modulation
ENKEPHALINS ( AGONISTS)o Precursor: preproenkephalin (PPE-A)
DYNORPHINS ( AGONISTS)o Precursor: leucine-enkephalin (PPE-B)o DYNORPHIN A: found in dorsal horn
OPIOID AGONISTS Primarily act on the opioid receptor Chemical classifications
o PHENANTHRENES ("phine", "codeine", "codone"): morphine, codeine,nalbuphine, buprenorphine
o PHENYLHEPTYLAMINES: methadone, propoxypheneo PHENYLPIPERIDINES: meperidine, fentanyl, diphenoxylate, loperamideo MORPHINANS ("orphanol"): levorphanol, butorphanolo BENZOMORPHANS: pentazocine
-
#PharMasaya :P Page 10 of 13
Baby Katzung (Finals Reviewer)
o MISCELLANEOUS ("adol"): tramadol, tapentadol Routes: rectal suppositories, transdermal, intranasal, transmucosal,
parenteral (patient-controlled analgesia) Clinical uses: analgesia, acute pulmonary edema, cough, diarrhea,
shivering, preoperative anesthesia Toxicity: tolerance (2 to repeated doses), dependence (2 to withdrawal),
hyperalgesia (2 to persistent opioid administration) Interactions: sedative-hypnotics (CNS and respiratory depression),
antipsychotics (sedation), MAOI (hyperpyrexic coma)STRONGAGONISTS
MORPHINEo Clinical uses: moderate to severe pain
MEPERIDINEo Only opioid analgesic with antimuscarinic activity tachycardia
METHADONEo Blocks NMDA receptors and monoaminergic uptake
transporters (DAT, NET, SERT)o Clinical uses: difficult-to-treat pain (neuropathic or
cancer pain)o DOC for opioid dependenceo Detoxification of opioids and heroin
FENTANYLo SUFENTANIL: more potento ALFENTANIL: less potent, rapid-onset, short-actingo REMIFENTANIL: short t1/2
MILD TOMODERATEAGONISTS
CODEINE, OXYCODONE, DIHYDROCODEINE,HYDROCODONEo Combined in formulations containing aspirin,
acetaminophen, and others DIPHENOXYLATE, LOPERAMIDE
PARTIALOPIOIDAGONISTS-ANTAGONISTS
NALBUPHINEo Strong agonisto antagonist
BUPRENORPHINEo High affinity but low intrinsic activity at receptoro antagonisto Binds to orphanin receptor ORL1o Alternative to methadone for detoxification and
maintenance of opioid and heroin abuse PENTAZOCIN
ANTITUSSIVES DEXTROMETHORPHANo Levorphanol derivativeo Strong opioid agonist
LEVOPROPOXYPHENEOTHERS TRAMADOL
o Centrally-acting analgesic (SERT blockade)o Weak agonisto Toxicity: seizures, nausea, dizziness
TAPENTADOLo Modest affinity to receptoro Significant NET blockade
OPIOID ANTAGONISTS Morphine derivatives with bulkier substituent at N17 position Reverses opioid effects within 1-3 minutes Inert, no tolerance or withdrawal Toxicity: abstinence syndromeNALOXONE Short-acting (1-2 hours)
Clinical uses: acute opioid overdoseNALTREXONE Blocks effects of injected heroin
Maintenance of addictionNALMEFENE Parenteral naltrexone derivativeMETHYLNALTREXONE Opioid-induced constipationALVIMOPAN Post-bowel resection ileus
NOVEL ANALGESICSLIDOCAINE,MEXILETINE
Block tetrodotoxin-resistant voltage-gated Na+ channels
GABAANALOGS
GABAPENTIN, PREGABALIN
ZICONOTIDE Blocks voltage-gated N-type Ca2+ channels
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS sensitivity of blood vessels to bradykinin and histamine, lymphokines,
reverse vasodilation, inhibit platelet aggregation Newer NSAID
o Anti-inflammatory, antipyretic, analgesico Less GI irritation
Pharmacokinetics: enterohepatic circulation, renal elimination Found in synovial fluid Toxicity: tinnitus, abdominal pain, GI ulcers, hepatotoxicity (abnormal liver
function tests), asthma, pruritus, nephrotoxicity (renal insufficiency) Greatest toxicity: indomethacin, tolmetin Least toxicity: salicylates, ibuprofenNONSELECTIVECOXINHIBITORS
ACETYLSALICYLATE (ASPIRIN)o Irreversibly inhibits COX inhibits platelet
aggregationo incidence in TIA, unstable angina, coronary
thrombosis with MI or post-CABGo Valuable in preeclampsia-eclampsiao Toxicity: Reye's syndrome in children (fatal
fulminant hepatitis with cerebral edema) NON-ACETYLATED SALICYLATES (MAGNESIUM AND
SODIUM SALICYLATE, SALICYL SALICYLATE)o Alternative to aspirin if with renal insufficiency
SELECTIVECOX-2INHIBITORS("coxib")
CELECOXIBo Alternative to aspirin in patients with high risk of GI
bleedingo Interactions: sulfonamides (rashes)
ROFECOXIB, VALDECOXIBo Withdrawn due to CV thrombotic events
MELOXICAMo "Preferentially" selective but not highly selective
COX-2 inhibitor NIMESULIDE
o Relatively selective COX-2 inhibitoro Analgesic and antipyretic properties
OTHERS (ETORICOXIB, PARECOXIB)NONSELECTIVENSAIDS
DIFLUNISALo No CNS entry (no antipyretic effect)o Clinical uses: rheumatoid arthritis, cancer pain with
bone mets, pain post-third molar surgery FLURBIPROFEN
o Clinical uses: EENT (inhibits intraoperative miosis,perioperative analgesia in minor ear, nose, andneck surgeries)
o Toxicity: cogwheel rigidity IBUPROFEN (PHENYLPROPIONIC ACID)
o DOC for closure of patent ductus arteriosus inpreterm infants
INDOMETHACINo Inhibits phospholipase A and Co neutrophil migration and lymphocyte
proliferationo Clinical uses: patent ductus arteriosus closure,
initial treatment of gout, ankylosing spondylitis,ophthalmic uses, postlaminectomy syndrome
o Toxicity: pancreatitis KETOPROFEN
o Cyclooxygenase and lipooxygenase inhibitor KETOROLAC
o Substitute to morphine in mild to moderate post-
-
#PharMasaya :P Page 11 of 13
Baby Katzung (Finals Reviewer)
operative paino opioid requirement
MEFENAMIC ACIDo Relief of mild-moderate pain in patients 14 y/oo Clinical uses: primary dysmenorrhea, menorrhagiao Contraindications: status post-CABG, GI ulcers,
renal disease NABUMETONE
o Lone nonacid NSAID NAPROXEN
o DOC for tumor fever PHENACETIN
o Withdrawn due to nephrotoxicity (acute tubularnecrosis, papilary necrosis)
PHENYLBUTAZONEo Withdrawn due to aplastic anemia and
agranulocytosis PIROXICAM
o Inhibits PMNL migration and lymphocyte functiono oxygen radicals
SULINDACo Clinical uses: rheumatic disease, familial
adenomatous polyposis, risk of cancero Toxicity: Stevens-Johnson syndrome, toxic
epidermal necrolysis TOLMETIN
o Ineffective in gout OTHERS (DICLOFENAC, ETODOLAC, OXAPROZIN)
DISEASE-MODIFYING ANTI-RHEUMATIC DRUGSMETHOTREXATE Inhibits aminoimidazole carboxamide (AICAR)
transformylase and thymidylate synthetase First-line therapy for rheumatoid arthritis Clinical uses: arthritis, psoriasis, ankylosing
spondylitis, polymyositis, dermatomyositis,Wegener's granulomatosis, giant cell arteritis,SLE, vasculitis
Toxicity: nausea, mucosal ulcersGOLD SALTS AURANOFIN, AUROTHIOGLUCOSE
o Inhibits Schwartzmann phenomenonIMMUNOSUPPRESANTS AZATHIOPRINE
CHLOROQUINE CYCLOPHOSPHAMIDE CYCLOSPORINE LEFLUNOMIDE MYCOPHENOLATE MOFETIL SULFASALAZINE
o IgA and IgM rheumatoid factorsGLUCOCORTICOIDS Management of extra-articular manifestations
of rheumatoid arthritis (pericarditis, eyeinvolvement, exacerbation)
Clinical uses: SLE, vasculitis, giant cell arteritis,Wegener's granulomatosis, sarcoidosis, gout
ANALGESICS ACETAMINOPHENo Phenacetin derivativeo Weak nonselective COX inhibitoro No significant anti-inflammatory activityo Metabolized to N-acetyl-p-benzoquinone
(hepatotoxic and nephrotoxic)o Clinical uses: mild analgesiao Toxicity: Reye's syndrome, severe
hepatotoxicity with centrilobular necrosis(>15 g paracetamol)
o Antidote: N-acetylcysteine
BIOLOGICAL ANTI-RHEUMATIC DRUGS Toxicity: risk of bacterial infections (e.g. pulmonary tuberculosis) and
lymphomasANTI-TNF ADALIMUMAB
o Effective as monotherapy or in combination withmethotrexate and other DMARD
INFLIXIMABo Concurrent therapy with methotrexateo Contraindications: multiple sclerosis
ETANERCEPTo Monotherapyo Clinical uses: rheumatoid arthritiso risk of latent TB activation than other anti-TNF
OTHERS ABATACEPTo Inhibits T cell activation
RITUXIMABo Anti-CD20o Combined with methotrexateo Clinical uses: rheumatoid arthritis refractory to anti-TNFo Toxicity: infusion reactions (pre-treat with IV
glucocorticoids) TOCILIZUMAB
o Anti-IL-6o Moderate to severe rheumatoid arthritiso Same clinical uses as rituximab
ANTI-GOUTCOLCHICINE Binds to intracellular protein tubulinmicrotubule
polymerization Clinical uses: relief of pain and inflammation of gouty
arthritis in 12-24 hours, prophylaxis of recurrentepisodes of gouty arthritis
Overdose: burning throat pain, bloody diarrheaANALGESICS Inhibit prostaglandin synthase and urate crystal
phagocytosis INDOMETHACIN OXAPROZIN
o Very long t1/2 (50-60 hours)o renal excretion of uric acido Contraindications: renal stones
URICOSURICAGENTS
PROBENECID, SULFINPYRAZONEo Organic acidso Act at anion transport sites of renal tubuleso urate pool sizeo Reabsorbs tophaceous urate depositso Clinical uses: tophaceous gout, increasingly
frequent gouty attackso Toxicity: GI irritation (in sulfinpyrazone),
nephrotic syndrome (in probenecid), aplasticanemia (in both)
ALLOPURINOL Isomer of hypoxanthine Purine inhibitor of xanthine oxidase uric acid Combined with colchicine or NSAID Clinical uses: long-term or lifelong treatment DOC for intercritical period (between acute attacks) Toxicity: N/V, diarrhea, allergic reaction Interactions: mercaptopurine, probenecid
FEBUXOSTAT Nonpurine inhibitor of xanthine oxidase Clinical uses: chronic gout, prophylaxis of gout flares
(combined with colchicine or NSAID pre-therapy)PEGLOTICASE Recombinant mammalian uricase
Converts uric acid to allantoin Clinical uses: refractory chronic gout
GLUCOCORTICOIDS Clinical uses: severe symptomatic goutIL-1 INHIBITORS ANAKINRA, CANAKINUMAB, RILONACEPT
-
#PharMasaya :P Page 12 of 13
Baby Katzung (Finals Reviewer)
TRADITIONAL MEDICINES
BOTANICALSEchinaceapurpurea
Constituents: flavonoids, water-soluble polysaccharides andconjugates
Uses: immunomodulatory (colds, respiratory infections),anti-inflammatory, antimicrobial
Toxicity: flu-like symptoms, unpleasant taste, GIT upset Interactions: immunodeficiency disorders, tuberculosis,
alcohol-based medications (disulfiram-like reaction)Ginkgobiloba
Constituents: flavone glycosides, terpenoids Pharmacologic effects: vascular effects ( blood flow,
blood viscosity, vasodilation), antioxidant, CNS effects(dementia of Alzheimer type)
Miscellaneous uses: bronchoconstriction, short-termmemory, erectile dysfunction, hearing disturbances, maculardegeneration
Hypericumperforatum
St. John's wort Constituents: hypericin Uses: antidepressant, antiviral, anticarcinogenic Toxicity: photosensitization, mania Interactions: antidepressants
Serenoarepens,Sabalserrulata
Saw palmetto Constituents: phytosterol, aliphatic alcohols, polyprenic
compounds, flavonoids Uses: benign prostatic hyperplasia Toxicity: GIT upset, hypertension, libido, abdominal pain,
back pain, urinary retention, headache No drug interaction reported
PURIFIED NUTRITIONAL SUPPLEMENTSCOENZYME Q10 CoQ, CoQ10, uboquinone
Potent antioxidant found in mitochondria Clinical uses: cardiovascular diseases (hypertension,
heart failure, ischemic heart disease), prevention ofstatin-induced myopathy
Interactions: warfarin (CoQ10: similar to vitamin K)GLUCOSAMINE Derived from crustaceans (e.g. crabs)
Substrate for articular cartilage production Facilitates glycosaminoglycans (GAG) synthesis Clinical uses: knee osteoarthritis Interactions: warfarin ( INR and bleeding)
MELATONIN N-acetyl-5-methoxytryptamine (serotonin derivative) Produced by the pineal gland (suppressed in daylight) Regulates sleep-wake cycle Inhibits reproductive function ( ovulation in females
and sperm quality in males) Clinical uses: jetlag, insomnia Toxicity: day-after drowsiness, fatigue, dizziness,
headache, irritability Interactions: nifedipine ( BP)
GLUTATHIONE Major endogenous antioxidant Neutralizes free radicals and reactive oxygen species Maintains exogenous antioxidants (vitamin C and E) in
their reduced (active) forms Clinical uses: prevents toxic effects of chemotherapy,
aging, alcoholism, cancer, heart and liver disease,Alzheimer's and Parkinson's disease
Toxicity: rashes, stomachache, thyroid disease, fataleffects (renal failure, SJS, toxic epidermal necrolysis)
Contraindications: allergy to milk protein, organtransplant
PAPAYA SEEDS Uses: anti-inflammatory, anti-parasitic (ringworminfections), analgesic (stomachache)
Toxicity: allergic reaction (skin irritation)
HERBAL MEDICINESAKAPULKO(Cassia alata)
Constituents: saponins (laxative) Uses: antifungal, ringworms, scabies, eczema,
stomatitis, expectorant, anti-asthma, diuretic, laxative Toxicity: GIT effects (N/V, diarrhea)
AMPALAYA(Momordicacharantia)
Constituents: flavonoids, alkaloids (antihyperglycemic) Uses: antihyperglycemic, antirheumatic, antiseptic,
antihelminthic, immunomodulatory Toxicity: abortifacient
ATIS (Anonasquamosa)
Uses: gastrointestinal (dysentery, diarrhea), colds,fever, antirheumatic, dizziness and fainting,antipediculosis
Toxicity: blindness (seeds), abortion (paste)BANABA(Lagerstromiaspeciosa)
Queen's flower, crepe myrtle Constituents: corosolic acid (insulin-like effect) Uses: antihyperglycemic, obesity, blood pressure Cautions: antidiabetics
BAWANG (Alliumsativum)
Constituents: alliin Uses: antihypertensive, antifungal, fibrinolytic Toxicity: nausea, hypotension, allergy, bleeding Cautions: anticoagulants
BAYABAS(Psidiumguajava)
Uses: wound disinfectant, antiseptic gargle,astringent, vaginal wash
GUMAMELA(Hibiscus rosa-sinensis)
China rose or hibiscus Uses: expectorant, diuretic, emollient, anti-infective
and anti-inflammatory (boils, swelling, abscesses,mumps), antipyretic, sedative
Toxicity: abortifacient in large dosesLAGUNDI (Vitexnegundo)
Constituents: chrysoplenol D (antihistamine, musclerelaxant)
Uses: respiratory uses (asthma, pharyngitis, cough,colds, flu, bronchopulmonary disorders), boils,symptomatic management of chicken pox,antihelminthic
LUYA (Zingiberofficinale)
Uses: analgesic (rheumatic and muscle pain,toothache), alleviates sore throat and colds, GI uses(tympanism, flatulence, intestinal worms, diarrhea, gaspains, dyspepsia), serum cholesterol, PTB treatment
Contraindications: pregnancy (testosterone inhibition)MABOLO(Diospyrosblancoi)
Uses: gastrointestinal uses (stomach pains, diarrhea,dysentery), cardiovascular uses (heart disease,hypertension), cough, fever, skin ailments, diabetes
MALUNGGAY(Moringaoleifera)
Horse radish Uses: nutrient supplement (source of Ca2+, iron,
vitamin C, phosphorus), antioxidant, antidiabetic,antihypertensive, analgesic (rheumatic pain, headache,migraine), purgative, antifungal
MAKABUHAY(Tinosporarumphii Boerl)
Heavenly elixir Uses: antimalarial, wound cleansing, diarrhea,
indigestion, scabiesNIYOG-NIYOGAN(Quisqualisindica)
Chinese honey suckle Uses: antiparasitic
OREGANO(Origanumvulgare)
Winter marjoram Constituents: antioxidants Uses: respiratory uses (cough, colds, asthma), anti-
aging, arthritis, GI uses (upset stomach, dyspepsia,indigestion), UTI, dermal uses (heals wounds, insectbites or stings)
PANDAN(Pandanustectorius)
Fragrant screw pine Uses: analgesic, antiseptic and antibacterial
PANSIT-PANSITAN(Peperomiapellucida)
Ulasimang-bato Uses: arthritis, gout, skin diseases (boils, abscesses,
acne), headache, abdominal pain, kidney problems
-
#PharMasaya :P Page 13 of 13
Baby Katzung (Finals Reviewer)
SABILA OR ALOEVERA(Barbadensismiller)
Uses: skin conditions (acne, psoriasis, bites, minorburns), analgesic, antihypertensive, anti-aging,diabetes, eradicates intestinal bacteria and parasites,helps prevent cancer and tumors
SALUYOT(Corchoruscapsularis)
Constituents: Ca2+, phosphorus, iron, K+, vitamin A,thiamine, riboflavin, ascorbic acid, fibers
Uses: antioxidant, reduce wrinkles, anti-inflammatorySAMBONG(Blumeabalsamifera)
Uses: diuretic, kidney stones, hypertension,rheumatism, colds, fever, GI uses (diarrhea, stomachpains, dysentery), worms, boils, sore throat
Toxicity: hypokalemia (take with bananas or potatoes)SILYMARINE ORMILK THISTLE(Silybummarianum)
Constituents: silymarin (polyphenolic flavonoid withantioxidant properties)
Uses: hepatoprotection (improves liver function incirrhosis and chronic hepatitis), Amanita phalloidespoisoning, antidiabetic, anticholesterol, reducesgrowth of cancer cells (breast, prostate, cervix, skin),antioxidant
Nontoxic (no overdose symptoms)TANGLAD(Andropogoncitratus DC)
Lemon grass Uses: cleansing, stomach discomfort, antibacterial and
antifungal, antiuricemic, detoxifierTSAANG- GUBAT(Ehretiamicrophylla)
Forest or wild tea Uses: GI uses (gastroenteritis, intestinal motility,
dysentery, diarrhea or LBM, mouth gargle), body washYERBA BUENA(Menthacardifolia)
Uses: analgesic (headache, stomachache, rheumatic orarthritic pain, menstrual and gas pains), dental uses(swollen gums, toothache), nausea, fainting, pruritus
PHARMACOLOGY TRANSCRIPTION TEAM
Martin Joseph A. Calaunan@MARTINidazoleTransmaster/Editor
Nikka Mae A. Larcia@NIKKArdipine
Nina Carmela P. Pescante@PESKYcide
Marc Christopher F. Barbin@phenoBARBital
Clarice B. Palma@CLArithromycin
Ron Michael N. Olaguera@interfeRON