Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
328 Cards in this Set
- Front
- Back
|
Bethanechol trade name
|
Urecholine®, others
|
|
|
Bethanechol type of drug
|
Cholinergic Agonists
Direct |
|
|
Neostigmine type of drug
|
Cholinergic Agonists
Indirect |
|
|
Neostigmine trade name
|
(Prostigmin®, others)
|
|
|
Neostigmine adverse effects
|
miosis, NVD, abd cramps,
hypotension, … |
|
|
Neostigmine caution
|
asthma, epilepsy, bradycardia, peptic ulcer
|
|
|
Neostigmine type of drug
|
Cholinergic Agonists
Indirect |
|
|
Neostigmine trade name
|
(Prostigmin®, others)
|
|
|
Atropine type of drug
|
Cholinergic Antagonists
|
|
|
Atropine onset
|
within 30 min
|
|
|
Atropine dose
|
04mg(PO) 0406mg(SCIVIM)
0.4 mg (PO) 0.4-0.6 mg (SC, IV, IM) |
|
|
Atropine duration
|
several hours (renal elimination)
|
|
|
Atropine therapeutic use
|
prevent or treat bradycardia,
treat poisoning (mushroom, pesticide, sarin) |
|
|
Atropine adverse effects
|
tachycardia, hyperthermia, GI,
mydriasis and cycloplegia |
|
|
Atropine caution
|
glaucoma, bowel hypomotility
|
|
|
CNS neurotransmitter
|
–Monoamines –DA, NE, 5HT
–Aminoacids–aspartateglutamate GABAglycine Amino acids aspartate, glutamate, GABA, glycine –Peptides –AVP, CCK, endocannabinoids, neurotensin, NPY, opioids, oxytocin, somatostatin, tachykinins –Others –ACh, histamine, purines |
|
|
PNS neurotransmitter
|
• PNS
–Acetylcholine(ACh) Acetylcholine (ACh) –Norepinephrine(NE) –Epinephrine (Epi) –Dopamine (DA) |
|
|
Dopamine neurotransmitter
|
Dopaminergic
Dopaminergic(D) |
|
|
NE neurotransmitter
|
Adrenergic
Adrenergic(α1-2, β1-3) |
|
|
Serotinin neurotransmitter
|
Serotonergic
Serotonergic(5HT, 5HT, 5HT) |
|
|
GABA neurotransmitter
|
Gabanergic
Gabanergic (GABA GABA GABA)(GABA, GABA, GABA) |
|
|
Glutamate/aspart neurotransmitter
|
Glutamatergic
Glutamatergic AMPA AMPA(GLUA1-A4), KA KA(GLUK1-K2,K5-K7), NMDA NMDA(GLUN1-N3) |
|
|
Tachykinins neurotransmitter
|
Neurokinin
Neurokinin(NK1-3) |
|
|
Acetylcholine neurotransmitter
|
Cholinergic
Cholinergic(M1-5, NM, NN) |
|
|
pain transduction
|
Tissue injury with release of mediators that activate or
sensitize nociceptors |
|
|
pain transmission
|
Propagation of the signal up the nerve fibers
• Type A fiber (fast); Type C fiber (slow) |
|
|
pain modulation
|
–Descending inhibitory neural pathways meet pain signal
|
|
|
pain perception
|
–The conscious awareness of the pain
|
|
|
Pain treatment strategy
|
• Select the best analgesic for the pain
• Mild Pain –Non-steroidal anti-inflammatory drugs (NSAID), acetaminophen, tramadol • Moderate Pain Add i id –Add an opioid • Severe Pain –Opioids |
|
|
NSAIDs
|
–Aspirin 650 mg po q6h
–Ibuprofen (Advil®, Motrin®)400 mg po q4h |
|
|
Opioids
|
–Morphine 15 mg po q4h
|
|
|
Aspirin indication
|
pain associated with inflammation
|
|
|
Aspirin mechanism
|
inhibits cyclo-oxygenase (COX)
|
|
|
Aspirin dose
|
650 mg q6h
|
|
|
Aspirin elimination
|
–hepatic, then renal
|
|
|
Aspirin adverse effects
|
GI distress, tinnitus, altered
hemostasis, renal dysfunction; avoidif allergic; interactionwith warfarin, corticosteroids, ethanol |
|
|
Ibuprofen trade names
|
(Advil®, Motrin®, others … NeoProfen®)
|
|
|
Ibuprofen indication
|
pain associated with inflammation
|
|
|
Ibuprofen mechanism
|
inhibits cyclo-oxygenase
|
|
|
Ibuprofen dose
|
400 mg q4h (5-10 mg/kg IV)
|
|
|
Ibuprofen onset/duration
|
within 60 min / 4-6 h
|
|
|
Ibuprofen elimination
|
hepatic, then renal
|
|
|
Ibuprofen adverse effects
|
GI distress, tinnitus, renal
dysfunction; avoid if allergic |
|
|
Acetaminophen trade name
|
(Tylenol®, others)
|
|
|
Acetaminophen indication
|
mild to moderate pain, fever
|
|
|
Acetaminophen mechanism
|
inhibits prostaglandin synthesis
|
|
|
Acetaminophen
elimination |
hepatic
|
|
|
Acetaminophen adverse effects
|
nausea, vomiting; cautionin
patients with hepatic dysfunction, alcohol use or with protein-calorie malnutrition |
|
|
Tramadol trade name
|
(Ultram®, Ultram®ER, Ryzolt®)
|
|
|
Tramadol indication
|
mild-moderate pain
|
|
|
Tramadol mechanism
|
spinal inhibition of NE, 5HT reuptake;
metabolite is a mu-opioidpeptide receptor agonist |
|
|
Tramadol elimination
|
hepaticmetabolism, renal excretion
hepatic metabolism, renal excretion |
|
|
Tramadol adverse effects
|
sedation, dizziness, dry mouth,
constipation, seizure risk; … |
|
|
Tramadol adverse effects specific
|
Adverse effects –
f cautionrenal dysfunction; interactions •carbamazepine causes CYP3A induction •quinidine causes CYP2D6 inhibition •additive effect with CNS depressants p •hypertension risk with MAO-I •serotonin syndrome risk with SSRIs and TCAs |
|
|
narcotic
|
–Astupor-producingsubstanceassociatedwith
A stupor producing substance associated with analgesia; natural or synthetic opioid |
|
|
controlled substance
|
–A drug with the potential for abuse, risk to public
health, or dependence (physiologic or psychic) –Scheduled by degree of risk (CC--II through CC--VV) “controlled substance” = “scheduled drug” |
|
|
tolerance
|
–Physiologicfinding; duetoneuro-adaptationwith
Physiologic finding; due to neuroadaptation with continued drug use |
|
|
physical dependence
|
–Physiologic finding with a marked drop in dose (or
drug discontinuation) following chronic use |
|
|
addiction
|
–Behavioral finding; entails pre-occupation with
obtaining drug despite no apparent indication |
|
|
OpioidAnalgesics
agonist |
Morphine fentanyl
–Morphine, fentanyl |
|
|
OpioidAnalgesics
partial agonist |
–Pentazocine
|
|
|
OpioidAnalgesics
antagonist |
–Naloxone
|
|
|
Morphine indication
|
severe pain (acute or chronic)
|
|
|
Morphine mechanism
|
MOP-receptoragonist
MOP-receptor agonist |
|
|
Morphine elminiation
|
hepatic (metabolites excreted renally)
|
|
|
Morphine adverse effects
|
sedationmiosis vomiting
sedation, miosis, vomiting, constipation, urinary retention, cough suppression, respiratory depression; interactionadditive effect with CNS depressant and anticholinergic agents |
|
|
Fentanyl trade names
|
(Sublimaze®, Duragesic®, Atiq®)
|
|
|
Fentanyl indication
|
severe pain (acute or chronic)
|
|
|
Fentanyl mechanism
|
severe pain (acute or chronic)
|
|
|
Fentanyl elimination
|
hepatic
|
|
|
Fentanyl adverse effects
|
d i i i i i
sedation, miosis, vomiting, constipation, urinary retention, cough suppression, respiratory depression; interactionadditive effect with CNS depressant |
|
|
Naloxone trade name
|
(Narcan, others)
|
|
|
Naloxone indication
|
opioid reversal
|
|
|
Naloxone mechanism
|
MOP-receptor antagonist
|
|
|
Naloxone elimination
|
hepatic (t ½ ~1-2h)
|
|
|
Naloxone adverse effects
|
hyperalgesia, withdrawal
syndrome |
|
|
epilepsy
|
disorder of recurrentseizures
|
|
|
seizure
|
abnormal or excessive electrical
activity in brain neurons |
|
|
convulsion
|
abnormal and involuntary series of
muscle contractions |
|
|
Seizure Management
|
• Early control of seizure disorder to allow for
i t i i l lif ibl maintaining as normal a life as possible • Decrease seizure frequency and severity • Prevent morbidity of seizure recurrence • Select the best AED for the seizure type |
|
|
–Anti-epileptic drugs (AEDs) classic
|
carbamazepine, ethosuximide, oxcarbazepine,
phenobarbital phenytoin primidone valproate phenobarbital, phenytoin, primidone, valproate |
|
|
–Anti-epileptic drugs (AEDs)
2nd generation |
gabapentin, lacosamide, lamotrigine,
levetiracetam, rufinamide, topiramate, tiagabine, zonisamide |
|
|
decrease Sodium influx
seizure drug |
• Phenytoin, carbamazepine, valproicacid
• Lacosamide, lamotrigine, rufinamide, zonisamide |
|
|
decrease calcium influx
seizure drug |
• Valproicacid, ethosuximide
|
|
|
decrease glutamate influx seizure drug
|
• Topiramate
|
|
|
increase GABA activity seizure medication
|
• Benzodiazepines, barbiturates, gabapentin
• Valproicacid |
|
|
Phenytoin trade name
|
(Dilantin®, others)
|
|
|
Phenytoin indication
|
partial seizure, tonic-clonic seizure
|
|
|
Phenytoin mechanism
|
Na-channel inhibition
|
|
|
Phenytoin elminiation
|
hepatic (saturable); highly protein-bound
|
|
|
Phenytoin adverse reactions
|
sedationnystagmus ataxia
–sedation, nystagmus, ataxia, diplopia, cognitive impairment, gingival hyperplasia, hirsutism, rash; cautionteratogenic; interaction increases drug metabolism, additive to CNS depressants |
|
|
Carbamazepine trade name
|
(Tegretol®, others)
|
|
|
Carbamazepine indication
|
partial seizure, tonic-clonic seizure
|
|
|
Carbamazepine mechanism
|
Nachannel inhibition
Na-channel inhibition |
|
|
Carbamazepine elimination
|
hepatic metabolism
|
|
|
Carbamazepine adverse effects
|
neurologic side effects without
g cognitive impairment, bone marrow suppression, hyponatremia, rash; interactionincreases drug metabolism |
|
|
Valproic Acid trade name
|
(Depakene)
|
|
|
Valproic Acid
indication |
–partial seizure, generalized seizure
|
|
|
Valproic Acid
mechanism |
inhibits Na & Ca-channels, increased GABA |
|
|
Valproic Acid elimination
|
hepatic metabolism, renal excretion;
highlyproteinboundhighly protein bound |
|
|
Valproic Acid adverse reactions
|
–GI complaints, weight gain,
rash, hair loss, tremor, hepatotoxicity, pancreatitis |
|
|
Phenobarbital indication
|
partial seizure, tonic-clonic seizure
|
|
|
Phenobarbital mechanism
|
GABA receptor binding
|
|
|
Phenobarbital elimination
|
hepatic metabolism, renal excretion
|
|
|
Phenobarbital
adverse reactions |
lethargy, cognitive impairment,
depression, physical dependence; increases drug metabolism, additive to CNS depressants |
|
|
Gabapentin trade name
|
(Neurontin, others)
|
|
|
Gabapentin indication
|
adjunctive for partial seizure
|
|
|
Gabapentin mechanism
|
increases GABA release
|
|
|
Gabapentin elimination
|
not metabolized, excreted renally
|
|
|
Gabapentin
adverse reactions |
somnolence, dizziness, ataxia,
fatiguenystagmus fatigue, nystagmus |
|
|
Phenyotin dose formulation
|
–Na-phenytoin(Dilantin®)–capsule, injectable
–Phenytoin(free acid) –suspension, chewable tablet –Fosphenytoin(Cerebyx®)–injectable(in Na- phenytoinequivalents) |
|
|
Carbamazepine dose formulation
|
–Carbamazepine–extended release tablet, capsule
(Tegretol®XR, Carbatrol®); suspension |
|
|
valporate dose formulation
|
• ValproateNa –syrup, injectable
• Valproicacid –capsule, gel cap (delayed-release), liquid p p , g p( y ), q • Na-divalproex–sprinkles (enteric-coated), tablet (enteric-coated) and tablet (extended release) |
|
|
Parkinson’s Disease
|
• Degenerative neurologic disorder affecting
d i i i th bt ti i dopaminergic neurons in the substantia nigra to the striatum which regulates movement • Manifestations include: –Tremor at rest, rigidity, instability, bradykinesia Depression dementia impairedmemory –Depression, dementia, impaired memory |
|
|
Therapeutic Approach
Parkinson's Disease |
• Therapeutic goal
–Control symptoms –Slow degeneration –Maintain QOL • Pharmacologic approach decrese acetylcholine increase dopamine |
|
|
Anticholinergic agents for parkinson's disease
|
–Benztropine (Cogentin®)
–Trihexyphenidyl (Artane®) |
|
|
•• Dopaminergic agents for parkinson's
|
––Increase DA synthesis
Increase DA synthesis • Levodopa (Larodopa®) • Carbidopa/levodopa (Sinemet®) ––IncreaseDArelease IncreaseDArelease ––Increase DA release Increase DA release • Amantadine (Symmetrel®) ––Stimulate DA receptors Stimulate DA receptors • Apomorphine (Apokyn®) • Pramipexole (Mirapex®) • Ropinirole (Requip®) • Rotigotine (Neupro®) • Bromocriptine, pergolide ––Inhibit DA degradation Inhibit DA degradation • MAOBinhibitor –selegiline (Eldepryl®), rasagiline (Azilect®) • COMT inhibitor –entacapone (Comtan®), tolcapone (Tasmar®) |
|
|
Pramipexole trade name
|
mirapex
|
|
|
Levodopa indication
|
Parkinson’s disease (most effective)
|
|
|
Levodopa mechanism
|
Dopamine precursor
|
|
|
Levodopa elminiation
|
–metabolized by decarboxylase & COMT
|
|
|
Levodopa adverse effects
|
nausea, vomiting, dyskinesias,
postural hypotension, tachycardia, psychosis, discolored secretions |
|
|
Pramipexole indication
|
Parkinson’s disease (in early disease)
|
|
|
Pramipexole mechanism
|
selective D2 agonist
|
|
|
Pramipexole elmination
|
renally excreted (unchanged)
|
|
|
Pramipexole adverse effects
|
–[alone]nausea, dizziness,
[alone] nausea, dizziness, somnolence, insomnia, constipation, weakness, hallucinations hallucinations; [with levodopa] orthostatic orthostatic hypotension, dyskinesias, hallucinations hypotension, dyskinesias, hallucinations |
|
|
Selegiline
trade name |
(Eldepryl®)
|
|
|
Selegiline indication
|
Parkinson’s disease (2ndline)
|
|
|
Selegiline mechanism
|
selective, irreversible MAO inhibitor
|
|
|
Selegiline elimination
|
hepatic metabolism and renal excretion
|
|
|
Selegiline adverse effects
|
insomnia and possible interactions
|
|
|
Entacapone trade name
|
(Comtan®)
|
|
|
Entacapone indication
|
Parkinson’s disease (with levodopa)
|
|
|
Entacapone mechanism
|
selective, reversible COMT inhibitor
|
|
|
Entacapone elimination
|
hepatic metabolism, bile/urine excretion
|
|
|
Entacapone adverse effects
|
increases risk of side effects from
levodopa…; plus vomiting, diarrhea, constipation, and change in urine color |
|
|
Alzheimer's disease
|
• Degenerative neurologic disorder irreversibly
ff ti hli i i th hi affecting cholinergic neurons in the hippocampus and cerebral cortex • Risk factors –family history, > 65 yo • Manifestations include: Sh t t f il –Short-term memory failures –Language difficulty, loss of speech, incontinence –Presence of neuritic plaques and neurofibrillary tangles |
|
|
Alzheimer's Therapeutic Approach
|
• Therapeutic goal
–Improve symptoms, reverse decline (ideally) –Slow memory and cognitive losses –Maintain independence • Pharmacologic approach – increase acetylcholine |
|
|
Cholinesterase inhibitors
for Alzheimer's |
–Donepezil (Aricept®)
–Tacrine (Cognex®) –Rivastigmine (Exelon®) –Galantamine (Reminyl®, Razadyne®) |
|
|
Antiozidant's for Alzheimer's disease
|
Selegiline(Eldepryl®)
–Selegiline (Eldepryl®) –Vitamin E –Ginkgo |
|
|
Donepezil
trade name |
(Aricept®)
|
|
|
Donepezil
indication |
Alzheimer’s disease (drug of choice)
|
|
|
Donepezil
mechanism |
inhibit reversible cholinesterase inhibitor
|
|
|
Donepezil
elimination |
hepatic metabolism, renal > bile
|
|
|
Donepezil
adverse effects |
nausea vomiting diarrhea
nausea, vomiting, diarrhea, dizziness, headache, bradycardia, bronchoconstriction; interactionreduced effect with anticholinergic drugs |
|
|
Memantine trade name
|
(Namenda)
|
|
|
Memantine indication
|
moderate-severe Alzheimer’s disease
|
|
|
Memantine
mechanism |
NMDA receptor antagonist (↓ Ca entry)
|
|
|
Memantine
elimination |
renal (largely unchanged); t½ ~60-80h
|
|
|
Memantine
adverse effects |
dizziness, headache, confusion,
constipation; cautionwith ketamine, Na-bicarbonate |
|
|
Schizophrenia
|
Defined
–Chronicpsychoticillnesswithdisorderedthinking Chronic psychotic illness with disordered thinking and limited ability to comprehend reality • Characteristic symptoms –Negative= social and emotional withdrawal, lack of motivation, poverty of speech, blunted affect, poor insight poorjudgment andpoorself care insight, poor judgment and poor self-care –Positive= hallucinations, delusions, disordered thinking, disorganized speech, combativeness, agitation, paranoia • Etiology –Unknown –Appears to be associated with increase DA & decrease Glut activation • Presentation ––Acute Acute–delusions and hallucinations (A > V) ––Residual Residual –suspicious, poor insight, judgment, control over anxiety, and self-care ––Episodic Episodic–acute presentations between periods of residual symptoms or partial remission; progressive decline in mental status and social function |
|
|
Antipsychotic Drugs
(Neuroleptic Drugs) |
• Broad group of compounds for psychotic disorders
• Allow for patient management without “locking up” • Two classes of drug compounds: –Conventional (1st Generation) • Block CNS DA receptors; help manage (+) symptoms • Furtherclassifiedbypotency Further classified by potency –Atypical (2ndGeneration) • Block 5HT > DA receptors; manage (+) & (–)symptoms • Better patient compliance generally |
|
|
Chlorpromazine trade name
|
(Thorazine®, others)
|
|
|
Chlorpromazine indication
|
schizophrenia
|
|
|
Chlorpromazine mechanism
|
–blocks D2in mesolimbic region of brain
|
|
|
Chlorpromazine elimination
|
–low bioavailability; renal excretion of
metabolites |
|
|
Chlorpromazine adverse effects
|
related to neurotransmitters involved
–Sedation, anticholinergic effects, orthostasis, gynecomastia, galactorrhea, seizures, sexual dysfunction; interactionwith anticholinergics, CNS depressants, and levodopa |
|
|
Haloperidol trade name
|
(Haldol, others)
|
|
|
Haloperidol indication
|
–schizophrenia
|
|
|
Haloperidol mechanism
|
–blocks Din mesolimbic region of brain
|
|
|
Haloperidol elimination
|
–extensive hepatic metabolism; renal excr
|
|
|
Haloperidol adverse effects
|
related to neurotransmitters involved
( S) –Neuroleptic malignant syndrome (NMS), sedation, gynecomastia, galactorrhea, seizures, QT prolongation –Interactionwith anticholinergics, CNS depressants, and levodopa |
|
|
Clozapine trade name
|
(Clozaril®, FazaClo®, others)
|
|
|
Clozapine indication
|
–schizophrenia
|
|
|
Clozapine mechanism
|
–blocks 5HT2a and D2 receptors
|
|
|
Clozapine elimination
|
95% protein-bound, t½ ~12 h, extensively
metabolized, with renal and biliary excretion |
|
|
Clozapine adverse effects
|
–related to neurotransmitters involved
–Sedation, orthostasis, weight gain, hyperglycemia, QT prolongation, anticholinergic effects, seizures, myocarditis, agranulocytosis |
|
|
Olanzapine
trade name |
(Zyprexa®, Zyprexa®-Zydis™, others)
|
|
|
Olanzapine indication
|
schizophrenia, bipolar (acute mania)
|
|
|
Olanzapine mechanism
|
blocks 5HT2 and D2 receptors
|
|
|
Olanzapine elimination
|
t½ ~30 h, extensively metabolized
|
|
|
Olanzapine adverse effects
|
relatedtoneurotransmittersinvolved
related to neurotransmitters involved –Sedation, weight gain, hyperglycemia, anticholinergic effects |
|
|
depression pathophysiology
|
• Focus on neurotransmitter (NT) systems
symptoms serotoninnorepinephrinedopamine symptoms –serotonin, norepinephrine, dopamine • Monoamine hypothesis= synaptic NE, 5HT • Permissive hypothesis= 5HT role in influencing NE • Dysregulation hypothesis= dysregulated NT systems |
|
|
Fluoxetine trade name
|
(Prozac®, Prozac®Weekly™, Sarafem®, others)
|
|
|
Fluoxetine
indication |
–major depressive disorder
|
|
|
Fluoxetine mechanism
|
–selectively inhibits 5HT reuptake
|
|
|
Fluoxetine
elimination |
hepatic metabolism to an active
metabolite (norfluoxetine); t½ ~2d |
|
|
Fluoxetine
adverse effects |
nausea, headache, insomnia,
anxiety, weight gain, sexual dysfunction, bruxism, diarrhea, withdrawal syndrome; interaction with MAO- inhibitors |
|
|
Serotonin Syndrome
|
• Cognitive-behavioral changes
Ait ti i t / i f i –Agitation, anxiety, coma/unresponsive, confusion, hypomania, lethargy • Autonomic instability –Diaphoresis, diarrhea, dilated pupils, hyper/hypothermia, nausea, tachycardia, tachypnea, vomiting • Neuromuscularchanges • Neuromuscular changes –Ataxia, hyper-reflexia, muscle rigidity, myoclonus, restlessness, shivering, tremor, trismus |
|
|
Imipramine trade name
|
(Tofranil®)
|
|
|
Imipramine indication
|
–major depressive disorder
|
|
|
Imipramine mechanism
|
Inhibits NE and 5HT reuptake
|
|
|
Imipramine elimination
|
long half-life; serum level > 225 μg/L
|
|
|
Imipramine adverse effects
|
sedationorthostasis anticholinergic
sedation, orthostasis, anticholinergic effects, seizures, sweating, cardiotoxicity; interaction with MAO-inhibitors, sympathomimetics, anticholinergics, CNS depressants |
|
|
Bupropion
trade name |
(Wellbutrin®, Zyban®)
|
|
|
Bupropion
indication |
major depressive disorder
|
|
|
Bupropion
mechanism |
–(?) reduces DA reuptake
|
|
|
Bupropion
elimination |
half-life < 24 h
|
|
|
Bupropion
adverse effects |
seizures insomnia agitation
seizures, insomnia, agitation, headache, blurred vision, xerostomia, GI upset, constipation, weight loss |
|
|
Lithium
trade names |
(Eskalith®, Eskalith®CR, Lithobid®, others)
|
|
|
Lithium
indication |
bipolar disorder (“euphoric mania”)
|
|
|
Lithium
mechanism |
not known; effect on 2ndmessengers
|
|
|
Lithium
elimination |
renal excretion; short half-life
|
|
|
Lithium
adverse effects |
ANVDbloating transientfatigue
ANVD, bloating, transient fatigue and muscle weakness, tremor, headache, confusion, memory impairment, polyuria/thirst; interactionswith diuretics, NSAIDs, anticholinergics |
|
|
Valproic Acid
bipolar trade name |
(Depakote®)
|
|
|
Valproic Acid
indication |
–bipolar (“psychotic mania,” mixed)
|
|
|
Valproic Acid mechanism
|
inhibits Na & Ca-channels, increase GABA
|
|
|
Valproic Acid elimination
|
hepatic metabolism, renal excretion
|
|
|
Valproic Acid adverse effects
|
GI complaints, weight gain, rash,
hairloss tremor hepatotoxicity pancreatitis hair loss, tremor, hepatotoxicity, pancreatitis |
|
|
Lorazepam
trade name |
(Ativan, others)
|
|
|
Lorazepam
indication |
insomnia, anxiety, …
|
|
|
Lorazepam
mechanism |
potentiation of GABA at chloride channel
|
|
|
Lorazepam
elimination |
hepatic phase II metabolism without
active metabolites |
|
|
Lorazepam
adverse effects |
drowsiness, difficulty concentrating,
anterograde amnesia, paradoxical reaction; interactionadditive effects with CNS depressants |
|
|
Zolpidem
trade name |
(Ambien®, Ambien CR®, Edular®, Zolpmist®)
|
|
|
Zolpidem
indication |
insomnia (short-term)
|
|
|
Zolpidem
mechanism |
benzodiazepine receptor agonist
|
|
|
Zolpidem
elimination |
half-life ~2.4 h, metabolized to inactives,
renal excretion |
|
|
Zolpidem
adverse reactions |
drowsiness, headache, difficulty
concentrating, anterogradeamnesia, paradoxical reaction; interactionadditive effects with CNS depressants |
|
|
Ramelteon trade name
|
(Rozerem®)
|
|
|
Ramelteon
indication |
sleep induction
|
|
|
Ramelteon
mechanism |
ti t l t i t (MT MT)
activates melatonin receptors (MT1, MT2) • Dose –8 mg hs |
|
|
Ramelteon
elimination |
hepatic metabolism (CYP1A2), active
metabolite |
|
|
Ramelteon
adverse effects |
dizziness, hyperprolactinemia,
decreased testosterone; interactionadditive effects with fluvoxamine |
|
|
Alpha 1
Activation |
•• Vasoconstriction
Vasoconstriction –Hemostasis –Nasal decongestant –Local anesthetic combo –Perfusionpressure Perfusion pressure • Mydriasis |
|
|
Alpha 2 Activation
|
Reduced sympathetic
outflow |
|
|
Beta1 Activation
|
•• Cardiac arrest
Cardiac arrest •• Heart failure Heart failure •• Hypoperfusion Hypoperfusion •• AV heart block AV heart block |
|
|
Beta2 Activation
|
Asthma
Delay preterm labor |
|
|
dopamine activation
|
renal vasodilation
|
|
|
Epinepherine therpeutic uses
|
–Slow absorption of local anesthetics, reduce nasal
congestion, produce mydriasis, bronchodilation, restore cardiac function, treat anaphylaxis |
|
|
Isoproterenol therapeutic uses
|
–AV block, cardiac arrest, bronchospasm, asthma
|
|
|
Dopamine therapeutic uses
|
–Hypoperfusion, heart failure, acute renal failure
|
|
|
terbutaline therapeutic uses
|
–Asthma, delay of preterm labor
|
|
|
epinepherine adverse effects
|
–Hypertensivecrisis,dysrhythmia,angina, tissue
Hypertensive crisis, dysrhythmia, angina, tissue necrosis, hyperglycemia |
|
|
dopamine adverse effects
|
–Tachycardia, dysrhythmia, angina, tissue necrosis
|
|
|
terbutaline adverse effects
|
–Tremor, tachycardia
|
|
|
isoproterenol adverse effects
|
–Dysrhythmia, angina, hyperglycemia
|
|
|
Adrenergic Receptor Antagonists
Blockade |
• Direct
–Alpha adrenergic receptor binding (phentolamine) –Alpha-1 adrenergic receptor binding (alfuzosin, doxazosin, prazosin, silodosin, terazosin, tamsulosin) –Beta adrenergic receptor binding (nadolol, propranolol) –Beta-1 adrenergic receptor binding (atenolol, metoprolol) • Indirect |
|
|
AlphaBlockade Therapeutic Blockade
|
•• Hypertension
Hypertension –doxazosin, prazosin, terazosin •• Benign prostatic hyperplasia Benign prostatic hyperplasia –alfuzosin, silodosin, terazosin, tamsulosin • Reversal of α1toxicity • Raynaud’sdisease • Pheochromocytoma y |
|
|
BetaBlockade Therapeutic Uses
|
• Angina
• Hypertension • Myocardial infarction • Heart failure • Dysrhythmia • Other |
|
|
Diuretics
|
• Group of compounds used to mobilize fluid
• Several classesof diuretics: Several classes of diuretics: ––Loop Loop • Action at loop of Henle(e.g., furosemide) ––Thiazides Thiazides • Action at distal tubule (e.g., hydrochlorothiazide) Pt i Pt i ii ––Potassium Potassium--sparing sparing • Action at distal nephron(e.g., spironolactone) ––Osmotic Osmotic • Inhibits passive water reabsorption(e.g., mannitol) |
|
|
Furosemide
trade name |
(Lasix, others)
|
|
|
Furosemide indication
|
volume overload, edema
|
|
|
Furosemide mechanism
|
blocks Na & Cl reabsorption at TAL
|
|
|
Furosemide elimination
|
some hepatic metabolism, renal excretion
|
|
|
Furosemide adverse effects
|
volume depletion, hypotension,
p yp hypokalemia, hypomagnesemia, hypocalcemia, hyperglycemia, ototoxicity; cautionin pregnancy; interactionswith antihypertensives, digoxin, NSAIDs, lithium, aminoglycoside antibiotics |
|
|
Hydrochlorothiazide
trade name |
(HydroDiuril®, others)
|
|
|
Hydrochlorothiazide indication
|
hypertension, mild edema
|
|
|
Hydrochlorothiazide mechanism
|
blocks Na/Cl reabsorption at distal tubule
|
|
|
Hydrochlorothiazide adverse effects
|
volume depletion, hypotension,
hypokalemia, hypomagnesemia, hypercalcemia, hypokalemia, hypomagnesemia, hypercalcemia, hyperglycemia, hyperlipemia, hyperuricemia; cautionin pregnancy/lactation; interactionswith antihypertensives, digoxin, NSAIDs, lithium |
|
|
Spironolactone trade name
|
(Aldactone)
|
|
|
Spironolactone indication
|
hypertension, edema
|
|
|
Spironolactone mechanism
|
blocks aldosterone action at distal tubule
|
|
|
Spironolactone adverse effects
|
hyperkalemia, endocrine effects
(gynecomastiamenstrual irregularities); interactions (gynecomastia, menstrual irregularities); interactions with other diuretics, ACE-inhibitors, potassium supplements |
|
|
Eplerenone
trade name |
(Inspra)
|
|
|
Eplerenone indication
|
hypertension, heart failure
|
|
|
Eplerenone mechanism
|
aldosterone antagonist
|
|
|
Eplerenone adverse effects
|
hyperkalemia, GI effects, endocrine
effects; interactionswith other diuretics, ACE-inhibitors, potassium supplements, CYP3A4 inhibitors |
|
|
Eplerenone elimination
|
hepatic (CYP3A4), urine > intestinal
|
|
|
RAA System Drugs
|
• Angiotensinconverting enzyme inhibitors (ACE
ACE--Is Is) –Inhibits ACE at various tissue sites (eg lisinopril) –(e.g., lisinopril) • AngiotensinII receptor antagonists (ARBs ARBs) –Selective blockade of angiotensinII receptor type-1 –(e.g., losartan) • ReninInhibitor ReninInhibitor –Direct inhibition of reninactivity –(e.g., aliskiren) • Aldosteroneantagonists –(e.g., spironolactone) |
|
|
Lisinopril
trade name |
(Prinivil®, Zestril®)
|
|
|
Lisinopril indication
|
hypertension, HF, MI, nephropathy
|
|
|
Lisinopril mechanism
|
reduces angiotensin II, elevates bradykinin
|
|
|
Lisinopril elimination
|
renal excretion
|
|
|
Lisinopril adverse effects
|
hypotension, hyperkalemia, cough,
yp yp g angioedema, dysgeusia, rash; contraindicatedin pregnancy, bilateral renal artery stenosis; interactions with diuretics or other antihypertensives, potassium supplements |
|
|
Losartan
trade name |
(Cozaar®)
|
|
|
Losartan
indication |
hypertension, HF, nephropathy
|
|
|
Losartan
mechanism |
blocks type-1 angiotensin II receptor
|
|
|
Losartan
elimination |
renal excretion
|
|
|
Losartan
adverse effects |
hypotension, (hyperkalemia),
angioedema, dysgeusia, rash; contraindicatedin pregnancy, bilateral renal artery stenosis; interactions with diuretics or other antihypertensives, potassium supplements |
|
|
Calcium Channel Blocker
|
• Vasodilatesperipheral and coronary vessels
Rd di d ti • Reduces cardiac conduction ––Dihydropyridines Dihydropyridines(nifedipine, amlodipine, felodipine) • Potent vasodilation(with reflex tachycardia) • No change in cardiac conduction ––Non Non- -dihydropyridines dihydropyridines(diltiazem, verapamil) • Vasodilatoryeffect • Decrease AV conduction, inotropy, chronotropy |
|
|
Nifedipine
trade name |
(Adalat® CC, Procardia® XL,Procardia®)
|
|
|
Nifedipine indication
|
angina, hypertension
|
|
|
Nifedipine mechanism
|
blocksCachannelspredominantlyin
blocks Ca channels predominantly in vascular smooth muscle cells |
|
|
Nifedipine elimination
|
extensive 1st pass effect, renal excretion
|
|
|
Nifedipine adverse effects
|
–peripheral edema, reflex tachycardia,
dizziness, headache, flushing; interactionwith β-blockers |
|
|
Verapamil
trade name |
(Calan, Isoptin, Verelan)
|
|
|
Verapamil indication
|
angina, hypertension, dysrhythmias,
|
|
|
Verapamil mechanism
|
blocksCachannelsinvascularsmooth
blocks Ca channels in vascular smooth muscle, myocardium, and SA/AV nodes |
|
|
Verapamil elimination
|
extensive 1st pass metabolism, hepatic
|
|
|
Verapamil adverse effects
|
constipation, peripheral edema,
dizziness, headache, flushing, AV block; caution cardiac conduction disturbances, heart block; interactionswith digoxin, β-blockers |
|
|
Vasodilators
|
The ability to dilate arterioles, veins, or both are
tt ibt dt l d l attributed to several drug classes –ACE-Inhibitors –ARBs –Calcium channel blockers ––Sympatholytics Sympatholytics ––Sympatholytics Sympatholytics ––Organic nitrates Organic nitrates ––Others Others |
|
|
Nitroglycerin indication
|
angina
|
|
|
Nitroglycerin mechanism
|
vasodilation (veins) via nitric oxide ( )
|
|
|
Nitroglycerin elimination
|
rapid hepatic inactivation
|
|
|
Nitroglycerin adverse side effects
|
headache, orthostatic hypotension,
reflex tachycardia; interactionwith antihypertensives and phosphodiesterase inhibitors |
|
|
Hydralazine trade name
|
(Apresoline®)
|
|
|
Hydralazine indication
|
Used for hypertension, heart failure
|
|
|
Hydralazine mechanism
|
Arteriolar dilation within 30-45 min, lasting ~6 h
|
|
|
Hydralazine elimination
|
Eliminated by acetylation
|
|
|
viikset
|
moustache
|
|
|
Hydrochlorothiazide
trade name |
(HydroDiuril®)
|
|
|
Hydrochlorothiazide indication
|
hypertension, mild edema
|
|
|
Hydrochlorothiazide mechanism
|
blocksNa/Cl reabsorptionatdistal tubule blocks Na/Cl reabsorption at distal tubule
decrease blood volume, decrease arterial resistance |
|
|
Metoprolol trade name
|
(Lopressor, Toprol XL)
|
|
|
Hydrochlorothiazide adverse reactions
|
volume depletion, hypotension,
p yp hypokalemia, hypomagnesemia, hypercalcemia, hyperglycemia, hyperlipemia, hyperuricemia; cautionin pregnancy/lactation; interactionswith antihypertensives, digoxin, NSAIDs, lithium |
|
|
Metoprolol indication
|
hypertension, angina, MI, HF
|
|
|
Metoprolol mechanism
|
–β1adrenergic blockade
decrease HR, contractility, AV conduction |
|
|
Metoprolol elimination
|
extensive hepatic metab, renal excretion
|
|
|
Metoprolol adverse reactions
|
bradycardia decreasedcardiac
bradycardia, decreased cardiac output, heart block; cautionin heart block and HF; interactionswith antihypertensives |
|
|
Hydrochlorothiazide
trade name |
(HydroDiuril®)
|
|
|
Hydrochlorothiazide indication
|
hypertension, mild edema
|
|
|
Hydrochlorothiazide mechanism
|
blocksNa/Cl reabsorptionatdistal tubule blocks Na/Cl reabsorption at distal tubule
decrease blood volume, decrease arterial resistance |
|
|
Metoprolol trade name
|
(Lopressor, Toprol XL)
|
|
|
Hydrochlorothiazide adverse reactions
|
volume depletion, hypotension,
p yp hypokalemia, hypomagnesemia, hypercalcemia, hyperglycemia, hyperlipemia, hyperuricemia; cautionin pregnancy/lactation; interactionswith antihypertensives, digoxin, NSAIDs, lithium |
|
|
Metoprolol indication
|
hypertension, angina, MI, HF
|
|
|
Metoprolol mechanism
|
–β1adrenergic blockade
decrease HR, contractility, AV conduction |
|
|
Metoprolol elimination
|
extensive hepatic metab, renal excretion
|
|
|
Metoprolol adverse reactions
|
bradycardia decreasedcardiac
bradycardia, decreased cardiac output, heart block; cautionin heart block and HF; interactionswith antihypertensives |
|
|
Lisinopril trade name
|
(Prinivil®, Zestril®)
|
|
|
Lisinopril
indication |
hypertension, HF, MI, nephropathy
|
|
|
Lisinopril
mechanism |
reducesangiotensinII elevatesbradykinin reduces angiotensin II, elevates bradykinin
|
|
|
Lisinopril
elimination |
renal excretion
|
|
|
Lisinopril
adverse reactions |
hypotension, hyperkalemia, cough,
yp yp g angioedema, dysgeusia, rash; contraindicatedin pregnancy, bilateral renal artery stenosis; interactions with diuretics or other antihypertensives, potassium supplements |
|
|
Losartan
trade name |
(Cozaar®)
|
|
|
Losartan
indication |
hypertension, HF, nephropathy
|
|
|
Losartan
mechanism |
blocks type-1 angiotensin II receptor
|
|
|
Losartan
elimination |
renal excretion
|
|
|
Losartan
adverse reactions |
hypotension, (hyperkalemia),
angioedema, dysgeusia, rash; contraindicatedin pregnancy, bilateral renal artery stenosis; interactions with diuretics or other antihypertensives, potassium supplements |
|
|
Spironolactone trade name
|
(Aldactone)
|
|
|
Spironolactone indication
|
hypertension, edema
|
|
|
Spironolactone mechanism
|
blocks aldosterone action at distal tubule
|
|
|
Spironolactone adverse reactions
|
hyperkalemia, endocrine effects
(gynecomastiamenstrual irregularities); interactions (gynecomastia, menstrual irregularities); interactions with other diuretics, ACE-inhibitors, potassium supplements |
|
|
Nifedipine
trade name |
(Adalat®, Procardia®)
|
|
|
Nifedipine indication
|
angina, hypertension
|
|
|
Nifedipine mechanism
|
blocksCachannelspredominantl
blocks Ca channels predominantly in vascular smooth muscle cells |
|
|
Nifedipine elimination
|
–extensive 1st pass effect, renal excretion
|
|
|
Nifedipine adverse reactions
|
peripheral edema, reflex tachycardia,
dizziness, headache, flushing; interactionwith β-blockers |
|
|
Verapamil
trade name |
(Calan®, Isoptin®, Verelan®)
|
|
|
Verapamil indication
|
angina, hypertension, dysrhythmias
|
|
|
Verapamil mechanism
|
blocksCachannelsinvascularsmooth
blocks Ca channels in vascular smooth muscle, myocardium, and SA/AV nodes |
|
|
Verapamil elimination
|
extensive 1pass metabolism, hepatic
|
|
|
Verapamil adverse reactions
|
constipation, peripheral edema,
dizziness, headache, flushing, AV block; caution cardiac conduction disturbances, heart block; interactionswith digoxin, β-blockers |
|
|
Clonidine
trade name |
(Catapres®)
|
|
|
Clonidine indication
|
hypertension
|
|
|
Clonidine mechanism
|
central α2activationin the brainstem
|
|
|
Clonidine elimination
|
hepatic metabolism and renal excretion
|
|
|
Clonidine adverse reactions
|
bradycardia decreasedcardiac
bradycardia, decreased cardiac output, posture-independent hypotension, drowsiness, xerostomia, constipation, rebound HTN; cautionin pregnancy; interactionswith antihypertensives |
