Drugs Test 2 Flashcards
Morphine
-Opioid agonist
-Mu receptor
-
-
-sedate, constipate, resp depress, nausea/vomit
-euphoria, miosis
-Analgesia
Hydromorphone
- Mu Opioid analgesics
- Faster onset and more potent than morphine
- analgesia
[mnemonic] (put in brackets)
hydrocodone
- Mu Opioid analgesics
- metabolized to hydromorphone by CYP2D6
- analgesia
[mnemonic] (put in brackets)
oxycodone
- Mu Opioid analgesics
- metabolized to oxymorphone by CYP2D6
- analgesia
[mnemonic] (put in brackets)
oxymorphone
- Mu Opioid analgesics
- analgesia
[mnemonic] (put in brackets)
codeine
- Mu Opioid analgesics
- CYP2D6 pharmacogenetic variability is clinically significant
- converted to morphine by demethylation
- analgesia
[mnemonic] (put in brackets)
heroin
- Mu Opioid analgesics
- converted to monoacetyl morphine and morphine in the brain,
rapid onset pharmacokinetics - analgesia
[mnemonic] (put in brackets)
methadone
- Mu Opioid analgesics
- oral, long acting half life of 15-60 hours
- analgesia, maintenance for opioid drug addiction
[mnemonic] (put in brackets)
meperidine
- Mu Opioid analgesics
- prolonged half life in patients with renal failure due to decreased elimination
- faster onset and less potency than morphine, converted in liver
to nor-meperidine (CNS stimulation, convulsions) - can produce serotonin syndrome, esp. when combined with SSRIs or MAOIs
- analgesia
[mnemonic] (put in brackets)
tramadol
- Mixed agonists, antagonists
- partial mu agonist activity and monoamine reuptake inhibitor activity
- metabolized by CYP2D6 and CYP3A4; CYP2D6 produces the active metabolite
- for mild to moderate acute and chronic pain
[mnemonic] (put in brackets)
tapentadol
- Mixed agonists, antagonists
- partial mu agonist activity and monoamine reuptake inhibitor activity
- less pharmacogenetic variability than tramadol, greater mu receptor efficacy
- metabolized mainly by CYP2C9, CYP2C19, and a little by CYP2D6
- for mild to moderate acute and chronic pain
[mnemonic] (put in brackets)
pentazocrine
- Mixed agonists, antagonists
- kappa receptor agonists and mu receptor partial agonist, antagonist
- for acute, short term pain
[mnemonic] (put in brackets)
nalbuphen
- Mixed agonists, antagonists
- kappa receptor agonists and mu receptor partial agonist, antagonist
- for acute, short term pain
[mnemonic] (put in brackets)
buprenorphine
- Mixed agonists, antagonists
- kappa receptor agonists and mu receptor partial agonist
- high affinity for mu receptor, difficult to reverse its mu agonist effect
- for acute, short term pain, useful for drug abuse and addiction
[mnemonic] (put in brackets)
Diphenoxylate
- antidiarrheal opioids
- poorly absorbed or not absorbed after oral administration
- diarrhea
[mnemonic] (put in brackets)
loperimide
- antidiarrheal opioids
- poorly absorbed or not absorbed after oral administration
- diarrhea
[mnemonic] (put in brackets)
naloxone
- opioid antagonists
- bind to opioid receptors and antagonize effects of opioid agonists
- parenteral administration
- antagonize opiate effects
[mnemonic] (put in brackets)
naltrexone
- opioid antagonists
- bind to opioid receptors and antagonize effects of opioid agonists
- oral administration
- antagonize opiate effects
[mnemonic] (put in brackets)
alvimopan
- opioid antagonists
- bind to opioid receptors and antagonize effects of opioid agonists
- poorly absorbed or not absorbed after oral administration
- prevent GI side effects of opioids
[mnemonic] (put in brackets)
methylnatrexone
- opioid antagonists
- bind to opioid receptors and antagonize effects of opioid agonists
- quaternary ammonium derivative
- IV peripherally restricted antagonist
- constipation
[mnemonic] (put in brackets)
morphine-naltrexone
- abuse resistent opioids
- extended release morphine with sequestered naltrexone
- Provide pain relief but prevent or reduce opioid abuse
[mnemonic] (put in brackets)
oxycodone naltrexone
- abuse resistent opioids
- oxycodone with naltrexone
- Provide pain relief but prevent or reduce opioid abuse
[mnemonic] (put in brackets)
chlorpromazine
-Typical antipsychotic (phenothiazine)
-DA antag (more D2 than D1), also M, alpha-adrenergic, and H1 receptor antag
-piperazine side chains, high potency, 4-8 week delay in onset of action, metabolized by CYP2D6 & CYP3A4 for elimin
-
-neuroleptic malignant syndrome, striatal D block: Parkisonian effects, dystonias, akathisia; D receptor upregulation: tardive dyskinesias; block L-DOPA effects; at high doses: some tolerance, hypotension, hyper/hypothermia, seizures, coma, ventricular tachycardia; increased prolactin release (less prominent)
-M block: hyperthermia, tachycardia, urinary retention, memory impairment, blurred vision, constipation, and confusion; alpha-adrenergic block: vasodilation, orthostatic hypotension and light-headedness, reflex tachycardia, and sexual dysfuntion; H1 block: sedation & weight gain
-Antipsychotic
fluphenazine
-Typical antipsychotic (phenothiazine)
-DA antag (more D2 than D1)
-piperazine side chains, high potency, 4-8 week delay in onset of action, metabolized by CYP2D6 & CYP3A4 for elimin; fluphenazine decanoate-slow release formula, deep gluteal IM injection, for non-compliant patients
-
-neuroleptic malignant syndrome, striatal D block: Parkisonian effects, dystonias, akathisia; D receptor upregulation: tardive dyskinesias; block L-DOPA effects; at high doses: some tolerance, hypotension, hyper/hypothermia, seizures, coma, ventricular tachycardia; increased prolactin release (less prominent)
-
-antipsychotic
thiothixene
-Typical antipsychotic (thioxanthene)
-DA antag (more D2 than D1)
-medium potency, 4-8 week delay in onset of action, metabolized by CYP2D6 & CYP3A4 for elimin
-
-neuroleptic malignant syndrome, striatal D block: Parkisonian effects, dystonias, akathisia; D receptor upregulation: tardive dyskinesias; block L-DOPA effects; at high doses: some tolerance, hypotension, hyper/hypothermia, seizures, coma, ventricular tachycardia; increased prolactin release (less prominent)
-
-antipsychotic
haloperidol
-Typical antipsychotic (butyrophenone)
-DA antag (more D2 than D1)
-high potency, 4-8 week delay in onset of action, metabolized by CYP2D6 & CYP3A4 for elimin; haloperidol decanoate-slow release formula, deep gluteal IM injection, for non-compliant patients
-
-neuroleptic malignant syndrome, striatal D block: Parkisonian effects, dystonias, akathisia; D receptor upregulation: tardive dyskinesias; block L-DOPA effects; at high doses: some tolerance, hypotension, hyper/hypothermia, seizures, coma, ventricular tachycardia; increased prolactin release (less prominent)
-prominent prolactin release
-antipsychotic
aripiprazole
- Atypical antipsychotic
- competitive partial DA2 ag, 5HT2A antag; also alpha-adrenergic & H1 antag
- metabolized by CYP2D6 & CYP3A4 for elimin (inhib of CYP2D6 & CYP3A4 -> decr elimination; induction of CYP3A4 -> incr elimination)
- discontinue gradually to avoid withdrawal/relapse
- minimal increase in prolactin release, sedation & weight gain (5-HT block); potentiation of CNS depressant effects
- alpha-adren block: vasodilation, orthostatic hypotension & light-headedness, reflex tachycardia, and sexual dysfunction; H1 block: sedation & weight gain
- antipsychotic
clozapine
-Atypical antipsychotic
-DA2 antag, 5HT2A antag; also M, alpha-adrenergic, & H1 antag
-metabolized by CYP1A2, CYP2D6, & CYP3A4 for elimin (inhib of CYP2D6 & CYP3A4 -> decr elimination; induction of CYP1A2 & CYP3A4 -> incr elimination)
-
-minimal increase in prolactin release, sedation & weight gain (5-HT block); potentiation of CNS depressant effects
-M block: hyperthermia, tachycardia, urinary retention, memory impairment, blurred vision, constipation, confusion; alpha-adren block: vasodilation, orthostatic hypotension & light-headedness, reflex tachycardia, and sexual dysfunction; H1 block: sedation & weight gain; incr risk weight gain & metabolic effects (glucose intol, lipid abnormal, incr risk DM-type2, cardiovascular disease); incr risk agranulocytosis & leukopenia
-antipsychotic
olanzapine
-Atypical antipsychotic
-DA2 antag, 5HT2A antag; also M, alpha-adrenergic, & H1 antag
-metabolized by CYP1A2, CYP2D6, & CYP3A4 for elimin (inhib of CYP2D6 & CYP3A4 -> decr elimination; induction of CYP1A2 & CYP3A4 -> incr elimination)
-
-minimal increase in prolactin release, sedation & weight gain (5-HT block); potentiation of CNS depressant effects
-severe metabolic: major weight gain and glucose, cholesterol, and TGs increase; M block: hyperthermia, tachycardia, urinary retention, memory impairment, blurred vision, constipation, confusion; alpha-adren block: vasodilation, orthostatic hypotension & light-headedness, reflex tachycardia, and sexual dysfunction; H1 block: sedation & weight gain; incr risk weight gain & metabolic effects (glucose intol, lipid abnormal, incr risk DM-type2, cardiovascular disease)
-antipsychotic, bipolar
paliperidone
-Atypical antipsychotic
-DA2 antag, 5HT2A antag
-metabolized by CYP2D6 & CYP3A4 for elimin(inhib of CYP2D6 & CYP3A4 -> decr elimination - less extent than others in class)
-
-minimal increase in prolactin release, sedation & weight gain (5-HT block); potentiation of CNS depressant effects
-incr risk weight gain & metabolic effects (glucose intol, lipid abnormal, incr risk DM-type2, cardiovascular disease)
-antipsychotic
quetiapine
-Atypical antipsychotic
-DA2 antag, 5HT2A antag; also M, alpha-adrenergic, & H1 antag
-metabolized by CYP2D6 & CYP3A4 for elimin (inhib of CYP2D6 & CYP3A4 -> decr elimination; induction of CYP3A4 -> incr elimination)
-
-minimal increase in prolactin release, sedation & weight gain (5-HT block); potentiation of CNS depressant effects
-M block: hyperthermia, tachycardia, urinary retention, memory impairment, blurred vision, constipation, confusion; alpha-adren block: vasodilation, orthostatic hypotension & light-headedness, reflex tachycardia, and sexual dysfunction; H1 block: sedation & weight gain; incr risk weight gain & metabolic effects (glucose intol, lipid abnormal, incr risk DM-type2, cardiovascular disease)
-antipsychotic, bipolar
risperidone
-Atypical antipsychotic
-DA2 antag, 5HT2A antag
-major active metabolite is paliperidone, partially metabolized by CYP2D6 for elimination; risperidone microspheres (slow release IM formula for noncompliant patients)
-
-minimal increase in prolactin release, sedation & weight gain (5-HT block); potentiation of CNS depressant effects
-incr risk weight gain & metabolic effects (glucose intol, lipid abnormal, incr risk DM-type2, cardiovascular disease)
-antipsychotic, bipolar
prochlorperazine
-Anti-emetic, bit antipsychotic
-H1 antag, mild DA2 antag
-
-
-
-anti-emetic
promethazine
-Anti-emetic, bit antipsychotic
-H1 antag, mild DA2 antag
-
-
-
-anti-emetic
Diazepam
-Benzodiezapine
-Bind GABA-A receptors, enhance channel open frequency
-Antianxiety without sedation at low dose
- Long half life
-
-
-Anti-anxiety, withdrawal, muscle relaxant
Chlordiazepoxide
-Benzodiezapine
-Bind GABA-A receptors, enhance channel open frequency
-Antianxiety without sedation at low dose
-
-
-
-Anti-anxiety
Alprazolam
-Benzodiezapine
-Bind GABA-A receptors, enhance channel open frequency
-Antianxiety without sedation at low dose
-Short half life
-
-
-Anti-anxiety, insomnia
Oxazepam
-Benzodiezapine
-Bind GABA-A receptors, enhance channel open frequency
-Antianxiety without sedation at low dose
-
-
-
-Anti-anxiety
Lorazepam
-Benzodiezapine
-Bind GABA-A receptors, enhance channel open frequency
-Antianxiety without sedation at low dose
-Intermediate half life
-
-
-Anti-anxiety, insomnia
Midazolam
-Benzodiezapine
-Bind GABA-A receptors, enhance channel open frequency
-Antianxiety without sedation at low dose
-Ultrashort half life
-
-
-Preanesthetic medication
Flumenazil
-Benzodiezapine Antagonist
-Competitive binding at BZ binding site on GABA-A
-
-IV admin, multiple doses because short half life
-
-
-Reverse BZ induced respiratory depression
Zolpidem
-Non-Benzodiezepine
-Bind at BZ binding site on GABA-A
-
-Enhance GABA mediated GABA channel opening
-IV admin resulted in cardiovascular and respiratory depress.
-
-Induce Sleep
Zaleplon
-Non-Benzodiezepine
-Bind at BZ binding site on GABA-A
-
-Enhance GABA mediated GABA channel opening
-IV admin resulted in cardiovascular and respiratory depress.
-
-Induce Sleep
Pentobarbital
-Barbiturates
-Bind to barbiturate binding site on GABA-A, increase channel open time
-
-Can open channel in the absence of GABA, marked CYP induction, short/intermediate half life
-Respiratory and cardiovascular depression, drowsiness, confusion, diminished motor skills, impaired judgement
-
-Preoperative sedation
Phenobarbital
-Barbiturates
-Bind to barbiturate binding site on GABA-A, increase channel open time
-
-Can open channel in the absence of GABA, marked CYP induction, Long half life
-Respiratory and cardiovascular depression, drowsiness, confusion, diminished motor skills, impaired judgement
-
-Anticonvulsant
Amobarbital
-Barbiturates
-Bind to barbiturate binding site on GABA-A, increase channel open time
-
-Can open channel in the absence of GABA, marked CYP induction, ultrashort half life
-Respiratory and cardiovascular depression, drowsiness, confusion, diminished motor skills, impaired judgement
-
-Preoperative sedation
Thiopental
-Barbiturates
-Bind to barbiturate binding site on GABA-A, increase channel open time
-
-Can open channel in the absence of GABA, marked CYP induction, ultrashort half life
-Respiratory and cardiovascular depression, drowsiness, confusion, diminished motor skills, impaired judgement
-
-Anesthesia induction
Buspirone
-Serotonin Antagonist
-Partial 5HT-1A receptor blocker
-
-Anxiolytic effects, no CNS depression
-
-
-Anxiolytic
Propranolol
-Beta blocker - - - - - -Blocks palpitations, shaking, sweating, stage fright
carbamazepine
- antiepileptic
- Inhibit voltage-activated Na+ channels and thus prolong
the refractory period and reduce sustained firing - Induces P-450s, increases its own metabolism and metab. of other antiepileptics
during chronic administration - ## Oral, slow absorption, highly lipid soluble and good CNS penetration, metabolized by P-450s
- Hepatotoxicity, teratogenic effects
-Partial simple and complex and Tonic Clonic seizures, trigeminal neuralgia, bipolar disorder
[mnemonic] (put in brackets)
ethosuximide
- antiepileptic
- ## Inhibit voltage-activated Ca2+ channels and thus inhibit rhythmic activity in thalamic neurons
- well absorbed orally, no plasma protein binding, long half life (30-60 hours)
75% is metabolized by liver P450s, 25% excreted unchanged in urine
-
- - Absence seizures
[mnemonic] (put in brackets)
gabapentin
- antiepileptic
- ## Blocks Ca channels and release of glutamate, enhances GABAergic synaptic transmission
- Not metabolized and does not induce hepatic enzymes, not bound to plasma proteins,
short half life, eliminated by kidney
-
- - simple or complex partial, tonic-clonic seizures
[mnemonic] (put in brackets)
lamotrigine
- antiepileptic
- Inhibit voltage-activated Na+ channels and thus prolong
the refractory period and reduce sustained firing
Inhibits release of glutamate - Drug interactions: half life is decreased by enyzyme inducing drugs (eg carbam. and Phenyt.)
and is increased by valproic acid - ## Drug is metabolized by liver-
- simple or complex partial, tonic-clonic seizures, bipolar
[mnemonic] (put in brackets)
phenobarbital
- antiepileptic
- ## Enhance inhibitory GABAergic neurotransmission
- ## well absorbed orally, freely penetrates brain,75% inactivated in hepatic microsomal system
- teratogenic effects
- Simple partial, recurrent tonic-clonic, and febrile seizures
[mnemonic] (put in brackets)
phenytoin
- antiepileptic
- Mainly blocks voltage gated Na+ channels, also blocks Ca2+ channels
- oral absorption is slow, but distribution is rapid and brain concentrations are high
- Oral for chronic treatment, IV for emergency; high plasma protein binding
drug interaction: Enhances P-450 system and increases metabolism of doxycycline and cyclosporine
- - gingival hyperplasia, megaloblastic anemia, teratogenic effects
- partial simple, partial complex and tonic-clonic seizures, emergency treatment of status epilepticus
[mnemonic] (put in brackets)
valproic acid
- antiepileptic
- Inhibit voltage-activated Na+ channels and thus prolong
the refractory period and reduce sustained firing;
Inhibit voltage-activated Ca2+ channels and thus inhibit rhythmic activity;
Enhance inhibitory GABAergic neurotransmission
- - ## orally effective, rapidly absorbed, 90% plasma protein binding, metabolized by liver P450s
- hepatotoxicity, thrombocytopenia, teratogenic effects
- myoclonic seizures, second line treatment for tonic-clonic and absence seizures, bipolar
[mnemonic] (put in brackets)
pregabalin
- antiepileptic
- ## blocks Na channels and release of glutamate-
- - Thrombocytopenia
- simple and complex partial seizures
[mnemonic] (put in brackets)
topiramate
- antiepileptic
- ## blocks Na channels and increases activity of postsynaptic GABA receptors-
-
- - Simple and complex partial, tonic-clonic seizures
[mnemonic] (put in brackets)
levetiracetam
- antiepileptic
- ## modifies glutamate and GABA release via binding to synaptic protein SV2A-
-
- - Adjunctive treatment of simple and complex partial and tonic-clonic seizures
[mnemonic] (put in brackets)
clonazepam
- benzodiazepine
- ## Enhance inhibitory GABAergic neurotransmission
- ## tolerance develops after 1-6 months-
- myoclonic and absence seizures
[mnemonic] (put in brackets)
diazepam
- benzodiazepines
- ## Enhance inhibitory GABAergic neurotransmission
- ## tolerance develops after 1-6 months-
- Status epilepticus
[mnemonic] (put in brackets)
lorazepam
benzodiazepines - Enhance inhibitory GABAergic neurotransmission - - tolerance develops 1-6 months - - - Status epilepticus [mnemonic] (put in brackets)
Levodopa (L-DOPA)
- DA synthesis enhancers
- dopamine precurser
- Anorexia, hypotension, arrythmias
L-DOPA + carbidopa
-DA synthesis enhancers
Entacapone
- DA synthesis enhancers
- COMT inhibitor
- dyskinesia, confusion, hypotension
Amantadine
-DA synthesis enhancers
-increases DA release, blocks cholinergic and
NMDA receptors.
-Should not be given to patients with CHF and glaucoma.
Apomorphine
- Dopamine receptor agonists
- Used for acute “off periods” in parkinsons patients.
bromocriptine
-Dopamine receptor agonists
-D2 agonist, D1 partial agonist
-Depression, confusion, GI problems, arrythmias
(DO not give to patients with heart or mental problems.
pramipexole
-Dopamine receptor agonists
-D2 and D3 agonist
-Depression, confusion, GI problems, arrythmias
(DO not give to patients with heart or mental problems.
ropinirole
-Dopamine receptor agonists
-D2 and D3 agonists
-Depression, confusion, GI problems, arrythmias
(DO not give to patients with heart or mental problems.
benztropine
- anticholinergics
- Muscarinic antagonist
- typical antimuscarinic effects
trihexyphenidyl
- anticholinergics
- Muscarinic antagonist
- typical antimuscarinic effects
rasagiline
- MAO b inhibitors
- Not oxidized to amphetamines
selegiline
- MAO b inhibitors
- metabolized to methamphetamine and amphetamines
donepezil
-ACh inhibitors
Tremors, bradycardia, nausia, vomiting, diarrhea
galantamine
- ACh inhibitors
- Tremors, bradycardia, nausia, vomiting, diarrhea
rivastigmine
- ACh inhibitors
- Tremors, bradycardia, nausia, vomiting, diarrhea
tacrine
- ACh inhibitors
- Tremors, bradycardia, nausia, vomiting, diarrhea
- Hepatotoxicity
memantine
- NMDA antagonist
- Blocks NMDA receptor preventing large calcium influx within the cell.
- Dizziness, confusion, constipation
acetazolamide
-carbonic anhydase inhibitor
-NaHCO3 gets left in the urine
-
-
-allergy, ammonia exacerbates hepatic encephalopathy, bone marrow suppression, paresthesias
-metabolic acidosis, kidney stones
-open angle glaucoma, altitude sickness, counter metab. alkalosis from diuretics
glycerin
-osmotic agent
-Draw water into blood, increase urine production
-Oral administration
-
-Hyponatremia, hyponatremia w/ dehydration
-May cause hyperglycemia after its metabolism
-Acute renal failure, acute tubular necrosis, dialysis disequilibrium, reduce intraoccular pressure for glaucoma
mannitol
-osmotic agent
-Draw water into blood, increase urine production
-
-IV use only
-Hyponatremia, hyponatremia w/ dehydration
-
-Acute renal failure, acute tubular necrosis, dialysis disequilibrium, reduce intraoccular pressure for glaucoma, reduce brain swelling for neurosurgery
bumetanide
-loop agents
-Inhibit Na+/K+, 2Cl- symporter in thick ascending limb
-Enter the urine via organic anion transporter in proximal tubule
-Short halflife (0.8 hrs)requires frequent dosing, Works only if in the lumen, not subject to tubuloglomerular feedback
-Hyponatremia, hypokalemia, volume depletion, metabolic alkalosis, hyperurecemia
-
-Pulmonary edema, congestive HF, Hypertension, Nephrotic syndrome, Edema and ascites of cirrhosis, chronic renal failure
ethacrynic acid
- loop agents
- Inhibit Na+/K+, 2Cl- symporter in thick ascending limb
- Enter the urine via organic anion transporter in proximal tubule
- Short halflife (1.0 hrs)requires frequent dosing, Works only if in the lumen, not subject to tubuloglomerular feedback
- Hyponatremia, hypokalemia, volume depletion, metabolic alkalosis, hyperurecemia
- Ototoxicity
- Pulmonary edema, congestive HF, Hypertension, Nephrotic syndrome, Edema and ascites of cirrhosis, chronic renal failure
furosemide
- loop agents
- Inhibit Na+/K+, 2Cl- symporter in thick ascending limb, weak carbonic anhydrase inhibitor
- Enter the urine via organic anion transporter in proximal tubule
- Short halflife (1.5 hrs)requires frequent dosing, Works only if in the lumen, not subject to tubuloglomerular feedback
- Hyponatremia, hypokalemia, volume depletion, metabolic alkalosis, hyperurecemia
- Sulfa allergy
- Pulmonary edema, congestive HF, Hypertension, Nephrotic syndrome, Edema and ascites of cirrhosis, chronic renal failure
torsemide
-loop agents
-Inhibit Na+/K+, 2Cl- symporter in thick ascending limb
-Enter the urine via organic anion transporter in proximal tubule
-Short halflife (3.5 hrs)requires frequent dosing, Works only if in the lumen, not subject to tubuloglomerular feedback
-Hyponatremia, hypokalemia, volume depletion, metabolic alkalosis, hyperurecemia
-
-Pulmonary edema, congestive HF, Hypertension, Nephrotic syndrome, Edema and ascites of cirrhosis, chronic renal failure
chlorothiazide
-thiazide
-Block Na/Cl symporter in DCT, secondary carbonic anhydrase inhibiton activity
-
-Enter urine via organic ion transporter in proximal tubule, calcium sparing, doesn’t disrupt medullary gradient
-Hypotension, hypokalemia, hyponatremia, metabolic alkalosis, hypercalcemia, hyperuricemia
-Small risk of sudden death or renal cell carcinoma, sulfonilamide allergy
-Hypertension, Edema from CHF, calcium nephrolithiasis, osteoporosis, nephrogenic diabetes insipidus
hydrochlorothiazide
-thiazide
-Block Na/Cl symporter in DCT, secondary carbonic anhydrase inhibiton activity
-
-Enter urine via organic ion transporter in proximal tubule, calcium sparing, doesn’t disrupt medullary gradient
-Hypotension, hypokalemia, hyponatremia, metabolic alkalosis, hypercalcemia, hyperuricemia
-Small risk of sudden death or renal cell carcinoma, sulfonilamide allergy
-Acute diuresis with edema, Hypertension, Edema from CHF, calcium nephrolithiasis, osteoporosis, nephrogenic diabetes insipidus
metolazone
- thiazide-like
- Block Na/Cl symporter in DCT
- LOOOOONG half-life (20 hrs)
- Enter urine via organic ion transporter in proximal tubule, calcium sparing, doesn’t disrupt medullary gradient
- Hypotension, hypokalemia, hyponatremia, metabolic alkalosis, hypercalcemia, hyperuricemia
- Small risk of sudden death or renal cell carcinoma, sulfonilamide allergy
- Hypertension, Edema from CHF, calcium nephrolithiasis, osteoporosis, nephrogenic diabetes insipidus
Amiloride
-K+ Sparing Diuretic
-ENaC blocker (distal convoluted & collecting duct)
-
-21 hr half life. NSAIDS decrease efficiency.
-CNS, GI
-hyperkalemia (esp in AIDS)
-adjunct w/ thiazide or loop diruetic to reduce K loss. Edema, heart failure, LIDDLE’s syndrome. aerosol for cystic fibrosis. Also acts as an ANTI-DIURETIC for: Lithium-induced diabetes insipidus (blocks lithium uptake by Na channels)
Triamterene
-K+ Sparing Diuretic
-ENaC blocker (distal convoluted & collecting duct), folate antagonist
-
-4 hr half life. NSAIDS decrease efficiency.
-CNS, GI
-hyperkalemia (esp in AIDS), megaloblastic anemia in cirrhosis
-adjunct w/ thiazide or loop diruetic to reduce K loss. Edema, heart failure, LIDDLE’s syndrome. aerosol for cystic fibrosis.
Spironolactone
-
-NSAIDS decrease efficiency.
-diarrhea, gastritis, gastric bleeding, CNS, rash
-hyperkalemia, anti-androgen (feminization), anti-progesterone (menstrual prob), malignancies
-primary hyperaldosteronism, ascites & edema from cirrhosis! Adjunct w/ thiazide or loop diuretic.
Eplerenone
-
-clearance down by CYP3A4 inhibitors. NSAIDS decrease efficiency.
-diarrhea, gastritis, gastric bleeding, CNS, rash
-hyperkalemia, anti-androgen (feminization), anti-progesterone (menstrual prob)
-Adjunct w/ thiazide or loop diuretic.
Chlorpropamide
-Antidiuretic
-up ADH secretion
-
-
-
-
-
Desmopressin
-Antidiuretic
-V2 agonist (bit of V1)
-
-
-water intoxication
-coronary artery constriction
-Central Diabetes insipidus
Vasopressin
-Antidiuretic
-V1 & V2 agonist
-
-
-water intoxication
-coronary artery constriction
-desmopressin is better, but: Central Diabetes insipidus
Probenecid
-Uricosuric
-inhibit OAT (organic anion transporter)
-
-biphasic effect on gout
-kidney stones
-inhibits excretion of MANY drugs (including diuretics)
-gout
Allopurinol
- Misc (Anti-Gout)
- ## inhibit xanthine oxidase-
-
-
-gout
Colchicine
- Misc (Anti-Gout / Anti-inflammatory)
-reduces neutrophil activity (painful inflammation)
-
-
-
-
-gout
cyclophosphamide
-DNA alkylating agents (bischoloroethyl amines)
-dechlor. makes electrophile attacks nucleophile in DNA base
-nitrogen analog of mustard gas
-less reactive, must be activated in liver/tumor tissues
-
-anti-tumor
mechlorethamine
-DNA alkylating agents (bischoloroethyl amines)
-dechlor. makes electrophile attacks nucleophile in DNA base
-nitrogen analog of mustard gas
-Highly reactive
-
-anti-tumor
nitrosureas
-alkylating agents - - -cross BBB, little cross reactivity w/ other alkylators - -brain tumors
procarbazine
-alkylating agents (other) - - -little x-react w/ other antineo. MOPP reg., metab. to alkylate -leukemogenic 5-10% -Hodgkin's in the MOPP regimen
cisplatin
-platinum coordination complexes
-cross link DNA, inhibit DNA biosynthesis
-
-cell cycle non specific
-nephro toxic, acoustic nerve dysfunction [no myelosupression]
-ovarian and testicular cancer
methotrexate
-anti-tumor antimetabolites
-dihydrofolate reductase inh., blocks DNA syn., RNA precursor, blocks thymidylate formation
-folic acid analog, accumulates as polyglutamate
-S-phase specific, [folinic acid is antidote for rescue, leucovorin]
-
-anti-tumor
leucovorin
-anti-tumor antimetabolites (folinic acid rescue)
-replaces FH4 in thymidylate synthetase cycle
-formyl-FH4
-
-
-rescue to methotrecate
5-fluorouracil
-anti-tumor antimetabolites, pyrimidine antagonist
-metabolite FdUMP direct inh. thymidylate sythetase, incorp. into DNA/RNA
-Flourine on 5 carbin 5-FU
-S-phase
-
-anti-tumor
capecitabine
-anti-tumor antimetabolites, pyrimidine antagonist
- metabolized to 5FU, FdUMP direct inh. thymidylate synthetase
-
-oral prodrug of 5-FU, pref. activ. in tumor tissue
-
-colon cancer, refractory breast cancer
cytosine arabinoside (cytarabine, ara C)
-anti-tumor antimetabolites, pyrimidine antagonist
-araC–>araCMP—>araCTP inh. DNA synthesis, high rates DNA breaks
-
-activation requires deoxycytidine
-
-anti-tumor
6-mercaptopurine
- anti-tumor antimetabolites, purine antagonist
- metabolite inhib. purine synthesis, xDNA, xRNA –>fraud base incorporation
- thiol derivative on purine
- s-phase, activ. by HGPRT, inactiv. by xanthine oxidase, low bioav. w/ milk
- must decrease dose when allopurinol use
- anti-tumor
6-thioguanine
-anti-tumor antimetabolites, purine antagonist
-metabolite inhib. purine synthesis, xDNA, xRNA –>fraud base incorporation
-thiol derivative on purine, guanine
-s-phase,activated by HGPRT
-
-anti-tumor
bleomycin
- anti-tumor antibiotics
- DNA strand scission
- natural
- small doses at first!
- anaphylaxis, pulmonary fibrosis [no myelosuppression]
- broad spectrum of tumors, combination regimens
daunorubicin
-anti-tumor antibiotics, topoisomerase inhibitors
-DNA intercalation, topo II binding, DNA scission
-
-
-irreversible cardiac toxicity
-anti-tumor
doxorubicin
-anti-tumor antibiotics, topoisomerase inhibitors
-DNA intercalation, topo II binding, DNA scission
-
-
-irreversible cardiac toxicity
-anti-tumor
paclitaxel
-mitotic spindle poisons
-enhances tubulin polymerization (blocks disassembly)
-plant alkaloid
-
-
-ovarian and advanced breast cancers
vinblastine
-mitotic spindle poisons (vinca alkaloids)
-inhibit tubulin polymerization
-
-M-phase
-myelosuppression(limits dose), nausea
-hodgkin and lymphomas(AVBD regimen)
vincristine
-mitotic spindle poisons (vinca alkaloids)
-binds to microtubules
-
-
-mild non-dose limiting supression, significant neurotoxicity
-child leukemia, Hodkins MOPP regimen (o=oncovi=vincristine)
irinotecan
-topoisomerase inhibitors (camptothecins)
-bind topo/dna complex, block religation, also double strand break
-
-s phase for replication blocking double strand
-severe diarrhea
-colorectal cancer
topotecan
-topoisomerase inhibitors (camptothecins)
-bind topo/dna complex, block religation, also double strand break
-
-s phase for replication blocking double strands
-myelosupression
-ovarian and lung cancer
daunorubicin
-anti-tumor antibiotics, topoisomerase inhibitors
doxorubicin
-anti-tumor antibiotics, topoisomerase inhibitors
etoposide
-topoisomerase inhibitors
-ternary complex with topo II, scission, block religation of double strand
-
-s phase
-
-
tamoxifen
-antagonist of hormone action(estrogen)
-competitive inhibitor of estrogen binding to ER (SERM)
-
-partial agonist
-hot flashes, blood clots, increased risk of uterine cancer
-female and male breast, uterine endometrium
raloxifene
-antagonist of hormone action (SERM)
-SERM
-
-partial agonist
-
-prevent breast cancer in osteoporosis women
anastrozole
-antagonist of hormone action (aromatase inhibitor)
-inhibit androgen to estrogen conversion
-
-post menopause not pre menopause
-joint pain, loss of bone density
-ER+ breast cancer, especially tamoxifen resistant
letrozole
-antagonist of hormone action (aromatase inhibitor)
-inhibit androgen to estrogen conversion
-
-post menopause not pre menopause
-joint pain, loss of bone density
-ER+ breast cancer, especially tamoxifen resistant
exemestane
-antagonist of hormone action (aromatase inhibitor)
-inhibit androgen to estrogen conversion
-
-post menopause not pre menopause
-joint pain, loss of bone density
-ER+ breast cancer, great reducer of high risk postmenopause!
leuprolide
-antagonist of hormone action-(anti-androgen)
-GnRH-R agonist
-synthetic analog of GnRH
-pulsatile-elevates levels, cont. high doses greatly lowers levels(castration)
-
-prostate cancer
flutamide
-antagonist of hormone action
-androgen recetor antagonis
-
-ineffective alone due to rapid receptor mutation
-
-prostate cancer, must use with leuprolide
prednisone
-adrenocorticosteroids
-induce apoptosis in leukemia cells
-
-
-
-multi drug reg. (MOPP) leukemia, lymphoma, myeloma. Palliative in other cancers
lapatinib
-“Targeted” agents (EGFR kinase inhibitors)
erlotinib
-“Targeted” agents (EGFR kinase inhibitors)
-EGF receptor protein tyrosine kinase inhibitor
-
-
-
-non small cell lung cancer (brain head and neck trials)
lapatinib
-“Targeted” agents (HER2 kinase inhibitor)
-small protein HER 2 kinase inhibitor
-
-
-
-breast cancer
imatinib
-“Targeted” agents (bcr/abl kinase inhibitor)
-small molecule inhibitor of abl protein tyrosine kinase
-
-
-
-chronic myelogenous leukemia
cetuximab
-“Targeted” agents (chimeric/humanized antibodies)
-chimeric EGFR antibody
-
-
-
-
-colon cancer, head and neck cancer
trastuzumab
-“Targeted” agents (chimeric/humanized antibodies)
-HER2 antibody, immune system mediated effects
-humanized antibody
-
-
-refractory metastatic breast cancer
brentuximab vedotin
-“Targeted” agents (chimeric/humanized antibodies)
-IgG binds CD30 surface antigen, vedotin enters & mitotic spindle poison
-chimeric IgG conjugated vedotin
-
-
-some Hodgkin and non-hodgkin lymphoma(anaplastic large cell)
desflurane
-Volatile general anesthetics
-inhib in CNS at GABA & glycine receptors & reduce glutamate transmission
-blood-gas part coef=0.42; metabolized at 0.02%; produces prompt recovery
-
-malignant hyperthermia; respiratory depression; decreased arterial BP (decr. HR, CO, & syst vascular res)
-airway irritation, minimal myocardial depression
-anesthesia maintenance
isoflurane
-Volatile general anesthetics
-inhib in CNS at GABA & glycine receptors & reduce glutamate transmission
-blood-gas part coef=1.4; 0.2% metabolized
-
-malignant hyperthermia; respiratory depression; decreased arterial BP (decr. HR, CO, & syst vascular res)
-airway irritation, minimal myocardial depression
-anesthesia maintenance
nitrous oxide
-Volatile general anesthetics
-inhib in CNS at GABA & glycine receptors & reduce glutamate transmission
-blood-gas part coef=0.46; very insoluble
-
-malignant hyperthermia; respiratory depression; decreased arterial BP (decr. HR, CO, & syst vascular res)
-little side effects
-adjunct to potent volatile anesthetics
sevoflurane
-Volatile general anesthetics
-inhib in CNS at GABA & glycine receptors & reduce glutamate transmission
-blood-gas part coef=0.68; metabolized at 2-5%; produces prompt recovery
-
-malignant hyperthermia; respiratory depression; decreased arterial BP (decr. HR, CO, & syst vascular res)
-no airway irritation; minimal myocardial depression
-anesthesia maintenance
dantrolene
- - - - - - -Treats malignant hyperthermia
succinylcholine
-N2 non-competitive depolarizing inhibitor
-agonist for Na channel and keeps it open
-
-hydrolysis from plasma ChE nor AChE!, short DOA
-K–>cardiac arrest, contraction of eye muscles
-can cause malignant hypothermia
-relax muscles during surgery/vent
etomidate
- - - - - - -
ketamine
- - - - - - -
methohexital
- - - - - - -
propofol
- - - - - - -
thiopental
- - - - - - -
alfentanil
- - - - - - -
fentanyl
- - - - - - -
remifentanil
- - - - - - -
sufentanil
- - - - - - -
flumazenil
- - - - - - -
midazolam
- - - - - - -
benzocaine
-Local Anesthetics- Esters
-Binds intracell. portion of voltage-gated Na channels blocks depolarization
-
-Topical ester
-Numb tongue,lighthead,convulse/uncon,coma,resp arrest,cardiac tox.
-methemoglobeniemia, rare allergic response
-nerve block to eliminate sensory and motor response to stimulus
cocaine
-Local Anesthetics- Esters
-Binds intracell. portion of voltage-gated Na channels blocks depolarization
-
-topical ester
-Numb tongue,lighthead,convulse/uncon,coma,resp arrest,cardiac tox.
-Vasoconstriction!, MI, Seizures
-nerve block to eliminate sensory and motor response to stimulus
procaine
-Local anesthetic-Ester
-Binds intracell. portion of voltage-gated Na channels blocks depolarization
-
-45-60min, lowest potency and hydrophobicity
-Numb tongue,lighthead,convulse/uncon,coma,resp arrest,cardiac tox.
-rare allergic response
-nerve block to eliminate sensory and motor response to stimulus
tetracaine
-local anesthetic-ester
-Binds intracell. portion of voltage-gated Na channels blocks depolarization
-
-plasm esterase metab. 60-180min (longest ester), highest potency
-Numb tongue,lighthead,convulse/uncon,coma,resp arrest,cardiac tox.
-rare allergic response
-nerve block to eliminate sensory and motor response to stimulus
bupivicaine
-Local Anesthetics-Amides
-Binds intracell. portion of voltage-gated Na channels blocks depolarization
-
-240-480min (longest), highest potency
-Numb tongue,lighthead,convulse/uncon,coma,resp arrest,cardiac tox.
-
-nerve block to eliminate sensory and motor response to stimulus
lidocaine
-Local anesthetic- amide
-Binds intracell. portion of voltage-gated Na channels blocks depolarization
-tertiary amine
-liver metab. 60-120, intermediate potency, TOPICAL or SubQ
-Numb tongue,lighthead,convulse/uncon,coma,resp arrest,cardiac tox.
-
-nerve block to eliminate sensory and motor response to stimulus
mepivacaine
-Local Anesthetics-Amides
-Binds intracell. portion of voltage-gated Na channels blocks depolarization
-
-90-180 min, intermediate potency
-Numb tongue,lighthead,convulse/uncon,coma,resp arrest,cardiac tox.
-
-nerve block to eliminate sensory and motor response to stimulus
prilocaine
-Local Anesthetics-Amides
-Binds intracell. portion of voltage-gated Na channels blocks depolarization
-
-60-120min
-Numb tongue,lighthead,convulse/uncon,coma,resp arrest,cardiac tox.
-
-nerve block to eliminate sensory and motor response to stimulus
ropivacaine
- Local Anesthetics-Amides
- Binds intracell. portion of voltage-gated Na channels blocks depolarization
- S-isomer of the racemic mixture
- 180-360min (2nd longest amide)
- Numb tongue,lighthead,convulse/uncon,coma,resp arrest,cardiac tox.
- Less toxicity with similar potency to RACEMIC BUPIVICAINE
- nerve block to eliminate sensory and motor response to stimulus
amitriptyline
- tricyclics (TCA’s)
- block ser & NE reuptake
- block histamine, muscarinic, adrenergic R’s.
- 2 weeks to work, long half-life, kidney elim & bit hepatic microsomes
- antimuscarinic, sedation (H1 R), sex down, weight up, delirium, tachycardia
- seizures, slowing A-V conductance, orthostatic hypotension (alpha 1 R)
- Antidepressant
amoxapine
- tricyclics (TCA’s)
- block ser & NE reuptake
- block histamine, muscarinic, adrenergic R’s.
- 2 weeks to work, long half-life, kidney elim & bit hepatic microsomes
- antimuscarinic, sedation (H1 R), sex down, weight up, delirium, tachycardia
- seizures, slowing A-V conductance, orthostatic hypotension (alpha 1 R)
- Antidepressant
imipramine
- tricyclics (TCA’s)
- block ser & NE reuptake
- block histamine, muscarinic, adrenergic R’s.
- 2 weeks to work, long half-life, kidney elim & bit hepatic microsomes
- antimuscarinic, sedation (H1 R), sex down, weight up, delirium, tachycardia
- seizures, slowing A-V conductance, orthostatic hypotension (alpha 1 R)
- Antidepressant
nortriptyline
- tricyclics (TCA’s)
- block ser & NE reuptake
- block histamine, muscarinic, adrenergic R’s.
- 2 weeks to work, long half-life, kidney elim & bit hepatic microsomes
- antimuscarinic, sedation (H1 R), sex down, weight up, delirium, tachycardia
- seizures, slowing A-V conductance, orthostatic hypotension (alpha 1 R)
- Antidepressant
citalopram
- SSRI’s
- block ser reuptake
- neurogenesis in hippocampus (via BDNF)
- 2 wks to work, kidney elim, block P450, high first-pass effect, binds plasma proteins
- nausea, anxiety, insomnia… late: sex down
- late: anorexia, mania
- Antidepressant
escitalopram
- SSRI’s
- block ser reuptake
- neurogenesis in hippocampus (via BDNF)
- 2 wks to work, kidney elim, block P450, high first-pass effect, binds plasma proteins
- nausea, anxiety, insomnia… late: sex down
- late: anorexia, mania
- Antidepressant
fluoxetine
- SSRI’s
- block ser reuptake
- neurogenesis in hippocampus (via BDNF)
- demethylated to active. 2 wks to work, kidney elim, block P450, high first-pass effect, binds plasma proteins
- nausea, anxiety, insomnia… late: sex down
- late: anorexia, mania
- Antidepressant, bipolar
sertraline
- SSRI’s
- block ser reuptake
- neurogenesis in hippocampus (via BDNF)
- 2 wks to work, kidney elim, block P450, high first-pass effect, binds plasma proteins
- nausea, anxiety, insomnia… late: sex down
- late: anorexia, mania
- Antidepressant
duloxetine
-SNRI’s
-block ser, NE reuptake (but UNRELATED to TCA’s)
-
-1/4 bound to plasma proteins, elim mostly kidney. metab by CYP1A2, CYP2D6
-nausea, anxiety, insomnia, sex down [same as SSRI’s!]
-high dose up blood pressure
-depression refractory to SSRI’s
venlafaxine
-SNRI’s
-block ser, NE reuptake (but UNRELATED to TCA’s)
-
-mostly bound to plasma proteins, elim mostly kidney. metab by CYP2D6
-nausea, anxiety, insomnia, sex down [same as SSRI’s!]
-high dose up blood pressure
-depression refractory to SSRI’s
bupropion
-atypicals
-inhibit dopamine reuptake
-often combined w/ TCA’s
-
-nausea, insomnia, nervous, headache
-tinnitus
-rapid-cycling bipolar, depression
mirtazapine
-atypicals
-blocks alpha2 R’s. (down Ser, NE)
-often combined w/ TCA’s
-
-nausea, insomnia, nervous, headache
-tinnitus
-rapid-cycling bipolar, depression
nefazodone
-atypicals
-inhibit reuptake of 5HT & blocks 5HT2 R’s
-often combined w/ TCA’s
-
-nausea, insomnia, nervous, headache
-tinnitus
-rapid-cycling bipolar, depression
phenelzine
-MAOi’s
-3rd-line after SSRI’s & TCA’s
-inhibit MAO-A & B
-
-orthostatic hypotension, tachycardia, agitated, pyschoses
-serotonin syndrome, cheese effect
-depression
selegiline
-MAOi’s
-3rd-line after SSRI’s & TCA’s
-inhibit MAO-B (and A @ high conc)
-
-orthostatic hypotension, tachycardia, agitated, pyschoses
-serotonin syndrome, cheese effect
-depression
tranylcypromine
-MAOi’s
-3rd-line after SSRI’s & TCA’s
-inhibit MAO-A & B
-
-orthostatic hypotension, tachycardia, agitated, pyschoses
-serotonin syndrome, cheese effect
-depression
lithium
- bipolar treatment
- unclear. block hyrolysis of IP to inositol, blocks GSK-3B, inhibits 5HT1A & 1B, enhances glutamate reuptake
- onset takes 3-4 wks, substitutes for Na (adverse!).
- Low therapeutic index! kidney elim. 20 hr half-life.
- tremors, confusion, teratogenic, down thyroid, diabetes insipidus
- arrhythmias, coma, convulsions
- bipolar
amphetamine
- Stimulants
- this drug not specifically described in lecture, just know it’s same as other amphetamine stimulants
atomoxetine
-Stimulants but “not stimulant”
-NE reuptake inhibitor
-NOT habit-forming
-
-
-
-ADHD
dextro-amphetamine
-Stimulants
-Up pre-synaptic cytoplasmic DA, NE release from vesicles. inhibit MAO. Thus DA, NE released into cleft by vesicles & non-vesicles.
-
-Full GI aborption, liver metab, urine excrete
-euphoria, insomnia, anxiety, vertigo, confusion, nausea, hypertension, diarrhea
-arrhythmias, addiction
-narcolepsy, ADHD
methylphenidate
-high conc. to brain
-Full GI aborption, liver metab, urine excrete (as ritalinic acid)
-euphoria, insomnia, anxiety, vertigo, confusion, nausea, hypertension, diarrhea
-arrhythmias, addiction
-narcolepsy, ADHD
modafinil
-Stimulants
-unclear
-
-euphoria, insomnia, anxiety, vertigo, confusion, nausea, hypertension, diarrhea
-arrhythmias, addiction
-Fewer psycho, euphoric, & cognition effects!
-narcolepsy
