PDA B3 Drugs & Terms Flashcards
0
Q
Propofol
A
Class: General Anesthetic
Action: GABA(a) activation
Use: Induce and maintain anesthesia; also an antiemetic
Routes: IV
Kinetics: Onset similar to Na Thiopental, but T1/2 only 3.5hrs («_space;hang over than barbiturates!) - useful for OUTPATIENT surgeries
S/E: Pain on injection, initial excitation on induction
1
Q
Sodium Thiopental
A
Class: General Anesthetic Action: Activates GABA(a) receptors Use: To induce anesthesia: 10-30sec after injection Route: Oral, IV Kinetics: 10min duration, 12hrs T1/2
2
Q
Etomidate
A
Class: General Anesthetic
Action: GABA(a) activator
Use: Induce anesthesia in pts at risk for hypotension
Route: IV
S/E: Pain on injection, myoclonus, severe N/V, suppression of adrenocortical response to stress (dangerous) - other S/E better than thiopental
3
Q
Ketamine
A
Class: General Anesthetic
Action: NMDA receptor antagonist
Use: Dissociative anesthesia (no respiratory depression!) - bromchospasm pts or short procedures on children only
Route: IV, IM, oral, rectal
S/E: Emergence delirium (PCP-like drug), Hypertension and increased ICP, nystagmus, salivation, lacrimation, increased muscle tone
4
Q
Midazolam
A
Class: General Anesthetic - Benzodiazepine
Action: GABA(a) activator
Use: Conscious sedation & induction agent (tooth extraction); anxiolytic (adjunct to another anesthetic to reduce anxiety)
Route: Oral, IV, IM
S/E: respiratory depression, C/V similar to thiopental
Contra: Caution in pts w/ neuromuscular disease
Kinetics: Slower induction, longer T1/2 than thiopental (hydroxylated to active metabolite)
5
Q
Isoflurane
A
Class: General Anesthetic
Action: likely activates GABA channels, inhibits NMDA channels
Use: Maintain anesthesia, sometimes induce; use w/ NO to reduce amount of NO needed
Route: Inhaled
Kinetics: Moderate induction & recovery
S/E: Cough, lower tidal volume and higher respiratory rate, respiratory depression
6
Q
Desflurane
A
Class: General Anesthetic
Action: GABA(a) agonist, K+ channel agonist, glutamate antagonist
Use: Maintenance only - useful for extending anesthesia in long outpatient surgeries
Route: Inhaled
Kinetics: Rapid induction and recovery
S/E: Similar to isoflurane but a worse respiratory irritant
7
Q
Sevoflurane
A
Class: General Anesthetic
Action: Activates GABA(a)
Use: Induce and Maintain in adults and children (popular)
Kinetics: Very fast induction and recovery
S/E: Potential renal damage from metab. to Fluorine (in liver) or breakdown into Compound A (in anesthetic apparatus), other similar to isoflurane but a lesser respiratory irritant
8
Q
Nitrous Oxide
A
Class: General Anesthetic
Action: Uptake increases concentration of other Anesthetics
Use: useful to ENHANCE induction with another anesthetic; also useful for sedation and analgesia but not as an anesthetic itself
Route: Inhaled
Contra: pneumothorax
S/E: negative inotrope but also sympathomimetic, respiratory effects minimal except for O2 dilution; abuse liability
9
Q
Cocaine
A
Class: Local Anesthetic - Ester
Action: voltage-gated Na+ channel blocker (binds in pore)
Use: Anesthesia of the upper respiratory tract
Route: Topical
10
Q
Procaine
A
Class: Local Anesthetic - Ester
Action: voltage-gated Na+ channel blocker (binds in pore)
Use: infiltration anesthesia; largely replaced by other drugs
Route: Parenteral
Kinetics: Slow onset, low potency, short duration of action
11
Q
Tetracaine
A
Class: Local Anesthetic - Ester
Action: voltage-gated Na+ channel blocker (binds in pore)
Use: Spinal anesthesia; topical or ophthalmic preparations
Route: Topical, epidural, spinal
Kinetics: Potent and longer duration than procaine
12
Q
Benzocaine
A
Class: Local Anesthetic - Ester
Action: voltage-gated Na+ channel blocker (binds in pore)
Use: Long lasting relief to wounds or ulcerated surfaces
Route: Topical
Kinetics: Low H2O solubility so absorbed too slowly topically to be toxic; Long duration
13
Q
Lidocaine
A
Class: Local Anesthetic - Amide
Action: voltage-gated Na+ channel blocker (binds in pore)
Use: Many; Antiarrythmetic - use with vasoconstrictors to decrease toxicity
Route: IV, SC, Topical
Kinetics: Intermediate duration - Faster onset, more intense, longer lasting, more extensive than procaine
14
Q
Bupivacaine
A
Class: Local Anesthetic - Amide
Action: voltage-gated Na+ channel blocker (binds in pore) - more sensory than motor loss
Use: long-acting; favorable for prolonged anesthesia
Route: Parenteral, Topical
Kinetics: long-acting
S/E: More cardiotoxic than lidocaine; S-enantiomer formulation is less toxic
15
Q
Ropivacaine
A
Class: Local Anesthetic - Amide (S enantiomer)
Action: voltage-gated Na+ channel blocker (binds in pore)
Use: Epidural and regional anesthesia
Route: Parenteral
Kinetics: Long acting
S/E: Less cardiotoxic and even more motor sparing than bupivacaine
16
Q
Order of Sensation Blocking in Local Anesthetics
A
- Pain
- Cold
- Warmth
- Touch
- Deep Pressure
- Motor
- Recovery in reverse order
17
Q
Amitriptyline
A
Class: Antidepressant - Tricyclic
Action: SNRI, multitude of other receptors (L-type Ca2+ blocker, Na+ blocker, antihistamines, anticholinergics, others)
Use: MDD; chronic pain
Route: Parenteral or Oral
S/E: Less REM and more Stage 4 sleep, anticholinergic effects, sedation, cardiotoxicity
Kinetics: rapidly absorbed, high conc. found in heart and brain, long T1/2; demethylated to active metabolite
Drug Int: blocks guanethidine uptake, simpathomimetics, absorption & metab. of other drugs
18
Q
Clomipramine
A
Class: Antidepressant - Tricyclic
Action: SNRI, multitude of other receptors (L-type Ca2+ blocker, Na+ blocker, antihistamines, anticholinergics, others)
Use: MDD; OCD
Route: Parenteral, Oral
S/E: Less REM and more Stage 4 sleep, anticholinergic effects, sedation, cardiotoxicity
Kinetics: rapidly absorbed, high conc. found in heart and brain, long T1/2; demethylated to active metabolite
Drug Int: blocks guanethidine uptake, simpathomimetics, absorption & metab. of other drugs
19
Q
Fluoxetine
A
Class: Antidepressant - SSRI
Action: SSRI
Use: MDD, OCD, PTSD, Bulimia Nervosa
Route: Oral
Kinetics: Active metabolite has long T1/2
S/E: N/V, insomnia, nervousness, sexual dysfunction; LESS TOXICITY THAN TCAs and MAOIs
Drug Int: Impacts metab. of several drugs
20
Q
Sertraline
A
Class: Antidepressant - SSRI
Action: SSRI
Use: MDD, OCD, Panic Disorders
Route: Oral
Kinetics: Active metabolite has long T1/2
S/E: N/V, insomnia, nervousness, sexual dysfunction; LESS TOXICITY THAN TCAs and MAOIs
Drug Int: Lesser drug metabolic effects than fluoxetine
21
Q
Bupropion
A
Class: Antidepressant - Atypical Action: Blocks dopamine and NE reuptake Use: MDD; SAD; nicotine withdrawal Route: Oral S/E: insomnia, headaches Drug Int: Potent inhibitor of CYP2D6
22
Q
Mirtazapine
A
Class: Antidepressant - Atypical Action: Blocks presynaptic alpha2 adrenergic receptors in brain Use: MDD, Mood disorders Route: Oral S/E: increased appetite
23
Q
Duloxetine
A
Class: Antidepressant - SNRI Action: SNRI Use: MDD, chronic pain (fibromyalgia, diabetic neuropathy, back pain, osteoarthritis) Route: Oral Contra: Caution in pts w/ liver disease Kinetics: 12-18hr T1/2
24
Phenelzine
Class: Antidepressant - MAOI
Action: Irreversible MAOI - blocks deamination of NE, DA, 5-HT. MAO subtype A believed to mediate antidepressant effects
Use: MDD, dysthymia, bipolar, panic/anxiety disorders
Route: Oral
S/E: N/V, dizziness, headache, sedation, sexual dysfunction, etc.
25
Chlorpromazine
Class: Antipsychotic - Typical - Aliphatic Phenothiazine
Action: Antagonist of: DA antagonist - low to medium potency
Use: schizophrenia, acute psychotic episodes, bipolar mania, Tourette's syndrome, antiemetic
Route: Oral, rectal, IM, IV
S/E: Sedation, extrapyramidal effects, pronounced anticholinergic effects, neuroendocrine effects, orthostatic hypertension, weight gain, neuroleptic malignant syndrome
26
Clozapine
Class: Antipsychotic - Atypical
Action: DA and 5-HT2 antagonist
Use: Schizophrenia: More effects on negative sxs. acute psychotic episodes, bipolar mania, Tourette's syndrome, antiemetic
Route: Oral
S/E: More weight gain, fewer extrapyramidal effects than typical antipsychotics. Rare: agranulocytosis
27
Thioridazine
Class: Antipsychotic - Typical - Piperidine Phenothiazine
Action: DA antagonist - low potency
Use: schizophrenia, acute psychotic episodes, bipolar mania, Tourette's syndrome. NOT ANTIEMETIC
Route: Oral
S/E: Sedative, fewer extrapyramidal effects than other typicals, anticholinergic
28
Fluphenazine
Class: Antipsychotic - Typical - Piperazine Phenothiazine
Action: DA antagonist - high potency
Use: schizophrenia, acute psychotic episodes, bipolar mania, Tourette's syndrome, antiemetic
Route: Oral, IM
S/E: Less sedation & less anticholinergic, BUT MORE extrapyramidal effects
29
Haloperidol
Class: Antipsychotic - Typical - Butyrophenone
Action: DA inverse agonist! - high potency, pharmacologically similar to Piperazine phenothiazines
Use: schizophrenia, acute psychotic episodes, bipolar mania, Tourette's syndrome, antiemetic
Route: Oral, IM, IV
S/E: sedation, hypotension, anticholinergic effects, extrapyramidal effects
30
Olanzapine
Class: Antipsychotic - Atypical
Action: DA and 5-HT2 antagonist; Related to Clozapine, w/ more 5-HT2 action
Use: schizophrenia, acute psychotic episodes, bipolar mania, Tourette's syndrome, antiemetic, AUGMENTATION of antidepressant therapy
Route: oral, IM
S/E: Weight gain and diabetes risk (more than Typicals), few extrapyramidal sxs no agranulocytosis,
31
Risperidone
Class: Antipsychotic - Atypical
Action: Combined DA and 5-HT receptor antagonist - active metabolite is paliperidone
Use: schizophrenia, acute psychotic episodes, bipolar mania, Tourette's syndrome, antiemetic
Route: Oral, IM depot
S/E: Weight gain & diabetes risk (more than Typicals), few extrapyramidal effects
32
Quetiapine
Class: Antipsychotic - Atypical
Action: D2 and 5-HT2 receptor antagonist; related to Clozapine
Use: schizophrenia, acute psychotic episodes, bipolar mania, Tourette's syndrome, antiemetic, AUGMENTATION of antidepressant therapy
Route: Oral
S/E: ABUSE POTENTIAL, others
33
Aripiprazole
Class: Antipsychotic - Atypical
Action: D2 partial AGONIST, 5-HT2 antagonist, other agonist/antagonist functions
Use: schizophrenia, acute psychotic episodes, bipolar mania, Tourette's syndrome, antiemetic, AUGMENTATION of antidepressant therapy
Route: Oral, IM depot
S/E: N/V, weight gain, headache, insomnia, anxiety, light-headedness
35
Lithium
Class: Antimanic
Action: Inhibits the phosphatase that converts IP2 to IP1
Use: Bipolar Disorder, other manias, (off label) unipolar depression antisocial behavior, cluster headaches
Route: Oral, parenteral
S/E: Weakness, tremor, GI upset, slurred speech & ataxia. Severely toxic (2-3x therapeutic level): rigidity, impaired conciousness & coma
Kinetics: Peak serum conc. in 2-4hrs, T1/2 18-24hr young 30-36hr old, unbound to plasma proteins, Vd = Total body H2O
Drug Int: Increased Na excretion (e.g. diuretics) increase Li concentration. Narrow therapeutic window; must monitor.
Contra: Pregnancy, nursing
36
Valproic Acid / Divalproex
Class: Antimanic
Action: Blocks repetitive neuronal firing; reduces T-type Ca2+ currents and incr. GABA
Use: Absence seizures, tonic-clonic seizures, myoclonic seizures, partial seizures
Route: Oral, IV
S/E: GI, weight gain, hair loss, hepatotoxicity
Kinetics: Bound to plasma protein
Contra: Pregnancy (neonatal spinal bifida)
Drug Int: Inhibits metab. of phenobarbital, phenytoin, carbamazepine
37
Carbamazepine
Class: Antimanic
Action: Blocks Na+ channels; similar to phenytoin
Use: Drug of choice for partial seizures
Route: Oral
S/E: Diplopia, ataxia, GI, drowsiness, rare: blood dyscasias
Kinetics: unpredictable absorption & liver enzyme induction
Contra: ABSENCE SEIZURES, Pregnancy (neonatal spinal bifida)
38
Alprazolam
Class: Antianxiety / Hypnotic - Benzodiazepine
Action: Enhances GABA action at GABA/Cl- complex
Use: Anxiety disorders, PANIC DISORDER, sleep disorders, seizure treatment
Route: Oral, Sublingual
S/E: Daytime sedation, ataxia, rebound insomnia, dependence
Kinetics: Short duration
Drug Int: Additive CNS depression with other sedatives / depressants, drugs that affect hepatic metab.
39
Buspirone
Class: Antianxiety / Hypnotic
Action: Partial agonist of 5-HT1A (inhibits adenylyl cyclase, open K+ channel), also antagonizes D2
Use: Generalized Anxiety Disorder
Route: Oral
S/E: Dizziness, headache, premature ejaculation, somnolence; Little sedation, NO dependence
Kinetics: Delayed onset
Drug Int: CYP3A4 Metab.
40
Chloral Hydrate
Class: Antianxiety / Hypnotic
Action: Enhances GABA, similar to barbiturates
Use: Insomnia
Route: Oral, Rectal
S/E: Dependence & tolerance, rashes, GI effects. Less sleep effects than benzos & barbits, but OD can be deadly
Kinetics: Metab. to active trichloroethanol
41
Diazepam
AKA: Valium
Class: Antianxiety / Hypnotic / Muscle Relaxant - Benzodiazepine
Action: GABA enchancement
Use: Anxiety & sleep disorders, MUSCLE RELAXANT, IV sedation & anesthesia
Route: Oral, IM, IV, Suppository
S/E: Dependence, Anterograde amnesia (IV), Sedation, Supression of REM sleep
Kinetics: Long duration
42
Flumazenil
Class: Antianxiety / Hypnotic
Action: Pure antagonist of GABA/Cl- complex; competitive inhibitor of benzodiazepine receptor
Use: Benzodiazepine OD / Dependency, Hypersomnias
Route: IV
S/E: Dizziness, Restlessness, Headache
43
Flurazepam
Class: Antianxiety / Hypnotic - Benzodiazepine
Action: Enhances GABA @ GABA/Cl- complex
Use: Anxiety disorders, SLEEP DISORDERS
Route: Oral
S/E: Dizziness & lightheadedness, sedation, ataxia, abuse
44
Lorazepam
Class: Antianxiety / Hypnotic - Benzodiazepine
Action: Enhances GABA @ GABA/Cl- complex
Use: Anxiety disorders, SLEEP DISORDERS, seizures
Route: Oral, IM, IV, Sublingual, Transdermal
S/E: Dizziness & lightheadedness, sedation, ataxia, abuse
Kinetics: NOT METAB. TO ACTIVE FORM
45
Pentobarbital
Class: Antianxiety / Hypnotic - Barbituate
Action: Bind GABA(a) receptor @ beta subunit to enhance GABA; different binding site than benzodiazepines
Use: Sleep disorders / sedative hypnotic
Route: Oral, IV, IM, rectal
S/E: Sedation, anesthesia, respiratory depression, dependence & tolerance, acute poisoning w/ OD
Kinetics: Readily absorbed & distributed, short-acting
Drug Int: Additive w/ other depressants; drugs that affect microsomal metab.
46
Zolpidem
Class: Antianxiety / Hypnotic - imadazopyridine
Action: Binds GABA(a) Omega-1 BDZ receptor to enchance GABA; specifically HYPNOTIC effects w/ little anxiolytic or myorelaxant activity
Use: Insomnia
Route: Oral, sublingual, spray
S/E: BDZ effects, headache, N/V
Drug Int: Like BDZs, antagonized by flumenazil
47
Baclofen
Class: Muscle Relaxant
Action: GABA(b) (!!!) receptor agonist - causes presynaptic inhibition, decreasing excitatory neurotransmission by Glutamate
Use: Muscle Spasticity
Route: Oral, topical, intrathecal
S/E: N/V, headache, dizziness, less sedation than others
47
Tizanidine
Class: Muscle Relaxant
Action: Alpha-2 agonist, related to clonidine
Use: Muscle spasticity
Route: Oral, IV, intranasal
S/E: Drowsiness, hypotension, dry mouth, asthenia (weakness)
48
SSRI Discontinuation Syndrome
Cause: Cessation of SSRI drugs. Most common with short-acting drugs: sertraline & fluvoxamine. Not with fluoxetine.
Sxs: dizziness, light-headedness, vertigo, anxiety, fatigue, headache, tremor, visual disturbances, etc.
49
Effects of Dopamine Receptors
D1 Type (D1 & D5) - Activate Adenylyl Cyclase
D2 Type (D2-4) - Inhibit Adenylyl Cyclase
50
Six Intrinsic Effects of Benzodiazepines
1. Anxiolysis
2. Anterograde Amnesia
3. Sedation / Hypnosis
4. Anticonvulsion
5. Antiemesis
6. Muscle Relaxation
Various BDZs may have much more or less of each effect
51
Caffeine
Class: Stimulant
Action: Competitive antagonist of adenosine receptors (inhibiting the inhibitor); high doses inhibit cAMP phosphodiesterase; DILATES systemic and CONSTRICTS cerebral blood vessels
Use: ADHD, narcolepsy; asthma (high doses); headache
Route: Oral, typically
S/E: increased alertness & attention, decreased fatigue & drowsiness, nervousness, restlessness, tremors, diuresis, incr. gastric secretions, bronchodilation, (high doses) tachycardia and tachypnea
52
Cocaine
Class: CNS Stimulant
Action: Binds to receptors & inhibits reuptake of NE, DA, & 5-HT;
Use: Local anesthetic for URT (nose surgeries); recreational drug
Route: Oral, IV, Smoking
S/E: Vasoconstriction, tachycardia, incr. alertness, euphoria & elation, psychological (NOT physical) addiction; OD causes seizures, MI, arrythmias
Contra: Pregnancy (teratogen - similar to alcohol)
53
Amphetamine, Methylphenidate, Methamphetamine
Class: CNS Stimulants
Action: Release & block reuptake of NE, DA, 5-HT; partial alpha adrenergic agonist; (high doses) MAOI - MORE NE EFFECTS THAN COCAINE
Use: ADHD, Narcolepsy
Route: Oral
S/E: insomnia, decreased appetite (anorexia), abdominal pain, growth suppression, high body temp, FACIAL TICS
OD: restlessness, dizziness, tremor, psychosis, permanent neurotoxicity, severe tooth decay (meth mouth), abuse liability
Kinetics: Much longer than cocaine
Metab: inactivated to benzoic acid
54
Nicotine
Class: CNS Stimulant
Action: Nicotinic agonist (Epi release, GI effects), incr. DA release & neuronal excitation via cation channels, muscle relaxant (desensitizes NMJ)
S/E: nausea w/ 1st exposure, severe addiction
Note: FAST tolerance - "tachyphylaxis"
55
Bupropion
Class: CNS Stimulant / Antidepressant
Action: NA & (major) DA reuptake inhibitor
Use: Smoking cessation - reduces withdrawal symptoms & cravings
56
Varenicline
Class: CNS Stimulant / Antidepressant
Action: partial agonist of Nicotinic receptor (antagonist relative to smoking!)
Use: Smoking cessation - reduces withdrawal sxs & cravings w/o desensitizing like nicotine itself does
S/E: nausea, insomnia, headache,a constipation, INCR. SUICIDAL THOUGHTS & DEPRESSION
58
Morphine
Class: Opioid Mu agonist
Action: mimics beta-endorphins to stimulate the Gi protein on GCPRs to lower intracellular cAMP, increase potassium efflux, hyperpolarizing the cell.
Use: Analgesia (4-5 hours)
Route: parenteral; high first pass, low oral potency and bioavailability
S/E: Constipation, euphoria, respiratory depression, nausea, increased ADH
59
Fentanyl
Class: Opioid Mu agonist
Action: mimics beta-endorphins to stimulate the Gi protein on GCPRs to lower intracellular cAMP, increase potassium efflux, hyperpolarizing the cell.
Use: Analgesia (1-1.5 hours)
S/E: Constipation, euphoria, respiratory depression, nausea, increased ADH
***EXTREMELY POWERFUL***
60
Methadone
Class: Opioid Mu agonist
Action: mimics beta-endorphins to stimulate the Gi protein on GCPRs to lower intracellular cAMP, increase potassium efflux, hyperpolarizing the cell.
Use: Analgesia (6-8 hours)
S/E: Constipation, euphoria, respiratory depression, nausea, increased ADH
61
Meperidine
Class: Opioid Mu agonist
Action: mimics beta-endorphins to stimulate the Gi protein on GCPRs to lower intracellular cAMP, increase potassium efflux, hyperpolarizing the cell.
Use: Analgesia (2-3 hours)
S/E: Constipation, euphoria, respiratory depression, nausea, increased ADH, toxicity with frequent use, interacts with MAOs
62
Heroin
Class: Opioid Muagonist
Action: mimics beta-endorphins to stimulate the Gi protein on GCPRs to lower intracellular cAMP, increase potassium efflux, hyperpolarizing the cell.
Use: Analgesia
S/E: Constipation, euphoria, respiratory depression, nausea, increased ADH
**Pro-drug**
63
Codeine
Class: Opioid Mu agonist
Action: mimics beta-endorphins to stimulate the Gi protein on GCPRs to lower intracellular cAMP, increase potassium efflux, hyperpolarizing the cell.
Use: Cough suppression
S/E: Constipation, euphoria, respiratory depression, nausea, increased ADH
**Pro-drug**
64
Oxycodone
Class: Opioid Mu agonist
Action: mimics beta-endorphins to stimulate the Gi protein on GCPRs to lower intracellular cAMP, increase potassium efflux, hyperpolarizing the cell.
Use: Analgesia
S/E: Constipation, euphoria, respiratory depression, nausea, increased ADH
64
Hydrocodone
Class: Opioid Mu agonist
Action: mimics beta-endorphins to stimulate the Gi protein on GCPRs to lower intracellular cAMP, increase potassium efflux, hyperpolarizing the cell.
Use: Cough suppressant w/ analgesia
S/E: Constipation, euphoria, respiratory depression, nausea, increased ADH
66
Hydromorphone
Class: Opioid agonist
Use: Analgesia
**2-3 X as potent as Morphine**
67
beta-Endorphin
Class: Endogenous Opioids
Action: activates the mu receptor
68
Dynorphin
Class: Endogenous Opioids
Action: activates the kappa receptor
69
Enkephalin
Class: Endogenous Opioids
Action: activates the delta receptor
70
Nalbuphine
```
Class: Mu Antagonist and Kappa Agonist
Action:
Use: Analgesia with low abuse potential
Route: Injection
S/E: Withdrawal in opioid dependent patients
```
70
Buprenorphine
Class: Partial Mu Agonist
Action: mimics beta-endorphins to stimulate the Gi protein on GCPRs to lower intracellular cAMP, increase potassium efflux, hyperpolarizing the cell.
72
Naloxone
Class: Opioid Antagonist
Action: Strongly antagonizes the Mu receptor and slightly antagonizes Kappa and Delta receptors
Use: Treatment of opioid overdose, prevention of opioid abuse (combined with other drugs)
Route: parenteral activity >> oral activity
73
Dextromethorphan
Class: Cough supressant
Action: NMDA antagonist
Use: Anti-tussive
74
Naltrexone
```
Class: Opioid Antagonist
Action:
Use: treatment of opiate and alcohol addiction
Route: oral
**Long half-life**
```
74
Suboxone
Class: Misc. Opioid
Use: Treats opioid abuse
75
Infections in which -cidal antibiotics are preferred to -static drugs
```
A) Immunocompromised pts
B) 4 sites in immunocompetent pts (BEAM)
1) Deep BONE Infections
2) ENDOCARDITIS
3) ARTIFICIAL Device Implants
4) MENINGITIS
```
76
Time-dependent Killing
Goal: Maximize duration of effective concentration
Optimal: When [drug] > (4 x MIC) for more than 50% of total time
Example: beta-Lactams (penicillins, cephalosporins, monobactams)
77
Concentration-dependent Killing
Goal: Maximize peak concentration (Cmax)
Optimal: (Cmax / MIC) > 8
Example: Aminoglycosides (have persistent effect even once [drug] falls below MIC)
78
AUC-dependent Killing
Aka: Area-under-the-curve-dependent killing
Goal: Maximize area under ([drug] x time) curve
Optimal: When (AUC24hrs / MIC) > 125 hrs
Examples: Quinolones (also Cmax), Macrolides (also time), Clindamycin (also time), Vancomycin (also time), Daptomycin (also Cmax)
79
beta-Lactams (General)
Class: Antibacterial - bacteriCIDAL (some -static)
Action: Bind PBPs (transpeptidases) to inhibit cell- wall cross linking; weakened wall leads to osmotic lysis
Use: Wide-spectrum, most useful on actively growing bacteria
S/E: Rapid bacterial lysis can cause chills, fever, aching due to release of components
Kinetics: TIME DEPENDENT; Short t1/2, so shorter dosing intervals
Resistance: 1) beta-Lactamase, 2) Altered PBPs (MRSA, PRSP), 3) Limited drug access (I.e. Intrinsic resistance of some G-'s
80
Features of beta-Lactamases
b-Lactamases can protect other bacteria in the vicinity
Important as some normal flora may have b-Lactamases
Over 400 b-Lactamases have been described
81
Penicillin G & V
Class: b-lactam antibiotic
Action: Binds PBPs to prevent bacterial cell wall cross-linking
Spectrum:
G+ anaerobes - clostridium, peptococcus, peptostreptococcus, veillonella, actinomyces, NOT b. fragilis
G+ other - most Strep (1st line strep throat), bacillus anthracis, NOT Staph (b-Lactamases) or enterococcus
Limited G- - N. Meningitidis
Spirochetes - treponema pallidum (syphilis)
Route: Oral (V), IV or IM (G)
82
Methicillin & Oxacillin
Class: b-Lactam antibiotics
Action: Binds PBPs to prevent cell wall cross linking
Spectrum: Useful for b-Lactamase+ G+, e.g. Staph. Aureus (MSSA)
83
Ampicillin, Amoxicillin
Class: b-Lactam antibiotic
Special Uses: UTIs; amox. is DOC for otitis media and good alternative for Lyme disease (young children, pregnant/breast feeding)
Spectrum:
Maintain reasonable G+ spectrum: listeria, strep, ENTEROCOCCUS (UTIs)
Expanded G- spectrum: neissera, haemophilus, E. Coli, Salmonella
Weakness: b-Lactamases
Route: oral (amox.), oral or IV (ampi.)
84
Ampicillin VS. Amoxicillin
Ampicillin has two uses Amoxicillin does NOT:
- Meningitis (Neissera, listeria) [can give IV ampi.]
- GI infections [much of oral ampi. stays in GI]
Amoxicillin is DOC for otitis media, good alternative for Lyme disease
85
Ticarcillin
Class: b-Lactam antibiotic
Route: IV
Spectrum:
EXPANDED G- spectrum - incl. p. aeruginosa
Retains some G+ activity
Good for some anaerobes, incl. G-
Weakness: b-Lactamases (can give w/ clavulanate)
86
Piperacillin
Class: b-Lactam antibiotic
Route: IV
Spectrum:
EXPANDED G- spectrum like Ticarcillin, but also other Pseudomonas and Klebsiella, incl. those that are Ticarcillin resistant (give with b-Lactamase inhib. or aminoglycoside)
87
Penicillin adverse rxns & S/Es
- Rare but potl. very severe
- Still causes a few hundred deaths annually
- 70% have had penicillin before
- 33% have reported penicillin rxn before
- Synthetics typically safer than naturals, but ALL pose a risk
- Can test for with PRE-PEN; prior rash
- Other S/E: Fever, diarrhea, enterocolitis, elevated liver enzymes, hemolytic anemia, seizures
88
Aminoglycosides - general properties
Class: Antibiotic - BacteriCIDAL (only protein synth. Inhib. To do so)
Action: Transported into bacteria by energy-requiring process. Bind sites along 30S-50S interface to prevent initiation, premature mRNA release, and misreading
Route: IV, IM, topical
Spectrum: Primarily for G- "aerobic" bacilli (enterobac, p. aeruginosa). Poor vs. Anaerobes & facultatives in anaerobic environment. G+ requires combinations
Kinetics: Cmax-dependent w/ post-antibiotic effect allows less frequent dosing (1-2x/day)
Side effects: nephrotoxicity (rev.), ototoxicity (irrev.), neuromuscular blockade (treat w/ IV Ca+)
Antagonism: Do not mix b-Lactams with Aminoglycosides
Limited (up to 20%) CNS penetration
89
Gentamicin, Tobramycin, Amikacin
Class: Aminoglycoside Antibiotics - BacteriCIDAL
Action: Binds sites along 30S-50S interface
About 1/2 of Gentamicin-resist. Pseudomonas susceptible to Tobramycin
Amikacin is DOC for Tobramycin and Gentamicin-resistant strains
90
Tetracyclines - General
Class: BacterioSTATIC Antibiotics
Action: Prevent binding of aminoacyl-tRNA to 30S ribosomal subunit. Transported into cells by protein-dependent mech.
Resistance: Often efflux pumps. Resistance to ONE tetracycline usually means resistance to ALL!
Spectrum: "unusual" bugs - rickettsia, borellia (Lyme), chlamydia, mycoplasma, ureaplasma
Int: Bind divalent cations (Ca, Mg, Fe) and are then NOT absorbed well. Avoid taking with Ca2+/etc. supplements
S/E: GI effects, candida in colon, photosensitization with rash, teeth staining in children
Contra: young kids, pregnancy
91
Doxycycline, Minocycline
Class: Tetracycline antibiotics (prototypical)
Use: Alternative for penG-sensitive Syphilis; uncomplicated gonorrhoeae w/ another drug
S/E: Ca2+ binding - doxycycline < monocycline < tetracycline
92
Tigecycline
Class: Glycylcycline antibiotic
Action: Similar to tetracyclines, but also bind additional unique sites on ribosomes
Use: Skin & skin structure infections, complicated intra-abdominal infections, CAP (community-acquired pneumonia)
Spectrum: Staph, Strep, E. Coli, enterobacter, bacteroides, c. Perfringens, NOT PSEUDOMONAS
No cross resistance with tetracycline-resistance bugs
S/E: N/V, enterocolitis, Ca2+ binding and other tetracycline-like effects
OFTEN USED AS A LAST RESORT
93
Chloramphenicol
Class: tetracycline (?) antibiotic
Action: Inhibits binding of aminoacyl-tRNA to 50S & peptide bond formation
Spectrum: Very broad - generally -static, -cidal for a few bugs
Use: Meningitis, Brain abscesses
S/E: BONE MARROW SUPRESSION, GRAY BABY SYNDROME, OPTIC NEURITIS & BLINDNESS, GI effects
USE AS A LAST RESORT!
94
Macrolides - general
Class: Antibiotics - usually BacterioSTATIC
Action: Binds 50S and prevents translocation along ribosomes
95
Erythromycin
Class: Macrolide antibiotic
Action: Binds 50S, prevents ribosomal translocation
Spectrum: Primarily G+ (strep throat for pen-allergic pts), also good vs. Unusual bugs - chlamydia, Mycoplasma, legionella, bordetella. Many G- are resistant
S/E: N/V, incr. Risk of arrythmias and cardiac arrest
Int: INHIBITS CYP3A metabolism!
96
Clarithromycin
Class: Macrolide antibiotic
Action: Binds 50S, prevents ribosomal translocation
Vs. erythromycin: better kinetics, fewer GI effects, wider spectrum. Still some C/V risk (prolongs QT interval)
Spectrum: That of erythromycin, plus H. Influenzae, Moraxella, pen-resist s. Pneumoniae, atypical mycobacteria, H. Pylori (2 antibac + an acid blocker is the normal treatment)
97
Azithromycin
Class: Macrolide antibiotic
Action: Binds 50S, prevents ribosomal translocation
Use: Common for outpatient RTIs & genital infections (chlamydia, gonorrhoeae W/ CEFTRIAXONE), NOT H. Pylori
S/E: few - least of macrolides (little CYP3A4 effect). Still some C/V risk
98
Clindamycin
Class: antibiotic - similar to macrolides, but not one of them
Action: Binds 50S, prevents ribosomal translocation
Spectrum: G+ cocci (Strep & MSSA), useful vs. Flesh-eating strep (blocks toxin production among other effects); many anaerobes incl. B. Fragilis but not C. Diff
S/E: Significant risk of enterocolitis/N/V; hepatotoxicity
99
Linezolid
Class: oxazolidinone antibiotic - BacterioSTATIC
Action: Binds 50S and prevents formation of 70S ribosome
Use: Skin (structure) infections; Nosocomial pneumonia
Spectrum: G+ (VRE, MSSA AND MRSA, Strep A & B; other staph & strep)
Route: Oral, IV (High F)
S/E: Non-selective MAOI!, N/V, enterocolitis, headache, MARROW SUPPRESSION
100
Antifolates - general
Class: Antibiotics - incl. Sulfonamides & Trimethoprim
Action: Inhibits folate synthesis
101
Sulfonamides
Class: Antifolate antibacterial - BacterioSTATIC
Action: Inhibits folate synthesis by acting as competitive analogs of p-aminobenzoic acid, a folate precursor
Use: historically broad spectrum, now much resistance. Typically used with other drugs.
S/E: Hypersensitivity, GI effects, Renal damage, inhibits CYP2C9 (potentiates drugs like warfarin)
102
Silver Sulfadiazine
Class: Sulfonamide antibiotic
Action: Inhibits folate synth
Use: Prevent infections in burn pts
Route: topical
103
Sulfamethoxazole + Trimethoprim
Aka: TMP/SMX (Trade name: Bactrim)
Class: Combination of antibiotics
Action: Both inhibit folate synth. Sulfa is p-aminobenzoic acid analog and Trimeth is dihydrofolate analog
Use: working together, these two -STATIC drugs become -CIDAL!
First choice therapy for Uncomplicated UTIs & pneumocystis jiroveci (carinii); URT and ear infections, GI infections
S/E: All sulfa effects. TMP adds N/V, diarrhea, rashes, MARROW SUPRESSION. TMP effects greatest in long-term use (e.g. AIDS pts)
104
Four Categories of Antibacterial Usage
1) Prophylaxis. E.g. Prevent surgical would infections. Based on predominant flora at site of interest.
2) Empiric. Organism unknown but syndrome known. Based on which drugs have good activity against most common pathogens.
3) Pathogen-directed. Pathogen known but susceptibility unknown. Based on which drugs likely target this pathogen.
4) Susceptibility-guided. Both pathogen and susceptibility known. Based on susceptibility results.
105
A common use of EMPIRIC THERAPY
Uncomplicated cystitis in pregnant women.
1st choice: TMP/SMX
Afterwards (no particular order): Nitrofurantoin, Nor/Ciprofloxacin, Fosfomycin
106
Drugs for HA-MRSA
1) Vancomycin
2) Linezolid
3) Daptomycin
4) Tigecycline
- All are given IV (Linezolid can be oral)
107
Drugs for CA-MRSA
1) Linezolid
2) Doxycycline / Minocycline
3) Clindamycin
4) TMP-SMX
- these are all orally given
- drugs for HA-MRSA also effective, but are all IV and so inconvenient for outpatient therapy
108
Clavulanic Acid / Tazobactam
Class: b-Lactamase inhibitors
Action: b-Lactam analogs that irrev. bind SOME b-Lactamases, potentiating the action of b-Lactam antibiotics
Use: Amoxicillin + Clavulanate; Piperacillin + Tazobactam
Resistance: Works well on classes A and D; AmpC types are resistant
109
Cephalosporins - general
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Class: Antibiotic
Action: Same as penicillins
Resistance: Similar to penicillins
Route: Most IV, only a few oral
Kinetics: Mostly short T1/2s, well-distributed. Only some penetrate CNS
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