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206 Cards in this Set
- Front
- Back
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Km
Represents? What axis on the graph? What happens to affinity when you decrease Km? |
reflects affinity of enzyme for substrate
graphically, substrate concentration that is half of Vmax (X-axis) decreased Km, increased affinity |
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Vmax
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Y-axis
directly proportional to enzyme concentration |
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Competitive inhibitor
What does it look like graphically on Lineweaver-Burke plot? What happens to Km and Vmax? What happens to curve on 'Agonist dose vs Maximum effect' plot? |
Graphically, on Lineweaver-Burke plot, competitive inhibitors cross each other
Change Km, but not Vmax Decreased potency, increased EC50. Shifts curve to the right. |
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Non-competitive inhibitor
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Changes Vmax, but not Km
Decreased efficacy Agonist Dose vs. Maximum Effect Plot: shifts curve down, no change in EC50. |
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Volume of distribution
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Relates amount of drug in the body to plasma concentration.
Vd = amt of drug in body/plasma drug concentration Vd of plasma protein-bound drugs can be altered by liver and kidney disease. |
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Low Vd
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(4-8L)
Drug distributes in blood. |
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Medium Vd
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Distributes in extracellular space or body water.
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High Vd
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> body weight
Distributes in tissues |
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Clearance
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relates rate of elimination to the plasma concentration
CL = Vd x Ke (elimination constant) CL= rate of elimination of drug/plasma drug concentration |
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Half-life
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Time required to change amount of drug in the body by 1/2 during elimination (or during constant infusion)
A drug infused at a constant rate reaches about 94% of steady state after 4 half-lives (or 6% remains is not continuous infusion) Property of first-order elimination t1/2 = (.7 x Vd)/CL |
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Loading dose
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Loading dose= Cp x Vd/F
Cp = target plasma concentration F = bioavailability (=1 if IV) This is the dose you give to overcome Vd. |
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Maintenance dose
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Cp x CL/F
Dose to overcome excretion and elimination In patients with impaired renal or hepatic function, loading dose remains unchanged, but maintenance is decreased |
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Zero-order elimination
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Rate of elimination is constant regardless of concentration.
Constant amount of drug eliminated per unit time (Cp decreases linearly with time) Ex of drugs: PEA Phenytoin Ethanol Aspirin (high/toxic concentrations) |
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First-order elimination
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Rate of elimination is proportional to the drug concentration
Constant fraction of drug eliminated per unit time Cp decreases EXPONENTIALLY with time. |
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Urine pH and drug elimination--what happens to ionized species?
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They get trapped.
Weak acids: get trapped in basic environments. Tx overdose with bicarbonate. Weak bases: Trapped in acidic environments. Tx overdose with ammonium chloride. |
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Phase I metabolism
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Reduction, oxidation, hydrolysis.
Usually yields slightly polar, water-soluble metabolites (often still active). Geriatric patients lose Phase I first. Ex: cytochrome P450 |
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Phase II metabolism
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Acetylation, glucoronidation, sulfation
Usually yields very polar, inactive metabolites (renally excreted). Ex: Conjugation |
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Efficacy
Definition What type of inhibitor decreases efficacy? |
Maximal effect a drug can produce.
Non-competitive inhibitors decrease efficacy. |
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Potency
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Amount of drug needed for a given effect.
Competitive inhibitors decrease potency. |
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EC50
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Half of the maximally Effective Concentration for producing a given effect.
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Potency and efficacy: relationship
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They are independent of each other.
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Partial agonist
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Same receptor as agonist, but lower maximal efficacy regardless of dose.
May be more, less or equally potent--potency is an independent factor. |
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Therapeutic Index
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Measurement of drug safety.
TI= LD50/ED50 "TILE" LD50 = median lethal/toxic dose ED50 = median effective dose Safer drugs have higher TI values. |
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Parasympathetic Neurotransmitters and Receptors:
Cardiac and smooth muscle Gland cells Nerve terminals |
Pre-ganglionic: ACh (Nicotinic R)
Post-ganglionic: ACh (Muscarinic R) |
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Neurotransmitter and receptors for sweat glands
Parasympathetic or Sympathetic? |
Pre-ganglionic: ACh (Nicotinic R)
Post-ganglionic: ACh (Muscarinic R) Sympathetic |
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Sympathetic Neurotransmitters and Receptors:
Cardiac and smooth muscle Gland cells Nerve terminals |
Pre-ganglionic: ACh (Nicotinic R)
Post-ganglionic: NE, (alpha and beta adrenergic R) |
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Neurotransmitters and receptors for renal vascular smooth muscle:
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Pre-ganglionic: ACh (Nicotinic R)
Post-ganglionic Dopamine (D1) |
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Sympathetic Neurotransmitters and Receptors:
Adrenal medulla |
Pre-ganglionic: ACh (nicotinic R)
Post-ganglionic: Epi, Norepi |
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Somatic Neurotransmitter and receptor
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ACh (Nicotinic R)
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All pre-ganglionic synapses use what neurotransmitters and receptor?
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Ach, nicotinic receptor
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Which system uses Ach and and the muscarinic receptor as the post-ganglionic synapse?
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Parasympathetic (cardiac and smooth muscle, gland cells, nerve terminals)
Sweat glands (sympathetic) |
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Long pre-ganglion, short post-ganglion
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Parasympathetic
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Short pre-ganglion, long post-ganglion
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Sympathetic
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Nicotinic ACh receptors
What type of channel? Where is it found? |
ligand-gated Na/K channels
Autonomic and neuromuscular junction subtypes |
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Muscarinic ACh receptors
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GPCR, 2nd messenger system
5 subtypes: M1 - M5 |
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Sympathetic receptors
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alpha adrenergic 1 and 2
beta adrenergic 1 and 2 |
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Alpha 1 adrenergic receptor
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Sympathetic, Gq
Increases vascular smooth muscle contraction Mydriasis (increases pupillary dilator muscle contraction) Increased intestinal and bladder sphincter muscle contraction |
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Alpha 2 adrenergic receptor
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Sympathetic, Gi
Decreases sympathetic flow Decreases insulin release |
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Beta 1 adrenergic
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Sympathetic, Gs
Increases: HR and contractility Renin release Lipolysis |
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Beta 2 adrenergic receptor
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Sympathetic, Gs
Vasodilation Bronchodilation Increased HR and contractility Increased lipolysis Increased insulin release Decreased uterine tone |
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M1 receptor
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Parasympathetic, Gq
CNS, enteric nervous system |
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Parasympathetic receptors
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M1-M5
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M2 receptor
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Parasympathetic, Gi
Decreases HR and atrial contractility |
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M3 receptor
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Parasympathetic, Gq
Increases: Exocrine gland secretion (sweat, gastric acid) Gut peristalsis Bladder contraction Bronchoconstriction Miosis (pupillary sphincter muscle contraction) Accomodation (ciliary muscle contraction) |
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D1 receptor
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Dopamine, Gs
Relaxes renal vascular smooth muscle |
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D2 receptor
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Dopamine, Gi
Modulates transmitter release, esp. in brain |
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H1 receptor
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Histamine, Gq
Increases nasal and bronchial mucus production Contraction of bronchioles Pruritus Pain |
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H2 receptor
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Histamine, Gs
Increases gastric acid secretion |
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V1 receptor
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Vasopressin, Gq
Increases vascular smooth muscle contraction |
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V2 receptor
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Vasopressin, Gs
Increases H2O permeability and reabsorption in collecting tubules of the kidney "V2 is found in the 2 kidneys" |
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Receptors and GPCRs
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"QISS and QIQ until your SIQ of SQS"
a1 a2 B1 B2 M1 M2 M3 D1 D2 H1 H2 V1 V2 |
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Gq receptors
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"HAVe 1 M&M"
H1 a1 V1 M1 M3 |
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Gs receptors
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B1
B2 D1 H2 V2 |
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Gi receptors
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"MAD 2's"
M2 A2 D2 |
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Gq
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Activates PLC
PIP2 --> IP3 and DAG IP3 increases Ca2+ from ER DAG activates PKC |
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Gs
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Adenylate cyclase
ATP --> cAMP cAMP activates PKA |
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Gi
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inhibits adenylate cyclase
decreases cAMP decreases PKA |
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Cholinergic synaptic terminal: Steps in NT release
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1. Choline (reuptake)
2. Acetyl-CoA + Choline + ChAT 3. Packaging in vesicle 4. Vesicle fusion/exocytosis 5. Broken down in terminal into choline and acetate by AChE |
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Noradrenergic synaptic terminal
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1. Tyrosine --> DOPA --> Dopamine --> NE/Epi
2. Packaging in vesicle 3. Vesicle fusion/exocytosis 4. Reuptake from terminal |
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Hemicholinium
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Blocks choline uptake transporter (rate-limiting in choline synthesis)
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Vesamicol
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Blocks intracellular transport of ACh in vesicles
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Botulinum
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Blocks vesicle fusion at the pre-synaptic terminal, preventing ACh release
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Ca2+ role in pre-synaptic cholinergic and noradrenergic nerve terminal
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Required for vesicle fusion
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Metyrosine
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Blocks conversion of Tyrosine --> DOPA in the pre-synaptic noradrenergic nerve terminal
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Reserpine
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Blocks transport of NE, Epi and Dopamine into vesicle.
Used as a HTNsive |
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Guanethidine
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Blocks vesicle fusion in noradrenergic pre-synaptic terminal.
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Amphetamine
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Causes release of NT (Epi, NE, Dopamine) in pre-synaptic terminal
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Cocaine, TCA, amphetamines
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Block reuptake of NE, Epi, Dopa into pre-synaptic nerve terminals
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Release of NE from sympathetic nerve terminal is modulated by:
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NE itself (negative feedback or re-uptake)
Acting on pre-synaptic alpha 2 receptors ACh, angiotensin II and other substances |
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Cholinomimetic Agents:
Direct Agonists (4) Indirect Agonists (5) - MOA? |
-Direct:
Bethanechol Carbachol Pilocarpine Methacholine -Indirect (AChE) Neostigmine Pyridostigmine Edrophonium Physostigmine Echothiphate |
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Bethanechol
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Direct cholinergic agonist
Activates Bowel and Bladder smooth muscle Use: Post-op and neurogenic ileus and urinary retention |
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Carbachol
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Direct cholinergic agonist
Glaucoma, pupillary contraction, release of intraocular pressure |
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Pilocarpine
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Contracts ciliary muscle of eye and pupillary sphincter
Potent stimulator of sweat tears, saliva |
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Methacholine
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Stimulates muscarinic receptors in airway when inhaled
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Neostigmine
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Post-op and neurogenic ileus
Urinary retention Myesthenia gravis Post-op reversal of neuromuscular junction blockade No CNS penetration "NEO CNS" |
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Pyridostigmine
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Myesthenia gravis (long acting)
Does not penetrate CNS |
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Edrophonium
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Indirect cholinergic agonist (AChE)
Dx of Myesthenia gravis (extremely short-acting) |
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Physostigmine
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Glaucoma (crosses BBB --> CNS)
Atropine overdose "Phys for the Eyes" |
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Echothiophate
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Parasympathomimetic - AChE inhibitor
Glaucoma |
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Cholinesterase inhibitor poisoning
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DUMBBELSS
Diarrhea Urination Miosis Bronchospasm Bradycardia Excitation of skeletal muscle and CNS Lacrimation Sweating Salivation i.e. organophosphates (irreversible inhibitors) Tx: Atropine (muscarinic antagonist) + Pralixodime (chemical antagonist used to regenerate active cholinesterase) |
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Muscarinic antagonists
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Atropine
Benztropine Scopolamine Ipratropium Methscopolamine Homotropine Tropicamide Oxybutynin Glycopyrrolate Pirenzepine Propantheline |
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Atropine:
1. Organ 2. Application 3. Other similar drugs |
1. Muscarinic antagonist --> Eye
2. Mydriasis Cycloplegia (paralysis of ciliary muscle of the eye--loss of accomodation) 3. Homatropine, Tropicamide |
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Benzotropine
1. Organ 2. Application |
1. Muscarinic antagonist --> CNS
2. Parkinson's Disease (PARK my BENZ) |
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Scopolamine
1. Organ 2. Application |
1. Muscarinic Antagonist --> CNS
2. Motion sickness |
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Ipratropium
1. Organ 2. Application |
1. Musc antagonist --> Respiratory
2. Asthma, COPD |
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Oxybutynin, Glycopyrrolate
1. Organ 2. Application |
1. Musc. antagonist --> GU
2. Reduce urgency in mild cystitis and reduce bladder spasms |
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Methscopolamine
1. Organ 2. Application 3. Other similar drugs |
1. Musc. antagonist --> GI
2. Peptic ulcer tx 3. pirenzepine, propantheline |
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Atropine
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Muscarinic antagonist
Blocks DUMBBELSS Eye: Increased pupil dilation, cycloplegia Airway: Increased secretions Stomach: Decreased acid secretion Gut: Decreased motility Bladder: Decreased urgency in cystitis Toxicity: Hot as a hare (incr temp) Dry as a bone (dry mouth) Red as a beet (flushed skin) Blind as a bat (cycloplegia) Mad as a hatter (disorientation) constipation, rapid pulse |
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Other side effects of atropine
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Elderly: acute angle-closure glaucoma
Men with BPH: Urinary retention Infants: Hyperthermia |
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Hexamethonium
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Nicotonic antagonist
Use: ganglionic blocker. Exp'l, prevent vagal reflex responses to changes in BP (i.e. reflex bradycardia caused by NE) Toxicity: Orthostatic hypotension Blurred vision Constipation Sexual Dysfunction |
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Epinephrine
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a1, a2, B1, B2
Low dose - B1 specific (Blow) Anaphylaxis Open angle glaucoma Asthma Hypotension |
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Norepinephrine
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a1, a2 > B1
Hypotension BUT, decreases renal perfusion!! |
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Isoproterenol
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B1 = B2
AV block (rare) |
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Dopamine
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D1 = D2 > B > a
ionotropic and chronotropic shock (increases renal perfusion through D1) HF |
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Dobutamine
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B1 > B2
Ionotropic but not chronotropic Shock HF Cardiac stress testing |
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Phenylephrine
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a1 > a2
Vasoconstriction Pupillary dilation Nasal decongestion might see reflex bradycardia due to increases systemic BP |
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Metaproterenol
Albuterol Salmeterol Terbutaline |
Selective B2 agonist
MAST MA: acute asthma S: long term asthma T: reduce premature uterine contractions |
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Ritodrine
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B2
Reduces premature contractions |
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Amphetamine
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Indirect sympathomimetic
Indirect general agonist, releases stored catecholamines Narcolepsy, obesity, ADD |
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Ephedrine
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Indirect general sympathetic agonist, releases stored catecholamines
Nasal decongestion, urinary incontinence, hypotension |
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Cocaine
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Indirect sympathomimetic, uptake inhibitor
Vasoconstriction Local anesthesia |
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HR after taking Norepi
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Reflex bradycardia
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HR after taking Epi
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Increased HR
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HR after taking Isoproterenol
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Increased HR
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Clonidine, alpha-methyl dopa
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Centrally acting a2 agonists
Decrease central adrenergic outlfow Tx HTN, esp with renal disease (no decrease in renal perfusion) |
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Phenoxybenzamine
Phentolamine |
Phenoxybenzamine: irreversible a1, a2 blocker
Phentolamine: reversible a1, a2 blocker Use: Pheochromocytoma Use phenoxybenzamine before surgery --> high levels of released catecholamines will not be able to overcome blockage Toxicity: Orthostatic hypotension, Reflex tachycardia |
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Prazosin (-zosin ending)
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a1 selective blocker
Use: HTN, urinary retention in BPH Toxicity: 1st dose orthostatic hypotension, dizziness, HA |
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Mirtazapine
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a2 selective blocker, 5-HT blocker
Use: Depression Toxicity: Sedation, increased serum cholesterol, increased appetite |
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Net depressor effect
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Alpha blockade after large dose of epinephrine -->
Net depressor effect (depresses mean BP due to B2 response) |
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Suppression of pressor effect
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Alpha blockade after alpha antagonist -->
BP goes back to normal --> no Beta action |
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B-blockers: Application and effects
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HTN: decrease CO and renin secretion
Angina: decrease HR, contractility --> decreased MvO2 MI: decrease mortality SVT: decrease AV conduction velocity (class II antiarrythmic) CHF: slows progression of HF Glaucoma: decrease secretion of aqueous humor |
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B-blockers: toxicity
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Impotence
Exacerbate asthma CV adverse effects (bradycardia, AV block, CHF) CNS adverse effects (sedation, sleep alteration) Use with caution in diabetics |
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Non-selective B-blockers
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Propanalol
Timolol Nadolol Pindolol Labetalol |
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B1 selective blockers
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Acebutolol
Betaxolol Esmolol (short actin) ATENOLOL METOPROLOL "A BEAM of b1 blockers" |
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Non-selective a and B antagonists
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Carvedilol
Labetalol |
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Partial B-Agonists
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Pindolol
Acebutolol |
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Acetaminophen antidote
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Mucomyst/N-acetylcysteine
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Salicylates antidote
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Sodium Bicarbonate (alkalinize urine)
Dialysis |
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Amphetamines antidote
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NH4Cl (acidify urine)
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Anti-AChE, organophosphates antidote
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Atropine, Pralidoxime
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Anti-muscarinic/Anti-cholinergic antidote
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Physostigmine salicylate
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B-blockers antidote
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Glucagon
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Digitalis antidote
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Stop dig
Normalize K+ Lidocaine Anti-dig Fab fragments Mg2+ |
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Fe antidote
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Deferoxamine
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Lead antidote
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CaEDTA
Dimercaprol succimer penicillamine |
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Mercury, Arsenic, Gold antidote
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Dimercaprol
Succimer |
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Cu, Arsenic, Gold antidote
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Penicillamine
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Cyanide antidote
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Nitrite
Hydroxycobalamin Thiosulfate |
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Methemoglobin antidote
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Methylene blue
Vitamin C |
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CO antidote
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100% O2
Hyperbaric O2 |
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Methanol, Ethylene glycol (antifreeze) antidote
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Ethanol
Dialysis Fomepizole |
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Opioid antidote
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Naloxone
Naltrexone |
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Benzodiazepine antidote
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Flumazenil
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TCA antidote
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NaBicarbonate (serum alkalinization)
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Heparin antidote
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Protamine
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Warfarin antidote
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Vitamin K
Fresh frozen plasma |
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tPA, streptokinase antidote
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aminocaproic acid
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theophylline antidote
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B-blocker
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Iron poisoning
Mechanism and Sx's |
One of the leading causes of fatality from toxicologic agents in kids
Mechanism: cell death due to peroxidation of membrane lipids Sx's: Acute: gastric bleeding Chronic: metabolic acidosis, scarring leading to GI obstruction |
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Drug rxn:
Atropine-like side effects |
TCA
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Drug rxn:
Coronary vasospasm |
Cocaine, sumatriptan
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Drug rxn:
Cutaneous flushing |
VANC
Vancomycin Adenosine Niacin Ca channel blockers |
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Drug rxn:
Dilated cardiomyopathy |
Doxorubicin (Adriamycin)
Daunorubicin |
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Drug rxn:
Torsades de Pointes |
Class III (Sotalol)
Class IVA (quinidine) antiarrhythmics Cisapride |
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Drug rxn:
Agranulocytosis |
Clozapine
Carbamezapine Colchicine Propylthiouracil Methimazole Dapsone |
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Drug rxn:
Aplastic anemia |
Chloramphenicol
Benzene NSAIDs Propothiouracil Methimazole |
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Drug rxn:
Direct Coombs + hemolytic anemia |
Methyldopa
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Drug rxn:
Grey baby syndrome |
Chloramphenicol
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Drug rxn:
Hemolysis in G6PD deficient patients |
hemolysis IS PAIN
Isoniazid Sulfonamides Primaquine Aspirin Ibuprofen Nitrofurantoin |
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Drug rxn:
Megaloblastic anemia |
having a BLAST with PMS
Phenytoin Methotrexate Sulfa drugs |
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Drug rxn:
Thrombotic complications |
OCPs (estrogens and progestins)
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Drug rxn:
Cough |
ACE-inhibitors
(ARBs like losartan do not have this) |
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Drug rxn:
Pulmonary fibrosis |
"BLAB"
BLeomycin Amiodorone Busulfan |
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Drug rxn:
acute cholestatic hepatitis |
Macrolides
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Drug rxn:
focal to massive hepatic necrosis |
Halothane
Valproic acid Acetaminophen Amanita phalloides (poisonous fungus) |
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Drug rxn:
Hepatitis |
INH
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Drug rxn:
Pseudomembranous colitis |
Clindamycin
Ampicillin |
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Drug rxn:
Adrenocortical insufficiency |
Glucocorticoid withdrawal (Hypothalamic-Pituitary Axis suppression)
Adrenal gland atrophies due to lack of tropic effect from ACTH |
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Drug rxn:
Gynecomastia |
Some Drugs Create Awesome Knockers
Spironolactone Digitalis Cimetidine Alcohol use (chronic) estrogens Ketoconazole |
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Drug rxn:
Hot flashes |
Tamoxifen
Clomiphene |
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Drug rxn:
Hypothyroidism |
Lithium
Amiodorone |
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Drug rxn:
Gingival hyperplasia |
Phenytoin
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Drug rxn:
Gout |
Furosemide
Thiazides |
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Drug rxn:
Osteoporosis |
Corticosteroids
Heparin |
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Drug rxn:
Photosensitivity |
SAT for a PHOTO
Sulfonamides Amiodorone Tetracycline |
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Drug rxn:
Rash (Steven-Johnson's syndrome) |
Ethosuxomide
Lamotrigine Carbamezapine Phenobarbital Phenytoin Sulfa Drugs Penicillin Allopurinol |
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Drug rxn:
SLE like syndrome |
HIPP
Hydralazine INH Procainamide Phenytoin |
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Drug rxn:
Tendonitis, tendon rupture, cartilage damage (kids) |
Fluoroquinolones
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Drug rxn:
Fanconi's syndrome |
Expired tetracycline
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Drug rxn:
Interstitial nephritis |
Methicillin
NSAIDs Furosemide |
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Drug rxn:
Hemorrhagic cystitis |
Cyclophosphamide
Ifosfamide |
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Drug rxn:
Cinchonism |
Quinidine, Quinine overdose
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Drug rxn:
Diabetes insipidus |
Lithium
Demeclocycline |
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Drug rxn:
Parkinson-like syndrome |
Haloperidol
Chlorpromazine Reserpine Metoclopramide |
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Drug rxn:
Seizures |
Bupropion
Imipenem/cilastatin Isoniazid |
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Drug rxn:
Tardive dyskinesia |
antipsychotics
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Drug rxn:
Disulfiram-like reaction |
Metronidazole
Certain cephalosporins Procarbazine 1st generation sulfonylureas |
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Drug rxn:
Nephrotoxicity/neurotoxicity |
Polymyxins
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Drug rxn:
Nephrotoxicity/ototoxicity |
Aminoglycosides
Vancomycin Loop diuretic Cisplatin |
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Cytochrome P-450 inducers
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Queen Barb Steal Phen-Phen and Refuses Greasy Carb Chronically
Quinidine Barbiturates St. John's Wort Phenytoin Rifampin Griseofulvin Carbamezapine Chronic EtOH use |
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Cytochrome P-450 Inhibitors
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Sulfonamides
Isoniazid Cimetidine Ketoconazole Erythromycin Grapefruit Juice Acute alcohol use |
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Competitive substrates for Alcohol dehydrogenase and their toxicities
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Ethylene glycol --> acidosis, nephrotoxicity
Methanol --> severe acidosis, retinal damage Ethanol --> Nausea, vomitting, HA, hypotension |
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Antidote for Methanol or Ethylene glycol toxicity
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Fomepizole
Alcohol dehydrogenase inhibitor |
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Sulfa drugs (8)
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Celecoxib
Furosemide Probenecid Thiazides TMP-SMX Sulfasalazine Sulfonylureas Sumatriptan |
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Sulfa drug allergy
|
Fever
Pruritic rash Steven's Johnson syndrome Hemolytic anemia Thrombocytopenia Agranulocytosis Urticaria (hives) Mild to life-threatening |
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-afil
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Erectile dysfunction
sildenafil |
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-ane
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inhalational general anesthetic
Halothane |
|
|
-ezepam
|
Benzodiazapine
Diazepam |
|
|
-azine
|
Phenothiazine (neuroleptic, antiemetic)
Chlorpromazine |
|
|
-barbital
|
Barbiturate
Phenobarbital |
|
|
-azole
|
Antifungal
Ketoconazole |
|
|
-caine
|
Local anesthetic
Lidocaine |
|
|
-cycline
|
Abx, Protein synthesis inhibitor
Tetracycline |
|
|
-etine
|
SSRI
Fluoxetine |
|
|
-ipramine
|
TCA
Imipramine |
|
|
-navir
|
Protease inhibitor
Saquinavir |
|
|
-operidol
|
Butyrophenone (neuroleptic)
Haloperidol |
|
|
-oxin
|
Cardiac glycoside
Digoxin |
|
|
-phylline
|
Methylxanthine
Theophylline |
|
|
-terol
|
B2 agonist
Albuterol |
|
|
-tidine
|
H2 antagonist (decreases gastric secretion)
Cimetidine |
|
|
-triptan
|
5-HT agonists (migraine)
Sumatriptan |
|
|
-triptyline
|
TCA
Amytriptyline |
|
|
-tropin
|
Pituitary hormone
Somatotropin |
|
|
-zolam
|
Benzodiazepine
Midazolam |
|
|
-zosin
|
a1 antagonist
Prazosin |
