Notes from the first 3 practical powerpoints Flashcards
Usual size of drugs, molecular weight
most are 100-1000 g/mol
drugs with MW more than 1000 are limited by diffusion
CYP450 inhibitors
SICKFACES.COM, G
Sodium Valproate Isoniazid Cimetidine Ketoconazole Fluconazole Acute Alcohol Chloramphenicol Erythromycin - Macrolides Sulfonamides Ciprofloxacin Omeprazole Metroniddazole Grapefruit Juice.
CYP450 Inducers
CRAP GPS
Carbamazepines (phenytoin) Rifampicin Alcoholism Phenytoin Griseofulvin Phenobarbitone Sulphonylureas
Chronic alcohol St John's wort Phenytoin Phenobarbital Nevirapine Rifampin Griseofulvin Carbamazepine.
Chronic alcoholics Steal Phen-Phen and Never Revamp Grandpas Carbarator.
What is the NOAEL
No observed adverse event level.
What is the modified therapeutic index?
TD10/ED90
Toxic dose 10% / Effective dose 90%
What is the safety index?
TD1/ED99
Therapeutic index?
humans TD50/ED50
animals LD50/ED50
What are the drugs with a narrow therapeutic index?
Warning My Phriend, These Drugs are Lethal Digoxin Lithium Theophylin Warfarin Phenytoin Methotrexate
Warning, These Drugs are Lethal
Warfarin, Theophylin, Digoxin, Lithium
Nicotinic receptor structure and subtypes
Nm - muscle NMJ receptors, can be embryonic, alpha1, beta1, gamma, and delta subunits. 2:1:1:1, or adult: alpha1, beta1, delta, and epsilon. 2:1:1:1
Nn - neuronal receptors. Many kinds, can be homomeric or heteromeric. 10 different alpha subunits, 4 different beta subunits and many others.
Minimum of 2 ACh ligands are required for opening. 2-5 depending on type.
ACh binds receptors at junctions between alpha-alpha junctions or alpha-beta, alpha-epsilon/delta junctions
Where do spasmolytics act?
In the CNS, decrease muscle tone
Where do muscle relaxants act?
Pre or post synaptically at the peripheral NMJ.
Presynaptic muscle relaxants (list)
Botulinum toxin
Omega-conotoxin
Aminoglycoside and tetracycline side effect
Post synaptic muscle relaxants (list)
Curare derivatives - Isoquinolines and Steroids
Depolarizing agents - Succinylcholine
Ryanodine antagonists
Isoquinoline muscle relaxants
Tubocurarine
Mivacurium
Atracurium
Cisastracurium
Doxacurium
Steroid muscle relaxants
Pancuronium
Pipecuronium
Vecuronium
Rocuronium
Pan Pipe Vec Roc
Which muscle relaxants are metabolized by the liver, and need to have dose reduced in liver disease?
Vec Roc
Vecuronium
Rocuronium
Which muscle relaxants are excreted unchanged in the urine?
Pancuronium and Pipecuronium
Which muscle relaxant can release histamine?
What is its other dangerous side effect?
Atracurium releases histamine
Laudanosine, the atracurium metabolite, can provoke seizures.
What is the short acting muscle relaxant?
How is it metabolized?
10-15 minutes
Mivacurium
By pseudocholinesterase/Butrylcholinesterase.
What are the long acting muscle relaxants?
1-3 hours
DPP
Doxacurium
Pancuronium
Pipecuronium
Which relaxants are hydrolyzed spontaneously in the plasma?
Atracurium and Cisatracurium
What types of drugs target voltage gated Na channels?
Local anesthetics
Antiarrhythmics
Antiepileptics
Order of sensation loss from local anesthetics
In reverse order of the level of fiber myelination
Pain Temp Touch Deep pressure Motor function
What is the mechanism that local anesthetics use to inhibit action potentials?
They must enter the nerve cells in the uncharged form, and the bind to Na+ channels from the intracellular side, in their ionized form.
List the Ester linked anesthetics
How are these metabolized?
Long or short T1/2?
Cocaine Procaine Benzocaine Tetracaine Cinchocaine
Esterases in plasma and tissue degrade them
Short half life
List the Amide linked anesthetics
How are these metabolized?
Long or short T1/2?
Lidocaine Prilocaine Bupivicaine Articaine QX-314
Metabolized by the liver
Long half life
What drugs are used topically for surface anesthesia?
Where are these used?
Lidocaine
Tetracaine
Benzocaine
Dibucaine
Used in the nose, mouth, pharynx, bronchial tree, as a spray.
Urinary tract and uterus, for scopy procedures
Cornea
What is infiltration anesthesia? What is it used for?
Local injection into tissue to anesthetize nerve branches locally. Most/any of the local anesthetics are used.
Only used for small areas and definitely not used for fingers or toes, may cause ischemic necrosis. Excessive use for large areas can cause serious systemic toxicity.
Used for minor surgery, in conjunction with a vasopressor like epinephrine.
What drugs are used for IV regional anesthesia?
When is this technique used?
Lidocaine and Prilocaine
They are injected distally to a pressure cuff, remaining effective until the cuff is lifted.
Cuff must remain in place for at least 20 minutes while they are metabolized to a degree or there is risk for major toxicity.
Used for limb surgery.
What drugs are used for Nerve Block anesthesia?
When is this technique used?
Most/any of the local anesthetics can be used.
the LA is injected to a nerve trunk, ie, brachial plexus, intercostal nerve, dental nerve.
Used in many surgeries,
Dental surgeries.
Pain relief.
Has a slower onset
What anesthetics are used for spinal anesthesia?
When is the technique used?
Lidocaine
It is injected into the CNS of the Subarachnoid Space. Acts directly on the spinal cord as well as on the nerve roots.
May be formulated with glucose and kept cold in order to cause ‘hyperbaricity’ so that the LA sinks and does not rise higher to affect the brainstem.
Used for abdominal, pelvic, or leg surgeries.
Can be used in conjunction with general anesthesia to reduce stress, and to reduce post-op pain.
What drugs are used for Epidural anesthesia?
When is the technique used?
Lidocaine or Bupivacaine
Drug is injected into the Epidural space, affecting only the spinal nerver roots.
Used abdominal, pelvic, leg surgeries,
Also administered to relieve childbirth pain.
What are the important side effects and toxicities of Local Anesthetics?
Side effects occur if the drug reaches systemic circulation in too high concentrations.
Early symptoms: Tongue/Mouth numbness Tinnitus Vertigo Tremor Confusion
CNS depression, at lower plasma LA concentrations Confusion LOC, coma Resp. Depression Cardiovascular collapse
CNS excitation, at higher conc.
Anxiety, Agitation
Vomiting
Tonic-Clonic seizures
Cardiovascular suppression,
negative: chrono, ino, dromo
peripheral vasodiulation
cardiovascular collapse
Cocaine is the exception to all of this, its overdose effects are of NE excess, and are excitatory. tachy, vasoconst. arrythmias, HTX, tremor, etc.
What are the major components of the local anesthetics chemical structure?
Aromatic region
an Ester or Amide bond linking region
Ionizable Basic Amine side chain
Interactions of local anesthetics with NMJ blockers?
small doses of LAs facilitate both depolarizing or non-depolarizing blockers
Large doses, cause non-specific nAChR block
What are the MAO inhibitors
Tranylcypromine, Pargyline - irreversible, nonselective, cheese effect, lots of side effects. Not used.
Moclobemid: Reversible, MAO-A inhibitor, for mental depression. causes cheese effect.
Selegiline - Irreversible, MAO-B inhibitor for parkinson’s, no cheese effect, somehow discovered by people at semmelweis.
Which local anesthetic has cardiac toxic effects if accidentally given IV?
What should be done to prevent this?
Bupivicaine.
Always aspirate when injecting sub-cutaneous to insure you are not in a vessel.
