Notes from the first 3 practical powerpoints

Question 1

Usual size of drugs, molecular weight

Answer 1

most are 100-1000 g/mol

drugs with MW more than 1000 are limited by diffusion

Question 2

CYP450 inhibitors

Answer 2

SICKFACES.COM, G

Sodium Valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Acute Alcohol
Chloramphenicol
Erythromycin - Macrolides
Sulfonamides
Ciprofloxacin
Omeprazole
Metroniddazole
Grapefruit Juice.

Question 3

CYP450 Inducers

Answer 3

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.

Question 4

What is the NOAEL

Answer 4

No observed adverse event level.

Question 5

What is the modified therapeutic index?

Answer 5

TD10/ED90

Toxic dose 10% / Effective dose 90%

Question 6

What is the safety index?

Answer 6

TD1/ED99

Question 7

Therapeutic index?

Answer 7

humans TD50/ED50

animals LD50/ED50

Question 8

What are the drugs with a narrow therapeutic index?

Answer 8

Warning My Phriend, These Drugs are Lethal
Digoxin
Lithium
Theophylin
Warfarin
Phenytoin
Methotrexate

Warning, These Drugs are Lethal

Warfarin, Theophylin, Digoxin, Lithium

Question 9

Nicotinic receptor structure and subtypes

Answer 9

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

Question 10

Where do spasmolytics act?

Answer 10

In the CNS, decrease muscle tone

Question 11

Where do muscle relaxants act?

Answer 11

Pre or post synaptically at the peripheral NMJ.

Question 12

Presynaptic muscle relaxants (list)

Answer 12

Botulinum toxin
Omega-conotoxin

Aminoglycoside and tetracycline side effect

Question 13

Post synaptic muscle relaxants (list)

Answer 13

Curare derivatives - Isoquinolines and Steroids

Depolarizing agents - Succinylcholine

Ryanodine antagonists

Question 14

Isoquinoline muscle relaxants

Answer 14

Tubocurarine

Mivacurium
Atracurium
Cisastracurium

Doxacurium

Question 15

Steroid muscle relaxants

Answer 15

Pancuronium
Pipecuronium
Vecuronium
Rocuronium

Pan Pipe Vec Roc

Question 16

Which muscle relaxants are metabolized by the liver, and need to have dose reduced in liver disease?

Answer 16

Vec Roc
Vecuronium
Rocuronium

Question 17

Which muscle relaxants are excreted unchanged in the urine?

Answer 17

Pancuronium and Pipecuronium

Question 18

Which muscle relaxant can release histamine?

What is its other dangerous side effect?

Answer 18

Atracurium releases histamine

Laudanosine, the atracurium metabolite, can provoke seizures.

Question 19

What is the short acting muscle relaxant?

How is it metabolized?

Answer 19

10-15 minutes
Mivacurium

By pseudocholinesterase/Butrylcholinesterase.

Question 20

What are the long acting muscle relaxants?

Answer 20

1-3 hours

DPP
Doxacurium
Pancuronium
Pipecuronium

Question 21

Which relaxants are hydrolyzed spontaneously in the plasma?

Answer 21

Atracurium and Cisatracurium

Question 22

What types of drugs target voltage gated Na channels?

Answer 22

Local anesthetics
Antiarrhythmics
Antiepileptics

Question 23

Order of sensation loss from local anesthetics

Answer 23

In reverse order of the level of fiber myelination

Pain
Temp
Touch
Deep pressure
Motor function

Question 24

What is the mechanism that local anesthetics use to inhibit action potentials?

Answer 24

They must enter the nerve cells in the uncharged form, and the bind to Na+ channels from the intracellular side, in their ionized form.

Question 25

List the Ester linked anesthetics How are these metabolized? Long or short T1/2?

Answer 25

``` Cocaine Procaine Benzocaine Tetracaine Cinchocaine ``` Esterases in plasma and tissue degrade them Short half life

Question 26

List the Amide linked anesthetics How are these metabolized? Long or short T1/2?

Answer 26

``` Lidocaine Prilocaine Bupivicaine Articaine QX-314 ``` Metabolized by the liver Long half life

Question 27

What drugs are used topically for surface anesthesia? | Where are these used?

Answer 27

Lidocaine Tetracaine Benzocaine Dibucaine Used in the nose, mouth, pharynx, bronchial tree, as a spray. Urinary tract and uterus, for scopy procedures Cornea

Question 28

What is infiltration anesthesia? What is it used for?

Answer 28

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.

Question 29

What drugs are used for IV regional anesthesia? When is this technique used?

Answer 29

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.

Question 30

What drugs are used for Nerve Block anesthesia? When is this technique used?

Answer 30

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

Question 31

What anesthetics are used for spinal anesthesia? When is the technique used?

Answer 31

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.

Question 32

What drugs are used for Epidural anesthesia? When is the technique used?

Answer 32

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.

Question 33

What are the important side effects and toxicities of Local Anesthetics?

Answer 33

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.

Question 34

What are the major components of the local anesthetics chemical structure?

Answer 34

Aromatic region an Ester or Amide bond linking region Ionizable Basic Amine side chain

Question 35

Interactions of local anesthetics with NMJ blockers?

Answer 35

small doses of LAs facilitate both depolarizing or non-depolarizing blockers Large doses, cause non-specific nAChR block

Question 36

What are the MAO inhibitors

Answer 36

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.

Question 37

Which local anesthetic has cardiac toxic effects if accidentally given IV? What should be done to prevent this?

Answer 37

Bupivicaine. Always aspirate when injecting sub-cutaneous to insure you are not in a vessel.