Pharm Block 2

Alzheimers
o Beta amyloid plaque
o Neurofibrillary tangles hyperphosphorylated tau
o APP on chromosome 21 increases chance of getting Alzheimers
o ApoE4 increases risk
o Drugs
4 drugs -
Mech: reduced Ach you want to increase it within the brain
o stigmines (must be lipophilic to enter the CNS)
Acetycholinesterase inhibitor
Phizostigmine Rx for atropine poisoning (boards)
Donepezil very common; most people with Alzheimers are on this
drug
o Memantine
NMDA receptor antagonist
Blocks Glu (blocks excitation/works like PCP)
Parkinsons Disease
o Epidemiology
Older age increases risk
AA and Asians are less likely to develop it compared to Caucasians
o MPTP
Not active form needs to be activated by monoamine oxidase B (MAO-B)
Can stop this poisoning by giving Selegiline (MAO-B inhibitor)
Side note:
MPTP is a byproduct of Meperidine production (opioid analgesic)
Michael J. Fox has Parkinsons and supposedly he had PD because he was taking
Meperidine to get high and it was contaminated with its byproduct MPTP
o Path
Low dopamine and High ACh
TRAP
T tremor pill rolling and resting
R rigidity cogwheel
A akinesia/bradykinesia masked faces
P postural instability and shuffling gait
Small hand writing micrographia
o Substantia nigra has a little dopamine, because the neurons are dying
Alpha-synuclein (Lewy bodies)
o Drugs
Must give L-dopa and carbidopa together
Carbidopa will stop L-dopa from being used in the periphery
o Blocks peripheral dopa decarboxylase enzyme
Ergot agonists
Not really used in PD, more endocrine function
Used in prolactinoma
 o Bromocriptine dopamine agonist which blocks release of prolactin
Restless leg syndrome
Give DA agonist ropinerole/pramipexole
-capones
COMT inhibitors
o Blocksdegradation of DA
Amantadine
Levido reticularis
o Cholesterol emboli (boards)
o Mottle reticulated vascular pattern appearing as purplish discoloration of skin
Anticholinergics
Benzotropine park your benz
o Parkinsenz and benz
Selegeline
MAO B inhibitor
o MAO B: only works on DA
o MAO A: works on DA, NE and 5-HT
Phenelzine: non-selective irreversible MAO inhibitors
Used as an antidepressant and anxiolytic
Seizures
o Definition of seizure (rapid excitation of cortical neurons in the brain) and epilepsy (unprovoked
seizures)
o Types
Generalized incorporates most of the neurons in the brain
Partial involves part of brain
Absence ethosuximide some kid is staring out into space
Simple did not lose consciousness
Complex lost consciousness
o Drugs
5 mechanisms
Increase GABA
Decrease Glu
Block Na and Ca entry
Increase Cl- entry
Increase K+ exit
GABA a postsynaptic
Linked to Cl- channel
Benzo increase freq of Cl- channel opening
o Ben is a guy wants sex more freq
Barbs increase duration of Cl- channel opening
o Barb is a girl she wants sex to last longer
GABAb presynaptic
Baclofen
Phenytoin
Blocks Na+ channels
DOC: partial seizures and generalized seizures
 Dont give to preggos
Carbamazepine
Blocks Na+ channels
Ethosuximide
Works on Ca2+ channels
DOC: absence seizures
Valproate
Increases GABA
Increases K+ efflux
Blocks Ca2+ channel
Know the benzos
End in pam
Lorazepam
o Fastest acting benzo
o DOC: status epilepticus
Phenobarbital only ever used in neonates for something other than seizures
Will learn later
Dont need to know newer drugs
Migraines
o Epidemiology
Usually female of birthing age
o Cluster HA
DOC: oxygen
Case: male wakes up every night with pain behind his eye (boards)
o Know definition
o Dating and married females have migraines
After the death of their husbands migraines go away
o Path
5-HT 1D and 5-HT 1B
Release neuropeptides
Brain doesnt feel pain (no receptors)
Inflammation of meninges is painful
o Drugs
Valproate prevent migraine
Stimulates the formation of GABA
o Glutamic acid decarboxylase makes GABA
Stops the breakdown of GABA
Not good for babies
Triptans abort migraine
51HT 1A and 51HT 1B agonists
Notice the aura take a triptan and it will abort the HA
o Epidemiology
Migraines increase the risk of having
Depression
Stroke
 Diabetes
Anti-Parasitic
o Metronidazole
Side note (boards): if you consume alcohol with this drug disulfiram (antabuse) reaction
Disulfiram reaction: causes acetylaldehyde to remain in your system
o Acetylaldehyde: makes you feel crappy and vomit
Alcoholics that want to quit will take antabuse to induce this reaction
o Filariasis
DOC: Diethylcarbamazapine

NSAIDs
o Acetominophen not an anti-inflammatory
Not a true NSAID b/c of this property
o MOA: Block cyclooxygenase (COX )
Stops formation of prostaglandins (PGE2 pain)
Primarily block COX -1
This enzyme is protective when working in gastric mucosa (secretes mucus and reduces
gastric secretion)
o If blocked eventually get gastric ulcer
o Aspirin
Low dose blocks ThxA2 (platelet aggregator)
History of Heart attack or at risk of CVA will be put on baby aspirin 81 mg/day
o Celecoxib
COX-2 specific
Less side effects (does not lead to gastric ulcer)
o Disease modifying anti-rheumitic (DMARDs) drugs
Methotrexate blocks dihydrofolate
Anti-TNF alpha
Drug names end in mab
MOA: monoclonal AB blocker
o Gout
Colchicine
MOA:
o Reduction of lactic acid by leukocytes, resulting in a decrease in uric acid
deposition
o Reduction in phagocytosis, with abatement of the inflammatory response
Do not use aspirin in acute gout attack (when theyre in pain)
Competes with uric acid in the kidneys more uric acid reabsorption
Always give indomethacin (ibuprofen)
Chronic gout
Allopurinol give once the attack has cleared
o MOA: blocks xanthine oxidase
Opioids
o Important!!!!
o Opioid agents
Morphine
Strong
Hydromorphone
Stronger than morphine (dilaudid)
Methadone
Use: to Rx heroin addicts that want to quit
Meperidine
Doesnt behave like other opioids
o MOA: anti-cholinergic (specifically anti-muscarinic)
o Dilates pupils and doesnt constipate you
Fentanyl
Lollipop and patch given in micrograms ONLY
o Really strong easy to OD
Codeine
Codeine w/acetaminophen (APAP) = Tylenol number 3
Hydrocodeine w/APAP = Vicodin (guy on House is addicted to this)
Oxycodone w/APAP = Percocet
All opioids work on mu receptor
Analgesia
Euphoria
Respiratory depression
Cough suppression
Sedation
Miosis pinpoint pupils
o Exception: Meperidine
Constipation and cramps
o Exception: Meperidine
Diphenylhydramine Benadryl (antihistamine)
Take opioids sometimes you get a rash and are itchy
Massive histamine release
This is normal
Roxicodone for hospice patients (not considered physician assisted suicide)
Benefits
o Respiratory depression makes them work less
o Get rid of pain
Cough suppression
Dextromethorphan over the counter opioid
Diarrhea
Loporamide
Build a tolerance to everything except
Miosis and constipation
Young man taken to EM because of OD on opioid
Must give naloxone (narcan)
o Blocks the mu receptor (antagonist)
 o Always given to people that have collapsed in case they OD on opioid (no bad
SE)
Wont hurt you but it also might not work if the drug isnt an opioid
Opioids are the number one drug that causes OD in the US (boards)
Managing opioid addiction
Give methadone
o Issue: harder to get off of methadone than it is to get off of heroin
o Why is it used:
o Methadone is longer lasting so you dont have to shoot up as much
o Also its much cheaper than Suboxone
Suboxone new drug
o Composition: Buprenorphine (partial agonist/partial antagonist) w/naloxone
(not active orally, only given IM, IV or nasally)
o Brilliant comes orally
IV drug users crush it and melt it to take it IV to avoid FIRST PASS EFFECT
Naloxone becomes active when injected into blood and the
patient doesnt get high
Immunopharmacology
o Tacrolitmus
MOA: know detailed biochem
o Cyclosporine
MOA: blocks Ca2+ and IL-2 (second signal)
Know the detailed biochem
o Hypersensitivity
Identify the types
Spur
o Drug classes
o Spectrums
Narrow, broad
Bactericidal/bacteriostatic
o Bacteriostatic w/bacteriostatic synergistic
o Bacteriostatic w/bactericidal antagonistic effect
o Drugs
Penicillin
MOA: block transpeptidase
Very narrow spectrum : gram positives
Amoxicillin (amino penicillin)
Broader spectrum
Cephalosporin
MOA: work on transpeptidase
o Cell wall inhibitors
Generations:
o 1st gen and 2nd: narrow
o 3rd: very broad
o 4th: gram neg
o 5th: very good works on MRSA
 Carbapenem and monobactam
Calvulanic acid /tezobactam
MOA: beta lactamase inhibitor
Augmentin amox and clevulonic acid
Vancomycin
MOA: very strong bactericidal cell wall inhib
o Can identify: D-alanine, D-alanine
If staph/enterococcus is resistant it makes this D-ala, D-lac
VRS/VRE Rx with linezolid
Sulfonamides - bacteriostatic
MOA: block dihydrofolate synthase
Trimethoprim bacteriostatic
MOA: blocks dihydropyridine reductase
Specific for bacteria
Sulfonamides bacteriostatic
o Synergistic effect of Sulfonamide and Trimethoprim Bactrim (bactericidal)
Methotrexate
Blocks dihydrofolate reductase in eukaryotic cells
DMARs
Need to know which ones they are
Quinolones
MOA: block topoisomerase (DNA gyrase)
Bactericidal
Names end in floxacin
Very broad spectrum
Cannot give to preggos and children under the age of 18
o Inhibit cartilage, bone and tendon growth
Side note (boards): quinolones popular for Rx UTI
o Ex 1. 16 yr old boy has a UTI and hes allergic to penicillin and sulfur drugs
o Ex 2. preggo patient allergic to penicillin and sulfa drugs what do you want to Rx
them
Cannot give quinolones
Cannot give Bactrim (sulfamethoxazole and trimethroprim)
Cannot give Amoxicillin
Preggos give nitrofurantoin
Antibiotics
o Buy at 30 ccell at 50
A Aminoglycosides (30s)
Narrow spectrum: gram negatives
Names end in mycin
Boards: patient dealing with rabbits tularemia
o Rx with streptomycin
Cant give to preggos
Side effects:
o Ototoxicity (irreversible)
 o Nephrotoxicity (reversible)
Tetracyclines (30s)
Bacteriostatic
Cannot give to preggos/young kids (stains teeth and bones)
Case (boards): kids teeth are stained yellow brown
Cannot take these drugs with milk/any foods with metals wont work
o Chelating
Side note (boards): tetracycline is a component in acne medications
o Cream would come in purple/brown bottle because the drug is sensitive to light
o Phototoxic avoid excess sun exposure
o SAT FOR PHOTO 3 drugs that are phototoxic
S- Sulfonamides
A- Amiodarone
T- Tetracycline
C Chloramphenicol (50s)
Not used in US
Gray baby syndrome
o Glucourinyl transferase doesnt work as well in babies
Get jaundice
Put them in the box and shines light on them which breaks down
the bilirubin for them
C Clindamycin (50s)
Above the waist Rx of anaerobic bacteria
E - Erythromycin (50s)
Inhibits cytochrome P450
o Only macrolide that does this (macrolides end in thromycin)
L Lincomycin (50s)
L Linezolid (50s)
Rx for VRE/VRS
Drugs ending in -pristin
Extremely toxic not used