Pharmacology Flashcards
What system that packages and store dopamine and make it ready to release?
VMAT2 (vesicular monoamine transporter 2)
How do you get rid of dopamine in the synapses?
Dopamine transport (DAT) to reuptake/COMT and MAO-B to degrade
Which dopamine pathway systems control movement? hyper function cause? hypo?
Nigrastriatal systems (between striatum and substantia nigra)/dyskinetic movement/Parkinsonism
Which dopamine pathway systems control reward and perception?hyper function cause? hypo?
Mesolimbic system (between nucleus accumbens and tagmentum)/addiction/amotivation and apathy
Which dopamine pathway systems make you alert, awake and focused? hyper function cause? hypo?
Mesocortical system (tagmentum and the front of your brain)/hypervigilance/inattention
Which dopamine pathway systems control prolactin function? hyper function cause? hypo?
Tuberoinfundibular system (hypothalamus and pituitary)/hypoprolactinemia/hyperprolactinemia
Loss of dopamine activity in what part of the brain causes ADHD?
Anterior cingulate
Block dopamine can alleviate?
Nausea
How does L-methylfolate increase the production of dopamine?
Folic acid—>MTHFR—>L-methylfolate—>cross BBB—>1 carbon cycle—>increase tyrosine—>increase dopamine
What chemical also stimulate the 1 carbon cycle?
s-adenosyl methionine
Which drug block DA and NE reuptake?
Bupropion
2 mechanism of amphetamine?
Block DAT and might reverse it/promote VMAT2—>release more DA
How does methylphenidate compare with amphetamine?
methylphenidate just blocks DAT
Example of class I and II addictive drugs?
Cocaine (illegal)/amphetamine (allowed to prescribe)
What does modafinil and armodafinil do? how does it work?
For ppl who are fatigue (class IV)/increase histamine activity in TMN/increase orexin (arousal)/might block DAT/might up NE receptor
Should you prescribe class IV drugs to ppl who has addiction problems?
No
Can modafinil and armodafinil make you loss weight?
Yes
High dose of selegiline block?
MAO A and B
What gives you HTN crisis (stroke/MI) when you are on MAOi?
NE and food with tyramine in it
What is serotonin syndrome and what causes it?
high level of 5HT—>tremor/muscle spasm/hyerthermia/delirium/coma/death
takes 5HT when you are on MAOi
What does entacapone and tolcapone treat?
Parkinson’s
What is the side effect of entacapone?
Fatigue and nausea (unusual in stimulant drugs)
Why don’t we want to use levodopa right away?
It stops working 10-20 years and give you dyskinesias
Side effect of D2 agonists?
Mania (one of them)/too happy
What is D2 receptor?
Phasic DA—>release DA in short puff
What is D3 receptor?
Tonic DA—>goes up and down slowly in a day to keep you awake
What else can aripiprazole treat besides schizophrenia?
Depression
you want to __ DA in treating schizophrenia?
Lower
What are reserpine and tetrabenazine?
DA depleters—>reserpine: Psychosis (DA blocker—>shooting blank)
What is high potency first gen antipsychotic drugs (typical) and its side effect?
High affinity for D2/cause DA to be too low—>extrapyramidal syndromes
What is extrapyramidal syndromes?
Caused by FGA—>akathisia/dystonia (torticollis—>stiff neck)/Parkinsonism/neuroleptic malignant syndrome (all muscles contract—>hyperthermia/muscle rigidity/rhabdomyolysis
Why use anticholingeric drugs for Parkinson’s?
Block cholingeric system—>release DA
What is diphenhydramine (Benadryl) used for?
Anticholinergic—>treat EPS caused by FGA/SGA
What happen if D2 receptor (high potency FGA) is blocked for years?
Highly sensitive D2 receptor emerge—>tardive dyskinesia (fast quirky movement usually on face)
What else does low potency FGA block besides D2 receptor?
They are also anticholinergic/anti H1/anti alpha 1—>more side effects
What are the 3 high potency FGAs?
Haloperidol/fluphenazine/thiothixine
What are the 2 low potency FGAs?
chlorpromazine/thioridazine
Difference of high and low potency FGAs regarding side effects?
High potency is more prone for EPS/low potency has more side effects
What is the difference between SGA (atypical) and FGA?
SGA is more specific—>it blocks D2 and 5HT2a—>blocking DA in mesolimbic system and allowing better transmission in other DA pathways
Do you get more or less EPS with SGA?
Way less/but SGA has more metabolic side effects—>also make younger people suicidal
What else does SGA treat?
depression
What are the side effects for pines (SGA)?
More antihistamine—>more sedative
Make ppl eat more and gain more weight—>diabetes
What are the side effects for dones (SGA)?
More EPS
What is so special about clozapine?
Most effective SGA/risk of agranulocytosis/most metabolic risk/little to zero EPS
What is the most common type of headache?
episodic tension type
What gender is more prone to migraine?
Female (3 times more frequent than men)
What is the migraine phases?
Prodrome—>aura—>headache—>resolution
What is positive and negative visual phenomenon?
Positive—>see something
Negative—>missing vision
What is aura regarding migraine?
Cortical spreading depression—>reduction of cerebral blood flow—>focal neurological problem (last about 20mins—>visual is most common (distortion) )
Would migraine headache relive by rest?
Yes
How long does migraine last?
4-72 hours
Symptoms of migraine headache?
osmo/photo/phonophobia (seek dark room)
Is migraine w/ aura more common than w/o?
No w/o is more common
What is familial hemiplegic migraine?
Mutation of Ca channel on chromosome 19—>cause one side of the body paralyzed
What is special about migraine pt’s brain?
It is much more sensitive—>high response to stimuli
What is the pathophys of headache?
Activation of trigeminovascular system—>nerve fibers release vasodilating/permeability promoting peptides—>sterile inflammation—>increase mechanosensitivity and hyperalgesia to previous normal stimuli (blocked by triptans)—>pain perceived by the surface of the brain
Behavioral treatment for migraine involves?
healthy habits/stress/trigger avoidance
Mild to moderate migraine can be treated with?
Nonspecific med—>NSAIDs/analgesics and so on (overuse can cause headache)
What is the precaustion for barbiturates and opioids for acute treatment use?
Risk of overuse—>medication overuse headache
When to use corticosteroids for migraine?
Prolonged migraine
Why is dihydroergotamine (DHE) preferred over ergotamine?
Less side effects
How does triptans work?
Cross BBB—>agonize 5HT1b/d—>shut down trigeminovascular system (must take early take about 20mins to work)
What are some adjunctive treatments for acute migraines?
Antiemetics/neuroleptics (antipsychotic)
What to use for preventive treatment for migraine?
Antidepressants (TCA and SSRI)/antihypertensive (beta blocker and Ca channel blockers)/antiepiletpic
What are the 3 TCA that are used to prevent migraine?
Amitriptyline/protriptyline/nortiptyline
What is Ca channel blockers used for migraine prevention?
When pt has prolonged or disabling aura
What is the major side effect for topiramate (antiepileptic)?
Change in cognition
What is botox used for migraines?
Chronic migraine
What is tension type headache like?
Non-pulsating/dull/achy pain/not worsen by movement/not that severe
What defines chronic tension type headache?
More than 15 times per month
What do you treat acute TTH with? and prevent it from happening?
Analgesics/TCA like amitriptyline
What is cluster headache?
Happen at night and at the same time every year/mostly men—>heave facial features
How is the pain in cluster headache?
Unilateral/temporal/peaks quickly/really severe pain
What to use to treat acute cluster headache?
O2/triptan/DHE
What to use for short term preventive treatment for cluster headache?
Steroids
What to use for long term preventive treatment for cluster headache?
Verapamil (Ca channel blockers)/topiramate/valproic acid/lithium (avoid indomethacin and Ca depleting diuretics)
How is aqueous (eye) produced and traveled?
Made in ciliary body—>pass through between lens and iris—>anterior chamber—>drain out via trabecular meshwork
What is the angle in angle closure and open angle glaucoma? and how to tell if it is angle closure (prevent drainage of aqueous)?
The angle between iris and cornea/shine light from temporal side of the eye—>if both temporal and nasal iris are illuminated—>deep anterior chamber
At the age of 45, you start to loss the ability to ___?
Accommodate (thickening of the lens)
What does epi and dipivalyl do for glaucoma?
They lowered the intraocular pressure
Topical cocaine for the eye is testing for?
If pupil do not dilate—->symp dysfunction (Horner’s)
If eyes do not respond to paredrine, what order of neuron is damaged?
3rd order neuron (postganglionic)
Parasymp paresis?
Loss of parasymp function—>pupillary dilation
Parasymp runs with 3rd cranial nerve—>loss of eye movement and ptosis
Adie’s symdrome?
Damage to ciliary ganglion—>parasymp synapse at ciliary ganglion—>parasymp damage—>large pupil—>don’t respond to light but respond to accommodation
What happens with internal carotid aneurysm for the eyes?
Trauma to 3rd nerve—>pupillary dilation/loss of eye movement/ptosis
Aneurysm also comes with headache (medical emergency)
Distinguish Adis’s from intracranial aneurysm?
Denervation hypersensitivity happens in Adi’s—>small amount of ACh stimulates nerve (low dose of methacholine and pilocarpine will work)
1% pilocarpine constricts everybody’s pupil but?
Not for pharmacologic blockade
Pilocarpine causes?
Bifrontal headache
What are the 3 light-near dissociation disorder?
Adie’s/Parinaud’s syndrome (mid brain tumor)/Argyll Robertson syndrome (tertiary syphilis)
Antidepressant is used for ?
Depression/anxiety (and its subtypes like OCD and PTSD/enuresis/neuropathic pain/bulimia
What are the major mechanisms for antidepression drugs?
Block amine reuptake/block MAO/block presynaptic amine autorecetpors
How long will you see the clinical improvement for antidepression drugs?
Not till weeks or months
___ antidepressants are very effective especially for children and teens?
Placebo
What is the difference between all the amine reuptake inhibitors?
Their selectivity against NE or 5HT reuptake transporter
What are the side effects of tricyclics?
Also block muscarinic/alpha/histamine/DA reuptake pump
Overdose of tricyclics causes?
Cardiac arrhythmias—>lethal
Why is SSRI used more than TCAs?
SSRI has less side effects (might not as good)—->more compliance
What is one of the major side effect of paroxetine and fluoxetine?
P450 inhibitor
What is ketamine?
Party drug that has a faster clinical effect than other antidepression drugs
Is resistant to depression meds common? and how do we deal with it?
It is common/switch, combine or augment different drugs
What are the 2 atypical antidepressant?
Mirtazapine and bupropion
What is the definition of local anesthetics?
Reversibly prevents nerve impulse transmission w/o affecting consciousness
The cell membrane of neuron is permeable to __ and not to ___?
Permeable to K but not Na
What is preemptive analgesia?
Nerve block before incision
Local anesthetic works on Na channels that are ___?
being activated (less in resting or inactivated states)
What are the 3 structural characteristics of local anesthetics?
Aromatic ring (lipophilic)/intermediate linkage either Ester or Amide/terminal amine
Intermediate linkage of local anesthetics determine the way of biodegradation, how does Ester and Amide degraded?
Ester—>hydrolyzed in the plasma by pseudocholinesterase (CSF does not have this enzyme)/Amide—>transformed by P450 in the liver
The terminal amine in local anesthetics can accept ___ and become ___?
Accept a proton and become a weak base—->thus hydrophilic and active
Only the ___ form of local anesthetics can cross the lipid membrane and only the ___ form can act on the Na channel
unionized/ionized
In physiologic pH, local anesthetics are ___?
Ionized
What do we do when we have to inject local anesthetics into an infected tissues (acidic environment)?
Add bicarb first and then LA
What kind of nerve would be blocked first by LA?
Smaller and myelinated nerves
What are the 4 types of nerve fibers and their diameter and conduction speed?
Diameter and conduction speed in descending order: A-alpha—>A-beta—>A-delta—>B—>C
Which 4 nerve fibers are myelinated and which 2 fibers conduct pain?
All the A fibers and B are myelinated and A-delta and C fiber conduct pain
Which nerve fiber gets blocked first and which ones recovers first?
B/C get blocked first and then A fibers/A fibers recover first and then B and C fibers
Pain and temp sensation can be blocked but ___ can not be blocked?
Pressure sensation
What is Cauda Equina Syndrome and what caused it?
High dose of intraspinal lidocaine—>complete motor weakness and sensory lost/lost of bladder and bowel function
Lidocaine and other LA can also cause ___?
Transient neurologic symptoms (transient pain)
How to treat LA toxicity?
Intralipid infusion with ventilation to maintain normal blood pH
Which LA causes allergy, esters or amide?
Esters (PABA metabolites)
What is the difference between toxicity and adverse effect?
Toxicity is predicted reaction, adverse effects are not
What kind of seizures do phenytoin treat?
Tonic-clonic and acute seizures
Lamotrigine competes with __ for excretion?
Valproate
What are the 2 drugs that bind to GABA A and for antiepileptic?
Phenobarbitol and benzodiazapines
What is status epilepticus and what drug is for that?
Seizures that start right after one another (medical emergency)/benzodiazepine
Which antiepileptic drug has cognitive toxicity (word finding)?
Topiramate
Li can be used for ___ headache?
cluster
What is MAC (minimal alveolar concentration)?
The concentration of anesthetic vapor in the lungs that 50% of pt would not response to noxious stimuli/additive
GABA and Glutamate bind to and open ___ channels?
ligand-gated ion channels
NMDA receptor conduct what ions?
Na/K/Ca
GABA receptor conduct what ion and result in?
Cl/hyperpolarization
Glycine is inhibitory or excitatory NT in CNS or spinal cord?
Inhibitory in spinal cord
Anesthetics bind to ___ pockets of ___ protein?
Hydrophobic pockets of water soluble protein
Volatile anesthetic (liquid) needs to be ___ before giving to pts?
Vaporized (specific drug goes with specific vaporizer)
What is partial pressure regarding inhaled anesthetics?
concentration of gas dissolved in liquid is proportionate to the partial pressure of the gas above the liquid—>equilibrium exists between 2 phases (e.g. alveoli and blood)
What is partition coefficient?
Ratio of solubilities of gas between 2 compartments/it describes how inhaled anesthetics distribute themselves
What propel the anesthetic gas to go from the machine to the brain?
Partial pressure of the alveoli PA
Partial pressure of alveoli PA/pulmonary papillary blood Pa/brain partial pressure Pbr are?
equal
How to maintain a good partial pressure of anesthetic gas in the alveoli by increase delivery to alveoli?
Increase amount of gas/increase alveoli ventilation/ and decrease functional residual capacity
How to maintain a good partial pressure of anesthetic gas in the alveoli by decreasing uptake of blood?
Decrease blood solubility/decrease CO/increase con. of gas in the blood—>so gas stay in the alveoli
You can start with ___ con. of gas since the gas will be mixed with other gas in the lungs and get diluted
Higher
What is concentration effect?
When the gas is rapidly absorbed into the blood stream in the lung, the remaining con. of gas in the alveoli increase because the volume shrinks
What is the 2nd gas effect?
Potent gas and N2O are in the alveoli—>N2O got absorbed a lot faster than the potent one—>potent gas con. goes up
Speed of anesthetic induction (speed of pt fall asleep) is determined by?
The rate of rise of alveolar concentration of anesthetic agent
What kind of anesthetic agents achieve high PA and thus faster induction?
Poorly soluble ones (tend to stay in alveoli)
MAC measures the response of ___?
spinal cord
MAC is increased in?
hyperthermia/red hair ppl/increase catecholamine and NTs/hypernatremia/cyclosporin
MAC is decreased in?
Increase age/pregnancy
Why is N2O used with other volatile anesthetics?
So we don’t have to use too much of potent volatile anesthetics—>minimize side effects
What are the Guedel’s 4 stages of CNS depression from anesthesia?
Analgesia—>excitement and delirium—>surgical anesthesia—>medullary depression (need ventilator)
Volatile agents increase?
Cerebral blood flow (counted by hyperventilation)/increase ICP/blood flow to brain muscle and skin
Volatile agents decrease?
systemic vascular resistance (vasodilate)/BP/ventilatory response to hypoxia
Volatile agents’ effects on neuromuscular function?
Relax skeletal muscle/trigger malignant hyperthermia (genetic variant)
Barbiturates and propofol causes __ and results in ___?
Vasodilation and HoTN
For a elderly pt who can not tolerate drop in BP, use which general anesthesia?
Etomidate
What is ketamine’s (general anesthesia) effect on cardiovascular system and respiratory system?
Stimulate sympathetic system/broncodilator
What generalized anesthesia do we use for children with developmental delay?
Ketamine
What is the difference between dexmedetomidine and other generalized anesthesia?
Pt on dexmedetomidine resembles natural sleep
All neuromuscular blockers have ___ structure?
Quarternary ammonium
Neuromuscular blockers can be countered with?
Anti cholinesterase
What is the difference of Train of Four for depolarizing and non depolarizing neuromuscular blockade?
every succeeding twitch is smaller for non-depolarizing/decrease the same degrees for all 4 twitches for polarizing
If a pt has renal failure and need non depolarizing NMB, which one you shouldn’t give?
Pancuronium
Difference between sedative and hypnotic drugs?
Sedative—>calming/anti anxiety
Hypnotic—>induce sleep
Does GABAa agonist bind directly to the binding site of GABA?
No, they bind onto the structure allosterically and then enhance the receptor (can’t open them themselves)
GABA receptor has many subunits, resulting?
Different composition has different effect
What is BDZ1 receptor?
The receptor that zolpidem binds to (they made that receptor up just for zolpidem, aren’t you special)
Benzo binds to BDZ1 or 2?
Both
Why is benzo safer than barb?
Benzo has ceiling effect—->they only enhance the receptor can’t open them
Barb (and alcohol) in high dose act as agonist themselves—>can lead to much severe effect like coma and death
What determines the short and long acting benzo?
If they have active metabolites then they are long acting
Triazolam and zolpidem are used as a ___ pills
Sleeping (short half life)
___ is used for fear of flying (calm you down)
Alprazolam (Xanax)
GABA antagonist cause?
Seizure
Why Thiopental is rapid acting?
Lipid soluble—>access to brain fast—>redistribution out of the brain fast as well
What kind of drugs treat long term and short term anxiety?
Antidepressant/benzo
Alcohol is ___ in size therefore ___ absorbed
Small/rapidly
What determines the rate of absorption of alcohol?
Concentration of alcohol/stomach fullness
What happens to alcohol when there’s food in the stomach?
Dilute alcohol/delay stomach emptying/increase effective metabolism of alcohol
Alcohol is distributed throughout the __ content of the body, and resulting women to have ___ alcohol
Water content/male has higher water fraction than females
Where is alcohol metabolism takes place?
Liver and stomach
What is the alcohol metabolism process in the liver?
Alcohol —(alcohol dehydrogenase ADH)—>acetaldehyde—(acetaldehyde dehydrogenase—>ALDH1/2)—>acetate
Asians lack which enzyme that metabolize alcohol?
ALDH2—>higher ALD level—>higher alcohol sensitivity
When will the P450 metabolism of alcohol kick in?
When you drink too much or you are a seasoned drunk
What is the limiting factor for rate of alcohol oxidation, and how are other reactions involving this factor affected?
NAD+/all other NAD+ reaction are diverted to alcohol metabolism
When our system is fully saturated with alcohol (ya drunk), what is the order of kinetics regarding alcohol elimination?
Zero order (NAD+ is the limiting factor)—>turn to 1st order when the concentration is really low
Progression of alcohol intoxication?
Loss of inhibition—>impaired motor—>vision—>cerebellum—>medulla (respiration and temp)
Chronic alcohol usage causes ___? which can lead to ___?
Fatty liver—>cirrhosis
Moderate alcohol consumption can increase ___ and decrease ___?
HDL/coronary heart disease
Acute drug interaction of alcohol?
Metabolism of other drugs might be inhibited
Chronic drug interaction of alcohol?
Induce P-450—>enhance metabolism of other drugs
Alcohol has an ___ effect with other CNS depressant
Additive
What are methyl alcohol and ethylene glycol? and what is used for OD of these?
Their metabolites are toxic/use ethanol to compete with ADH (preferred substrate)—>pee out the toxic ones
Cocaine can be hydrolyzed via ___ or ___?
plasma cholinesterase or spontaneously
What is schedule I and II drugs?
Schedule I—>high potential for abuse and no medical use (hallucinogens/heroin/weeds and what not)
Schedule II—>high potential for abuse and some medical use (morphine/cocaine)
What are some examples of indole alkyl amines?
Serotonin like—>psilocybin and LSD
What is an example of phenylethylamines?
Mescaline
LSD’s affects?
Distortion of perception and heightened sensory awareness
Why it is hypothesized that LSD share the same site of action with mescaline and psilocybin?
Because there’s cross tolerance between LSD and mescaline and psilocybin
What is the mechanism of LSD?
agonists at inhibitory 5HT2a at raphe nucleus (raphe nucleus usually inhibit downstream 5HT)—->inhibit the inhibitor—->uncontrolled 5HT release
How is THC metabolized?
Highly lipid soluble/metabolized by P450
What are the 2 cannabinoid receptors and what do they do?
CB1—>euphoria
CB2—>immune system
What is endogenous opioid?
Endorphin
Where does opioid receptor agonist act on?
decrease release of substance P/Ascending spinothalamic tract/descending pain modulatory system
What kind of receptor is opioid receptor?
G protein coupled
Opioid side effects include?
Miosis/lower seizure threshold/depressed respiration
What is bolus effect for opioid and what do we do to prevent it?
Analgesic effect from bolus of opioid injected but then pain comes back with rapid excretion/give extended release or IV
What should we worry about opioid with acetaminophen?
Pt might take too much acetaminophen
What to do when a pt who’s on extended release opioid that is still in pain?
Use immediate release as a breakthrough, don’t escalate the extended release (OD)
How do we administer opioid for pt who has renal or liver problems?
Decrease dose or interval/use as needed only for pt with no urine/opioid is conjugated in the liver and excreted in the urine
What is peudoaddiction of opioid?
Under treatment of pain
What is tolerance of opioid?
Decrease effectiveness w/ repeated dose/decrease side effects EXCEPT for constipation
What is physical dependence of opioid and how to avoid it?
Pt goes through withdraw/decrease the dose slowly
What is equianalgesic dosing?
Switch an opioid to another or from one route to another (has to change dose too)
How do we adjust for cross-tolerance when equianalgesic dosing?
(might be more sensitive to new drug) Decrease dosing for new drugs—>give more if pain
What to give pt for nausea vomiting caused by opioid side effect?
DA blocker
Is there a limited dose of opioid (ceiling) that you can give?
No, limited by side effect
Which opioid you shouldn’t use for malnourished pt?
Fentanyl (patch form)
What are the 5 MS subtypes?
Clinically isolated syndrome (one location)
Relapsing-remitting (most common)
Primary progressive (slowly gets worse/no relapse)
Progressive relapse (has relapse, worse every time)
Secondary progressive (start like relapsing-remitting and then stop relapsing and just gets worse)
What does MS cause to the appearance of the brain?
White matter atrophy—>enlarged ventricles
Neutralizing antibodies interfere with ___ treatment?
IFN-beta for MS (antibodies neutralize IFN-beta)
Which IFN-beta drug has the highest neutralizing antibodies?
Betaseron (trade name)
Which MS drug slow disease progression?
IFN-beta-1a
The key for MS treatment is to treat?
Early
Which IFN-beta drug is preferably used over others?
Rebif (or glatiramer acetate)
How many years before the risk of getting PML from Natalizumab is increased and you should switch to other drugs?
About 2 years (JC antibody + pt has a higher chance of getting PML)
What are atypical antidepressants?
Mirtazapine and bupropion
What to give for alcohol withdraw
Benzo
What is Hoffman degradation
Spontaneous degradation
What causes Adie’s syndrome and what is its eye presentation?
Bacterial or viral infection damage the ciliary ganglion of the postganglionic of parasymp/bilateral mydriasis—>react slowly to light but react normally to accommodation
