First Aid Pharma Flashcards
-mixed w/ Sketchy Pharm for: antipsychotics and antidepressants
Sympathetic nervous system altering agents used in tx of glaucoma
- Alpha-agonists
- Epinephrine (alpha1) or brimonidine (alpha2) - Beta-blockers: Timolol, betaxolol, carteolol
Work to decrease aqueous humor synthesis
Diuretic used in the tx of glaucoma
Acetazolamide (works at PCT): carbonic anhydrase inhibitor to decrease aqueous humor production
Name two classes of drugs that increase outflow of aqueous humor in the tx of glaucoma
Increase aqueous humor outflow
- Cholinomimetics (pilocarpine, physostigmine): cause contraction of ciliary muscle and opening of trabecular muscle
- Prostaglandin F2alpha = Latanoprost
Mechanism of
(a) Loperamide
Mechanism of
(a) loperamide = immodium = opioid receptor agonist but specific to the gut
Mechanism of fentanyl
Fentanyl = opioid, works opioid receptors: opens K+ channels, closes Ca2+ channels => reduces synaptic transmission
2 Indications for opioids in addition to pain
- Diarrhea: loperamide = opioid w/o intestinal or CNS penetration, so just works to slow down gut w/o CNS effects
- maintenance for heroin addition (methadone, bupreorphine)
Mechanism of tramadol
Tramadol: “tram it all” so works on multiple nt
- agonist of mu-opioid receptor
- inhibits 5-HT and NE
- used for tx of chronic pain
First line drug for absence seizures
(a) Mechanism
Ethosuximide ‘sux to have silent seizures’
(a) Ethosuximide works by blocking thalamic T-type Ca2+ channels
First line anti-epileptic agent for
(a) Acute status epilepticus
(b) Ppx of status epilepticus
(c) Partial seizures
First line AED for
(a) Acute status = benzos!! Get that GABA action pumping
(b) Ppx for status = Phenytoin (inhibits Na+ channel)
(c) Partial seizures, both simple and complex, first line is carbamazepine (Na channel inhibitor)
AED used for both partial seizures and nerve pain
(a) Mechanism
Gabapendin: tx peripheral neuralgia and partial seizures (both simple and complex)
-not for generalized seizures
(a) Gabapending inhibits high-voltage-activated Ca2+ channels
AED that can also be used to tx bipolar d/o
(a) Mechanism
Valproate used to tx bipolar d/o and seizures: partial (both simple and complex) and GTC
(a) Valproate inhibits Na+ channels and increases GABA concentration by decreasing breakdown
AED that is first line in neonates
(a) Mechanism
Phenobarbital (barbiturate) is first line in neonates for partial (simple and complex) seizures and GTC
(a) Phenobarb increases GABA-A action (same as benzos)
Which AED must be titrated slowly 2/2 risk of Stevens-Johnsons?
Many AEDS carry risk of SJS (ethosuximibe, phenytoin, carbamazepine) but Lamotrigine has super high risk
Lamotrigine has to be titrated slowly
Differentiate mechanism of barbiturates and benzodiazepines
Both barbs and benzos bind to GABA-A receptor (at dif sites) but agonize receptor by increasing duration of Cl- channel opening vs. increasing frequency of opening
Barbs increase duration of Cl- channel opening
Tx of barbiturates vs. benzodiazepine OD
Benzo OD can be tx w/ Flumazenil which is a selective benzo receptor antagonist
-competitive inhibitor of benzo binding site on GABA-A receptor
Barbiturate OD tx is just supportive (assist respiration and maintain BP)
Explain the effect of blood and lipid solubility for anesthetics
The lower the blood solubility, the faster the induction and faster the recovery time
Higher lipid solubility = higher potency b/c more crosses the BBB
Main indication for thiopental
Thiopental = barbiturate IV anesthetic
-high potency and high lipid solubility (meaning it rapidly enters the brain), so used for induction of anesthesia and short surgical procedures
MC anesthetic used for endoscopy
Midazolam (benzo) = MC drug used for endoscopy
-can be used adjunctively w/ gaseous/inhaled anesthetics (isoflurane, N2O) and narcotics
Mechanism of ketamine
Ketamine = PCP analog that blocks NMDA receptors
-used as dissociative anesthetic
Mechanism of lidocaine as a local anesthetic
Lidocaine = amide that blocks Na+ channels (preferentially activated Na+ channels => most effective in rapidly firing neurons)
Depolarizing vs. nondepolarizing neuromuscular blocking agnets
Depolarizing (succinylcholine) are strong ACh receptor agonists that produce sustained depolarization to prevent muscle contraction
Nondepolarizing (vecuronium, rocuronium) competes w/ ACh for receptor (competitive antagonist for receptor)
Describe the tolerance developed by chronic opioid use
Tolerance meaning need higher dose of opioids for analgesia, BUT tolerance does NOT develop to mioisis and constipation!!!
So constipation is a chronic side effect!! Doesn’t subside
Differentiate how dantrolene and baclofen prevent muscle contraction
Dantrolene prevents Ca2+ release from SR of skeletal muscle
-used in malignant hyperthermia and NMS
Baclofen inhibits GABA-B receptors at the level of the spinal cord => causes skeletal muscle relaxation
-for muscle spasms
Differentiate nt imbalance in
(a) Parkinsons
(b) Huntingtons
Neurotransmitter imbalance
(a) Parkinsons 2/2 loss of dopamine innervation in nigrostriatal pathway and excess ACh tone
(b) Huntingtons 2/2 increased DA, reduced GABA and reduced ACh
Mechanism of Ropinirole
(a) Indication in addition to Parkinsons
(b) Risk of Ropinorole
Ropinirole = non-ergot Dopamine2 receptor agonist
a) First line tx for restless leg syndrome
(b) Can worsen impulse control d/o (gambling, shopping, hypersexuality
What side effects does carbidopa help reduce when added to Levodopa
Carbidopa reduces side effects seen 2/2 increased peripheral DA (b/c inhibits peripheral DOPA decarboxylase)
Decreases GI symptoms (N,V), cardiac arrhythmias, and orthostatic hypotension
Doesn’t relieve the central neuropsychiatric side effects of anxiety, agitation
When to add selegiline to Parkinsons tx regimen
Selegiline = selective MAO-B inhibitor to decreased central degradation of DA, used in adjunct to L-dopa therapy (not alone!)
-helps w/ the wearing off and on-off phenomenon of L-dopa therapy
Name the positive and negative symptoms of schizophrenia
Schizophrenia
Positive symptoms: hallucinations, delusions, disorganized thoughts and behaviors
Negative symptoms: apathy, flat affect, lack of energy
Differentiate high potency vs. low potency typical antipsychotics
High potency typicals = Haloperidol, Trifluoperazine, Fluphenazine
- high affinity for D2 receptor => greater risk of EPS
- but less anti alpha1, anti-H1, and anti-muscarinic effects
Low potency typicals = Chlorpromazine, Thioridazine
-lower affinity for D2 receptor (so lower risk of EPS), but more anti-alpha1 (ortho hypo), anti-H1 (sedation), and anti-muscarinic effects
Main distinction btwn first gen (typical) and second gen (atypical) antipsychotics
Typicals exert effect mainly on positive symptoms of schizophrenia by D2 receptor blockade- higher risk of EPS, hyperprolactinemia, ortho hypo, sedation
While atypicals weakly antagonize D2, but potently inhibit 5-HT2A => tx both the negative and positive symptoms of schizophrenia w/ smaller risk of the above side effects
Explain the three groups of side effects of low potency antipsychotics
Low potency antipsychotics (chlorpromazine and thioridazine) exert effect by D2 receptor blockade to tx positive symptoms of schizophrenia
- anti-alpha1 effects => orthostatic hypotension
- anti-H1 effects centrally => sedation
- anti-muscarinic effects => dry mouth, constipation, blurred vision, urinary retention
Name the 4 movement effects seen as a side effect of high potency typical antipsychotic use in the order in which they arise
High potency typical antipsychotics (haloperidol, trifluperazine, fluphenazine) carry greatest risk of EPS
1st get acute dystonia (sustained muscle contraction, ex: torticollis) w/in hours
W/in days get akathisia (subjective motor restlessness)
W/in days to weeks see symptoms of drug-induced Parkinsonism
W/in months to years see tardive dyskinesia- mainly oral-facial dyskinesias (tongue/lip smacking)
Explain how haloperidol can cause amenorrhea
Haloperidol = high potency typical antipsychotic w/ D2 receptor antagonism
D2 receptor blockade in the tuberoinfundibular pathway removes the tonic inhibition of dopamien on prolactin => hyperprolactinemia
-high prolactin suppresses GnRH levels => reduced LH/FSH => amenorrhea
Clinical picture of NMS
(a) How to distinguish from serotonin syndrome
Neuroleptic malignant syndrome: ‘lead pipe’ rigidity, hyperpyrexia (like super high fever), altered mental status, autonomic instability (tachycardia), rhabdo
(a) NMS is 2/2 too much DA blockade: see hyporeflexia and muscle rigidity
- while serotonin syndrome (2/2 excess 5-HT agonism) see similar presentation (hyperpyrexia, AMS, autonomic instability) except w/ hyperreflexia and clonus
EKG abnormality seen in typical vs. atypical antipsychotics
Both typical and atypicals can prolong QT => increased risk of Torsades and ventricular arrhythmias
Differentiate the ocular findings seen in chlorpromazine vs. thioridazine therapy
2 low potency typical antipsychotics
Chlorpromazine => corneal deposits
Thioridazien => retinal deposits
Benefit of atypical antipsychotics in schizophrenia
(a) Efficacy
(b) Side effects
Atypical antipsychotics (Olanzapine, arirpiprazole…)
(a) Tx both positive and negative symptoms of schizophrenia (vs. just positive symptoms tx by typicals)
(b) Less anti: alpha1, H1, muscarinic => reduced side effects of orthostatic hypotension, sedation, dry eyes etc
Highest risk of metabolic syndrome seen w/ what antipsychotics?
(a) Lower risk w/ which drug of the same class?
Clozapine and olanzapine (two atypical antipsychotics) carry a high risk of wt gain and metabolic syndrome: hyperlipidemia and hyperglycemia
think ‘COokie’ for clozapine and olanzapine
(a) While zyprasidone is an atypical antipsychotic that carries a lower risk of this metabolic syndrome
Explain mechanism by which atypical antipsychotics have a lower risk of EPS
Atypical antipscyhotics have lower D2 antagonist of the nigrostriatal pathway, whose fxn is to stimulate purposeful movement
Which 2nd gen antipsychotic carries the greatest risk of hyperprolactinemia and EPS?
Risperidone is the atypical w/ the ‘most typical’ features, aka it has the highest risk of EPS and hyperprolactinemia (seen in typical antipsychotics)
Name the potentially fatal consequence of a second gen antipsychotic
Clozapine carries real risk of agranulocytosis- requires weekly ANC monitoring
Mechanism of action
(a) Citalopram
(b) Imipramine
(c) Duloxetine
Mechanism of action
(a) Citalopram = SSRI = inhibits SERT (serotonin presynaptic reuptake)
(b) Imipramine = TCA that inhibits both NET and SERT (NE and 5HT reuptake presynaptically)
(c) Duloxetine = SNRI = inhibits presynaptic reuptake of both NE and 5-HT
Mechanism of action
(a) Venlafaxine
(b) Cyproheptadine
(c) Buproprion
Mechanism of action
(a) Venlafaxine = SNRI = inhibits NE and 5-HT reuptake
(b) Cyproheptadine = 5HT2 receptor blocker used to tx serotonin syndrome
(c) Buproprion = inhibits NE and DA reuptake (w/o effect on 5-HT)
Mechanism of action
(a) Mirtazapine
(b) Trazodone
(c) Sertraline
Mechanism of
(a) Mirtazapine = alpha2 antagonism to increase catecholamine release, also inhibits 5HT2 and 5HT3
(b) Trazodone = serotonin modulator (complicated mechanism), inhibits 5HT receptors but inhibits 5HT reuptake
(c) Sertraline = SSRI, inhibits SERT (serotonin reuptake)
Mechanism of SSRI vs. SNRI
SSRI inhibit SERT while SNRI inhibit both SERT and NET to inhibit presynaptic reuptake of both 5-HT and NE
Name the features of depression
SIGECAPS
- Sleep changes- insomnia or hypersomnia (more commonly insomnia)
- interest- lack of = anhidonia
- guilt/hopelessness
- energy decreased
- cognitive slowing/concentration deficit
- appetite decreased
- psychomotor agitation or retardation
- suicidality
Use of SSRIs in addition to MDD
SSRI other indications
- GAD
- OCD
- Bulimia
- panic d/o, PTSD
3 C’s of TCA toxicity
- cardiac (inhibition of fast cardiac Na channels)
- coma (H1 inhibition causes sedation)
- convulsions (can induce seizures)
Side effects of SSRI
SSRI side effects
- wt gain
- sexual dysfunction
- drowsiness, insomnia
- rare: SIADH
- rare but serious: serotonin syndrome
Describe serotonin syndrome
(a) Differentiate from NMS
Serotonin syndrome 2/2 excess 5-HT stimuli: autonomic instability, hyperthermia, hypertension, hyperreflexia, clonus
(a) SS syndrome you see hyperreflexia and clonus, while NMS (from excess DA blockade) you see rigidity and rhabdo
Benefit of secondary amines over primary amines
Secondary amines have much weaker anti-cholinergic effects
=> less dry mouth, constipation, blurred vision, urinary retention
Differentiate MAO-A and MAO-B
MAO-A breaks down all 3 monoamines: DA, NE, 5-HT
While MAO-B breaks down mainly DA
-hence why selective MAO-B inhibitor (Selegiline) is used in tx of Parkinsonian features
Describe features of depression that make them more likely to be responsive to tx w/ MAOI therapy
MAOIs used for atypical/refractory depression: characterized by hyperphagia, hypersomnia, laiden paralysis
Which antidepressant is similar to a CNS stimulant
Buproprion (inhibits NET and DAT w/ no effect on serotonin) is similar to a CNS depression => especially good for depression w/ hypersomnolence or low energy
Antidepressant helpful for
(a) tx tobacco dependence
(b) treating depression w/o causing sexual dysfunction
(c) tx depression w/ insomnia
(d) tx for depression in cachexic old lady
Antidepressant
(a) Buproprion (NE and DA reuptake inhibitor, no effect on 5HT) helps w/ tobacco dependence
(b) Buproprion is the one antidepressant w/o effect on 5-HT => no sexual side effects
(c) Mirtazapine (Remeron) and trazodone both have potent H1 antagonism => sedation so use for depression tx w/ insomnia
(d) Mirtazapine (alpha2 blocker) is associated w/ wt gain
Antidepressant associated w/
(a) Priapism
(b) Less wt gain than SSRIs
Antidepressant associated w/
(a) Priapism = Trazodone ‘traza-bone’, serotonin modulator also inhibits alpha1 => major vasodilation => priapism and orthostatic hypotension
(b) Less wt gain, even some wt loss = Bupropion (NE and DA reuptake inhibitor, no effect on 5-HT)
Drug that can be used to tx hypertensive symptoms of tyramine toxicity
MAOI inhibitors allow tyramine to get into the circulation and act as a sympathomimetic => can cause hypertensive crisis
Phentolamine (alpha1 and alpha2 blocker) can tx the hypertensive symptoms of tyramine toxicity
Mechanism of mirtazopine
(a) Good for depression w/ what concomitant features
Mirtazapine = Remeron
- blocks alpha2 receptors => increases catecholamine release, also inhibits 5HT2 and 5HT3 receptors
- potent H1 blocker => sedation
(a) Side effects include potent sedation and wt gain => great for elderly and insomnia
Antidepressant contraindicated in eating d/o
Buproprion contraindicated in pts w/ eating d/o or h/o seizures b/c it decreases the seizure threshold
Precursor to
(a) ACh
(b) NE
(a) ACh from choline plus acetyl coA (acetate)
(b) Tyrosine –> L-DOPA –> dopamine –> NE
Indication for bethanechol
Bethanechol = muscarinic agonist (cholinomimetic agent)
Indications: postop ileus, neurgenic ileus (basically non-obstructive ileus) and urinary retention
M3 (Gq) on GI and GU tract
Physostigmine vs. Pyridostigmine
Both are indirect cholinomimetics that inhibit AChE
Physostigmine crosses BBB (enters CNS): use to tx anticholinergic toxicity, aka tx atropine OD
Pyridostigmine doesn’t penetrate USE, used as long acting cholinomimetic in myasthenia tx
3 things to watch out for when giving any cholinomimetic agent
M3 receptors => increased gastric acid secretion and bronchoconstrict
So watch out for exacerbation of COPD, asthma, and peptic ulcers
Tx for cholinesterase inhibitor poisoning
Oranophosphate poisoning (ex: parathion) 2/2 irreversible inhibition of ACHe
Antidote = atropine (competitive inhibitor of muscarinic receptors)
Can use pralidozime if caught early to help regenerate AChE
Mechanism of fugu toxin
Fugu toxin (from poorly prepared pufferfish in Japan) binds fast voltage-gated Na channels in cardiac and nerve tissue -prevents depolarization => nausea, diarrhea, paresthesias, weakness, dizziness, loss of reflexes
Buzzword dx for temperature-related dysesthesia (‘cold feels hot and hot feels cold’)
Ciguatoxin from consumption of reef fish (barracuda, snapper, moray eel)
Toxin opens Na channels causing depolarization, often confused w/ cholinergic poisoning
Dopamine effect on sympathetic receptors
(a) Cardiac indications
Dopamine acts mostly on D1 and D2, but also mildly on beta and even less so on alpha
(a) Can be used for unstable bradycardia (beta1 inotropic and chronotropic effects), HF, schock
Indication for clonidine
Clonidine = selective alpha 2 agonist
Indications: hypertensive urgency
- ADHD
- Tourettes
Sympatholytic safe for tx hypertension during pregnancy
Alpha-methyldopa = selective alpha2 agonist (therefore vasodilates) is safe for use in pregnancy
Side effects of nonselective alpha blockers
Pehnoxybenzamine and phentolamine (both nonselective alpha blockers) side effects = orthostatic hypotension and reflex tachycardia
Need to be careful when giving these and alpha1 agonists for orthostatic hypotension
Differentiate the selective and nonselective beta blockers
Selective (beta1 over beta2) first A-M: atenolol, betaxelol, emololol, metoprolol
While nonselective (beta1 = beta2) from N-Z = Nadolol, Propranolol, Timolol
Name the 2 nonselective alpha and beta antagonists
Have modified version of beta-blocker “-olol”
- Carvedilol
- Labetalol
Antidote for overdose of
(a) Amphetamine
(b) Benzos
(a) Amphetamine overdose- tx w/ NH4Cl to acidify the urine
- amphetamines are basic
(b) Tx benzo OD w/ Flumazenil = competitive inhibitor of GABA-A binding site
Antidote for overdose of
(a) AChE inhibitors
(b) Antimuscarinics
(a) Same as organophosphate poisoning, tx w/ atropine (antimuscarinic)
(b) Antimuscarinic overdose- give physostigmine to control the hyperthermia
Antidote for toxins
(a) Methemoglobin
(b) Cyanide
(a) Methemoglobin- give methylene blue and vitamin C
(b) Tx cyanide toxicity w/ nitrite and thiosulfate
Antidote for toxins
(a) Beta-blockers
(b) Heparin
(c) tPA/streptokinase
(a) Beta-blocker toxicity, tx w/ glucagon
(b) Tx heparin overdose w/ protamine sulfate
(c) Reverse tPA/streptokinase w/ aminocaproic acid
Overdose of what two agents can be treated w/ NaHCO3
Alkalinize urine to get rid of salicylates (aspirin)
Alkalinize plasma to get rid of TCAs
Which antiarrythmics increase risk of Torsades
The two that prolong QT interval = Class IA (ex: quinidine) and class III (ex: sotalol)
Drug that can cause dilated cardiomyopathy
(a) Ppx
Dilated cardiomyopathy from anthracyclines chemo agents (doxorubicin and daunorubicin)
(a) Prevent w/ dexrazoxane- chelates iron to reduce number of metal ions that complex w/ the anthracycline acid and form superoxide radicals
Name 4 drugs that can cause cutaneous flushing as a rxn
Drug reaction of cutaneous flushing: ‘VANC’
Vancomycine
Adenosine (random classless antiarrhythmic)
Niacin (vit B3)
CCB
2 drugs w/ reaction causing direct Coombs-positive hemolytic anemia
- Methyldopa- used to tx HTN during pregnancy
- can also cause lupus-like rxn - Penicillins
4 drugs associated w/ hyperglycemia
Tracolimus (calcineurin inhibitor)
Protease inhibitors
HCTZ
Corticosteroids
Drugs commonly implicated in causing agranulocytosis
Ganciclovir Clozapine (atypical antipsychotic) Antiepileptics: carbamazepine Colchicine Methimazole and PTU (antithyroid drugs)
2 drugs associated w/ gingival hyperplasia
- CCBs, esp verapamil (also constipation)
2. Phenytoin (anti-epileptic)
4 drugs associated w/ seizure as drug rxn
BIItE Buproprion- esp in h/o eating d/o Isoniazid- 2/2 B6 deficiency Imipenem/cilastatin Enflurane- old inhaled anesthetic
Drugs associated w/
(a) Hemorrhagic cystitis
(b) Interstitial nephritis
(a) Cyclophosphamide can cause hemorrhagic cystitis, prevent by coadministering w/ mesna
- mesna metabolizes the urotoxic compounds
(b) Interstitial nephritis- methicillin (why we use Naf now), NSAIDs, furosemide
Classic drug causes of myopathy
Fibrates, statins
Sulfa drugs
(a) Diuretics
(b) Anti-gout
(c) NSAID
(d) Immunomodulator
(e) Oral diabetes agent
Sulfa drugs
(a) Thiazides, furosemide, and acetazolamide
(b) Anti-gout agent = probenecid
(c) COX2 selective NSAID = Celecoxib
(d) Sulfasalazine used in IBD and RA
(e) Sulfonyureas = Glimipiride and Glipizide
Cyp450 Inducers
Guinness, Corona, PBrS induce Chronic Alcoholism
Griseofulvin (antifungals against ringworms) Carbamazepine Phenytoin Barbituates (phenobarbitol) St. John's Wort Chronic alcoholism
4 substrates of cyt p450 system
Drugs broken down by cytp450- so especially interact w/ oter cyt p450 inducers or inhibitors
“War on anti-terrorism”
Warfarin
OCPs
Anti-epileptics
Theophylline (PDE inhibitor for COPD)
4 antihypertensives that are safe during pregnancy
“Hypertensive moms love nifedipine”
Hydralazine
Methyldopa
Labetalol
Nifedipine
Cyp450 inhibitors
CRACK AMIGOS
Cimetidine (H2 blocker like Ranitidine) Ritonavir (protease inhibitor) Amiodarone Ciprofloxacin Ketoconazole (and other azoles)
Acute EtOH use Macrolides (except Azithromycin) Isoniazid Grapefruit juice Omeprazole Sulfonamides (Bactrim)
