Pharmacology - B & B Exam 4

eem8u's version from 2016-10-22 19:04


for drugs listed: type (by mechanism) / why it might be picked over other drugs / major SE’s / special pharmaco properties / drug-drug interactions
Question Answer
line of tx for antidepressants1) ssri 2) bupriorprione (if they don’t want to gain weight and avoid sexual dysfx) or 3) mirtazapine (if you want to gain weight and also avoid sexual dysfx)
mechanism of action - MAO-I’sIRREVERSIBLE (take 2 weeks to recover after discontinuing) mechanism=degradation of MONOAMINES >> more in synaptic cleft and presynaptic terminal )
clinical indication-MAO-I’s atypical depression (tx-resistant: depression, panic disorder, and social anxiety disorder) or parkinson’s
Side Effects - MAO-I’sorthostatic hypotension, weight gain, insomnia, sexual dysfunction, **Serotonin syndrome, **hypertension/hypetensive crisis
mechanism of action - Tri and Tetracylci Anti depressants (TCA)inhibit NE reuptake (and some SE reuptake) **Dirty drug = blocks a1/h1/na channel, m1
clinical indication-Tri and Tetracylci Anti depressants (TCA)**not first line for any indication: tx resistant depression (**often in patients with MDD and pain), GAD, panic disorder, neuropathic pain, diabetic neuropathy, OCD, migraine prophylaxis,
Side Effects -Tri and Tetracylci Anti depressants (TCA)LETHAL in overdose, M1( constipation, blurred vision, dry mouth, sedation, urinary retention), h1 (weight gain/sedation), a1 (orthostatic hypotension, drowsiness, dizziness), Na channel blockade >> arrhythmia
Contraindications -T (TCA)narrow angle glaucoma (b/c is anticholinergic), pt w/ cardiac events, cardiac conduction delays, prolonged QT)
TCA preferable for the elderlysecondary amines (Desipramine, Nortriptyline) - b/c less anticholinergic, less antihistamine
***TCA w/ less anticholinergic propertiessecondary amines (Desipramine, Nortriptyline) "northside prep"
***TCA - most sedatingdoxepin (H1)
***TCA for Childhood EnuresisImipramine
***TCA for Obsessive Compulsive Disorderclomipramine


Question Answer
anticholinergic toxidromeRed as a beet/ dry as bone/ blind as a bat/ mad as a hatter/ hot as a hare/ full as a flask
drug-drug interactions - TCA’s**p450 metabolism - antihypertensives (block effects), many drugs increase toxicity, **Must wait 14days before prescribing MAOI
***drug-drug interactions - MAO-I’savoid hypertensive crisis triggered by NORADRENERGIC drugs = Decongestants (ephedrine, pseudoephedrine, phenylephrine)/ Stimulants (amphetamines, methylphenidate) / Appetite suppressants / Antidepressants with NRI (TCAs, SNRIs, Buproprion)
type of drug - PhenelzineMAO-I (A) wine “funnel”
***type of drug - tranylcypromineMAO-I (A) “try a sip”
type of drug - selegilineMAO-I (B) — parkinson’s
serotonin syndrome-symptoms and CAUSEsx (**hyperthermia, **hypertension, **HYPERclonus/ MYOclonus, **hyperreflexia, abdominal pain, diarrhea, sweating, tremor, tachycardia, irritability, delirium, death) cause (up regulation of serotonin system, due to SSRI overdose or SS/SNRI drug interaction with MAO-I/TCA/amphetamines)
***hypertensive crisis- sx and causesx (** BP > 120mm Hg, headache, palpitations, stiff neck, nausea, vomiting, sweating, DILATED pupils, photophobia) cause (noradrenergic drugs - decongestants, stimulates, appetite suppressants / antidepressants with NE interaction (TCA, SNRI, Bupropion) or **TYRAMINE induced
Tyramine- what foods, how it induces hypertensive crisistyramine (soy, beer, red wine, aged cheese, cured meet, fava, liver, smoked fish, sauerkraut) - catecholamine releasing agent - causes release of NE in sympathetic system (but will be destroyed by MAO-A) —> MAO-A is blocked in presence if MAO-I >>> super high blood pressure
type of drug - imipramineTCA
type of drug - amitriptylineTCA
type of drug - desipramineTCA
type of drug - nortriptylineTCA


Question Answer
mechanism of action - SSRIbinds transporter, inhibiting reuptake (there are many different subtypes of receptors w/ different clinical features), also have some inhibition of DA/NE uptake
***clinical indication - SSRI**1st line MDD, GAD, panic, PTSD, OCD, **Bulimia
***Side Effects - SSRIsexual dysfunction (5h2), weight gain, GI (5ht3), sweating, akathisia/tremor, headache, **serotonin syndrome, *SIADH/hyponatremia, ***Mania (in bipolar 1)
general metabolism - SSRIliver - significant first pass, LONG HALF-LIFE (up to 2 weeks for active metabolite)
***SSRI w/ longest half-lifefluoxetine
***SSRI with most AND least withdrawalleast (fluoxetine)/ most (fluvoxamine, paroxetine)
***2 SSRI with least drug interactionscitalopram, escitalopram
2 SSRI with MOST drug interactionsfluvoxamine, fluoxetine
advantages of SSRI’smuch harder to dose overdose, no arrhythmia/seizure/coma/respiratory depression
mechanism of action - SNRI??????
clinical indication - SNRIMDD (2nd to SSRi), anxiety disorder, neuropathic/diabetic pain, fibromyalgia, pain related to depression, perimenopuase vasomotor symptoms
venlafaxine- type/mechanism of action/side effectsSSRI at low dose/SNRI at higher doses / SE (hypertension, tachycardia)
venlafaxine- type/mechanism of action/side effectsSNRI (similar affinity for 5ht and NE) / rare hepatotoxicity **Very good for pain
***Drug for MDD w/ no 5ht interactionBupropion (no weight gain or sexual dysfx)
bupropion- mechanism and useNE/DA reuptake/ some nicotinic action // use (MDD, smoking cessation, **ADHD)
bupropion - side effectsanxiety, headaches, nausea, **avoid in seizure-prone (eating disorders, alcohol, bento withdrawal), hypertensive crisis w/ MAOIs
mirtazapine- mechanism and useunclear mechanism - a2 antagonism, indirect SE up regulation
mirtazapine- side effectssedation / weight gain
***trazadone- mechanism and use5ht2a receptor against/NE antagonism/a1 and h1 antagonist / sleep aid
trazadone-side effectsorthostatic hypotension, sedation, priapism


Introduction, Atypicals
Question Answer
typical vs atypical antipsychotics - mechanismd2 blockers vs d2 + 5ht2 blockers
***4 dopaminergic projections in brain and general fx1-nigrostriatal (extrapyramidal motor fx), 2-mesolimbic (regulates emotional behavior), 3- mesocortical (regulates cognition), 4-arcuate-pituitary (inhibits prolactin secretion)
d2 receptors (structure, function)GPCR, inhibitory
DA hypothesis for +/- sx of psychosis+ due to overactivity of mesolimbic, - due to under activity of mesocortical
**high potency typicals and SE’sfluphenazine, haloperidol (**LOWER ki for d2, more d2 SE’s but less m1/a1/ach SE’s)
***lower potency typicals and SE’schlorpromazine < perphenazine (medium) — lower d2 SE’s but higher Ach/H1/a1 SE’s
***Typicals - therapeutic useprimary psychotic disorders, MDD w/ psychotic features, secondary psychosis (w/ brain tumor, TBI, seizures), delirium, tourrettes, severe agitation
Typical - DA-related side effectsextrapyramidal motor system (Parkisonian cogwheel rigidity, masked faces), prolactin secretion (tubueroinfundibular pathway), increase in negative symptoms (mesocortical pathway)
Extrapyramidal Sx in Anti-psychotics - cause/type1) parkinsonism, 2) acute dystonia 3) akathisia
***Tx for Acute Dystoniaanticholinergics (benztropine, trihexyphenidyl, diphenhydramine) or Da agonist (both to reestablish DA/Ach balance on GABA-ergic neurons in striatum)
Akathisia - Cause/Fea/Txd2 side effect of typical antipsychotics/ subjective inner restlessness + increased motor activity / B-blocker, benzo, anticholinergic for tx
Tardive Dyskinesia - Cause/Fea/Txchronic D2 blockers causing *hypersensitivity of DA stratum response / *often irreversible writhing (esp tongue, mouth, fingers hands) / *increaseing d2 block will make it worse
***Neuroleptic Malignant Syndrome - Cause/Fea/LAB fidnings/ Txd2 block *at any point in tx / motor rigidity, akinesia, mutism, obtundation & autonomic fever, sweating, hypertension / lab = increased WBC/creatinine PK, liver enzymes / tx - supportive/ stop drug IMMEDIATELY
m1/cholinergic blockade SE’sdry mouth, constipation, urinary retention, tachycardia
h1 block SE’ssedation /weight gain
a1 block SE’sorthostatic hypotension, dizziness (priapism)
Typicals- Cardiac SE’sprolong QT, ventricular arrhythmia, sudden death


Question Answer
2 mechanisms of reduced DA SE’s in Atypicals 5ht2a theory (blockade increase release from DA neuron >> maintain efficacy of DA block while lowering DA sideffects, esp nigrostriatal pathway) and RAPID Dissociation (hit and run of D2 antagonists)
***higher potency (lower ki) AtypicalsRisp, Zipras, Olanz
Atypicals - therapeutic useprimary psychotic disorders, bipolar disorder (regardless of psychotic fx), MDD w/ psychosis, **autism for kids (only drug approved)
***Aripiprazole-mechanism of actionPARTIAL d2 agonist, 5ht2a antagonist (“better modulation)
DOC for tx-resistant schizophreniaclozapine (in spite of relatively low d2 potentncy)
atypical w/ highest risk of extrapyramidal SE’sRisperidone
atypical - side effectmetabolic syndrome, cardiac (prolonged QT), h1- sedation, da- extrapyramidal, prolactin secretion, a1 - orthostatic hypotension, dizziness, M1
***2 aytpicals w/ highest weight gain SE’sclozapine, olanzapine (2nd line choice b/ cos risks)
****2 aytpicals w/ lowest metabolic effects SE’sziprasidone, aripiprazole
aytpical w/ risk of agranulocytosisCLOZAPINE (ANC < 500 mm3)
***2 aytpicals w/ high sedation tendencyclose, olanz

Mood Stabilizers

Question Answer
Mood stabilizers - therapeutic usemania and MDD - acute/extended tx/preventing recurrence (esp in bipolar disorder)
3 classes of mood stabilizerslithium, anti epileptics, antipsychotics
Lithium - therapeutic useacute mania, bipolar maintenance
***Lithium - mechanism (3 proposed)1- NT signaling (modulates DA, enhances 5HT) 2-2nd messenger (modifies cAMP levels, down regulates p.Kinase C via InositoI triphosphate pathway), 3- Neuroprotective (inactivates NMDA to prevent glut toxicity, decreases apoptosis, increase neuropil density)
Lithium - excretion and half-life95% glomerular filtration & urine excretion (**issue in renal disease) , HL = 20-24 hours
**Drugs (by type) that DECREASE lithium excretion(Li and Na compete for absorption) Diuretics, NSAIDs, BP medication
**Lithium - RENAL SE’s (short-term)effects on tubular fx = 1) polyuria, 2) nephrogenic diabetes (reversible)
Lithium - RENAL SE’s (long-term)effects on glomerular fx = 1) nephrotic syndrome (possible reversible) 2) nephropathy = chronic kidney disease
Lithium - non-renal SE’stremor (longterm), Nausea & voting, HYPOthyroid, cardiac (can lead to heart block), cognitive dulling, teratogen, psoriasis/acne


Question Answer
AE used for maintenance b/ not acute mania in bipolarLamotrigine
***Valproate- therapeutic useepilepsy (simple and complex absence, partial), migraine prophylaxis, **acute mania
*** Valproate-mechanism (3)inhibits v-dependent Na+ channel, enhance GABA fx, down regulates PKC (like Li)
***Valproate-drug interactions**active form is unbound (b/ 80% is bound to PLASM PROTEIN- toxicity w/ other bound drugs - NSAIDS!!) / **inhibits p450 (can increase levels of other drugs) - can increase WARFARIN levels
***Valproate Repro/Endo SE’steratogen (neural tube, lower IQ), polycystic ovarian syndrome (w/ weight gain)
Carbamazepine-therapeutic useepilepsy (partial & tonic-clonic), trigeminal neuralgia, manic + mixed episodes of bipolar
***Carbamazepine-mechanismstabilizes INACTIVATED Na+ channels (brain less excitable) / ?potentiate GABA receptors?
Carbamazepine-metabolismcity p450 (*inducer of hepatic metabolism and glucuronidation— induces its own!)
Carbamazepine-drug interactions(there are many) drugs that decrease Car (Phenytoin, Phenobarbital, Car) / Car decreases drugs (steroids, **estrogen contraceptives, benzos, warfarin)
Carbamazepine-SE’s*HEME (aplastic anemia, thrombocytopenia, agranulocytosis), neural tube defects, CNS (dizziness/ataxia/diplopia), GI nausea, Stevens-Johnson Syndrome, SIADH
Lamotrigine-therapeutic usepartial couple and generalized seizure, maintenance of bipolar I
Lamotrigine-mechanismblocks Na+ channels, modulates monamine repuptake, inhibits glutamate release
***Lamotrigine-drug interactions(**does not induce or inhibit hepatic enzymes) valproate doubles it / carbamazepine/phenobarbital and prim done REDUCE it
Lamotrigine-SE’suncomplicated rash, Steven’s johnson, CNS (dizzy/headache, double vision), **LESS PRONE to weight gain/cognitive slowing