drug (5, 12, 20, 23) Flashcards
(23 cards)
ischemic stroke: early presentation (1hr)
- 60yo woman wacute left hemiparesisfor 1hr
- dx:ischemic stroke(normal CT เพราะมาไว)
- thrombolytic therapy
- alteplase (tPA): mechanism → activate plasminogen at fibrin domain ทำให้ clot lysis / <4.5hrs / ADR → hemorrhage esp in brain / contraindication → high bleeding risk, BP >185/110
- ถ้า BP สูง ต้อง control BP ก่อน
- nicardipine, labetalol for maintain BP<185/110 & BP<180/105 after give thrombolytic [ใด ๆ คือถ้าจะไม่ให้ thrombolytic อาจปล่อยความดันได้ถึง 220/120 เลยนะ]
- หยุดยา anti-HTN อื่นก่อน ยกเว้น BB (in AMI, arrhythmia)
ischemic stroke: mechanical thrombectomy (5hrs) → stroke unit (24hrs+)
- mechanical thrombectomy: indicated for large vss occlusions if within6-24hrsof onset
- admitted to thestroke unit ~ rehab บลา ๆ ในลำดับถัดไป
intracerebral hemorrhage (ICH)
- 60yo woman wacute left hemiparesisfor 1hr
- dx: ICHat the rightbasal ganglia
BP Control ลดความดันให้เร็วที่สุด ⭐️
- usenicardipine or labetalolto maintain SBP ≈ 130-180
- aggressive BP control reduces the risk of hematoma expansion
tips
- reverse bleeding tendency (if any)
- surgical removal of blood clot (if needed)
- in case of spontaneous subarachnoid hemorrhage → search for possible aneurysm
- avoid thrombolysis: alteplasecontraindicated in hemorrhagic stroke
TOAST (2nd prevention based on etiology)
- cardioembolic: from AF, VHD, MI, or shunt
anticoagulants: vitK anta → warfarin / DOACs → dabigratan, -xaban - large vss atherosclerosis: extracranial or intracranial artery plaques
- CEA (carotid endartectomy ลอก plaque ออก) + anti-plt
- intensive anti-plt: aspirin (ASA) → inh plt aggregation, ADR ระวัง GI irritate or bleed / clopidogrel → P2Y12 inh, prodrug ~ CYP2C19, avoid using w omeprazole esomeprazole / cilostazol → PDE3 inh คือไป inh CAMP at plt and vss, CYP3A4 CYP2C19
- high-dose statin: goal LDL < 70 mg/dL to reduce future stroke risk
- small vss disease (lacunar stroke): HT, DM
useanti-plt(e.g. aspirin, clopidogrel) - undetermined: unknown cause
useanti-plt(e.g. aspirin, clopidogrel) - other causes: vasculitis, arterial dissection
tx: specific tx ตามโรคที่เป็น
melatonin เซฟ ใช้ง่าย
- indication: jet lag, circadian rhythm disorders, คนแก่ ∼ neurodegen
- melatonin receptor ago(e.g. ramelteon – not available in TH): action at MT1 MT2 receptor at SCN ทำให้หลับเร็วขึ้นหลังเข้านอน / ADR: can cause liver dysfx
- ADR รวม ๆ ฮะ headache, nightmare, mood change, paradoxical insomnia คิดว่าตัวเองนอนไม่หลับทั้ง ๆ ที่หลับอยู่
benzodiazepines— BZD (e.g. diazepam, lorazepam)
- mechanism: enhance GABA-A receptor activity → inh effect ↑
- form: short-acting <6hrs (more potent & ADR) → midazolam, clorazepate / intermediate-acting 6-24hrs → alprazolam, lorazepam (safest in liver disease bc dont form active metabolite) / long-acting >24hrs → clonazepam (long HL & high potency), clonazam, diazepam
- effect, symptom หลังใช้ยา: sedative, muscle relaxant, anxiolytic, antiseizure, alcohol withdraw (lorazepam)
- ADR: anterograde amnesia, induced delirium or dementia, daytime sedation may cause falls or accident, complex sleep behavior, rs depression //long-term use esp BZD cause tolerance, dependence, withdrawal ∼ anxiety, tremor, hyperreflex, orthostatic hypoten, rebound insomnia, seizure
- caution: liver toxicity and high protein binding esp clorazepate and diazepam
- antidote:flumazenil(for overdose)
Z-drugs(e.g. zolpidem, zaleplon)
- indication: insomnia (fast-onset)
- mechanism: relatively selective GABA-A receptors (α1 subunit)
- ADR: คล้าย BZD แต่น้อยกว่า ∼ dependence, tolerance, rebound insomnia, complex sleep-related behavior //long-term use cause tolerance, dependence, withdrawal ∼ anxiety, tremor, hyperreflex, orthostatic hypoten, rebound insomnia, seizure
- caution: metabolized by CYP3A4
- antidote:flumazenil(for overdose) ได้เหมือนกัง
barbiturates(e.g. phenobarbital)
- indication: phenobarbital PHB → seizure control / thiopental → anesthetic agent, anticonvulsant-status epilepticus
- mechanism: bind w GABA-A receptor แบบรุนแรวง [ลูกพี่ของ BZD]
- ADR: coma, lethal dose //long-term use cause tolerance, dependence, withdrawal ∼ anxiety, tremor, hyperreflex, orthostatic hypoten, rebound insomnia, seizure
- caution: cant antagonized by flumazenil (bc different binding site)
orexin receptor anta (e.g. suvorexant, lemborexant)
- mechanism: block orexin receptor → arousal signal ↓
- metabolized by CYP3A4
- ADR: sleep paralysis, nightmares
- contraindication: narcolepsy
อื่น ๆ ยาหลับ
1st gen antihistamines(e.g. diphenhydramine, hydroxyzine)
- mechanism: blockH1 receptor → sedation
- ADR: cognitive impairment (from REM↓), daytime drowsiness soooo pls avoid in elderly na
anti-psychotic
- mechanism: 5HTA2 5HT2C, alpha, H1 anta
- indication: aggression, agitation, hallucination
- ADR: QT prolong, extrapyramidal side effect (EPS)
sedating antidepressants(e.g. trazodone, mirtazapine)
- use: insomnia esp pt w depression
anti-seizure (e.g. gabapentinoid) ไม่เกี่ยวกับ GABA นะจ้ะ
- mechanism: inh presynaptic voltage gated P/Q type Ca2+ channel
- indication: neuropathic pain, antiseizure
มัดรวบ how to select sleep-promoting agent
- แก่: non-pharmaco (CBT, sleep hygiene), melatonin //avoid TCAs, antihistamine, BZD
- insomnia w depression/anxiety: agomelatine, mirtazapine, trazodone, TCAs
- insomnia w pain/anxiety: pregabalin, gabapentin
- hallucination and delusion: sedative antipsychotic e.g. olanzapine, risperidone, aripriprazole
- insomnia in AD: melatonin + symptomatic tx
- short-term insomnia adult: shortest course of BZD
- safety: melatonin>zolpidem, DORA (orexin anta)
- liver disease: avoid BZD (safest is lorazepam)
- heart disease: be careful use of antidepressant, antipsychotic เพราะอาจเกิด QT prolong
neurobiology and management of insomnia
neurobiology of insomnia: overactive arousal systems (e.g.,orexin, histamine) interfere with normal sleep onset and maintenance
management of insomnia
- behavioral interventions: CBT-I(Cognitive Behavioral Therapy for Insomnia) is gold standard / sleep hygiene (regular sleep schedule, no screen time before bed)
- pharmaco: short-term use ofZ-drugsorbenzodiazepines / melatonin→ circadian rhythm-related insomnia / orexin antagonists(e.g., suvorexant) → chronic insomnia.
caffeine
- mechansim: adenosine receptor anta → promotes wakefulness [not more than 400mg/day]
- ADR: Insomnia, jitteriness, increased heart rate
drug for narcolepsy here
modafinil / armodafinil
- mechanism: weak DA reuptake inh
- use: narcolepsy // also obstructive sleep apnea (residual sleepiness), shift work disorder
methylphenidate <3
- mechanism: DA and NE reuptake inh (เลยไปกองกันที่ synaptic cleft)
- use: narcolepsy, ADHD
- contraindication: glaucoma, severe HT, motor tics, tourette, FH of tourette syndrome
GABA-A receptor modulator (GABA-A ago → inhibitory activity ↑)
- benzodiazepines (BZD)
- drug: diazepam, midazolam
- mechanism: bind btw α & γ subunit
- caution: resistance, tolerance, withdrawal
- barbiturates (ลูกพี่ของ BZD🤘🏻💢)
- drug: phenobarbital (PHB)
- mechanism: bind α subunit
- ADR: adult → sedative effect / child → hyperactivity / dependence and withdrawal seizure
- caution: CYP450 inducer
presynaptic voltage-gated Na+ channel (sodium channel blocker)
- phenytoin (PHT)
- ADR: dose-dependent → vestibulocerebellar toxicity / dose-independent → STS/TEN, rapid infusion lead to arrhythmia & purple glove syndrome / chronic toxic → cerebellar atrophy, gingival hyperplasia, ลด bone density
- metabolized by CYP2C9 > CYP2C19
- carbamazepine (CBZ)
- indication: focal-onset seizure, neuropathic pain (trigem neuralgia)
- ADME: CYP450 inducer, auto-induction ระดับยาตกเองเมื่อให้ไปสักพัก
- ADR: toxic metabolite → epoxide / dose-dependent → vestibulocerebellar toxicity / dose-independent → aplastic anemia, SIADH, SJS/TEN w HLA-B*1502
- oxcarbazepine
- similar to carbamazepine but with fewer ADR (no enz inducer, no epoxide)
- ADR: SIADH อาจมีมากกว่า, AA น้อยกว่า, แพ้ยาได้เหมือนกันจ้า
- lamotrigine 👸🏼💅
- broad spectrum (also treats bipolar and migraines)
- slow onset of action, ยาเอกนางเอก gets reduced by other drugs, safe in preg
- ADR: vestibulocerebellar toxicity, rash (risk of SJS), paradoxical insomnia
multi-mechanism
- valproic acid / valproate (VPA)
- broad spectrum (used for generalized seizures, bipolar disorder, migraine), neuropsychiatric, abscense seizure
- mechanism: inh VGNC, inh post synaptic NMDA receptor, inh threshold T-type Ca2+ channel
- enz inh esp DI w lamogritine
- ADR: Many! hepatitis, hyperammonemia, tremor and parkinsonism (dose-dependent), cosmetic, metabolic syndrome, plt ต่ำ and dysfx, teratogenicity (NTD)
- topiramate (TPM)
- indication: broad-spectrum
- mechanism: inh VGNC NMDA non-NMDA, stimulate postsynaptic GABA, carbonic anhydrase inh
- ADR: neuro (numbness tingling, impair cognition), weight loss, metabolic acidosis may lead to kidney stone, teratogenicity (oral cleft in 1st tri)
presynaptic voltage α2-δ1 subunit Ca²⁺ channel blocker
Gabapentinoid group
- drug: gabapentin (GBP), regabalin (PGB)
- mechanism: block presynaptic voltage gated N and P/Q type Ca2+ channel (VGCC) ɑ2-δ1
- dose adjustment in renal impair เพราะขับที่ไตเปนหลัก
synaptic vesicle modulation (SV2A Modulators)
- levetiracetam (keppra)
- PK ดีดีดี – renally excreted and minimal interactions
- DI: w DOACs via P-gp inh
- Go-to drug when you are unsure of what else to use! คิดไรไม่ออกบอก keppra
summary by seizure type
- focal seizures
- Carbamazepine, Oxcarbazepine, Lamotrigine, Levetiracetam
- generalized tonic-clonic seizures
- Valproate, Phenytoin, Lamotrigine, Levetiracetam, phenobarbital
- absence seizures
- Ethosuximide (first-line), Valproate
- myoclonic seizures
- Valproate, Levetiracetam
- status epilepticus
- 1st line: benzodiazepines (IV diazepam repeated once คือให้ได้สองครั้ง)
- 2nd line (4 ตัวเท่าน้าน): phenytoin or fosphenytoin / valproic acid / levetiracetam / phenobarbital (ตัวนี้ high sedation)
- 3rd line: repeated 2nd line + anesthetic agent (midazolam, thiopental, pentobarbital, propofol)
- Infantile spasm
- vigabatrin (VGB) ไป inh GABA transaminase → increase GABA activity / ADR มี irreversible visual loss ได้
pd x dopamine หน้านั้นแหละ
- nigrostriatal - substantia nigra (A9 กก motor effect): Aก้าว มีผลกับมอเต้อ
- mesolimbic midbrain (A10): สิบหลอน
- tubulohypophyseal from hypothalamus: ไป pitui ก็ inh prolactin release
แล้วก้มี receptor ของ dopamine อีกหลายที่เลย ๆๆ area postrema ด้วย that’s why ADR have n/v
ultimate pd drug
- anticholinergic (benztropine, trihexyphenidyl): pros → some antiparkinsonian efficacy (ช่วยเรื่อง tremor), dystonia / cons → เยอะมากเลยไม่ใช้ละ, cognitive side effects**
dopaminergic drug
- levodopa (use w AADI: carbidopa, benserazide) ช่วยให้ไม่เปลี่ยนเป็น dopamine ที่ peripheral เลยเข้า BBB ได้ ละไปเปลี่ยนเป็น dopamine ในสมองแทนเพราะ AADI เข้าไปด้วยไม่ได้
- motor complication: motor fluctuation (wearing-off effect, on-off phenomena, dose failure, freezing) & dyskinesia (peak dose, di-phasic dyskinesia, off-period dystonia)
- form: extended-release, gel (LCIG), powder
- pros → most symptomatically efficatious antiparkinsonian drug, all pt response ยาปาติหาริย์ / cons → dyskinesia choreiform movement, motor fluctuation, neuropsychiatric problems like confusion or psychosis, sedation, nausea, it doesnt tx all feature of PD
- dopamine agonist
- ergot: bromocriptine, pergolide / non-ergot: rotigotine (ตัวนี้ชอบจับกับ D2 มีเปน transdermal patch), piribedil (D2/D3 ago with alpha-2 anta)
- ergot ass w serious cardiac complication from promote vulvular heart disease due to stimulate 5HT2B serotonin receptor ∼ also retroperitoneal fibrosis and ischemia
- ADR: orthostatic hypotension, psychosis, hypersomnia, sleep attack, pedal edema, impulsive disorder control (กก gambling hypersexual shopping binge eating อย่าลืมซักประวัติเวลาเจอคนไข้นะจ้ะ)
- COMT inh ช่วยลด peripheral conversion จะได้เข้า BBB ไปเย้อ ๆ: entacapone, tolcapone (tolcapone more potent but can cause hepatic failure)
- pros → decrease “off” time and increase “on” time, enhance motor, response in pt who levodopa motor fluctuation, improve motor in stable levodopa responder / cons → dopaminergic side effect esp dyskinesia, discoloration of urine
- MAOB inh ทำให้ dopamine อยู่ใน synapse นานขึ้น ไม่ถูกทำลาย (selegiline, rasagiline): becareful when use w SSRI SNRI TCA, อาหารที่มี tyramine สูง esp cheese อาจ increase BP
drug for tx its ADR
- แก้ motor fluctuation ด้วย: apomorphine (dopamine ago), zonisamide (antiepileptic)
- antidyskinetic: amantadine (NMDA anta and anticholinergiceffect), clozapine
pharmaco motor ที่ไม่ใช่ pd (4 โรคเท่าน้าน)
- tremor (essential tremor)
drug: propanolol, metropolol, pinolol (partial agonist so it may produce tremor), peripheral beta-2, others e.g. topiramate gabapentine - chorea
drug: tetrabenazine (เป็น VMAT2 inh) - dystonia (torticollis)
drug: botulinum toxin, dopaminergic, antidopaminergic, anticholinergic - tic
ควรลอง comprehensive behavioral intervention for tics (CBIT) ก่อนเริ่มยา / drug: alpha2-ago (guanfacine, clonidine), antipsychotics, topiramate, dopamine deplete (tetrabenazine, VMAT2 inh)
