Comprehensive Huber PDF

1 Comprehensive: Ptl - Receptors SHTIA partial agonism: anti-depression 5H12 antagonism: weight gain,diabetes SHT 2A antagonism: ↑ DA release in striatum → ↓ EPS agonism: psychedelic experiences α, antagonism: orthostatic hypotension,rebound tachycardia...

1 Comprehensive: Ptl - Receptors SHTIA partial agonism: anti-depression 5H12 antagonism: weight gain,diabetes SHT 2A antagonism: ↑ DA release in striatum → ↓ EPS agonism: psychedelic experiences α, antagonism: orthostatic hypotension,rebound tachycardia agonism: vasoconstriction,leongestant H 1 antagonism: sedation, weight gain DI (D, g Ds) Excitatory ↑ CAMP agonism: concentration, executive function, Pleasure/reward,anorexic, hyper locomotion, oboliction, insomnia,anxiety, Psychosis D2 (D2, Dz, Dy) inhibitory & auto receptors ↓ CAMP antagonism: EPS (nigro striatal),hyper prolactinmid (tubers infundibular), reduce + symptoms partial agonism: ↑ compulsive/risk-taking behavior h ERG (Na channels) blocker: QTc prolongation M, antagonism: anticholinergic effects (dryness, constipation, itchiness,mental sluggishness, blurred vision,urinary retention) agonism: ↓ DA release, mental acuity Mz antagonism: metabolic syndrome, insulin dysregulation, diabetes DAT blocker: ↑ DA in synapse SERT blocker: ↑ SHT in synapse NET blocker: ↑ NE in synapse - Brain regions Prefrontal cortex: executive decision making, appropriateness,organized thought, cognition,focus cingulate gyrus: emotional regulation, attention, pain striatum: motor control/coordination thalamus: sensory relay,motor relay, hypothalamus: regulation of autonomic LIMBIC responses CHR, breathing), endocrine function nucleus accumbens: reward center LIMBIC amygdala: fear, orgression,motivation LIMBIC hippocampus: memory formation + LIMBIC consolidation - Dopaminergic tracts Tubero infundibular (ventral Tegmental Area origin): D2 antagonism: ↑ risk gynecomastia gamemrrhea Meso cortical (ventral Tegmental Area origin): Prefrontal cortex D2 antagonism:often m effect but may worsen -symptoms ↓ DA → - j cognitive symptoms mesolimbic ventral Tegmental Area origin): cingulate cortex,LIMBIC D2 antagonism; Alleviation of hallucinations, delusions, y paramia ↑ DA → + symptoms Nigro striatal (Substantia Nigra origin): movement initiation D2 antagonism: ↑ incidence of Parkinsonism, dystonia agonism: hyper locomotion,fidgeting,restlessness - A n t ip s y c h o t ic c h a r t s ( l o w e r # → h i g h e r r e c e p t o r a c t iv it y - A n t a g o n is m ) F G A * A i r i n g lo o s e b ir lin g S G A D o m i M o d u la t o r s o o C lo z a p in e o ooo s o  - Brain networks g Pathology Default mode network: activated during mind- Direct, Indirect Pathway: wandering,self-referential thinking Parkinson's: ↓DA (daydreaming) Direct: Direceptors (D, j Dg- ADHD: deactivated,response attenuated excitatory ↑ thalamic drive to during tasks that require attention cortex glutamate) (not able to focus on one task, bring initiate motor function multiple tasks to bear at one time, ex: raise hand mini constantly generating tasks) indirect: D2 receptors (Da,Dg,Dy- E✗terled Amygdala: inhibitory) ↓ thalamic drive to Amygdalal + Bed Nucleus Striae Terminalis cortex (GABA) (NST) Enlarged in Anxiety filters unwanted/ Amygdala(otional nucleus) triggers extraneous movements fear resp se to concrete stimulus ex: raise hand to the left BNST stores, accesses fearful memories, especially from senses Anxiety: amygdala detects fear,BNST amplifies fear response to a perceived stimulus (↑ glutaminergic firing) trigeminvascular: Migraines: brainstem activation along cranial nerve 5 (trigeminal nerve) → activation of pain receptors → release of nociceptors that will release CORP that will go into sympse felicit pain response happens along trigemin vascular system (blood vessels that run along w/ nerve jrelease vasoactive substances & trigger pain receptors R eward center: Neuro circuitry for addiction AUD: nucleus accumbens (reward center) produces + reinforcement (OA, Direceptors) Stimulation → release of endogenous opioid o peptides → inhibit GABA inhibition of OA neurons ↑ connections/synapses inbrain from ↑ release of BDNF Brain Derived Neurotrophic Factor) sustained ↑ connections due to ER of BDNF ↑DA, ↑ ΔFosB activity,999 BDNF release, 999 synaptic connections - methylphenidate us Amphetamines MOA methylphenidate: inhibits DAINE reuptake transporters → ↑ NT in synapse (blocks DAS NE) similar to cocaine,↓ risk burning out neurons overtime than amphetamines Amphetamines: l reverses uptake transporters on presynaptic terminals of mordaminergic neurons 2 Activates Vesicular Mmamine Transporter 2 (VMAT2) → releases symptic held NT - Barbituates us Benzos MA Barbituates: Phenobarbital,Pentobarbital,Primline Allosteric modulator of GABAA receptors to ↑ Cl flux (hyperpolarization) ☆ 9 duration of channel openings Benzos: clonazepam,Corazepate, Clobazam, diazepam, Lorazepam, Midazolam Allosteric modulator of GABAA receptors to ↑ Cl flux (hyperpolarization) ☆ ↑ frequency of channel openings - Pathological indicators of Parkinson's/Alzheimer's AD: Amyloid plaques buildup that attach outside neuron Tau forms neurofibrillary tangles → neuron flimsy f cannot function properly/destabilization of axonal microtubules (inside neuron) PD: α-synuclein functions to regulate synaptic vesicle trafficking g NT release- main constituent of Lewy bodies - G E N E S A D : A p o l i p o p ro t e in E ( A P O E ) A P O E 2 P ro t e c t iv e ( g o o d ) A P O E Y ↑ r is k A D ( b a d ) M S : H L A -D R B /* 15 : 0 1 P D : f o c u s o n o x id a t iv e s t r e s s ,m ito c h o n d r ia l f u n c t i o n , P r o t e o s o m a l p ro c e s s in g S N C A : en c o d es α S y n u c l e i n ( m a in c o n s t it u e n t o f L e w y b o d ie s P R K N : e n c o d e s D a r k i n ( t a g s p r o t e in s f o r d eg ra d a t io n ) L R R K 2 : d a rd a ri n , P A R K 7 : d e g ly ca s e D J - 1 , P I N K I : P T E N - in d u c e d K in a s e i - T r ip t a n /D it a n re c e p t o r a f f in it ie s S H T IA - a n t id e p re s s a n t S H T IB - v a s o c o n s t ric t io n S H T ID - o n n e r v e s , ↓ r e le a s e C G R P 5 H T 2 A - p s y c h e d e l ic r e s p o n s e s , h a l l u c in a t i o n s ☆ h ig h er # → ↑ e f f ic a c y a t re c e p t o r ( o r g a n is m ) - major ADRS valproic Acid: neural tube defect Topiramate,zonisamite: kidney stones Lancaneman: cerebral edema, hemorrhage Triptans: vasoconstriction, CV Dopamine agonists: impulse control issues Bromcriptine, cabergoline apomorphine, rotioptine,pramipexoll,ropiniroll Antipsychotics: EPS, sedation,weight gain (varies) SSRI/SNRIS initial: insomnia, irritability,migraines, suicidal thoughts long-term: insomnia/sedation,sexual dysfunction,bone fracture risk, Platelet dysfunction, weight gain/1055, 61, withdrawal upon abrupt a/C,serotonin syndrome fluoxetine, Paroxetine, sertraline,citalopram, escitalopram,fluvoxamine Venlafaxine, Des venlafaxine, Duloxetine, Milracipran/Levominacipran, Bupropion, Trazo done/Nefazo done, vilazodone, Vortioxetine, Mirtazapine Phenytoin: gingival hyperplasia Mirtazapine: weight gain Trazo done,Mirtazapine, Olanzapine,quetiapine, clozapine: sedation Clozapine: blood dyscrasia Amphetamines/methylphenidate: CV-tachycardia, arrhythmia, ↑ BP Na channel blockers: skin rash, CV Phenytoin/Fos phenytoin,carbamazepine/oxcarbazepi.nl/Eslicarbezapine, Lamotrigine, zonisamine, Lacosamide, Rufinamide Ziprasid one, citalopram: QTC Prolongation  - % s 1 0 % n e u r o n d e s t r u c t io n b e f o r e P D s y m p t o m s A n t ip s y c h o t ic D 2 r e c e p t o r o c c u p a n c y ; 6 0 - 8 0 % f o r e f f ic a c y , 8 0 + y o ↑ E P S ( e x c e p t c l o z a p i n e ) - D o p a m in e a g o n is t s & D z D z r e c e p t o r a f f in it y lin k e d t o im p u ls e c o n t ro l d is o r d e r m n - e r g o t d ru g s : a p o m o r p h in e - h it s r o t ig o t in e - h ig h d e g r e e P r a m i p e x o le - h i t s r o p i n i r o ll - h i g h e r a f f in i t y - N T S R e g u la t o r y : e x c it a t o ry : N E ( l o c u s c e r u l e u s ) , A c h ( p o n t i n e n u c l e u s ) ,H i s t a m i n e i n h ib it o ry : D A C V T A I N M L.m e ,T I F J S N i n N S ) , 5 H T ( r a p h e n u c le u s ) m a jo r : e x c i t a t o ry : G l u t a m a t e i n h ib it o r y : G A B A - G A B A r e c e p t o r - A U D d r u g s w it h d r a w a l : b e n z o s l o n g - a c t i n g : D ia z e p a m , C h l o r o l ia z e p o x id e i n t e r m e d ia t e : L o r a z e p a m , A l p r a z o l a m ,O x e z a p a m A v e r s i o n : D is u lf ir a m A b s t in e n c e : N a l t r e x o n e , A c a m p ro s a t e E t h a n / a c u t e ef f e c t s : d r u n k C h ro n ic e f f e c t s : c a r d io P ro t e c t io n ,a b u s e p o t e n t i a l , l iv e r d i s e a s e ,m e s s /c y p 2 E l m e t a b o l is m ; liv e r ① e t h a no l a lc o h o l a c e ta ld e h y d e d e h y d ro g en a s e ( h a n g o v e r ec ts ) ② a c e t a l d e h y d e a d e n in e a c e t a t e d e h y d ro g e n a s e