General Pharmacology and Anti Psychotics Flashcards
Drugs with shorter half lives have _______ abuse potential.
-higer
Typical Antipsychotic Agents
- first generation
- high D2/5HT2A blocking ratio
- good efficacy against positive sxs
- high incidence of extrapyramidal toxicity
Haloperidol
- typical antipsychotic agent: D2 antagonist
- high potency typical antipsychotic agent
- inc. D2 side effects
- watch for extrapyramidal side effects
Chlorpromazine
- typical antipsychotic agent: D2 antagonist
- low potency typical antipsychotic agent
- adverse drug reaction (ADR) from M-H1-a1 block
Atypical Antipsychotic Agents
- 2nd generation
- low D2/5HT2A blocking ratio
- poor D2 block yet good antipsychotic efficacy
- good 5HT2A block good efficacy against negative symptoms
- poor D2 block + good 5HT2A block reduced incidence of EPSE
- clozapine, ariprprazole, olanzapine, quetiapine
- lower incidence of extrapyramidal side effects
Extrapyramidal Side Effects
- tremor
- slurred speech
- dystonia
- anxiety
- parania
Muscarinic Block Adverse Reactions
- dry mouth
- blurred vision
- urination difficulty
- constipation
- tachycardia
- sedation
Alpha 1 Adrenergic Block Adverse Reactions
-orthostatic hypotension
H1 Histamine Block Adverse Reactions
-sedation
D2 Block Extrapyramidal Side Effects
- acute dystonia (tx: anticholinergic agents ie. diphenhydramine-benztropine)
- akasthisia (tx: reduce dose, change drug, anticholinergic, beta blocker, benzodiazapine)
- pseudoparkinsonism (tx: anticholinergic agents)
- tardive dyskinesia (tx. rarely effective, prevention is best)
Pseudoparkinsons
- antipsychotic block of D2
- loss of inhibition of inhibitory indirect pathway leads to drug-induced movement disorder
Clozapine
- atypical antipsychotic agent: D2/5HT2 antagonist
- adverse rxns: lowered seizure threshold, AGRANULOCYTOSIS
- agranulocytosis- dose related
Antipsychotic Adverse Reactions
- muscarinic block
- alpha 1 adrenergic block
- H1 histamine block
- weight gain- risk of Type 2 diabetes
- D2 block- extrapyramidal side effects (acute dystonia, akathisia, pseudoparkinsonism, tardive dyskinesia)
- agranulocytosis
- altered thermoregulation
- photosensitivity
- lowered seizure threshold
- neuroleptic malignant syndrome
Absorption of Antipsychotic Agents
- incompletely absorbed
- variation can be reduced with use of liquid formulation
- significant first pass effect
Antipsychotic Agents Distribution
- extensively protein bound in plasma
- high lipid solubility
- cross the placenta to exert effects in the fetus
Antipsychotic Agents Metabolism- Excretion
- almost completely metabolized to more polar substances
- oxidized by CYP450 system, then conjugated
- can be excreted in breast milk
Psyc Drug Development in Past 50 Years
- most drugs mechanistically the same
- but newer drugs have fewer/better side effects
Pharmacodynamic Tolerance
- lessened response to active target site to the same drug concentration
- due to changes in receptor sensitivity or other adaptive changes
- a reduced effect of the drug generated by repeated administration of the drug in a particular environment
Metabolic (Dispositional) Tolerance
- change in pharmacokinetics results in lowered drug Cp at the active site
- inc. in metabolism is the primary mechanism
Cross Tolerance
-tolerance develops to one drug- then will be seen to other drugs of the same class/target
Learned Tolerance
- reduction in effects of a drug due to learned compensatory mechanisms
- behavioral tolerance and conditioned tolerance
Reverse Tolerance
- most common in CNS stimulants
- sensitization (inc. response) to drug following repeated doses
- sensitization in nucleus accumbens may play role in drug craving properties
Physical Dependence
- stop use abruptly -> withdrawal sxs
- neuroadaptation produced by repeated drug administration that necessitates continued administration to prevent the withdrawal syndrome from occuring
Psychological Dependence
- perceived need for drug (craving)
- related to pathologic learning in reward pathway
Cross Dependence
- ability of one drug to suppress the withdrawal associated with physical dependence on another drug
- related to pharmacological effects at target, not chemical similarities
- ex. EtOH and BDZs
Withdrawal
- characterized by rebound effects
- effects generally opposite of acute effects of drug
- can be fatal and may require emergent interventions
Quetiapine
-atypical antipsychotic agent: D2/5HT2 antagonist
D2 Receptor Block: Mesolimbic Pathway
-dec. positive sx of schizophrenia
D2 Receptor Block: Mesocortial Pathway
-inc. negative symptoms of schizophrenia
D2 Receptor Block: Nigrostiatal Pathway
- inc. extrapyramidal side effects:
- acute dystonia- tx with anticholinerics (diphenhydramine, benztropine)
- akathisia- tx with reduced dose, anticholinergic, beta blocker, BDZ
- pseudoparkinsonism- tx with anticholinergic agents
- tardive dyskinesia- tx: rarely effective, prevention
D2 Receptor Block: Tuberinfundibular Pathway
-hyerprolactinemia
D2 Receptor Block: Hypothalamus
- poikilothermia
- weight gain
D2 Receptor Block: Chemoreceptor Trigger Zone
-anti-emetic effects
5HT2A Receptor Block: Mesocortical Pathway
- dec. negative sx of schizophrenia
- CNS- weight gain
Muscarinic Cholinergic Block Side Effects
- ANS- blurred vision, dry mouth, constipation, difficulty urinating
- CNS- toxic confusional state
Alpha 1 Receptor Block Side Effects
-ANS- orthostatic hypotension, impotence, failure to ejaculate
Histamine H1 Receptor Block
-CNS- weight gain, sedation
