Scientific Foundation & Advanced Practice 2 Flashcards
What makes an antipsychotic “atypical”?
The mechanism of action that makes antipsychotics “atypical” is related to the serotonin (5HT2A) receptor antagonism.
Dopamine Pathways
- Explains the therapeutic effects and the side effects of the atypical antipsychotics
- Mesolimbic Pathway
- Mesocortical Pathway
- Nigrostriatal Pathway
- Tuberoinfundibular Pathway
Mesolimbic Pathway
- Hyperactivity of dopamine mediates positive psychotic symptoms
- Antagonism of D2 receptors treats positive psychotic symptoms (decreases positive symptoms)
Mesocortical Pathway
Decreased dopamine is responsible for the negative and depressive symptoms of schizophrenia
Nigrostriatal Pathway
- Mediates motor movements
- Dopamine blockade can lead to increased acetylcholine levels (increased salivation, lacrimation, blurry vision)
- Blockade of D2 can lead to EPS (dystonia, parkinsonian symptoms, akathisia)
- Long acting D2 blockade can lead to tardive dyskinesia
Tuberoinfundibular Pathway
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Blockade of D2 in this pathway can lead to increased prolactin levels
– hyperprolactinemia manifesting as amenorrhea, galactorrhea (risperdone), sexual dysfunction, gynecomastia - Long term hyperprolactinemia can be associated with osteoporosis
What is extrapyramidal side effects (EPSE)?
- It is caused by D2 receptor antagonism (dopamine receptors are blocked, ACh increases causing EPSE).
- Dopamine blockade in nigostriatal pathway.
What are the common EPSE?
- Akathisia
- Akinesia
- Dystonia
- Pseudo-Parkinson’s
- Tardive Dyskinesia
Acute Dystonia
- Muscle spasm
- Spasticity of muscle group (back or neck muscles)
- Stiff neck, painful
- Subjectively painful
- Facial grimacing
- Laryngeal spasms
-
Oculogyric crisis can lead to permanent damage.
–on physical exam, prolonged involuntary upward deviation of eyes bilaterally - Mistaken for agitation or unusual, stereotypic movements characteristic of schizophrenia
How do you treat Acute Dystonia?
Cogentin (Benztropine)
Akathisia
- Motor restlessness
- Inability to remain still
- Rocking, pacing, or constant motion of unilateral limb
- Common used rating scale: Barnes Akathisia Rating Scale and Extrapyramidal Symptom Rating Scale
- Mistaken for increasing anxiety
What is the treatment for Akathisia?
- Betablocker (Propranolol)
–can cause bronchospasm so contraindicated in patients taking bronchodilators like albuterol - Benztropine
- Benzodiazepine
Akinesia
- Absence of movement
- Difficulty initiating motion
- Subjective feeling of lack of motivation to move
- Mistaken for laziness or lack of interest
How do you treat Akinesia?
Cogentin (Benztropine)
Pseudo-Parkinson’s
- Stooped posture
- Shuffling gait
- Motor slowing
- Mask-like facial expression
- Pill rolling
- Tremors
- Muscle rigidity
- Mask-like facial expression often confused as affective blunting or flattening
How to treat Pseudo-Parkinson’s
Cogentin (Benztropine)
Tardive Dyskinesia
- Involuntary abnormal muscle movement of the mouth, tongue, face, and jaw that may progress to the limbs
- Can be irreversible
- Lip smacking and sucking
- Chewing motion
- Facial dyskinesia
- Can take up to 1-2 years to occur
- Can occur as an acute process at initiation of medication or as a chronic condition at any time
- The AIMS (Abnormal Involuntary Movement Scale) aids in the early detection of TD
- Tx: reduce the current dose or change to an atypical agent
- Deutetrabenzene (Austedo) and Valbenazine (Ingrezza) are FDA approved to treat TD
- Cogentin should NOT be used bc it can worsen symptoms
- Reglan (Metoclopramide) can cause EPS like TD and pseudoparkinson’s
What is pharmacokinetics?
Study of what the body does to drugs including absorption, distribution, metabolism, and excretion
What is absorption?
Method and rate at which drugs leave the site of administration.
– Oral medications: occurs in the small intestine and then in the liver
What is distribution?
Occurs after the drug leaves the systemic circulation and enters the interstitial and cells
– Drugs are redistributed in organs according to their fat and protein content
– Most psychotropic drugs are lipophilic and highly protein bound. Only the unbound (free) portion of the drug is active. – People with low protein (albumin) levels (malnutrition, wasting, or aging) can potentially experience toxicity from an increased amount of free drug.
What is metabolism?
- Process by which the drug becomes chemically altered in the body.
- First pass metabolism: Process by which the drug is metabolized by cytochrome P450 enzymes in the intestines and liver prior to going to the systemic circulation
What is elimination?
Process by which the drug is removed from the body.
What is half-life?
Time needed to clear 50% of the drug from the plasma.
– determines the dosing interval and the length of time to reach a steady state
What is a steady state?
Point at which the amount of drug eliminated between doses is approximately equal to the dose administered.
– it takes approximately 5 half lives to achieve a steady state and 5 half lives to completely eliminate a drug
How can liver disease affect pharmacokinetics?
Liver disease will affect liver enzyme activity and first pass metabolism that results in toxic plasma drug levels
How can kidney disease affect pharmacokinetics?
- Kidney disease or drugs that reduce renal clearance (NSAIDs) may increase serum concentration of drugs that are excreted by the kidneys (Lithium).
– Older adults are more sensitive to psychotropic drugs because of their decreased intracellular water, protein binding, low muscle mass, decreased metabolism, and increased body fat concentration
– body fat concentration is the only thing that increases because of less exercise
What is pharmacodynamics?
- Study of what drugs do to the body
- Target sites for drug actions include receptor, ion channels, enzymes, and carrier proteins
– Agonist effect
– Inverse agonist effect
– Partial agonist effect
– Antagonist effect - Example: Someone takes medication and it causes nausea, diarrhea, etc.
