Pharm Flashcards
What DA pathway controls movement?
Nigrastriatal
What DA pathway controls reward and perception?
Mesolimbic
What DA pathway controls executive function?
Mesocortical
What DA pathway controls pituitary prolaction function?
Tuberoinfundibular
2 Post-synaptic enzymes that terminate DA action:
MAO A or B
COMT
Hyperfunctioning Migrostriatal pathway causes:
Hypofunctioning causes:
Hyper: dyskinetic movemnt
Hypo: dyskinetic movement, parkinsonism
Hyperfunctioning Mesolimbic pathway causes:
Hypofunctioning causes:
Hyper: Addiction, hallucinations
Hypo: amotivation, apathy
Hyperfunctioning Mesocortical pathway causes:
Hypofunctioning causes:
Hyper: hypervigilance
Hypo: inattention
Hyperfunctioning Tuberoinfundibular pathway causes:
Hypofunctioning causes:
Hyper: hypoprolactinemia
Hypo: hyperprolactinemia
What drugs to enhance DA synthesis?
Levodopa: DA precursor
Carbidopa: combined therapy to prevent peripheral DA activity –> lower side effects
Results of low and high DA activity:
Low: distractable
High: hypervigilant
ADHD: ___ DA activity at ___
low, anterior cingulate
Parkinson: ___ DA activity at ___
low, striatum
Why is MTHFR enzyme important?
Genetics?
Creates L-methylfolate, which is the form that can cross BBB
TT alleles bad –> less DA made
Bupropion:
Treats?
Class?
Affects what pathway?
Antidepressant
NDRI
Mesocortical
Amphetamines mechanism:
- Block DAT
- Increase VMAT2 –>more DA release
Methylphenidate mechanism:
-Block DAT
2 wakefulness promoting stimulant drugs:
Treats?
Side effects?
- Modafinil, Armodafinil
- Narcolepsy
- Off label: ADHD
- P450-3A4 inducer
Selegiline:
low dose is used for for?
high dose is used for?
Low dose: MAO-B selective –> Parkinson
High dose: MAO A and B –> Depression
Rasagiline mechanism:
treats?
- MAO-B inhibitor
- Parkinson’s
MAOIs for Depression:
- Isocarboxazid
- Phenelzine
- Tranylcypromine
- Selegiline
Serotonin Syndrome
- MAOI decrease Serotonin breakdown
- Adding Serotonin drug –> toxic levels in CNS
- Tremor, muscle spasm, vital changes, hyperthermia, delirium, coma, death
COMTi drugs:
treats?
effect on neurotransmitters?
- Entacapone, Tolcapone
- Parkinson’s
- elevate DA and NE
D2 receptor agonists:
treats?
- Bromocriptine, pramipexole, ropinerole, Apomorphine injection
- Parkinson’s or Restless leg Syndrome
D3 receptor agonists:
treats?
- Aripiprazole
- Antipsychotic for Schizo
- Depression
Amantadine mechanism:
treats?
- Release DA, block DAT, stimulate D2
- Parkinson’s, Influenza
Reserpine treats:
HTN, Schizo psychosis, causes Depression
Tetrabenazine treats:
Huntington’s Chorea by lowering DA availability
D2 receptor antagonist affects which pathways?
treats?
classification?
ALL; they are non-selective
Schizophrenia
FGAs (high, low potency), SGAs
What causes EPS?
Symptoms?
- High Potency FGA
- Akathisia, Dystonia, Parkinsonism, Neuroleptic Malignant Syndrome
Symptoms of Neuroleptic Malignant Syndrome:
- Hyperthermia
- Muscle rigidity
- Vital sign instability
- Rhabdomyolysis
What is Tardive Dyskinesia
- Chronic D2 receptor antagonism
- Permanent movement disorder side effect
- Choreic or Athetotic movements
High vs Low Potency FGA drugs:
- Haloperidol
- Thioridazine
- Thiothixine
- Fluphenazine
- Chlorpromazine
High:
Haloperidol
Fluphenazine
Thiothixine
Low:
Chlorpromazine
Thioridazine
Blocking ___ receptor lowers EPS risk
Serotonin 2a (5HT2a)
Side effects of ‘Dones’ vs ‘Pines’
Dones: more EPS
Pines: more sedating, more metabolic syndrome
Clozapine risks and benefits
- Risk of agranulocytosis
- Most metabolic risk of any agent
- No neuromuscular effect –> no EPS/TD
Blocking what receptor stops psychosis?
D2
Mechanism of action for Beta blockers in Glaucoma?
Reduce aqueous production
Suffix for carbonic anhydrase inhibitors:
-zolamide
Mechanism of action for Carbonic Anhydrase Inhibitors in Glaucoma?
Reduce production of aqueous
Mechanism of action for Prostaglandin Analog in Glaucoma?
Increase uveoscleral outflow w/o effect on aqueous flow or trabecular outflow facility
Cocaine mechanism for diagnosing Horner’s Syndrome
- Cocaine = reuptake inhibitor –> NE flood –> pupillary dilation
- Horner’s Syndrome = dysfunctional PANS –> no pupillary dilation
What drug is used to differentiate preganglionic from postganglionic lesions in Horner’s Syndrome?
Hydroxyamphetamine: Releases NE
Hydroxyamphetamine mechanism for differentiating lesion location in Horner’s Syndrome
- Topical application
- No pupillary dilation = 3rd order neuron problem = Postganglionic = benign process
- Dilation = Preganglionic lesion –> requires investigation
How do you differentiate Adie’s syndrome from an intracranial aneurysm?
- Low dose muscarinic agonist (Methacholine or Pilocarpine)
- Chronic denervated nerve in Adie’s syndrom will be hypersensitive –> pupillary constriction
- Acute trauma neurved from aneurysm will not respond
What is light-near dissociation?
No pupil response to light, but does have accomodation
Most common cause and population affected by Parinaud’s Syndrome
- Midbrain tumor (pineal)
- Young children
Common presentation and population affected by Adie’s Syndrome
- Loss of patellar reflex
- Young females
What characterizes Argyll-Robertson Syndrome:
- Miotic irregular pupils
- Does not respond to cycloplegics
Triptan’s mechanism of action:
5HT1 B-D agonist –> vasoconstriction of intracranial EXTRACEREBRAL blood vessels (trigeminovascular system) –> block sterile inflammation reaction
In what patient population are triptans contraindicated?
Patients w/ vascular disease, uncontrolled HTN, and comlicated migraine syndromes
Migraine vs Tension vs Cluster Headache characteristics:
Migraine: unilateral, throbbing, moderate-severe, aggravated by activity, relieved by rest
Tension: dull, achy, non-pulsatile, pressure-like, bilateral, mild-medium
Cluster: severe, unilateral, in temporal, orbital or supraorbital areas
Most commonly used Beta blocker for Migraine?
Propranolol
Most commonly used Ca++ Channel Blocker for Migraine?
Verapamil
-useful for aura
For what patient population is Migraine prevantative therapy recommended?
- 3+ severe headaches/month or
- 2+ mild-moderate headaches/week or
- inability to use effective symptomatic therapy
2 Anti-epileptics used for migraine prevention
Valproic Acid, Topiramate
Cluster Headache characteristics:
- Clockwork daily and annual rhythm (same time)
- Men:women 4:1
- Some patients have heavy facial features
Long-term Cluster Headache prevention drugs:
- Verapamil (Ca++ channel blocker)
- Topiramate (antiepileptic)
- Valproic Acid (antiepileptic)
- Lithium (mood stabilizer)
Biogenic Amine Hypothesis of Depression:
Depression = too little CNS NE and/or 5HT
Scoring of Hamilton Depression Rating Scale (HDRS):
Mild= 8-13
Moderate= 14-18
Severe= 19-22
Very Severe= >23
What do MAO-A and -B mainly oxidize?
- A = NE, 5HT, Tyramine
- B = DA, phenyethylamine
What is the most used TCA for TTH prevention?
Amitriptyline
What is a common side effect of TCAs?
Cardiac arrhythmias
What 2 SSRIs have P450 Inhibition
Fluoxetine, Paroxetine
What is Ketamine’s mechanism of action?
Glutamate NMDA receptor antagonist
What drug can quitting smokers use to maintain nicotine abstinence?
Bupropion - Atypical antidepressant
What is the important side effect of Buproprion?
Lowers seizure threshold
What can happen if you give a Bipolar person tricyclics?
Precipitate mania
What are the 3 structural parts of local anesthetics?
- Aromatic ring
- Intermediate Linkage
- Terminal Amine
If there is a big difference between pKa of local anesthetic and physiologic pH, what form will be more common? (uncharged/charged)
Charged
The (charged/uncharged) form of a local anesthetic can penetrate membranes
Uncharged
Which structural part of a local anesthetic determines lipid solubility and potency?
Aromatic Ring
Metabolism of Ester vs Amide Local Anesthetics:
Esters: metabolized by plasma enzymes
Amides: Metabolized by hepatic P450 enzymes
How and where do local anesthetics bind intracellularly?
- Reversibly
- Intracellular portion of Na channel
High risk for CNS toxicity from which 2 Local Anesthetics?
Bupivacaine, Ropivacaine
Which requires higher dose of Local Anesthetics: CNS or Cardio toxicity
Cardiotoxicity
What is Transient Neurological Syndrome and which local anesthetics can cause it?
- Severe transient pain from local anesthetic use in spinal anesthesia
- Lidocaine, Procain, Mepivacaine
Which group (ester or amide) of local anesthetics have high allergic reaction rates?
Esters – PABA metabolites = known allergen
Which nerve fibers are first to be blocked by local anesthetics?
- B and A delta
- Generally: smaller, myelinated nerves blocked first
What are toxic side effects of Na+ channel blockers?
What is a side effect?
Toxicity = Dizzy, drunk, double vision
Side effect = 15% have rash, rare Steven Johnson syndrome
What is a contraindication for Valproate? Why?
Pregnancy – 4-8% Teratogenic
What drugs can be given for status epilepticus?
IV: Phenytoin, Lorazepam, Diazepam, Valproate
Absence seizure.
What drug? Mechanism?
Ethosuxamide
- T-type thalamus Ca++ channel blocker
Mechanisms for Anti-epileptics:
- Voltage-gated Na+ channel blockers
- Voltage-gated Ca++ channel blockers
- Glutamate receptor blockers
- GABA system agonists
Difference between Felbamate and Topiramate
Felbamate = NMDA blocker Topiramate = AMPA and Kainate receptor blocker
Difference between toxicity and side effect
Toxicity: Unwanted effect of drug
Side effect: unexpected effect, not related to mechanism of action
Which anti-epileptic exhibits no metabolism?
Gabapentin
What drug has synergistic action/competes with valproic acid
Lamotrigine
Antiepileptic drug with “word finding” problem toxicity
Topiramate
What is the Meyer-Overton Rule?
Potency of anesthetic gases directly related to their solubility in olive oil
What is the gold standard drug for maintenance of general anesthesia?
Isoflurane
