Ch 12-19 Flashcards
Neuropharmacolocy
Study of drugs that alter processes controlled by the nervous system
How do neurons eleicit responses from other cells?
Through axonal conduction and synaptic transmission; effect depends on neurotransmitter and cell type; can modify processes such as skeletal muscle contracton, cardiac output, vascular tone and GI function.
Types of postsynaptic cell:
neurons, muscle cells or cells with a secretory gland
Axon conduction
process of conductin an action potential down the axon of a neuron; not sellective; e.g. local anesthetic
Synaptic Transmission
process by which information is carried accross gap b/n neuron and post-synaptic cell; requires release of neurotransmitter molecules and their binding to receptors on postsynaptic cell; sellective; includes most drugs
5 steps in synaptic transmission
1) synthesis,
2) storage
3) release
4) binding
5) termination
Sythesis
molecules of transmitter must be present in nerve terminal
storage
UNTIL TIME OF RELEASE IN VESICLES IN AXOM TERMINAL
release
VESICLES UNDERGO FUSION WITH THE TERMINAL MEMBERANE, RELEASING CONTENTS INTO SYNAPTIC GAP
Binding
is reversible
termination
3 possible processes:
1) reuptatke, 2) enymatic degradation
3) diffusion
T or F: The activation of a synaptic transmission will have an effect on a receptor funtion equivalent to that produced by the natural transmitter at a particular synapse.
True. And the drug can either increase or decrease recptor activation
3 ways inwhich drugs can effect transmitter synthesis
increase transmitter synthesis - storage vesicles hold transmitter in elevated amounts and when action potential reaches the axon terminal more transmitter will be released and available to receptors or postsynaptic dell, thus a hightened activation of receptors.
2) decrease transmitter synthesis
3) cause synthesis of transmitters more effective than the natural transmitter itself (super treanmitters).
Agonists
Drugs that cause direct activation
Antoagonists
Drugs that prevent direct activation
Name some drugs that cause activation:
morphine, epinepherine, insuline
Name some drugs that prevent activation:
Naloxone, antihistimines, propranolol (for hypertension)
Benzodiazepinesw do poisions act:
bbind to receptors and thereby enhance their activity
divisions of the PNS
somatic motor system (SMS) - voluntary muscle movement
Autonomic nervous system (ANS) - parasympathetic and sympathetic
Functions of ANS
regulate heart, regulate secretory glands, regulate smooth muscles
functions of parasympathetic nervous system
Cholinergic: housekeeping, energy conservation: slow heart rate, increase gastric secretions, empty bladder empty bowel, focus - near vision, constrict pupil, contract bronchial smooth muscle
How do poisons work?
They act by mimicking or blocking affects of PNS stimulation. i.e. insecticides or nerve gases.
Functions of sympathetic nervous system
Regulate cardiovascular system;
regulate body temperature
Fight or flight - increase HR and BP, shunt blood, dilate bronchi, dilate pupils, mobilize glucose
Main elements of feedback loop:
1) a sensor - to monitor status of a physiologic process
2) an effector
3) neurons connecting the sensor to the effector
3 homeostatic objectives of the sympathetic nervous system
Maintenance of blood flow to the brain
Redistribution of blood flow during exercise
Compensation for loss of blood, primarily by causing vasoconstriction
3 ways inwhich sympathetic nervous system regulates body temp:
1) regulating blood flow to the skin; by dilating surce vessels, sympthtic nerves increase blood flo to the skin and accelerate heat loss, or by constricting cutaneous vessels they conserve heat
2) nerves to sweat glands promote secretion of sweat for cooling
3) inducing piloerection to promote heat conservation
Baroreceptor reflex
Feedback loop of autonomic nervous system that helps regulate blood pressure; most important feedback loop of the ANS from a pharmacologic perspective; frequently opposes attempts to modify BP with drugs.
Process of baroreceptor relex
1) Baroreceptors located in carotid sinus and aortic arch monitor changes in blood pressure and send info to brain;
2) in response, the brain sends impulses along nerves of autonomic nervous system, instructing heart and blood vessels to restore BP to normal
Autonomic tone
- the steady, day-to-day influence exerted by autonomic nervous system on a particular organ or organ system; provides a basal level of control over which relex regulation is superimposed,
Which nervous system is the predominant tone for the vascular system?
he sympathetic nervous system.
Most organs rely on which nervous system to provide the predominant tone?
The parasympathetic nervous system
3 patterns of autonomic innervation and regulation:
Innervation by both divisions of the ANS in which the effects of the 2 divisions are opposed
Innervation by both divisions of the autonomic nervous system in which the effects of the 2 are complementary
Innervation and regulation by only one
The general sites where drugs can affect the sympathetic and parasympathetic nervous systems:
1) the synapses b/n preganglionic and postganglionic neurons (includes adrenal meddula for sympathetic) and
2) the junctions between postganglionic neurons and their effector organs
Sympatholitic
(sympathetic antagonists)
(andronergic antagonists)
Drugs that decrease or block sympathetic nervous system response
Parasympatholitic
Drugs that decrease or block parasympathetic nervous system responses
T or F: Drugs that affect the autonomic system, affect many organ and have many uses.
True
Beta receptors are on the ____and on the ____, and alpha receptors are on the ______.
heart and lungs, receptors on the blood vessels
The sympathetic system, in response to a stimulus, will send epinephrine to shut down blood flow to the _____.
- gastrointestinal tract
Albuterol
- an adrenergic beta2 agonist used in asthma for bronchodilation; also causes rise in HR and BP.
Beta blockers are drugs often used to treat ______ and _____.
= high blood pressure and high eye pressure (glaucoma); main concern is bronchospasms in asthmatics b/s it constricts the lungs as well as the blood vessels to heart and eyes.
In parasympathetic nervous system, ______ binds to ______.
- acytelcholine, muscarinic receptors.
Bethanechol is a _____.
- cholinergic, muscarinic agonist; used to stimulate BM and urine output
Indirect cholinergic agonism
- Acetylcholinesterase inhibitors block breakdown of acetylcholine to increase its levels
The suffix for names of Acetylcholinesterase inhibbitors
“-ygmine”
Atropinecholinergic
- a cholinergic muscarenic antagonist; or an anticholinergic; or an antimuscarenic; or a parasympatholytic
Uses of Atropine
- speed up HR
- used as an antidote for organophosphate poisoning
- used to treat diarrhea
Mydriasis
-dilating the pupils; can be done with sympathomimetic adrenergic drugs or anticholinergic parasympatholytic drugs
Myosis
- constricting the pupils; can be done with sympatholytic adrenergic antagonist drugs or cholinergic parasympathomimetic drugs
Adrenergic blockers or cholinergic drugs can ____ lacrimal glands to _____.
stiumlate lacrimal glands to make tears
Inotropes
- drugs that increase the force of contraction
Etiology of Parkinson’s is idiopathic but some possible causes are:
- Oxidative damage
- Environmental toxins
- Genetic predisposition
- Accelerated aging
- Drugs
Discuss the dopamine/acetylcholine imballance in Parkinson’s:
- There is too little dopamine to inhibit neurons that release gamma-aminobutyric acid (GABA).
- There is too much ACh compared with dopamine, and the ACh excites the neurons that release GABA.
- The excess GABA causes the movement disorder.
The relative ACh excess in Parkinson’s disease also causes:
- diaphoresis, excess sebaceous secretion, salivation, lacrimation, constipation, prolonged urination and urinary incontinence.
Anticholinergic agents cause these CNS side effects in the elderly
(confusion, sedation, delirium, hallucinations),
Patients taking anticholinergic drugs for Parkinson’s disease should be warned of and assessed for the following side effects:
- Dry mouth
- Blurred vision, photophobia, and increased intraocular pressure
- Urinary retention and constipation
- Tachycardia
Dopaminergic drugs ______ the balance between dopamine and ACh in the CNS
- help restore
5 categories of dopaminergic drugs
- Dopamine replacement
- Dopamine agonist
- Dopamine releaser
- Catecholamine-O-methyltransferase (COMT) inhibitor
- Monoamine oxidase–B (MAO-B) inhibitor
_______ (e.g., donepezil [Aricept]) are FDA approved for the treatment of Alzheimer’s disease, but only slow the disease by a few months.
Cholinesterase inhibitors
Risk factors/ concerns with Cholinesterase inhibitors
- The drugs increase ACh and enhance transmission in remaining healthy neurons only.
- Systemic cholinergic effect can cause nausea, vomiting, dyspepsia, diarrhea, dizziness, headache, and bronchoconstriction.
- The drugs have vagotonic effects on the sinoatrial and atrioventricular (AV) nodes; they can cause bradycardia and AV block.
- Cholinergic effects can cause gastrointestinal (GI) bleeding, especially in those with a history of ulcer and those taking nonsteroidal anti-inflammatory drugs (NSAIDs).
- Anticholinergic drugs such as sedating antihistamines, tricyclic antidepressants and bladder control drugs reduce response and can worsen dementia.
- About 70% of patients will not respond. Those who do have only minimal improvements in memory and reasoning for a short time (months).
- Doses must be slowly titrated up until side effects are intolerable. Doses should be slowly tapered down when the drug is no longer effective to avoid rapid disease progression.
Memantine (Namenda) increases glutamate in the brain by blocking its ability to bind to the NMDA receptor. Glutamate is a neurotransmitter that has been associated with learning and memory. Memantine is FDA approved for use alone or in combination with cholinergic agents in the treatment of Alzheimer’s disease. Memantine improves cognition to a small extent and slows the rate of cognitive decline. What does NMDA stand for?
N-methyl-Daspartate (NMDA) Antagonists
Seizures are caused by ….
- spontaneous, uncontrolled, transitory, and disorganized discharges of hyperexcitable neurons in a specific area (focus) in the brain
There are two basic problems in a seizure:
- An abnormal focus of discharge origin
* An abnormal spread of the discharge across the brain
antiepileptic drugs [AEDs])
- antiseizure drugs; work by way of a number of different mechanisms involving sodium channels and GABA and glutamate neurons.
most common 1st generation AEDs
- Phenytoin (Dilantin)
- Fosphenytoin (Cerebyx)
- Phenobarbital and phenobarbital prodrug primidone (Mysoline)
- Carbamazepine (Tegretol, Carbatrol)
- Valproic acid (Depakene, Depakote, Depacon)
- Ethosuximide (Zarontin)
examples of 2nd generation AEDs
- Oxcarbazepine (Trileptal)
- Lamotrigine (Lamictal)
- Gabapentin (Neurontin)
- Pregabalin (Lyrica)
- Topiramate (Topamax)
- Levetiracetam (Keppra)
Diazepam
- a benzodiazepine used for sedative, muscle relaxant, anxiolytic and AED activity.
