Pharmacology Flashcards
What neurotransmitters are used in the sympathies nervous system?
At sympathetic ganglia is Ach
Neuroeffector junctions always NE
Adrenergic
What are the lengths of neurons and which neurotransmitters are used in the parasympathetic nervous system?
Long presynaptic Short post synaptic Synapse usually close to or within innervated organ Transmitter always Ach Cholinergic
How does the somatic motor nervous system contrast to the autonomic?
Long myelinated fibers in cranial and spinal nerves
Cells of origin in CNS
no ganglia outside CNS
synapse at motor end plates of skeletal muscle
Transmitter at NMJ is Ach
What are two additional enzymes that hydrolyze Ach in addition to ACE?
Butyrocholinesterase
Psuedocholinesterase
Less specific - found in plasma and liver
How do botulinum toxin and black widow spider venom act on Ach?
Botulinum - blocks exocytosis –> flaccid paralysis
BWSV - massive release of vesicles
What are the basics of nicotinic cholinergic receptors?
Ligand gates ion channels
Five subunits make single pore
Two Ach must bind to alpha subunits to open
At skeletal NMJ, many neurons, and chromaffin cells of adrenal medulla
Depolarization results in muscle contraction, firing in nerves, and secretion from adrenal medulla
Nm (muscle) and Ng (ganglionic) isoforms (includes adrenal)
What are the basics of muscarinic cholinergic receptors?
GPCRs
Five subtypes - M1, 3, 5 interact with Gq and activate phospholipase C –> contraction of smooth muscle and secretion - M2 and 4 interact with Gi/o inhibiting adenylyl cyclase –> negative inotropic and chronotropic effects on heart
M2 predominate in heart, others in smooth muscles, glands, autonomic ganglia, and CNS
How do adrenergic neurons synthesize neurotransmitters?
NE and DOPA from tyrosine
Adrenal medulla secretes 80% epi and 20% NE
rate limiting step is first tyrosine –> dopamine by tyrosine hydroxylase
Only adrenal medulla can make Epi from NE
How is NE inacitvated?
Predominantly by reuptake
Also diffusion away from site of action
monoamine oxidase and catechyl-o-methyltransferase inactivate catecholamines but play little role so drugs here not effective a prolonging action
What are the basics of adrenergic receptors?
GPCRs
Alpha 1 - couple to Gq - most imp on structures innervated by sympathetic neurons
Alpha 2 - coupled to Gi and Go - located presynaptically in periphery –> feedback inhibition of NE release
Both betas - coupled to Gs, beta 1 in heart, beta 2 responsible for smooth muscle relaxation
How do Epi and NE act at adrenergic receptors?
Epi excellent agonist for all
NE excellent for all but beta 2
Which system does not innervate the vascular system?
Parasympathetic system
What are two important functional properties of Ach?
Quarternary amine with positive charge
Ester bond for degradation
What is an example of an agonist and an antagonist at nicotinic and muscarinic receptors?
N - increased by nicotine, inhibited by d-tubocurarine
M - increased by muscarine, inhibited by atropine
What is the effect of inhibiting Ach binding to receptor?
Hyper polarization of post synaptic membrane
What is the mechanism of botulinum toxin?
Protease that cleaves proteins required for fusion of synaptic vesicles and exocytosis of Ach
Selective action at NMJ
Systemic spread can lead to cessation of respiration
What is a reversible inhibitor of ACE and an irreversible inhibitor?
Physostigmine Organic phosphates (DFP)
What is a dual response at nicotinic receptors?
Continuous or massive stimulation can lead to:
Failure to repolarize post synaptic junction or desensitization of receptors so you get stimulation followed by desensitization
What is the main difference of response seen at nicotinic vs muscarinic receptors?
N - all or nothing response
M - slower, graded response due to less structured synapse and slower degradation of Ach - used to relate intrinsic activity of organs
What two things does the utility of cholinergic agents depend on?
Specificity of receptor subtype
Availability - ability to penetrate to desired sites (lipophilic vs hydrophilic, tertiary vs quarternary)
Which types of cholinergic agents can penetrate the CNS?
Tertiary amines - quarternary excluded
More hydrophobic compounds
What is the difference between predictable adverse reactions and unpredictable ones?
Predictable - dose dependent, related to known pharmacological parameters of drug, in otherwise normal patients
Un - dose independent, not related to known pharmacological actions, in susceptible patients
What are some features of allergic reaction?
Limited number of syndromes
Allergic person will react at dose far below therapeutic range
What is the hapten hypothesis?
In order for hypersensitivity, most drugs must be bio activated
Drug metabolism is a type of detoxification
First step - oxidation, reduction, hydrolysis (phase I reactions)
Second step - conjugation (phase II reactions)
When a drug bio activated, prompt detoxification occurs
Can a hapten produce an immune response?
No - must have a multivalent immunogen
How is in vivo skin testing used in diagnosis of drug allergy?
Most of the time we don’t know what to test for
Can only teat for penicillin minor and major determinants, large molecular weight compounds (foreign antisera, hormones, enzymes, toxoids, egg containing vaccines)
What is tryptase and how is it used in diagnosis of drug allergy?
Selective marker of mast cells
Beta tryptase stored and released upon degranulation
Levels elevated after anaphylaxis and remain elevated for up to 8 hrs
Levels should be obtained 1-2 hrs after onset of anaphylaxis
Indicative of severe reaction
What is desensitization in hypersensitivity to antibiotics?
Conversion of drug allergic individual from highly sensitive to state where drug is tolerated
Procedures involves careful admin of incremental doses of drug over hours to days
When is desensitization to antibiotics performed?
In patients where IgE antibodies to particular drug are known or presumed to exist and no alternative drug available
