Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
96 Cards in this Set
- Front
- Back
|
What are the 5 steps where drugs regulate neurotransmission?
|
1. Synthesis of the NT
2. Vesicular Storage 3. Synaptic Release of Vesicles 4. NT/receptor Binding 5. NT reuptake (ending transmission of signal) |
|
|
Generally, how is the synthesis of NT's modulated by drugs?
|
Either restricting or supplying the precursors to the NT. Example: L-DOPA (supply)
|
|
|
Generally, how do amphetamines work?
|
Reversing re uptake pumps for Dopamine, NE, Ach.
This causes up-regulation of these signals. Note also that amphetamines cross the BBB and are highly addictive due to their dopamine up-regulation. |
|
|
SNAREs are involved in what? What drug inhibits them?
|
SNAREs are involved in vesicle fusion and release.
Botulinum Toxin is a well known inhibitor of SNAREs by preventing Ca2+ from entering the presynaptic cell (required for SNARE function) |
|
|
What is Metyrosine's mechanism of action?
|
It is an analogue of Tyrosine which is a precursor in the DOPA, Dopamine, NE, Epe. synthesis chain.
In binds to the enzyme Tyrosine Hydrolase and inhibits it from making DOPA. Thus decreasing DOPA and all its products. This is an example of modulating the synthesis of NT's |
|
|
What is Respirine's mechanism of action?
|
Respirine is a VMAT inhibitor (Vesicular monoamine transporter). Thus it prevents dopamine (a monoamine) from entering vesicles.
The end effect is a decrease of the release of dopamine OR NE (it is made from dopamine once it inside a vesicle normally) |
|
|
What is Bretylium's mechanism of action?
|
It is a Ca2+ channel blocker. Thus, it reduces the presynaptic membrane's excitability preventing NT release
|
|
|
How and where does a COMT inhibitor work?
|
COMT inhibitors prevent the degradation of NT's that have already been released into the synaptic cleft. Thus they are free to keep stimulating longer.
|
|
|
Where does an MAOI inhibitor work? What is the net result of MAOI's?
|
MAOI inhibitors work within the presynaptic cell.
The net result is more NT is placed inside vesicles AND some NT can seep out of the vesicle via concentration gradients. |
|
|
Name an important MAOI interaction.
|
Tyramine - Foods high in Tyramine cause extreme hypertension in patients on MAOI's. This is known as "the cheese effect" as tyramine is found in bacteria related foods.
Tyramine is a toxic compound normally easily degraded in cells by MAO. Its effect on the body is to cause extreme release of dopamine, NE, Epe from cells. |
|
|
Contrast NT release with Neuropeptide (angiotensin, substance P, etc) release.
|
Neuropeptides are slow to release, stored in the cell body, and require mRNA for synthesis.
|
|
|
Carbidopa and L-DOPA are used a lot in tandem. Why?
|
The intent of L-DOPA is to treat Parkinson's and thus to get it across the BBB. A side effect of L-DOPA treatment is dramatic increase of dopamine and its cousins in all cells of the body, not just in the CNS. This can cause a cardiovascular crisis.
Carbidopa, is an inhibitor of the conversion of DOPA to dopamine but can't cross the BBB. It essentially counteracts the effects of L-DOPA everywhere but in the CNS. Thus, localizing therapy nicely and reducing side effects. |
|
|
Review the locations of the sympathetic and parasympathetic nervous systems
|
Sympathetic - Thoracolumbar Region
Parasympathetic - Craniosacral Region |
|
|
Can the gut function without autonomic influence?
|
Yes, the myenteric system functions alone. However, it functions much better with autonomic influence
|
|
|
Review the NT release of autonomic nerves
|
All presynaptic: Ach
Parasympathetic Post: Ach Sympathetic Post: NE EXCEPTION: Sympathetic post to ecrine sweat glands and vasculat smooth muscle - Ach |
|
|
What is the parasympathetic effect on the eye?
|
Constriction (miosis)
|
|
|
What is the parasympathetic effect on the heart?
|
Bradycardia (Negative chrontropic effect)
|
|
|
What is the parasympathetic effect on the bronchioles?
|
Constriction
|
|
|
What is the parasympathetic effect on the GI tract?
|
Increased Motility
|
|
|
What is the parasympathetic effect on the bladder?
|
Stimulates Emptying
|
|
|
What is the sympathetic effect on the eye?
|
Mydriasis (dilation)
|
|
|
What muscles in the eye are controlled by the sympathetic input?
|
Dilator - Radial opening of the pupil.
Ciliary Body - Lens accomdation. |
|
|
What are the muscles of the eye controlled by parasympathetic innervation?
|
Sphincter - Pupilary contraction
|
|
|
Aquaeous Humor is made where in the eye and exits where?
|
Made in the Ciliary body and neae the Ciliary muscle - exits at the canal of Schlemm
|
|
|
In glaucoma, the pressure of the Aquaeous Humor is elevated. Name 2 ways to alleviate this.
|
1: Constrict the sphincter muscles
2: Alter formation at the ciliary body |
|
|
What receptor requlates heart rate and generally how does it work?
|
B1 receptors control heart rate and they do it by increasing Ca2+ influx.
This increases pacemaker rate AND contraction strength |
|
|
What effect does the sympathetic nervous system have on the bronchioles?
|
Smooth muscle relaxation leading to bronchiolar dilation
|
|
|
What effect does the sympathetic nervous system have on blood vessels?
|
BOTH contraction and dilation, generally shunting flow to vital areas.
|
|
|
What hormone increases blood sugar and where does it preferentially bind?
|
Epe, it preferentially binds to B receptors.
So increase in heart rate and BP from B1 and vasoconstriction and bronchiolar dilation from B2 |
|
|
What are the primary functions of A1 receptors?
|
-Contract vascular smooth muscle.
-Conttracts the dilator muscle |
|
|
What are the primary functions of A2 receptors?
|
- Acts as a GI protien ligand to inhbit NT release on adrenergic and cholenergic nerve terminals.
Note that this is a critical feedback loop in the ANS |
|
|
What is the primary effect of B1 receptors?
|
-Increase heart rate and contractility.
-Increase renin release |
|
|
What are the major function of B2 receptors?
|
-Respiratory, uterine, and vasculat smooth muscle relaxation
-Gluconeogenisis in the liver -Stimulates somatic nerve terminals in the skeletal muscle (this results in the tremor side effect) |
|
|
What is the major function of D1 receptors
|
Relaxes renal and spelenchinc vessels
|
|
|
What type of receptor is an A1 receptor (think about the function of A1's)
|
GQ receptor. It causes PLC to release IP3 and activated PKC resilting in CA2+ release to contract smooth muscle.
Remember Ca2+ binds to calmodulin which phosphorylates myosin light chain kinase leading to activation. |
|
|
What type of receptor is a B1?
|
GS. It acts to increase cAMP which then has 3 different ways of increasing cytosolic Ca2+ One of those ways is PkA
|
|
|
What type of receptor is a B2 receptor?
|
GS.
By increasing cAMP and PkA MLcK is phosphorilated and inactivated leading to smoth muscle dilations |
|
|
What type of receptor is A2?
|
GI
It inhicits cAMP production acting as a check against GS in B2 in the smooth muscle. This ENABLES A1 to constrict as the phosphorylation of MLCK is inhibited |
|
|
Describe the two ways indirect acting adrenergic agonists function.
|
Releasers (release vesicles)
Reuptake Inhibitors (inhibit NT reuptake extending action) |
|
|
What is the order of NT preference for alpha receptors? (there are 3 NT's including one drug)
|
EPI > NE >> Isoproterenol
Little or no iso really |
|
|
What is the order of NT preference for beta 1 (B1) receptors? (there are 3 NT's including one drug)
|
Isoproternol > EPI >> NE
|
|
|
What is the order of NT preference for beta 2 (B2) receptors? (there are 3 NT's including one drug)
|
Isoproternol > EPI = NE
|
|
|
Mean Arterial Pressure is a function of what?
|
Total Peripheral Resistance AND Cardiac output
Both are modulated by autonomic drugs |
|
|
How does low dose EPI alter systolic and diastolic BP?
|
Systolic BP is increased
(increase in contractility via B1) Diastolic BP is decreased (B2 receptors vasodilate) |
|
|
How does high dose EPI alter systolic and diastolic BP?
|
Systolic BP is increased
(increase in contractility via B1) Diastolic BP is relatively unchanged (B2 receptors vasodilate BUT A1 vasoconstrict AND A2 inhibit to offset) |
|
|
What are epenephrine's effects (low and high dose)
|
Low Dose: Up HR and contractility (CO), Up Systolic BP, Lower diastolic BP, Bronchodilate
High Dose: Up HR and contractility, Up Systolic BP, diastolic BP, Bronchodilate |
|
|
What are epenephrine's indications
|
Anaphylaxis
Cardiac Arrest Bronchospasm |
|
|
What are norepenephrine's effects
|
Increase CO via contractility, Decrease HR (barroreflex), Increase MAP (so systolic and diastolic BP)
|
|
|
What are norepenephrine's indications?
|
Limited to shock (make sure they are euvolemic)
|
|
|
What are epenephrine's contraindications and toxicities of note?
|
Contraindicaiton: Late term pregnancy
Toxcicity: Arrythmeas, pulmonary edema, anxiety |
|
|
What are norepenephrine's contraindications?
|
Preexisting vasoconstrictors, noted ischemia, late term pregnancy
|
|
|
What are norepenephrine's toxicities of note?
|
Arrythmeas, Ischemia, htn
|
|
|
What are dopamine's effects (low and high drip rate)?
|
Low Rate: Decreases TPR (specifically renal vascular resistance), increases CO
High Rate: Increases MAP and TPR (via additional a1,2 effect at high concentration) |
|
|
What are dopamine's indications?
|
Cardiogenic shock
|
|
|
What is a major contraindication of dopamine?
|
Tachyarrythmea (it would exacerbate it)
|
|
|
What are the effects of isoproterenol?
|
Increase HR, (initially by B1) Decrease TPR (B2), Increase HR more (by a barroreflex brought on by low TPR) Broncodilation (not used for this purpose any more)
|
|
|
What are the indications of isoproterenol?
|
Bradycardia or heart block. Only when TPR is high.
|
|
|
What are isoproterenol's contraindications?
|
Angina with arrythmeas. This would stress the heart more.
|
|
|
What are the effects of dobutamine?
|
It is a selective B1 antagonist
Effects: Increased CO |
|
|
What are the indications of dobutamine?
|
Short term treatment of CHF, Cardiogenic shock with a systolic BP above 80, Overdose on B blockers
|
|
|
What are the toxicities of dobutamine?
|
Arrythmias (B1)
Hypotension (B2, only if overdosed) |
|
|
What are the effects of Terbutaline and Albuterol?
|
They are selective B2 agonists
Bronchodilation, uterine relaxation |
|
|
What is the difference between Terbutaline and Albuterol?
|
Albuterol is given via inhaiation terbutaline is given via IV, sub cu, or nebulization
|
|
|
What are the indications of Terbutaline and Albuterol?
|
Bronchospasm
|
|
|
What are some of the interesting toxicities of Terbutaline and Albuterol
|
Tremor, Developed tolerance (emergency inhaler, not every day), Tachycardia (in OD)
|
|
|
What are the effects of phenylepherine?
|
It is a selective A1 agonist.
Increased TPR, Decreased HR (via barroreflex), Mydriasis (pupilary dilation), Decreases bronchial and sinus secretions |
|
|
What are the indications of phenylepherine?
|
Hyoptension while under anesthesia, SV Tachycardia, Dilating Agent, Nasal conjestion
|
|
|
What are the contraindications of phenylephrine?
|
Hypertension, Ventricular tachycardia
|
|
|
What are the effects of clonadine?
|
It is an A2 agonist.
Peripheral increase in BP iniitially with a central decrease in BP next. |
|
|
What are the indications of clonadine?
|
Hypertension due to sympathetic activation.
|
|
|
What are the toxicities of clonadine?
|
Sedation, bradycardia, dry mouth, hypertensive crisis after accute withdrawl
|
|
|
List the indirect acting sympathetomemetics
|
Amphedimine
Methamphedimine Ephedrine Pseudoephedrine Methylphenidate Tyramine |
|
|
What are the indications of an indirect sympathetomemetic?
|
ADD, Narcolepsy, Nasal Congestion (Pseudoephedrine/Ephedrine)
|
|
|
What are the physiological effects of an indirect sympathetomemetic?
|
Increased TPR and diastolic BP via A1,A2,
Ionotropic and chronotropic effects on the heart resulting in increases CO and systolic BP CNS Stimulant, Anorexia |
|
|
What are the contraindications of an indirect sympathetomemetic?
|
Hypertension, tachycardia, MAO inhibitors, history of drug abuse
|
|
|
Describe how MAO inhibitors interact with indirect sympathetomemetics.
|
Tyramine is normally metabolized by MAO in the nerve cells.By blocking them tyramine can build up in the body causing unwanted effects.
This is interesting because tyramine can be found in many cured meats and cheeses. You need to warn PTs on MAOI's about this. |
|
|
Discuss B blockers and T1DM patients
|
By blocking the B2 receptor, a diabetic can not perceive that they have low blood glucose levels.
This is dangerous as they can go into a diabetic coma. |
|
|
What are the effects of Propanolol
|
It is a non selective B blocker
Decreased HR, decreased contractility, decreased renin release, decreased sypmathetic effects and, inhibition of aquaeous humor production |
|
|
Name three non selective B blockers
|
Propanolol, Nadolol, Timolol
|
|
|
What are the indications for one of the non selective B blockers?
|
Hypertension, Glaucoma, Angina, Thyrotoxicosis, Anxiety, and Early Heart Failure.
(It has been shown that long term sympathetic suppression of a failing heart reduces hypertrophy) |
|
|
What is the super important contraindication for all B blockers?
|
Asthma@!!!!!1111!!
|
|
|
Name three selective B1 blockers
|
Metoprolol, Atenolol, Esmolol (only in emergent cases)
|
|
|
What are the effects of a selective B1 blocker such as Atenolol?
|
Decreased HR, decreased contractility, decreasesd renin release, decreased sympathetic input
|
|
|
What are the indications of a selective B1 blocker such as Metoprolol?
|
Hypertension, angina, arrhythmia
|
|
|
What are the contraindications of a selective B1 blocker such as Esmolol?
|
Heart block, severe heart failure, cardiogenic shock, sinus bradycardia
|
|
|
What are the effects of Pindolol?
|
It is a partial B1 agonist.
This functions by competing with endogenous NT's and tapering high sympathetic input. Effectively it acts as a B blocker but only when the SNS is active. Decreased BP, Decreased contractility, decreased renin release, decreased sympathetic activation. |
|
|
What are the indications of Pindolol?
|
Hypertension
|
|
|
What are the contraindications of Pindolol?
|
Heart block, severe heart failure, cardiogenic shock, sinus bradycardia (same as a B blocker)
|
|
|
What are the effects of phentolamine?
|
It is a reversable A blocker.
The effects are: decreased BP, increased chronotropy and ionotropy (barroreflex) |
|
|
What are the effects of Phenoxybenzamine and what class is it?
|
It is an irreversible A blocker.
The effects are: decreased BP, increased chronotropy and ionotropy (barroreflex) |
|
|
What are the indications of an A blocker such as phentolamine?
|
Hypertension associated with pheochromocytoma, vasoconstrictor induced extravasation (local vasoconstriction caused by an IV of an A1 agonist such as propofol)
|
|
|
What are the contraindications of an A blocker such as Phenoxybenzamine?
|
Coronary artery disease
|
|
|
List three A1 selective blockers
|
Prazosin, Doxazosin, and Teraszosin
|
|
|
What are the effects of an A1 blocker such as Prazosin?
|
Inhibition of vasoconstriction, relax prostate smooth muscle
|
|
|
What are the indications of a selective A1 blocker such as Doxazosin?
|
Hypertension, benign prostate hyperplasia
|
|
|
What are some of the side effects of a selective A1 blocker such as Terazosin?
|
Syncopy, orthostatic hypotension
|
