Pharm test 2 Exam review Erin's Flashcards
Afferent
Going towards the CNS
Efferent
Going away from the CNS
Ganglia
Cell bodies in the PNS
Nuclei
Cell bodies in the CNS
Which are parasympathetic fibers originating from?
Craniosacral region
Where are sympathetic fibers originating from?
Thoracolumbar
Where are the ganglia located in the sympathetic division?
Close to the spinal cord
Where are the ganglia located in the parasympathetic division?
In the visceral effector organs
Which receptors are GQ?
Alpha 1, M1, M3, M5
What does GQ activate?
Phospholipase C
What is the end result of GQ activation?
Contraction
What receptors are G inhibitory (Gi)
Alpha 2, M2 and M4
What does Gi inhibit?
Adenylyl cyclase
Which receptors are G stimulatory?
Beta 1 and 2
What is the end result of G inhibitory?
Decreased cAMP
What is the end result of G stimulatory?
Increased cAMP
What happens when a G stimulatory signal is activated? (first thing)
Stimulates adenylyl cyclase
Briefly explain the hormonal feedback loop
Kidneys sense drop in BP –> renin release –> renin converts angiontensinogen (liver) into angiotensin I –> angiontensin I converted to angiotensin II by ACE (lungs) –> Angiotensin II causes vasoconstriction as well as stimulating the adrenal cortex to release aldosterone –> aldosterone release causes water and sodium reabsorption –> this increases blood volume –> increases venous return –> increases CO and finally increases MAP
Briefly explain autonomic feedback loop
Baroreceptors sense drop in BP and talk to the vasomotor center to increases sympathetic outflow and decrease parasympathetic outflow. (HR, PVR, Contractile force, Venous tone) End result is increased MAP
Neurotransmitter fates (4)
Diffuse away
Broken down in the synapse
Taken back up into presynaptic cell
Taken up by surrounding cells
What is an example of an ester?
Acetylcholine
What are the three monoamines?
Norepi, serotonin, dopamine
What does CHT do?
Transports choline into the neuron
What does CHAT do?
Combines acetyl-coa and choline into acetylcholine
What does VAT do?
Transports ACh into the vesicle
What are the steps in neurotransmitter release from vesicle?
Docking, priming, fusion
What does the SNARE complex do?
Anchors vesicles near release site
What is synaptogamin and what is its purpose?
Calcium sensor that serves for the release of neurotransmitter
Where is VAMP located?
On the vesicle
Where is SNAP-25 located?
Presynaptic membrane
Name the four components of the SNARE complex?
Syntaxin, SNAP-25, VAMP and Synaptogamin
Explain priming for a neurotransmitters
Prepares neurotransmitter for release (think pulling back hammer on gun) It is ATP dependent
Why does the neuron not become giant with docking, priming and fusion?
Two hypotheses: Kiss and run and clatherin coated pit
How does botulinum toxin mess with neurotransmitter release?
Prevents fusion by acting on SNAPs and VAMPs
How does Sarin nerve gas mess with neurotransmitters? Treatment?
Blocks AChE, too much acetylcholine. Treatment is atropine
Tyrosine is a precursor to ___
dopamine
How does cocaine and tricyclic antidepressants effect the reuptake of norepinephrine?
Block the NET –> excess of norepinephrine at the synapse
What are the direct acting cholinomimetics (class) ?
Choline esters and alkaloids
What are the indirect acting cholinomimetics?
Inhibit AChE, can be reversible or irreversible
Are esters of choline soluble or insoluble in lipids? How does this impact their absorption?
Insoluble in lipids, permanently charged, poorly absorbed
This ester of choline is primarily used for pupillary constriction (miosis)
ACh
This ester is used for the diagnosis of asthma
Methacholine
This ester is used to decrease intraocular pressure
Carbachol
This ester is used for bladder dysfunction and reflux disease
Bethanechol
Why is atropine contraindicated in narrow angle glaucoma?
It relaxes the ciliary muscle which obstructs drainage from the canal of schlem causing a build up of aqueous humor, which increases IOP
Name the indirect (block AChE) cholinomimetics
Simple alcohols (edrophonium)
Carbamic acid esters of alcohols (neostigmine)
Organic derivatives of phosphoric acid (organophosphates)
This drug is used for MG diagnosis
Edrophonium
Explain cholinomimetic effects (SLUDGE-M)
Salivation, lacrimation, urination, GI motility, Emesis, Miosis
What do antimuscarinics block?
Parasympathetic nervous system response, they block ACh receptors
What would you use tropicamide for?
Mydriasis (dilation) and cycloplegia (paralysis of ciliary muscle)
Explain symptoms and tx for organophosphate exposure
SLUDGE-M (blocks AChE)
Tx: atropine and pralidoxime
Give ASAP because bond between organophosphate and AChE ages and becomes harder to break
Treatment for atropine OD and symptoms
BRAND (blind, red, absent bowel sounds, nuts, dry)
Tx: Neostigmine
Explain phase I and II for succinylcholine
Phase I - depolarization of post synaptic cell
Phase II - If we continue giving this drug for a long period of time and we give larger and larger doses of it, the end plate will actually repolarize over time
When this happens, we enter phase II block
In the phase II block, the succinylcholine is still there but the muscle is no longer reacting to that succinylcholine binding to that receptor
Phase II is a deeper block and we get more repolarization and phase I keeps the muscle in a depolarized state
Sodium channels never reset
Reversal for non depolarizing muscle relaxants:
Neostigmine, pyridostigmine and suggamadex (Roc, Vec)
What is an example of a direct and indirect acting adrenergic agonist?
Ephedrine
What does COMT do?
Inactivates catecholamines in the gut
What does MAO do?
Inactivated catecholamines in the presynaptic cell
What happens when you substitute the alpha carbon on a catecholamine?
Alpha carbon substitutions are not recognized by MAO and therefore not broken down as readily as something like norepinephrine.
Tell me the receptors that the following drugs work on:
Phenylephrine (neo)
Epinephrine
Isoproterenol
Neo - alpha agonist
Epinephrine - mixed (alpha and beta)
Isoproterenol - beta agonist
How does isoproterenol impact the blood vessels?
Vasodilates them
What receptor does midodrine hit? What is it used for?
Postural hypotension, alpha 1 receptor agonist
Name the reversible and irreversible alpha antagonists
Phentolamine (reversible) and Phenoxybenzamine (irreversible)
What is a pheochromocytoma? What class of drugs is given for this?
A tumor of the adrenal medulla producing excess epinephrine
Treatment: alpha antagonists such as phentolamine and phenoxybenzamine
-osins are what class? What are they used for?
Alpha antagonists
Used for BPH to shrink prostate
Highly selective for alpha 1
Explain labetolol
Racemic mixture that is both an alpha and beta blocker
Why avoid propranolol in an asthmatic?
It’s non selective and can block Beta 2 and cause bronchoconstriction
Why is esmolol good for surgery?
Ultra short acting and beta one selective
Hydraulic equation
BP = CO X PVR
Four anatomical control sites and how we can manipulate them for BP control
Resistance Arterioles: can dilate these
Capacitance Venules: increase capacitance by relaxing them
Pump output Heart: use BB to decrease CO
Volume Kidneys: can block excess renin, ang 1, ang 2, aldosterone (RAAS system)
Name the four antihypertensives and how they work
Diuretics: deplete sodium
Sympathoplegics: decrease PVR, reduce CO
Direct vasodilators: relax vascular smooth muscle
Anti-angiotensins: block activity or production
Define: Pre HTN, HTN, HTN urgency, HTN emergency
Pre HTN: >140
HTN >160
HTN urgency: >180 with no organ damage
HTN emergency: >180 with organ damage
What class is methyldopa? What is it used for?
Sympathoplegic (alpha 2 agonist), used for pregnancy induced HTN - works like clonidine
What does cAMP do in the heart?
PKA –> Ca release from SR –> contraction
What does cAMP do in the blood vessel?
Inhibits MLCK –> can not phosphorylate myosin –> relaxation
How does monoxidil work? What is the end result?
K channel opener, vasodilation
How does Hydralazine work?
Dilates arterioles, K channel activation, possible NO production
Hydralazine toxicity
HA, nausea, flushing, worse in slow activator, symptoms similar to SLE
What are the concerns with sodium nitroprusside toxicity? What is the treatment?
Cyanide toxicity (metabolic acidosis, arrhythmias, death)
Treat with sodium thiosulfate
Mechanism of sodium nitroprusside
Release NO to relax vascular smooth muscle and increase intracellular cGMP
What receptors does Fenoldopam act on? What is it useful for?
Vasodilator that is good for HTN emergencies
Agonist of D1 receptors and good for renal perfusion
What is a major side effect of ACE inhibitors? Why?
Cough, because bradykinins are not broken down and this causes inflammation
What does alliskiren do?
Renin inhibitor
What class is losartan and valsartan? How do they work?
ARBs
blocks angiotensin II from binding to its receptors, so no vasoconstriction or aldosterone is released
What is the mechanism of action of ACE inhibitors? What is their common name ending?
inhibits ACE enzymes so angiotensin I is not converted to angiotensin II
-pril
How does aldosterone inhibitors lower BP?
Block aldosterone, essentially a diuretic effect to lower BP
What class is bonsentan? How does it work? What is it used for?
Endothelin receptor antagonist
Prevents endothelin from binding to its receptor which prevents proliferation and vasoconstriction
Pulmonary HTN treatment
How much blood does the venous system contain? (%)
70%
Most common type of angina? How is it relieved?
Stable / angina of effort
Relieved by rest
What is variant angina?
Angina caused by vasospasms, pain at rest
What is unstable angina?
Pain at rest, caused by ACS - an emergency
What does cGMP do to MLCK
dephosphorylates it can causes relaxation
Steps of contraction in relation to calcium in the heart
For contraction - calcium influx binds to calmodulin and forms the calcium calmodulin complex. Calcium calmodulin complex activates myosin light chain kinase (MLCK) → MLCK is phosphorylated → interacts with actin and causes a contraction.
Define concerns with overexposure to nitrates and nitrites.
Overtime, you develop a resistance to nitric oxide.
Can develop tolerance with complete continuous exposure→ blood vessels stop dilating → this is why you have an off period to clear nitric oxide form system
History of high nitrate/nitrite exposure can cause headaches
Problematic for workers on meat processing plants and fertilizer plants because they have a lot of nitrate that gets into air and they breathe it in.
Farmers around crops sprayed with this had problems with this
Nitrite ion can attach to hemoglobin to form methemoglobin (excess of amount of nitrite Attached to it)
Very low affinity for oxygen
Pseudocyanosis at very high levels (Raynaud’s essentially)
Benefit: very high affinity for cyanide so inducing pseudocyanosis can be useful in treating cyanide poisoning.
Methemoglobin can facilitate the removal of cyanide.
Describe targets of pFOX inhibitors
What pFOX inhibitor is approved in the US?
By using the pFOX inhibitors (like ranolazine), this decreases fatty acid oxidation and causes the heart to switch over to glucose utilization (more efficient); less likely to flip into anaerobic metabolism
Ranolazine
4 drug classes to treat angina
CCBs, pFOX inhibitors, Beta blockers, nitrates
Explain systolic HF patho
Heart itself is not pumping effectively due to THIN heart muscle walls → could be due to infection or drugs ex.
Describe patho of diastolic HF
Hypertrophy of myocardium– heart muscle too THICK
Does diastolic or systolic HF have a reduced ejection fraction?
Systolic
Describe the normal process of cardiac contractility
Depolarization causes voltage gated calcium channels to open and “Trigger calcium” enters the cell.
Trigger Calcium binds to channels in SR and calcium is then released from the SR
Calcium frees actin to interact with myosin. This causes a contraction.
SR calcium goes back into SR via SERCA pump (ATP dependent)
NCX pump allows exchange of sodium into cell for trigger calcium to be pumped out of cell
What are the four factors of cardiac performance?
Preload, after load, contractility, and HR
What three factors contribute to SV?
Preload, after load, contractility
This is the end diastolic pressure that stretches out the ventricles
Preload
What things contribute to EDV?
Passive filling, atrial contraction and ESV
Drugs used for heart failure
Calcium
Cardiac glyocosides (digoxin)
PDE inhibitors (milrinone)
Catecholamines
Others:
Vasodilators
Beta blockers
What is the only oral positive inotrope for heart failure?
Digoxin
MOA PDE3 inhibitors
Stop the inactivation of cAMP and cGMP. This results in more cAMP and cGMP to have vasodilatory effects as well as positive inotropic effects
What are the M and H gates doing during the resting state of a Voltage gated sodium channel?
M gates closed, H gates open
What are the M and H gates doing during the activated state of a Voltage gated sodium channel?
Both are open
What are the M and H gates doing during the inactivated state of a Voltage gated sodium channel?
H gate closed
M gate open
What ion is moving during phase 0? Is it going in or out of the cell?
Sodium, into cell
What ion is moving during phase 1? Is it going in or out of the cell?
Potassium, out of the cell
What ion(s) are moving during phase 2? Is it going in or out of the cell?
Calcium in, potassium out
What ion is moving during phase 3? Is it going in or out of the cell?
Potassium out
What is happening during phase 4?
Sodium/potassium ATPase pump resets the concentration gradient of sodium/potassium
Two main classifications of arrhythmias
Disturbances in impulse formation
Disturbances in impulse conduction
What are the three things that can cause disturbances in impulse formation?
SA/AV node abnormalities
Ion changes
SNS stimulation
What are the two things that can cause disturbances in impulse conduction?
Block and reentry
What does vagal discharge do to the pacemaker rate? How does it impact the phase 4 slope?
Slows PM rate
Reduction in phase 4 slope
How does acceleration of the pacemaker rate impact phase 4?
Increases the phase 4 depolarization slope
Explain the three requirements for a reentry disturbance of impulse conduction
There must be an obstacle (scar tissue)
Block must be unidirectional
Conduction time must be long enough to reenter same areas after the refractory period
Class I antiarrhythmics
sodium channel blockade
Class II antiarrhythmics
sympatholytics
Class III antiarrhythmics
prolong action potential duration (other mechanisms besides sodium channels - blocks K channels)
Class IV antiarrhythmics
block cardiac calcium channel currents
Examples of Class IA anti antiarrhythmic agents
Quinidine, procainimide, disopyramide
What effect do Class IA drugs have on the APD and ERP?
prolong APD and increase ERP
Examples of Class IB anti antiarrhythmic agents
Lidocaine
What effect do Class IB drugs have on the APD and ERP?
Shorten APD, decrease ERP
Examples of Class IC anti antiarrhythmic agents
Flecainide, propafenone
What effect do Class IC drugs have on the APD and ERP?
No effect on APD or ERP but causes slow dissociation
What W-V class is satolol?
Class II
What W-V class is amiodarone?
III
What W-V class is verapamil?
IV
Risks of amiodarone toxicity
-Bradycardia/ heart block
-Precipitate HF
-Fatal pulmonary fibrosis
-Concentration in tissues, found in almost every organ
How does verapamil work?
Blocks activated and inactivated calcium channels to slow SA node. Also has a hypotensive action
Initial treatment for bradycardia
Treat underlying cause, d/c drugs
Treatment for symptomatic bradycardia
1st - atropine
2- epinephrine, dopamine
Treatment for chronic symptomatic bradycardia
Pacemaker
Treatment for symptomatic heart block
Atropine, pacing
Treatment for symptomatic SVT
Adenisone
Treatment for wide complex Tach
amiodarone
V fib treatment (drugs)
amio, lido
