Exam 2 Pharmacology

central nervous system functions

recognizes internal and external environment - processing and integrating changes in the environment - react to environment - learning and memory 

peripheral nervous system arms

motor and sensory

Motor - 2 types

Autonomic - controls basal function,

somatic - voluntary

2 types of autonomic NS

Sympathetic, paraSympathetic

Sympathetic main neurotrans

* epi, norepi, and dopamine

Sympathetic main receptors

* Alpha 1, alpha 2,alpha 3 alpha 4, alpha 5
* Beta 1 beta 2 beta 3

Parasympathetic -main neurotrans

acetylcholine

Parasympathetic -main receptors

M1, m2, m3 (m= muscarinic)

Sympathetic nervous system

* FIGHT OR FLIGHT - inc. heart rate, inc bp control, bronchial dilation, shunt blood to muscles, increase in liver glucose production, increase in lipolysis from adipose. Piloerection (hair on back of neck standing up). Relaxation of bladder and anal spincter (scare the piss outta you), dry mouth

Parasympathetic

* - REST AND DIGEST - inc digestion, decreased HR and BP, urinary control

Reproductive system - male and female

* uses both sympathetic and parasympathetic

how does the reproductive system use both sympathetic and parasympathetic

* Parasympathetic - in female - increases lubrication
* Sympathetic -in female -  orgasm
* Parasymp in male - inc erection
* Sym in male - orgasm/ejaculation

what is a ganglion

 like a relay center, Still driven by acytlcholine

Beta 3 receptors act at

adipose tissues - when were excited and muscles need energy, main source of energy is our fatty acids

Glucose is mainly used in the

* brain, NOT muscles

parasymp M1-

salivary glands, stomach, emesis

PSNS M2

* decrease HR, decrease contracile frorve of heart, dec avnode velocity

PSNS M3

*  smooth musc contract, brochiole constrict, inc endocrine/exocrine function (think salivary glands, iris (eye accommodation)), emesis, vasodilation. Bladder (aka contracting)

How can we have vasodilation and smooth muscle contraction? Theyre opposites??

* This happens due to inc calcium in vasculature
* This increases nitric  oxide which is a potent vasodilator
* Nitric oxide related to erection - diabetetic and older males may have issues with erectile dysfunction - drugs that increse nitric oxide used to treat this

Alpha 1

* prefers norepi over epi - inc smooth musc (oncluding vascular smooth muscle) constriction, dilates pupil. Decreases GI motility

Alpha 2

*  epi=norepi in terms of sensitivity - decreases insulin and increases glucagon (happens in pancreas), platelet activation, smooth muscle mixed effects

Beta 1

*  norepi> epi - heart rate increases (chromotropic response), increase AV node conduction (dromotropic response), ionotopic response (force of contraction), increase amylase

Beta 2

*  epi> norepi - smooth muscle relaxation - bronchial dilation, increase GI motility, inc liver glucose production, helps glycolysis (liberation of stored fatty acids)

Beta 3

*  epi=norepi - increaeses adiposelipolysis (freeing fatty acids), relaxes bladder

Parasympathetic drugs are

* hard to control

parasymp drugs

physostigmine, donezapil

Physostigmine MOA

* blocks acetylcholine esterase (AChE) - by blocking this you decrease breakdown of ACh

Physostigmine use

* Used for myasthenia gravis - disease that decreases Ach receptors at muscle, oftentimes have droopy face (like a bassett hound)
* Physostigmine inhibits AchE to increase ACh in synapse, increases likelihood of positive response with receptor
* Autoimmune disease
* Deadly nightshade poisoning - tomatoes in this family - physostigmine is an antidote
* can be used if too much anticholingergic drug like atropine

Donezapil (aricept) MOA

crosses BBB, used in Alheimers Disease (AD) to block AchE which increases ACh in synapse

donezapil uses

* Used for alzheimers
* If we increase amt of time that Ach is in synapse, we increase cholinergic function and let the person to have a few more years

Bethocol

*  agonist -acts to increases parasympathetic activation

bethecol facts

* Direct acting
* Doesnt cross BBB, not useful in brain, cant be used for alzheimers for this reason 
* Mostly used in urinary and digestive dysfunct because it increases smooth muscle tone
* Used in pts with low bladder tone
* Contraindicated (aka do not use) in peptic ulcer disease, parkinson’s, epilepsy, hyperthyroidism, bradycardia (benthecol already drives HR down), asthma

Sarin gas (pesticides)

* otent inhibitors of Achetylcholine esterase - increase in ach in synapse - leads to cholinergic storm.crisis 

Cholingeric storm characterized by

* bradycardia, defecation, drowsiness, difficulty breathing (dyspnea), salivation, sweating, tremors (muscle twitching), urination, blurred vision, 

to treat cholinergic storm

 give Atropine which blocks acetylcholine receptor (inhibitor). Called an anticholingergic, the classic anticholinergic

Atropine essentially

* increases sympatetic response by blocking parasympathetic

Atropine can

* reduce sexual function - if a pt is sexually active atropine might not be the best drug
* Giving a lot of atropine gives dry mouth, dry eyes, dilated pupils, photophobia (due to dilated pupils), relax bronchi, increase heart rate
* In roman times, to make themselves more attractive women would put atropine on their face (gives big “doe eyes” aka pupil dilation, and made cheeks rosy because of vasodilation)
* Blocks only muscarinic receptors, not nicotinic
* Atropine used in IBD - blocks GI tract and receptors, slows it down
* Side effects: constipation
* Contraindications: glaucoma, obstructive GI disease, bladder obstruction, myasthenia gravis

Problem with all cholinergics is

*  they cna induce a cholinergic crisis

Sympathetic Nervous System

adrenergic - epi/norepi mainly - we think agonist or antagonist mostly - this is what we use to treat BP, HR, heart rhythm, asthma, glaucoma, nasal congestion

 the only part of the sympathetic system taht are not epi/norepi driven

Sweat glands

how do sweat glands work

 use acetylcholine with no ganglion

Catacholamines

epi, norepi, and dopamine

Epi has greater activity at

beta

Norepi greater at

alpha

When norepi released

* goes to synapse and stimulates an adenergic receptor (alpha and betas), —-Norepi in synapse is reuptaken and reused/recycled (put into a vecicle) PRESYNAPTIC SIDE. postsynaptic side - monoamine oxidase oxidizes it 

Andrenergic receptor -

* in synapse gets broken down by COMT (catacholamine o-methyl transferase) breaks it down in the synaptic cleft

Adrenal gland

* takes epi and norepi - lasts minutes - mainly broken down by liver metabolism

d2=

 emesis

Give dopamine/epi/noepi thru injection (parentrally) =

 short half life bc of liver metabolism

Sympathomimetics

 similar func to anticholinergic but more specific

Alpha 1

* nasal conjection (afrin stimulates it) treats hypotension, dilate pupils

Alpha 2 stim

hypertension, when stimulated, decrease norepi release at nerve terminal

Beta 1

* shock, heart failure,cardiac arrest,

Beta 2

* asthma, premature labor

Beta 3

*  another approach to overactive bladder

isoproteronol

* b1 and b2 agonist
* Increase HR, increase force, inc conduction velocity

Pseudoephedrine (sudofen)  -

* timulate (agonize) alpha 1 receptors, decrease size of vasculature in nose, giving you more room to breathe ALPHA 1 SHRINKS VESSELS
* Visine - does this for eyes (shrinks vessels)
* Side effects: tachycardia, hypertension, dysrhythmia, dry mouth, nausea, vomiting

the most widely used adrenergic drugs

Adrenergic Antagonists

Alpha 1 blockers

* relax smooth muscle in vasculature and elsewhere

Alpha 1 blockers example

tamsulin, prazosin

Prazosin  (minipress)

* hypertension - inhibit alpha 1 on vasculature on arterial side, CAN ALSO BE USED FOR HYPERTENSION CRISIS (rapid decrease in hypertension without changing cardiac output/heart rate), does not have ethanol
* Side effects -
*  can get hypotension - vasculature doesnt resond to sympathetic system as well, 
* Orthostatic hypotension - when you go from laying to standing and get woozy
* Can lead to reflexive tachycardia - your body senses youre hypotesnive so the symp system increases your HR, but your vasculature doesnt respond
* Reflexive tachycard Also occurs with decrease in blood volume
* Voiding better - alpha 1 stims urinary tract

Tamsulosin (flomax)

*  prostate issues like benign prostate hypertrophy (BPH), alpha 1 sphincters + relax smooth muscle in urethra = void (pee) better

SIDE EFFECTS OF ALPHA1 BLOCKERS

* reflexive tachycardia, nasal congestion, hypotension, orthostatic hypotension,urinary

Beta blockers

* tend to decrease HR )chromotropic), decrease force (ionotropic), and decrease AV node (dromotropic),

Atenolol (tenormin)

* very cardioselective (only works on beta 1) vs propranolol (beta 1 and beta 2 antagonist)

Metoprolol

* most widely used, been around a long time,

Beta blockers work great for angina because

* they decrease the metabolic demands of the heart bc youre decreaesing force, heart rate

SIDE EFFECTS of beta blockers -

* can cause hyper and hypoglycemia - can mask systems of hypoglycemia in diabetics, 
* Cramping
* Fatigue
* Depression

Angelitics

*  used to treat anxiety - generally benzodiazepines

Anxiety

state of apprehension, tension, dread, fear, uneasiness,Heightened state of awareness (walking down a dark alley after flashing cash)

* When we perceive danger
* Oftentimes what happens is anxiety is much much greater than the actual danger

Main area of brain involved in anxiety

limbic system -

Situational anxiety

*  stressful environment - oftentimes it is a great motivator to get things done (ei test coming up)

GAD

* generalized anxiety disorder - true clinical problem, difficult to control, lasts longer than 6 months and interferes w day to day living. This is one of the most common stress disorders
* Symptoms include restlessness, fatigue, muscle tension, inability to focus/concentration, autonomic signs (sympathetic or parasympathetic signs - these can be anything from dry mouth to shaking to elevated/depressed heartrate)
* Women impacted slightly more than men
* Mostly ages 20-35

Panic disorder -

* immediate fearfulness
* Terror- feeling of impending doom - massive inc in autonomic activity mainly sympathetic. Generally lasts less than 10 minutes
* Perception of danger is generally greater than danger itself

Social Anxiety Disorder

* social phobia - social situations make you uneasy, feeling of failure, autonomic activation

Limbic system

* limbic system - KNOW BLUE BOXES
* Limbic system - in the middle of the brain - place where emotions, learning, and memory run through - routed to the hypothalamus

Hypothalamus - helps us

* understand danger when we dont even know it (knows threat before we know threat) - unconscious response to stress - autonomic responses

Reticular formation

* connected to the hypothalamus - goes the entire length of the brainstem - long and skinny
* When stimulated = increased alertness and arousal (more aware of environment)
* Inhibit = sleepiness/drowsiness

Reticular activation system (RAS)

* brainstem to thalamus - makes its way to the cortex - ALERT function - responsible for alertness - awakenes + sleep
* Also routes signals from hypothalamus to cortex

* Anxiety management 

* First uncover the underlying reason for anxiety - work to manage your fears
* Use angiolytics - drugs that treat anxiety
* CNS depressants - benzodiazepines + barbituates (barbs are dangerous and not used that much anymore)
* Anti-hypertensive agents - control BP
* Anti-dysrhythmics - control heart dysrhytmias
* Emotion stabilizers - SNRIs SSRIs TTAs( trycyclics,, MAOI (monoamine oxidase inhibitors)
* Take a few weeks to get function

\n

* Insomnia

* nability to fall asleep or stay asleep

We need to sleep for

* body repair and memory consolidation and repair

Sleep -

* - decrease in body temp, decrease in BP, hormone lvls change, respiration change - key is circadian rhythm — JET lag 

Short term insomnia- generally

*  stress related, mind runs —> dont sleep well

Narcolepsy

when you fall asleep during the day, can fall asleep at the wheel (generally arent allowed to drive)

narcolepsy treatmnet

modofimil (novigil) - increase dopamine uptake, increase dopamine in synapse, inhibit dopamine transporter

modofimil (novigil) warnings

* Decreases effectiveness of oral contraceptives- can last up to one month after cessation of drugs
* Decreases effectiveness of a1 antagonist

Long term insomnia

lasts longer that 30 days, can lead to depression, mania, paranoia, and other disorders. Often times caused by PTSD, head injury (large reason a lot of athletes kill themselves) chronic pain,

Rebound insomnia -

*  recurrence after treatment

* Nonpharmacological approaches for insomnia

* Limit caffeine
* Limit ethanol
* Increase time from dinner to bed
* Reduce use of screens 
* Cool room

Non-rem sleep

* can get depression, apathy, and fatigue. Linked to lack of repair and restoration of the body

Barbituates

* (SCHEDULE II) used to be called tranquilizers- STIMULATE GABA receptors (glutamate is the accelerator, GABA is the brakes) —- are old school - #1 narrow therapeutic index - dangerous - brain activity becomes so low that people die, psycological ad physical dependacne so people must be weaned off. You can get malignant hyperthermia (increase in body temp over 106 F) are deadly.

barbituates withdrawal

*  broad, dec BP, inc HR, dec appetite, inc muscle cramps, inc memory, blurred vision, agitation, anxiety, auditory hallucinations

Main use of barbituates today

* ontrolling epilepsy

Benzodiazepenes

* (SCHEDULE IV)- more widely prescribed - came out in the 60s - are safer - have breoader TI. (DONT MIX ETHANOL AND BENZOS) increase chloride conduction and brain becomes so negatively charged that it doesnt work

* Antidepressants

* Used for panic/anxiety disorders - TCA, MAORI, SSRI
* Ptsd ocd and gad - TCA, MAOI, SSRI, SNRI
* Also used to treat anticipatory anxiety (shortness of breath, inc HR, muscle tension)
* Problem - thoughts of suicide - esp in teens and young adults - sometimes go the wrong way and increase slepepnessness leading to hostility and irritability

SSRI  -work by

keeping serotonin in the receptor longer - increases half life in synapse by blocking its uptake -

SSRI problems

* Problems: weight gain, decrease in sexual function

Tricyclics (TCAs) - work by

* increase half life of serotonin

tricyclics notes

* No ethanol, do not use in pts with heart dysrhytmia or who have had a heart attack or heart block
* Anticholinergic side effects - dry mouth, hypertension