1
Q
What does the term ‘surmountable’ refer to in pharmacology?
A
Word used when agonist counters competitive receptor with increasing amounts of agonist
More doses of agonist will bind to the other thousands of receptors, while only the one dose of antagonist is bind to once receptor.
2
Q
What happens to EC50 in a surmountable situation?
A
EC50 changes, need a greater dose to achieve the same max response.
3
Q
Define ‘insurmountable’ in the context of receptor interactions.
A
Irreversible, cannot out compete it.
4
Q
How does EC50 behave in an insurmountable situation?
A
EC50 remains the same; max response changes.
5
Q
What are the four main causes of drug variation?
A
- Drug reaching receptor
- Presence/absence of endogenous ligand
- Inc/Dec of endogenous receptors
- Inc/Dec of downstream effectors
6
Q
What factors affect the drug reaching the receptor?
A
• Rate of absorption
• Distribution
• Clearance
• Age
• Weight
• Sex
• Illness
7
Q
What is considered the most important cause of drug variation?
A
Increase or decrease of downstream effectors.
8
Q
What is the formula to calculate the therapeutic index?
A
TD50/ED50
The therapeutic index (TI) indicates the safety margin of a drug.
9
Q
What does a higher therapeutic index indicate?
A
Safer drug
A higher TI suggests a larger margin between effective and toxic doses.
10
Q
What is ED50?
A
Median effective dose
ED50 is the dose at which 50% of the population experiences the desired effect.
11
Q
What is TD50?
A
Median toxic dose
TD50 is the dose at which 50% of the population experiences toxic effects.
12
Q
What is LD50?
A
Median lethal dose
LD50 is the dose at which 50% of the population dies from the drug.
13
Q
How does binding to a drug carrier affect drug distribution?
A
Bound drugs cannot cross barriers
When drugs are bound to carriers like albumin, they cannot reach target tissues.
14
Q
What is a common inert drug carrier in the blood?
A
Albumin
Albumin binds primarily to acidic drugs and plays a crucial role in drug transport.
15
Q
Which protein binds to acidic drugs?
A
Albumin
Albumin is the main carrier for acidic drugs in the bloodstream.
16
Q
Which protein binds to basic drugs?
A
Alpha 1-acid glycoprotein
This protein is essential for the transport of basic drugs in the blood.
17
Q
Which carriers bind mostly neutral drugs?
A
Lipoproteins
Lipoproteins are involved in the transport of neutral drugs in the bloodstream.
18
Q
Who is known as the father of toxicology?
A
Paracelsus
His famous adage ‘the dose makes the poison’ highlights the importance of dosage in toxicity.
19
Q
Define agonist.
A
Mimics natural endogenous response
Examples include Epi and Norepi.
20
Q
What are the three types of agonists?
A
Full agonist, Partial agonist, Inverse agonist
Each type has distinct effects on receptor activity.
21
Q
What is a partial agonist?
A
Produces lower response than full agonist; competes with full agonist
Examples include Pindolol and Acebutolol.
22
Q
What is an inverse agonist?
A
Binds to site and has opposite effect; goes negative —> turns off cell constitutive activity (to zero)
Examples include Carvedilol and Nadolol.
23
Q
What is an antagonist?
A
Blocks natural/endogenous response; competitive inhibitor
Examples include Propranolol and Atenolol.
24
Q
What distinguishes an allosteric inhibitor? Are they competitive or non-competitive?
A
Binds at different site other than where normal binding occurs
NON-competitive
Alters natural binding, may be positive or negative.
25
Define orthosteric binding.
Binding where normal endogenous response binds
## Footnote
Both agonists and antagonists can bind orthosterically.
26
What is the difference between toxins and poisons?
Toxins are from living organisms; poisons are from non-living organisms
## Footnote
Toxins can sometimes be used beneficially (e.g., botox), while poisons always have harmful effects.
27
How can a partial agonist also act as an antagonist?
A partial agonist can act as an antagonist by binding to a receptor in greater quantity than the agonist, blocking the agonist from binding to the site
## Footnote
A partial agonist is not as strong as a full antagonist and may result in fewer side effects.
28
Define stereoisomerism.
Stereoisomerism is when molecules have mirror images with the exact same molecular structure but are not superimposable
## Footnote
These are also known as optical isomers, akin to the right and left hand of a drug.
29
What are racemic mixtures?
A racemic mixture contains 50% of each stereoisomer
## Footnote
An example is ketamine, which is broken into R and S forms.
30
What is the relationship between bond strength and drug specificity?
Stronger bonds result in lower specificity of a drug
## Footnote
A drug does not need to have a specific interaction or shape to bind to a receptor if a strong bond is present.
31
What type of bond is the strongest in aqueous systems?
Covalent bonds are the strongest in aqueous systems
## Footnote
These bonds are difficult to break and do not require specific interactions with receptors.
32
When does a partial agonist act as an agonist?
When it is by itself without the presence of a full agonist.
## Footnote
In this scenario, it can activate the receptor, albeit less effectively than a full agonist.
33
What is an example of an agonist mimic/ indirect agonist?
Cocaine and Amphetamine.
34
What happens if a drug blocks the enzyme that suppresses receptor response?
The pathway will be available longer, enhancing the agonist effect.
35
What does physiologic antagonism refer to?
Drugs acting at different receptors to counteract the effects of other drugs.
36
Provide an example of physiologic antagonism.
Clonidine versus norepinephrine.
37
What does it mean if a drug is more potent?
Less amount of drug we have to give to see effect
38
What is efficacy in pharmacology?
Greatest therapeutic response a drug can deliver
39
Fill in the blank: Potency is the concentration or dose of a drug required to produce _______.
50% of that drug maximal effect
40
Which is more potent? More efficacious?
Potent- B
Efficacious- A,C,D
41
Explain what chemical antagonism is.
Occurs when administration of opposite charge drugs
ex: protamine(+) and heparin (-)
42
What effects receptor interactions?
-Appropriate size
-Electrical charge
-Shape
-Atomic composition
43
Explain weak acid drugs in solution
Acidic: release H+ into solution
44
Name 4 transmembrane signaling methods by which drug-receptor interactions exert their effects.
Direct crossing to intercellular receptor (lipid soluble)
Enzymatic action mediated by ligand binding
- Tyrosine kinase activated receptors
Ligand gated ion channel
G protein receptor
45
Define structure of GPCR
2 proteins in one (G protein couples with receptor)
alpha, beta, gamma
Seven trans-membrane: N terminal domain -->amino acids through cell membrane in and out of cell membrane (7) times--> C terminal domain
46
Explain desensitization and its molecular components
"Receptor stops signaling."
Drug binds to GPRC--> activates amino acids and changes conformation of protein--> swings in other direction--> if drug still bound stays in active confirmation= exposes OH to G-receptor KINASE= add phosphates to OH= becomes Phosphate groups on receptor = Beta Arestin protein = arrests the signal
47
How can does beta-arestin fall off?
Once drug comes off= dephosphorylated and goes back to normal and can be restimulated
48
What happens if the beta-arestin stays on?
Moves receptor and membrane interal to cell to Clatherin proteins
49
What two options happen after clatherin proteins come into play?
Merge with lysosome if drug will not detach
OR
if drug comes off; phosphatase will strip Phosphate and receptor will come back to native form then moved back up to surface of cell
50
Explain ligand gated ion channels
Binds to something then opens
51
What is an example of an inotropic ion channel?
nACh Receptor
52
Cholinergic subtypes
Muscarinic & Nicotinic
53
Muscarinic secondary messengers
M1,3,5 = GPCR-Q (inc IP3, DAG)
M2&4= GPCR-I (dec cAMP)
54
Nicotinic secondary messengers
Nm→ skeletal muscle (more somatic nervous system)
Nn → CNS
^^ All open Ion channels
55
Adrenergic subtypes
Alpha 1, 2
Beta 1, 2, 3
Dopamine
56
Alpha 1 secondary messengers
Located in peripheral vasculature
Effects
GPCR-Q → inc phospholipase C; IP3/DAG
IP3→ Ca++ release→ smooth muscle (myosin light chain kinase) → contraction
57
Alpha 2 secondary messengers
Alpha 2→ located in CNS mostly, some in peripheral vasculature
Effects
GPCR- I → dec adenylate cyclase; Ca/K channels
58
Beta secondary messengers & location
****All beta → Stimulate adenylate cycles; Ca+ channels; inc cAMP
Beta 1→ located in heart--> Ca+ release from SR in heart= contraction
Beta 2→ located in lungs, smooth muscle, skeletal muscle
Beta 3→ located on fat cells
59
How does cAMP effect B2 in skeletal muscles?
In smooth muscle B2 = relaxation
Stimulates adenyl cylase= Inc cAMP= relaxation
60
Explain autonomic feedback loop with INC in MAP
Baroreceptors sense: CNS (vasomotor system-brainstem) → parasympathetic→ vagus nerve → dec HR → dec BP
61
Explain autonomic feedback loop with DEC in MAP
SNS increases: Peripheral vascular resistance → arterioles
-Venous tone
-HR & Heart contraction
Results
Inc CO, SV, venous return → inc BP
62
Explain hormonal feedback loop with DEC in MAP
Kidneys regulatory - RAAS
Dec blood flow pressure → renin → angiotensinogen → angiotensin (constrict blood vessels) → release aldosterone (inc water @ kidneys) → inc blood volume
63
What is a dendrite?
Receives information and sends to body of a neuron
Contains many dendrites
64
What is the cell body of a neuron?
Interprets and sends information
Response can be excitatory or inhibitory
(makes proteins- has nucleolus)
65
What is the axon hillock ?
Sends interpreted information from cell body to telodendria
Most have 1 axon
66
What is the telodendria?
Branches off axon and connects to other cells; where synapse occur between telodendria and next cell
67
What are the 6 main classes of neurotransmitters?
1) Esters- ACh
2) Monoamines- NE, Epi, serotonin, dopamine (all are GPCR mostly)
3) Amino Acids- GABA, glutamate
4) Purines- adenosine, ATP
5) Peptides- substance P, endorphins, enkephalins
6) Inorganic gases - nitric oxide
68
Beta 2 in the heart vs smooth muscle/ skeletal muscle
Heart- increase contraction
Smooth muscle- relaxation
69
ID difference between parasympathetic & sympathetic structure, drugs
70
Effect of heart from stimulation of B receptors
Inc CO; Dec peripheral resistance
71
Direct Catecholamine: Ex?
Bind at synapse
albuerol, clonidine, dobutamine (B1), dopamine, epi, isoproterenol, NE
72
Indirect Catechoalmine
Prolong NE at synapse but don't bind themselves (cocaine, amphetamines)
^^Inhibits dopamin reuptake in brain= addiction
73
Epi effects with alpha & beta (direct catechalimine)
Alpha= potent vasocosntrictor
Beta1= inotropic, chronotopic
B2- dilation in bronchioles/skeletal muscle
NE same but not B2 stimulatory
74
Isoproterenol: Type of agonist, indirect or direct ?
B agonist- B1 & B2
Direct
75
List the alpha blockers described in class.
Reversible:
Phentolamine
Tolazoline
Labetalol
Tamsulosin
Phenoxybenzamine- irreversible
THINK alpha 1 blocking= lower BP
76
Adrenoceptor Antagonist Drugs used to Tx?
Pheochromocytoma
77
Beta blockers effect what mostly?
HEART- neg ionotropic & chronotropic
78
Beta blocker effect on blood vessels?
Blocks B2
Acute: Inc peripheral resistance
Chronic: Dec peripheral resistance
79
Propranolol (Inderal)
Works on B1 & B2- no partial agonist activity
Dec HR & airway constriction
80
B1 selective drugs ? Who are they safer for ?
Metoprolol
Atenolol
(Safer for COPD, diabetes)
81
Esmolol
B1 selective- short acting
Good for OR tachycardia, Supraventricular arrhythmias
82
Explain the triphasic effects of dopamine.
Depending on the dose of dopamine, then you can have a triphasic effect
(1) Activates dopa receptors at low dose
(2) Beta receptors- increase CO
(3) Alpha receptors- vasoconstriction
83
Ephedrine: Direct or Indirect?
direct & indirect adrenergic agonist
84
Direct vs Indirect Cholinomimetics
Direct- act like ACh and bind where ACh would
Indirect- inhibit AChE (prevents acetylcholinesterase), prolong ACh at junction
85
Effect of cholinomimetics in eyes
Muscarinic agonists: contraction (miosis)
Increase intraocular drainage
86
Effect of cholinomimetics in CV
Vasodilation → reduction in BP - reflexive increase in HR
87
What are the 3 categories of indirect acting cholinomimetics and examples ?
1)Simple Alcohols- ex: edrophonium (Quat ammonium group)
2) Carbamic acid esters of alcohol- ex: neostigmine & carbamate (tertiary/quaternary ammonium groups)
3) Organic derivatives of phosphoric acid - ex: organophosphates, echothiophate
88
S/S of toxicity in direct acting Cholinomimetics & Cholinesterase inhibitors
SLUDGE-BM
89
Tx for toxicity from direct acting Cholinomimetics & Cholinesterase inhibitors
Therapy- atropine, pralidoxime (if pesticide expose, decontamination)
90
Atropine Toxicity S/S
(Anticholinergic Toxidrome): Tx?
Hot, Blind, dry, red, mad
TX: Physostigmine ( fro belladona)
91
What are the regulators of blood pressure?
Cardiac output and PVR.
Hydraulic equation: BP= CO x PVR
92
List 4 major groups of antihypertensive drugs
1) Diuretics: deplete sodium
2) Sympathoplegics: decrease PVR, reduce CO
3) Direct Vasodilators: relax vascular smooth muscle
4) Anti-angiotensins: block activity or production
93
Give examples of centrally acting sympathoplegics.
Clonidine & Methyldopa
94
Explain methyldopa alpha 1 or 2?
Receptor & location : Agonist at CNS α2 adrenoceptors- more alpha 2
Major side effect: SEDATION
95
What can effect CO?
SV, HR, venous capacitance (preload)
96
Explain clonidine alpha 1 or 2?
Receptor/ Location: Stimulates α2 receptors in arterioles in CNS (Partial Agonist***)
Side effect: Sedation
Common use: ADHD, Tourettes, Withdrawl symptoms
97
Explain Variant angina. What are the other names for it?
Coronary vasospasm of blood flow= dec O2 delivery
(Vasospastic; Prinzmetal)
98
Explain unstable angina
Microvascular disease: Angina at rest
Plaque build up; Clots within arteries of heart
99
Fill in missing info
100
Define concerns with overexposure to nitrates and nitrites: Good vs Bad
BAD: HEADACHE, Orthostatic hypotension, Syncope
GOOD: Inc venous capacitance, dec venous preload, dec heart size, dec CO
101
1st Generation of BB
Beta 1 & Beta 2
- inhibits renin; dec CO
NonSelective (ex: Propanolol- tox associated w B blockade)
102
2nd Generation BB
Beta 1
Selective- Atenolol, Esmolol, Metoprolol
103
Which CCB does Dr. T want us to know?
Verapamil- more cardiac acting
Diltiazem- in between of cardiac & peripheral acting
Dihydropyridines- peripheral vasculature
104
CCB Effects on: Smooth muscle & Blockade
Blocks L-type
Smooth muscle: Relaxation (Mainly vascular; Some effects on GI, GU, bronchi, uterine)
Reduce blood pressure
Blockade: Long lasting smooth muscle relaxation
Effect on Heart:
↓ contractility
↓ SA node pacemaker rate
↓ AV node conduction velocity
105
What are the beneficial effects of BB?
Dec oxygen demand (dec HR, BP, Contractility)
106
NO, Nitrates, Nitrites MOA
Activate GC, increase cGMP - Relaxation
107
Sildenafil MOA
Blocks PDE5, increase cGMP - Relaxation
108
CCB Tox?
Bradycardia, arrest
AV block
CHF
109
Prazosin, Terazosin, Doxazosin
Blocking where? Effect?
Blocking: Block α1 receptors in arterioles and venules
Effect: Dilates both resistance and capacitance vessels
BP is reduced more in upright position
110
Minoxidil : MOA
MOA: Opens K+ channels in smooth muscles
Stabilizes potential, less likely to contract
Dilates arteries, arterioles
111
Hydralazine: MOA, TOX?
MOA: Dilates arterioles (NO Production)
Toxicity
HA, nausea, sweating, flushing
112
Explain sodium nitroprusside MOA & Common Use
Effects: Arteriole & Venuous blood vessel (very strong)
Breaks down in blood to release NO (bc NO in its molecule), inc intracellular cGMP= close Ca channels
Use: HTN Emergencies, Cardiac Failure
113
What is the mechanism of action of Fenoldopam ?
Agonist of D1 receptors in kidneys= inc in blood flow to kindey
(less blood in vasculature; more filatration of blood at kidneys= inc urine output)
**can be used for kidney transplant not only for HTN
114
Describe the differences between the 2 types of angiotensin antagonists.
ACE- blocks angiotensive coverting enzyme (DIRECT)
ARBs: competitive inhibitors; blocks downstream effects of aldosterone & angiotensin II (INDIRECT)
115
Define heart failure
HF: fails to meet the metabolic demands of tissues
Congestive= fluid backup
116
Explain systolic HF vs diastolic HF
Systolic HF: Reduced cardiac function (dilated cardiomyopathy); thin heart walls
Diastolic HF: Reduced cardiac filing (can be peripheral); chronic (HTN caused- Hypertrophy)
117
Congestive HF: R Ventricle vs L Ventricle Failure
R Vent: peripheral congestion
L Vent: Pulmonary congestion
118
Ventricular dysfunction: Diastolic HF
Dec CO; normal EF (% is being pumped out well BUT DECREASE total amount in amount within heart to begin with)
(hypertrophy of myocardium)
Tx: target BP ( inotropic drugs don't really help)
119
Ventricular Dysfunction: Systolic HF
Dec CO; DEC EF
Acute failure
(MI)
120
Compare the four factors of cardiac performance
1) Preload- how much is coming back to heart
2) Afterload- resistance heart has to overcome
3) Contractility- force of heart pumping
4) HR
121
Draw the molecular mechanisms controlling normal cardiac contractility.
1) Depolarization through cell- opens L Ca++ channels
2) Ca+ into cell (aka trigger Ca)--> binds to ryanodine receptors
3) Opens Ca++ --> Binds to Trop Ca= CONTRACTION
RELAXATION (goes back to Vrm)
1) SERCA- dec Ca in SR
2) Na/Ca Exchanger from ECF Ca+ back out
3) Na/K ATPase Pump
122
Describe the mechanism of action of digitalis and its major effects.
Inhibits Na/K ATPase pump
Maintains normal resting potential
Positive inotrope
(Inotropic)
123
Explain phosphodiesterase inhibitors: MOA, Ex?
Known as: Bypridines
Blocks the Enzymes that inactivate cAMP and cGMP
Positive inotropic effects
Main action from vasodilation
Milrinone
124
Illustrate the intrinsic conduction system and subsequent EKG reading.
1) SA NODE- in RV, crescent shape ; will depolarize by itself (primary one in heart)
2) AV - within junction of atria & ventricles; slow (gotta wait for SA signal)
3) Atrioventricular bundle of His- down the septum (inter ventricular septum)
4) Purkinje Fibers - spreads within the muscle of the ventricle walls
125
Explain the Cardiac AP & Ion channel currents
Phase4-K out???
Phase 0- threshold occurs; Na comes in through channels
Phase 1- K leaves cell
Phase 2- Plateau; Ca+ in ;K out (balance each other out kinda) ; Ca channels close at end of plateau
Phase 3- K continues to leave cell
Phase 4- Bunch of K outside and Na inside (Na/K Pump to re-establish Vrm)
126
List the 4 types of anti-arrhythmic agents
1) Class 1- Na channel blockade "state dependent" - quinidine, lidocaine, flecainide
2) Class 2- Sympatholytic (BB) - Propanolol
3) Class III- Prolong action potential duration (other mechanism besides sodium channels - commonly block K+) - Amiodarone
4) Class IV- Block cardiac Ca channel currents (CCB)- Verapamil
127
Know Tx: Bradycardia, Heart Block, SVT, ST, VTACH, A-fib, V-Fib
128
FIll in the blank :
129
Carbonic Anhydrase Inhibitors: MOA, Ex?
EX: Acetazolamide
MOA: Block CA in PCT, waste Na, K, and bicarb
130
Loop DIuretics: EX? Loss of what electrolytes
Ex: Furosemide
Loss- Na, K
131
Thiazides: EX? Loss of what electrolytes?
Ex: Hydrochlorothiazide
Loss- NA, K
132
Potassium Sparing Diuretics: ex?
Spironolactone
Conivaptan
133
Osmotic DIuretic?
Mannitol
134
Histamine Receptors
H1- H4
All GPCR
135
H1- Effects on Resp & CV?
Bronchoconstriction
Vasodilation + reflex tachycardia
136
Antihistamines are H1 selective inverse agonists- Ex?
Diphenhydramine (benedryl)
Most useful for Type I hypersensitivity
137
Histamine effect: CNS
Pain & itching
138
Explain the triple response of allergy testing
Wheal and Flare- welt= wheal; flare= redness
Histamine effects
Caused by:
1) Microcirculation smooth muscle
2) Capillary endothelium- leaky
3) Sensory nerve endings- activation of nerve endings (flare)
139
How do histamines effect the stomach?
Secretory- releases gastrin= releases hydrochloric acid
140
Histamine Effect in GI Smooth Muscle
Helps cause peristalsis/contraction
141
First generation histamine antagonist effects
1) Sedative effects- crosses BBB
2) ANS blocking
-antinauseua, antiparkinsonsim (suppresses extrapyramidal s/s)
142
H2 Receptor Antagonists
Very selective for stomach acid
PPIs STRONGER
143
Drug classes:
Short term Relievers vs Long Term in Asthma
Short term
1) Bronchodilators: Beta agonist, anti-muscarinic, methylxanthines
Long term
1) Anti-inflam- steroids, antibodies
2) Leukotriene antagonists- lipoxygenase & receptor inhibitors
144
Adrenergic receptor agonist - β2 Effect in Asthma
B2- relax airway smooth muscle
-inhibit mast cells, dec microvascular leakage, inc mucociliary transport
145
Albuterol (SABA)
MOA- B2 selective
Use- Rescue inhaler
Effect- bronchodilation
Duration- 3-4 hrs
146
Salmeterol & Formoterol
Long acting B2 agonist (duration- 12 hrs)
-high lipid solubility, dissolve cell membrane, slowly release to receptor
147
Adrenergic receptor agonist for asthma- Drug Ex? Toxic Effect
Toxic- Skeletal muscle tremor
Drugs- Terbutaline, albuterol, salmeterol,
No selective- Epi, Isoproterenol
148
If you give epi for an asthma attack, how would the route of the medication given effect your further treatment?
Inhalation- 60-90 min duration
Must monitor for late reaction & tachycardia, arrhythmias due to B1 stimulation as well as B2 (nonspecific)
149
Explain isoproterenol given for asthma (SABA)
Non- specific
Potent bronchodilator-- but high doses = arrhythmias so replaced by albuterol
150
What medication is available parenteral for asthmatics?
Terbutaline- B2
151
What are muscarinic antagonist commonly used for?
COPD
152
Atropine for COPD
Lower dose than normal for cardiac parasympathetic blockade
(Short Acting Muscarinic Antagonist)
153
Ipratropium bromide for COPD- Drug class, Pharmackinetics
Long Acting Muscarinic Antagonist (LAMA)- more selective than atropine when inhaled
Synergistic w beta-2-agonist
A: poorly absorbed, no CNS effects
154
Tiotropium: Drug class, duration, common use?
Drug class: Muscarinic antagonist (LAMA)
Duration: Longer acting (24hrs)
Uses- COPD (limited in asthma)
155
Monoclonal Antibodies: asthma ?
Injection of IgE monoclonal antibodies
Ex: Xolair (Omalizumab)
156
How do anti-IgE monoclonal antibodies for asthma work?
Targets IgE portion that binds to mast cells - prevents degranulation of mast cell & allergen from binding to it
- lessens asthma severity
-dec corticosteroid requirement
- reduce hospitalizations
157
Zileuton: Drug Class, MOA
Drug Class- Leukotriene pathway inhibitor
MOA- inhibits 5-lipoxygenase
158
Which meds inhibit leukotrienes from binding to their receptors ?
Zafirlukast
Montelukast
159
Serotonin neural effect
Mood, sleep, appetite, temp, pain perception, depression, anxiety, HA, vomiting, pain/itch
chemoreceptor reflex= bradycardia & hypotension
160
Serotonin: Non-neural effects
5-Hydroxytryptamine -
1) Platelet clotting process= inc tone = vasoconstriction
2) Enterochromophone cells in Gut- 90% of serotonin in body = stimulates peristalsis
161
Serotonin is a precursor to?
Melatonin
(Tryptophan converted to serotonin to melatonin)
162
5HT3: Function, Location, Drug to suppress it?
Function: Receptor is a Na/K ion channel (works quickly)
Location- Area prostrema = Illicts vomiting reflex
Drug- Ondansetron
163
Serotonin- Resp Effect & CV
Facilitate ACh release= constriction
Hyperventilation
CV- contraction vascular SM (not in heart); plt aggregation, inotrope
164
Buspirone: MOA, Use?
Serotonin Agonist Partial
MOA: 5-HT1A
USE: GAD, OCD (anxiolytic)
165
Sumatriptan: MOA, Use?
MOA: 5-HT1D/1B Agonist
Use: Tx of Migraine HA
166
Triptans toxicity
Coronary/ Cerebral vasospasm
Serotonin syndrome- when taking w SSRI, MAOIs
167
Serotonin syndrome: Tx s/s
Caused by: SSRI, MAOIs
S/S- Diarrhea, HTN, tremor
Tx- Sedation (benzos) paralytic, intubation, ventilation
168
Neuroleptic Malignant Syndrome
Caused by- D2- Blocking drugs
(inc dopamine)
S/s- no bowel sounds, mimic parkinson's (slow over 1-3 days)
TX- Diphenhydramine
169
Malignant Hyperthermia
Caused by: Volatile anesthetics
S/s: HTN, rigidity, HTN (w/in minutes)
Tx: Dantrolene
170
Phenoxybenzamine & Cyproheptadine are ...? Uses?
Serotonin antagonists @ 5-HT2 receptors
Uses-Carcinoid tumors, cold induced urticaria
171
5-HT3 Inhibitors
Ondansetron
Use- surgery, Ca chemotherapy
172
Major Tx of Antidepressant Meds
(Tx for minor to major severity)
1) SSRI- Prozac, Zoloft
2) Selective serotonin-NE reuptake inhibitors (SNRIs) - Cymbalta, Pristique
3) Tricyclic antidepressants- SERT, NET, anticholinergic (Elavil)
4) MAOIs
173
Simple Partial OR Focal Aware Seizures Characteristics
-Minimal spread of discharge
-Does not affect consciousness or awareness
- EEG may show normal discharge
174
Focal-Impaired Awareness Sz (Complex partial focal)
- Affects LOC= unresponsive or LOC
- has automatisms
175
Focal to Bilateral Tonic Clonic
Starts as a focal then spreads to the whole brain= tonic clonic
176
Types of generalized seizures
1) Generalized Tonic-Clonic
2) Generalized absence
3) Myoclonic
4) Atonic/Tonic
5) Infantile Spams
177
Generalized Absence (petite mal)
Stare off into space; no notice of sx, some automatisms
178
Generalized Tonic Clonic
"aka grand mal"
-Starts all over ENTIRE surface of brain (diff from focal to bilateral)
(fall; urinary incontinence, jerky)
179
How do they tx infantile sz?
1) Corticosteroids- Prednisone IM (chronic tx)
2) Vigabatrin- GABA analog= tx s/s
180
Dilantin: MOA, Use?
MOA: ALL
1) ALL; mostly Limit Na activity in neuron (block)= neuron can't release NT
Use: Generalized T/C & All Focal
181
Carbamazepine (Tegretol) : MOA
Tricyclic antidepressant but also anti-seizure
MOA: blocks Na channels
182
Clinical use for Tegretol
1) Drug choice for focal sx
2) Trigeminal neuralgia
3) Bipolar D/o
183
Phenobarbital: MOA, Use?
MOA: Enhance GABA transmission (sedative hypnotic)
Use: Focal, Generalized Tonic-Clonic
184
Ethosuximide MOA, Use? Tox?
MOA: Ca channel inhibition
Use: General absence sz
Tox: GI, Lethargy, hiccup, euphoria
185
Valporic Acid, MOA: Use? Tox?
MOA: Unknown; ALL
Broad Spectrum AED
Use: All kinds of sz
Tox: Hepato, GI, sedation, fine tremor
ADME : A:80%, 90% PP bound, T1/2 = 9-18 hr
186
Benzodiazepines: Use?
Psychoactive drugs
MOA: Inc GABA
Use:Status epilepticus (SE) Commonly for anxiety d/o
187
lamotrigine
Phenytonin, Phenobarb, Carbamazapeine
Ethosux
Valporic aacid
Vigabatrin
188
What are the four phases of platelets within thrombogenesis?
1) Adhesion- activated by collagen & vWF
2) Aggregation
3) Secretion: ADH, TXA2, 5HT
4) Cross linking of adjacent plts- fibrin (mesh) links plts together
189
Explain thrombogenesis pathway.
1) Damage to endothelial cells= Collagen & vWF exposed
2) C & vWF bind to glycoproteins (GP1) on plts= plts ADHERE = cascade event= degranulation of plts
3) Plt release: ADP, TXA2, 5-HT
4) Main functions- activate additional plts = go to their receptors on other plts= allows for other plts to come= aggregation
5) More degranulation of more plts
190
Know the components of the intrinsic coagulation casacade
1) Activated by plt interaction with phospholipids
2) Factor 12--> 11--> 9--> 10 --> thrombin activated
191
Know the extrinsic coagulation pathway
1) Tissue damage= tissue factor release= activates extrinsic pathway
2) Tissue factor & F7= activate thrombin
192
DIC- What is it? Cause?
Over stimulation of blood clotting mechanism (run out of clotting factors)
(Massive tissue injury, malignancies, abruptio placenta)
193
DIC Tx?
Plasma transfusions
Tx underlying cause
10-50% Mortality
194
What does the body use to regulate coagulation?
1) Fibrin inhibition
2) Fibrinolysis
3) Protease Inhibitors- antithrombin
195
Examples like t-PA?
Urokinase
Streptokinase
196
What protects clots from lysis?
Aminocaporic acid- anti-activator
blocks conversion of plasminogen to plasmin
197
Drug Ex of indirect thrombin inhibitors
Un-fractionated heparin
LMW heparin
Fondaparinux (Arixtra)
198
Heparin- High Molecule weight/ Un-fractionated: MOA
MOA: inc Antithrombin x1000= Inhibits F10 & thrombin by inc
199
LMW heparin & Fondaparinx have less side effects than unfractionated heparin, why?
Activate antithrobin= only blocks F10
(not as effective/strong)
200
Heparin toxicity
Bleeding- monitor aPTT
Transient thrombocytopenia (temp dec in plts) - HIT
201
Protamine sulfate
From salmon eggs
For unfractionated heparin reversal only
202
Warfarin MOA?
Warfarin blocks Vit K reductase= so shits down Vit K cycling= fewer proteins produces for coagulation cascade
- blocks proteins production process (not ones made already)
(essentially blocks F10, 7,9)
INR- 2-3
203
How long does warfarin take to kick in?
8-12 hr delay in onset of action
Heparin - warfarin bridge
204
Explain the fibrinolytic system
1) Injured cells releases tPA (tissue plasminogen activator)
2) tPA--> plasminogen into plasmin
3) Breaks down fibrinogen & fibrin (lyse thrombi)
(acts on clot where it is)
205
Aspirin MOA:
COX1- Selective: TXA2 blocks thromboxane A2 = plt changes shape, no granule release or aggregation
Inc bleeding time
Anti-platelet
206
Clopidogrel and Ticlopidine MOA
MOA inhibits ADP receptors on platelets= reduce plt aggregation
(dec ischemic events)
207
IIb/IIIa Receptor Blockers MOA, ex?
MOA: Blocks F2& F3 receptor complex = fibrin cant bind to help with cross linking in plts
ex: Abciximab (monoclonal antibody)
208
How does Vit K help with bleeding d/o?
Activity on prothrombin, factors 7,9,10= all need to be carboxylated by Vit K
209
What are fibrinolytic inhibitors used for?
Adjunctive hemophilia therapy
Bleeding from fibrinolytic therapy
Intracranial Aneurysms
Post surg bleeding
210
What is an example of fibrinolytic inhibitor?
Aminocaproic acid
211
Direct thrombin inhibitors
1) Bind to active & substrate site of thrombin - Hirudin, Bivalirudin
2) Binds to only thrombin active site- argatroban, melagatran
212
What are the 4 types of DM?
Type 1- insulin dependent (juvenile)
Type 2- Non- insulin dependent
Type III- other causes inc BG (pancreatitis, drug therapy)
Type IV- Gestational (OB)
213
Explain insulin secretion w GLUT-2 (low affinity transporters; cells in pancreas)
Low affinity Transporter
1) High glucose--> transported into cell by GLUT-2
2) Glycolysis= Metabolism --> ATP made
3) ATP goes to K-channels= makes inside cell more (+) charged
4) VG Ca channels- floods into cell when membrane depolarizes = goes to cells
5) Vesicles have insulin in them =insulin released (exocytosis)
214
What type of receptors are the insulin receptors (in cells in body)?
Tyrosin kinase receptors - insulin bind to Tyrosine R=dimerization & phosphorylation = IRS (insulin receptor substrates) phosphorylated= makes
1) IP3- fast GLUT-4 channels go to cell membrane= glucose comes into cell
2) MAPK- long term (cell division
215
Rapid acting insulin
Lispro, aspart, gluisine
216
Short Acting Insulin (regular)
Novalin, Humulin
217
Intermediate acting insulin
Neutral protamine hagedorn
218
Long Acting Insulin
Glargine, Detemir
(mimics constitutive insulin activity)
219
Biguanides- Oral AntiDM: MOA, Side Effect, Ex?
First line therapy
MOA: Reduction in hepatic glucose production (gluconeogensis)
Side effect: GI Tox
Ex: Metformin (Glucophage)
220
Insulin Secretagogues: MOA
MOA: Bind to K channel = blocks it= depolarizes cell= Ca comes into cell= helps inc glucose uptake
Inc insulin secretion
221
Sulfonylureas: 1St gen Ex & 2nd Gen ex
1st Gen- Tolbutamide : higher doses, shorter duration
2nd Gen- Glyburide
(has sulfa group & urea molecule)
222
Thiazolidinedions (Tzds) MOA, EX?
MOA: Dec insulin resistance, inc insulin signal transduction
Ex: Rosiglitazone
223
Alpha-Glucosidase Inhibitors: MOA, SIde Effects, Ex?
Beneficial for Pre-DM
MOA: Block digestion of complex carbs ; blocks enzyme that breaks down sucrose= prevent production of monosaccharide & transports cant tansport glucose into body
Side effects: Flatulence, diarrhea, Abd pain (since sucrose has to be broken down in GI)
Ex: Acarbose
224
Bile Acid Binding Resins: MOA, Side Effect
MOA: bind bile acids- prevents reabsorption of them
SIde Effect: GI Upset
225
Amylin Analog: MOA, EX?
MOA: Suppresses glucagon release; slows stomach emptying & dec circulating glucose
Ex: Symlin
226
Incretin-Based Therapies: MOA, Risk?
MOA: Slows gastric emptying; inc Insulin release; inhibits glucagon release
Inc risk- pancreatic risk
227
GLP-1 Agonist: MOA, EX?
MOA: Acts like GLP-1
EX: Semaglutide
228
DPP-4 Antagonist : MOA, EX?
MOA: inhibits DPP-4 = more GLP1 available
EX: Sitagliptan
229
Gliflozins: MOA? Ex?
MOA: Targets kidneys; prevents glucose reabsorption in PCT
Ex: SGLT2 Inhibiors (Dapagliflozin
230
Insulin Receptor Effects
Membrane translocation of GLUT
Increased glycogen formation
Activation of multiple transcription factors
231
1) TOO much LDL
2) Entrapment in vessel
3) WBC comes= foam cell made
4) Oxidation= over years= crystallization in foam cell
5) Rupture of cell= inc inflammation
6) Inc WBC = vicious cycle WBC
7) Calcification & necrosis = plaque forms = dec blood flow
232
Cholesterol formation pathway
Know HMG-Coa= Mevalonate= makes cholesterol
HMG-CoA= converted into ketone bodies in blood=
233
Lipoproteins: Structure
Structure- Part lipid & protein
Apolipoprotein- outer surface (mostly protein)
Formed in liver
234
Chylomicrons
Formed in intestine, carries triglycerids, cholesterol- dietary fat
235
VLDL
Secreted by liver- converted to IDL , LDL
236
LDL: transport to cells?
From production in liver- transports to cell to LDL receptors- binds & internalizes LDL = excess goes into arteries
237
HDL
Scavenerge of cholesterol from CELLS; not from endothelial cells
238
Desired Total cholesterol, LDL, HDL levels
Total Cholesterol < 200
LDL< 120
HDL> 50
239
Statins: MOA, Ex,
MOA:
1) HMG-CoA Reductase Competitive Inhibitor = dec cholesterol synthesis
2) Inc LDL-Receptors= dec circulating diet cholesterol since more receptors
Ex: -Statin
240
Niacin (VItamine B3) : MOA, Dosing?
MOA: Blocks packaging of cholesterol in VLDL= Dec VLDL & LDL, inc HDL
Dosing- 2-6 g daily : inc from regular multivitamin dose
241
FIbrates: MOA, Ex?
MOA: PPAR mediated lipolysis- inc breakdown of lipids & cholesterol in liver = dec VLDL
Ex: Gemfibrozil, Fenofibrate
242
Binding Resins: MOA, Use? Ex?
MOA: Cationic bile acid binding= prevent reabsorption of bile acids & cholesterol
Use: Primary Hypercholesterolemia
Ex: Colestipol, Cholestyramine
243
Absorption Inhibitors: MOA, EX?
MOA: BLOCKS NPC1L1- block reabsorption of Cholesterol when it goes out to liver in bile & out to gut
Ex: Ezetimbe
244
Monoclonal Antibodies for cholesterol: MOA
MOA: PCSK9 Inhibitors- allows for increased LDL-Receptors by blocking PCSK9
Ex: Evolocumab (Repatha)
245
Short acting statins should be taken when?
At night since cholesterol synthesis occurs at night w food
246
Statins should be avoided in ?
AVOID in Pregnancy & lactating women
Restricted in children
247
Statins Tox?
Inc liver enzymes
CK elevations - excess creatinine= muscle pain or weakness
248
Niacin Tox?
Cutaneous vasodilation - FLUSHING
249
Explain GABA-R Activity
GABA-A: primary- induces sedative hypntoic state; Cl- channel
Opens channel; lets Cl- come into cell= hyperpolarization= harder to excite cell (can work on pre & post synaptic cells)
250
Benzos: MOA
MOA: Enhance GABA= depresses all levels of CNS
Diazepam, Midazolam
May contribute to a persistent postanesthetic respiratory depression
Reversible with flumazenil
251
Barbituates: Use, Dose Index
Use: RARE d/t easy OD; anticonvulsants, anesthesia
Dose index: VERY NARROW therapeutic range
(tolerance, dependence, abuse)
252
Common anesthesia meds
Barbituates- Thiopental &
Methohexital= can induce sz if sensitive to it
Benzodiazpenes
253
Flumazenil
Reversal for benzodiazepines
254
General Anesthetics Types
1) Inhaled
2) Injected
255
Propofol: Use, Pharmacokinetics
Route: Injectable anesthetic
Use: Day care surgery
ADME: Highly lipid soluble, T1/2= 2-8 min
E:kidney excretion
256
Propofol MOA
Incs GABA-A
INC Glycine
Supresses 5HT, nicotinic
(does not work at glutamate= not amnesic)
257
Propofol adverse effects
1) Thrombophlebitis
2) Allergy
3) Hypotension
4) Propofol Syndrome
5) PE
258
What med is used to tx anxiety that doesn't cause sedation?
Buspirone – 5-HT1A Receptor Agonist
259
Sleep D/o Tx
Nonpharm= diet, no caffeine
Pharm= Zolpidem (Ambien) or Escopiclone (Lunesta) only after sleep study & for short period ; antihistamines
260
5 Properties of antimicrobial agents
Selective Toxicity
Spectrum of Activity- how wide they toss their net
Modes of Action- 5 main modes
Side effects
Resistance of Microorganisms
261
5 Main mechanism of Drug action
Cell wall inhibitors: Better at gram (+)
Cell Membrane: Better @ gram (-)
DNA/RNA- inhibits replication or transcription/translation
Inhibit DNA/RNA Synthesis = Block Folic acid synthesis of bacteria
Protein Synthesis Inhibitors- target ribosomes (broadest category)
262
Ex of drugs that inhibit cell wall synthesis. Useful for treating?
Penicillin
Cephalosporin
Tx: Gram (+)
263
Vancomycin Benefit, Use?
No beta-lactam ring
Benefit: resistance to beta-lactamase
Use- MRSA, Gram (+) stuff
264
Vanco MOA?
Binds to glycoproteins which prevents cross linking enzyme = cell wall of bacteria falls apart
265
Vanco Side effects/Tox?
Irritating to tissues
Chills/Fever
Ototoxicity, Nephrotoxicity
Red "neck"
10% have adverse rx
266
Disruption of Cell Membrane Drugs? Useful for?
Amphotericin - acts a detergents= binds to phospholipids
Use- Gram (-)
267
Polymyxin- MOA, Routes? Use?
MOA- disruption of cell membrane
Route- Topical (Neosporin) or Systemic (oral)
Use- Gram (-)
268
Tetracyclines MOA, Use?
MOA- Bacteriostatic- slows down growth
Widest spectrum of activity of all abx; kills lots of good bacteria too
Useful- better for Gram (-)
269
Adverse effect tetracyclines?
C-diff
Bone: TEETH= breakdown of enamel if teeth growing in
Neurotoxicity
Allergy
Nephrotoxicity
Ototoxicity
270
Macrolides Drugs?
Protype: Erthromycin
Semi- Sythetic: Clarithomycin, Azithromycin (very lipid soluble; short duration)
271
Fluoroquinolones MOA, Use, Ex?
MOA: Inhibit DNA gyrase
Use- Gram (+ & -)
EX: Cipro, Levaquin, Floxin
272
How do sulfonamides block folic acid synthesis in bacteria?
Blocks PABA since structure if very similar
273
274
Abx- Target DNA/RNA
Rifamycin
Floroquinolones- Ciprofloxacin
275
Sulfonamides- adverse side effect?
Aplastic Anemia
276
Pneumocystis, toxoplasmosis- TX?
Sulfonamides + Conjunction with trimethoprim
Bactrim, Septra
277
Viral components
- Nucleic acid- RNA or DNA
-Protein Coat aka Capsid
- Spike: recognition particle= specific for certain cells
- infectious particles : active vs inactive
278
Acyclovir: Use, MOA?
Use: anti-herpes drug (HSV & VZV infections)
Prototype
MOA: Inhibits viral DNA synthesis/polymerases
279
Explain why acyclovir is termed a chain terminator.
Has similar structure to DNA-Guanine strand but missing strand to make chains
Missing part blocks further chains= chain terminator blocks further DNA replication
280
AZT MOA
Inhibitor of reverse transcriptase
Combined with other antivirals in HAART (cocktail)
281
Lamivudien MOA/ Use
Inhibits HBV DNA polymerase and HIV reverse transcriptase
282
Flu Tx?
Oseltamivir (Tamiflu)
Zanamirivir (Xofluza)
Baloxivir Marboxil (Reneza)
283
COVID-19 Tx
Paxlovid- 2 antivirals, emergency use authorization
Remdesivir- chain terminator
Monoclonal Antibodies- blocks COVID entry into cells
Dexamethason - cytokines
284
Tremor Definition
Rhythmic movement around a joint; postural; intentional movement (CNS involvement)
(hallmark of parkinsonism)
285
Chorea Definition
Muscle jerks in various areas; impairs movement & coordination
Jerky; flips back and forth
286
Ballismus Definition?
Violent abnormal chorea movement
287
Explain neuronal Communication between the areas of the brain to cause movements
1) Motore Cortex- Stimulated by gluatmine= sends signal to striatum
2) Striatum= stimulated by ACh goes to
3) Substantria Nigra= produces dopamine= inhibits some GABA
4) GABA goes to thalamus and goes back to motor cortex
288
Explain parkinson's patho
Substantia nigra- loss of neural melanin cells (makes dopamine)
Loss of Dopamine neurons= blocking signal to GABA receptor no longer there; more GABA to thalamus (inhibition)= no signal to help control fine muscle movement of motor cortex = jerky movements
289
Parkinsonism S/s
Rigidity
Bradykinesia
Tremor
Postural Instability
Cognitive decline
290
Explain how SNCA - α-Synuclein can be associated with Parkinsons
Protein responsible for NT release- dec dopamine release
291
Where are - α-Synuclein found?
Lewy bodies
292
Parkinson's TX
Exercise & PT important
1) Levodopa- (L-DOPA) or Dopamine agonists
2) CNS Antimuscarinics
3) MAOi- Selegiline, Rasagiline
COMTis- Tolcapone
4) Amantadine, Apomorphine (off periods)
Dopamine agonists- Pramipexole, Ropinirole
293
What meds should be avoided in parkinsons?
Antipsychotics- Dopamine receptor antagonists
MPTP- can destroy dopaminergic neurons
294
Levodopa MOA, Given with ?
MOA: Inc dopamine w inc L-Dopa (since dopamine cant cross BBB)
Given with carbidopa to prevent breakdown from DOPA- decarboxylase
295
Risk of taking levodopa? Tx?
Hallucinations & delusions due to high dopamine---esp w carbidopa
Tx: Pimavanserin
296
Duchenne's MD Main S/s
Grower's sign
297
Duchenne's TX
No cure; gene therapy
1) Corticosteroids, Beta-2 agonist, orthopedic braces
PT, RT
298
Cerebral Palsy Tx
Baclofen : GABAr agonist; centrally acting
Botulinum Toxin
Dantrolene
(through intrathecal pump)
299
Huntington's Disease TX
Opposite of parkinsons= inhibit dopamine by inc GABA
Tetrabenazine - inhibits VMAT
Haloperidol- dopamina receptor blocker
300
ALS Tx
Riluzole- NA channel blocker (damaged neurons)
Edaravone
301
NSAID -MOA, Use?
MOA: Blocks COX pathway- inhibits prostaglandin synthesis
Use: Antipyretic, analgesic
302
Aspirin MOA
MOA: Irreversibly block of cyclooxygenase
COX1 > COX2
303
304
Acute inflam mediators
Histamine, serotonin, bradykinin, prostaglandins, leaukotrienes
305
Chronic inflammation mediators
Interleukins, GM-CSF, TNF, Interferons, PDGF
306
Three fibers for transmission of sensation
1) Nociceptors- free nerve endings pain receptors
A(Beta) fibers- light touch (fast)
A(delta)- fast pain
C fiber- slower pain
307
Noxious Chemicals
Tissue damage – bradykinin
Receptors – B1 (inflammatory) and B2 (constitutive)
Activate PKA and PKC
308
Affective Sensation? Travels through what tracts?
Want to do something about
Sphinothalamic vs Spinorecticular
309
Spinoreticular allows us to ID what?
Travels through reticular formation of the pons=
Location of pain; slower
310
Spinothalamic
Pain- spinal cord neuron- reflex arch- thalamus- post-central gyrus
Fastest travel of pain
311
Spinomesencephalic pathway
Familiarization of pain; rich in μ (mu)
goes through PAG (DIC pathway)- endorphins & enkephalins
(gate theory)
312
Which drug has a low 1st pass metabolism?
Codeine (Prodrug- activated to morphine as active drug)
313
Morphine metabolism
Phase II to active forms
314
Opioid MOA
Bind to receptors in brain & spinal cord= hyper polarize postsynaptic neurons
Dec neurotransmitter release--> Glutamate, ACh, NE, serotonin, Substance P
315
Opioid system effects- CNS
Analgesia
Miosis (ALWAYS)
Euphoria or dysphoria
Sedation, Resp depression
Cough suppression
Constipation
316
Phenanthrenes- Strong Agonist Ex? Use?
Morphine, Hydromorphone
Heroin
Use- severe pain
317
Phenylheptylamines- Agonist? Use? Half life?
Methadone
Use- Chronic pain; opioid abuse
Shorter duration analgesia; long half life
318
Phenylpiperidine- Strong Agonist?
Fentanyl
Meperidine (Demerol)
319
Meperidine- Use? MOA? Can Induce?
MOA- antimuscarinic effects
Use- Post-op shivering
Induce- Serotonin syndrome, seizures
320
Moderate Agonists- Phenanthrenes
Codeine, oxycodone
Oxy + aspirin = percodan
Oxy + Acetaminophen= percocet
321
Opioid antagonists?
Derivatives of morphine- Naloxone, Naltrexone, naloxegol
Effects in 1-3 min & short duration; little effect in absence of agonist
322
Esters (heorin): Metabolism
Tissue esterases to morphine
323
Neoplasm: Def
New growth; abnormal mass of tissues, growth of which exceeds and is uncoordinated with the normal tissues
324
Carincoma: Cell Origin?
Epithelial origin
(Basal cell carcinoma, breast carcinoma )
325
Sarcome Origin?
Connective tissue or muscle (soft tissue cell)
(Osteosarcoma, kaposi sarcoma)
326
Leukemia & Lymphomas Origin?
Immune cells
(Hodgkins, AML)
327
Three Traditional Tx of Ca
Surgery
Radiation
Chemotherapy
328
Primary Chemotherapy: Used when? Goal?
Tumor is inoperable
Advanced disease – goal is to limit spread, improve QOL
329
Neoadjunct Chemo therapy for Ca: What is it? Use?
Surgery + chemo as adjunct (chemo before & after surgery) ; chemo is secondary
Useful in many GI cancers, breast, lung
330
Adjuvant Chemo Therapy for Ca: When is it used? Goal?
After surgery – reduce incidence and resurgence of tumor
Both surgery and chemotherapy equally important, possibly radiation
Goal is disease-free survival (DFS) and overall survival (OS)
331
Chemo toxicity
N/V, Bone marrow depression, alopecia, abortion, fetal death, teratogenicity, carcinogenicity, immunosupression
332
Alkylating Agent MOA
MOA: Transfers alkyl group (organic molecule missing H) to DNA or binds to DNA & interferes by cross linking (platinum compounds)
largest & most diverse class
333
Alkylating Groups & Ex for each?
Nitrogen Mustards- Cyclophosphamide (Ca & immunosuppressive) , Chlorambucil (least toxic ok for long term)
Nitrosoureas- crosses BBB (good for brain tumors)
Alkyl Sulfonate
Platinum Analogs: Cisplatin, Carboplatin
334
Cisplatin: MOA
1) Enters cell
2) Forms highly reactive platinum complexes
3) Intra strand & interstrand cross links
4) DNA damage
5) Inhibits cell proliferation
335
Cisplatin Pharmacokinetics
A: Highly bound to plasma proteins
Concentrated in kidneys, intestine, testes
E: Slowly excreted in urine
336
Methotrexate: MOA
MOA: Inhibits dihydrofolate reductase (DHFR); interferes w DNA/RNA synthesis
337
Methotrexate: 3 Actions
1) Cytotoxic actions: ulceration of intestinal mucosa
2) Immunosupressive action: prevents clonal expansion of B & T lymphocytes
3) Anti-inflammatory action : interferes w release of inflam cytokines
338
Antimetabolites Ca Drugs: Ex?
6-MP: 6 Mercaptopurine
5-FU: 5 fluoruracil
339
Plant Based Ca Drug – Ex?
Vincristine, Paclitaxel (Taxol)
340
Antibiotics Ca Drug Ex?
Dactinomycin, Doxorubicin, Bleomycin
341
Hormonal Agents Ca Ex?
Corticosteroids, Tamoxifen, Fulvestrant
342
Miscellaneous Ca Drug Ex?
Imatinib- inhibits specific receptors inside cell
Trastuzumab, Rituximab- Mab targeting specific protein outside cell
343
What are the defense mechanisms of the body?
Innate: 1) Physical, chemical, genetic barriers
2) cellular system (phagocytosis, inflam, fever)
Acquired- Active (infection) or Passive (maternal antibodies) = B & T cells
344
Hyposensitivies of immune response
Primary immunodeficiency: loss of immune system
Secondary- HIV (acquired immune issues)
Immune system not working
345
4 Types of Hypersensitivities
1) Type 1: antibody mediated (anaphylaxis)
2) Types 2- antibody mediated (blood tx rx)
3) Type 3: immune complex (RA)
4) Type 4: Cell mediated; t cells (delayed hypersensitivity)
346
DiGeorge Syndrome?
Primary immunodeficieny- no thymus (no T cells)
347
Agammaglobinemia?
Primary immunodeficieny : No B cells (no antibodies)
348
Severe combined immunodeficiency disorder (SCID)
Primary Immunodeficiency: No B or T cells
349
Secondary Immunodeficiency
Acquired Immune def Syndrome
350
Hypersensitivity Immunological D/o: Def & types?
Too much – overreaction of the immune system to innocuous stimuli (allergy)
Types I-IV
A – Anaphylaxis, allergies
C - Cytotoxic
I – Immune complex
D - Delayed
351
Hashimotos & Graves Disease is assoc w?
Thyroid
352
Addison's disease associated w?
Hypocortisolism
353
Systemic Lupus?
Autoantibodies agains DNA
354
Multiple Scerlosis vs Myasthenia Gravis?
MS: Autoantibodies & T cells agains neurons, myelin
MG- destruction of ACh-R
355
Autoimmune d/o common in?
Women
356
Autoimmune disease of pancreas?
Insulin dependent DM
357
Calcineurin Inhibitors: MOA? Ex?
MOA: inhibits T cell- R signaling & activation
Cyclosporine (toxic)
Tacrolimus
358
Cytotoxic Agents: Azathioprine : MOA, USE
Antimetabolite targeting rapidly proliferating cells
• Immunosuppressive, anti-cancer
– Metabolized by xanthine oxidase (XO) to mercaptopurine
– Interferes with purine metabolism
– Graft rejection, lupus, RA, Crohn’s, MS
– Main side effect – leukocytopenia caused by bone marrow
suppression
359
Cyclophosphamide: MOA?
MOA: Alkylating agent = destroys proliferating lymphoid cells/ Ca cells
Small dose - potent autoimmune d/o
High dose - Cancer agent
Metabolism- CYP 450 phase 1
breaks down to acrolein = tissue tox
& Phosphoramide mustard= cell death
360
361
Glucocorticoids- for immunosuppression
MOA: Suppress immune response, mimic naturally occurring adrenal corticosteroids
Ex: Prednisone, hydrocortisone, Dexamethasone
362
Immunosuppressive Antibodies- Mab
MOA: Antibodies created in lab, directed against cell-surface antigens/receptors
EX: Muromonab (CD3), RhoGAM, Adalimumab (TNF-a)
363
Additional Agents for Immunosuppression
Sirolimus, Mycophenylate Mofetil, Thalidomide Derivatives
364
365
BBB Components?
366
T/F: Some metabolites become active AFTER biotransformation
TRUE
367
368
P450 INDUCTION
Enhance synthesis; inhibit degradation
-IF metabolism deactivated drug= dec drug effect
- If metabolism activated drug= inc drug effect
369
P450 Inihibition
Dec or irreversible inhibit P450
Competitive inhibition – co-administered drugs metabolized by same P450
370
Permeation Factors
Aqueous diffusion
Lipid diffusion
Special carriers
Endocytosis and exocytosis
371
Define Vd
Concentration of the drug in the body COMPARED to the concentration in the blood
372
High Vd means?
Drug is more likely to leave blood and go into tissues
373
Low Vd
Drug is more likely to stay in blood
374
How will a high Vd affect the dose given for a drug?
Higher Vd= more likely to leave blood = more dose to reach target concentration
375
How do you figure out the dose when given the Vd and target concentration?
Vd x target concentration
376
Define clearance
Ability of body to eliminate drug; amount of drug that leaves a certain volume of the blood
Ex: blood is 5.6L; 10mL of blood, how much blood is in this 10mL?
377
Clearance vs elimination
CL= filtering out a certain amount of the blood compared to total amount of blood over time (volume/time)
Elimination= how much drug is leaving / time (concentration/time)
378
Explain clearance and ROE of 1st Order Elimination Drugs
Clearance is CONSTANT
ROE changes as concentration decreases (less drug in body= slower to eliminate)
379
Explain clearance and ROE of Zero Order Elimination Drugs
Clearance VARIES
ROE is constant
380
Define T1/2 (half life)
Time required to change drug in body to ½ of concentration
Pharm 2025
flashcards
Decks in class (26)
# Cards
-
Exam 1139
-
CH 3 - Pharmacokinetics48
-
CH 4- Drug Biotransformation39
-
CH 5- Pharmacogenomics7
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Drug Transport32
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9/17- Nervous System90
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9/24 Cholinomimetics & Antimuscarinics56
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Adrenergic Agonist/Antagonis50
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10/1- HTN / Angina/ Vasodilators109
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HF/ Arrhythmias68
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Diuretics E3 Start81
-
Asthma62
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Histamine, Serotonin, Depression67
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Seizures49
-
Sedative/Hypnotics46
-
Coagulation D/O E3 Done60
-
DIabetes (Exam 4 start)55
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Dyslipidemia42
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NSAIDs & Non-Opioids Analgesics55
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Opioids54
-
Antibiotics52
-
Antivirals34
-
Parkinson's55
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FINAL380
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Ca/Immunosuppression43
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OTC11
