Transcript 4-ANS applied pharm(Lec.1,2,3)

ANS practice problems
Reading assignments:
Kaplan Pharmacology USMLE Step1 ,
Lecture notes;2009,p53-67 ;
2 types of ANS practice problems asked by NBME
 1.Classic presentation :In the body of Q. you will see
a graph/tracing showing effect/s of an unknown drug
alone or in combination with other drugs. By looking
at the response you will have to identify that unknown
drug.
 2.Other Qs : Effect of unknown drug/s are shown in
non graphical pattern (in bars or charts or as
pictogram or others).Few working examples are given
in practice problem in this PP.
Effect of an unknown drug on Heart rate
and blood pressure
Control drug effect
Increased diastolic
Decreased diastolic
Increased Heart rate
Decreased Heart rate
Increased pulse pressure
Increased TPR (Increased α1)
decreased TPR (increased β2, decreased α1, directly
acting vasodilators and cholinomimetics.
increased β1 (May be reflex *)
Increased Cholinergic (May be a reflex)
increased β1 (increased inotropic activity)
Effect of α1 activators on Heart rate and
blood pressure
•Systemically , increase mean blood pressure via vasoconstriction.
•Increased BP may elicit a reflex bradycardia.
•Cardiac output may be decreased but also offset by increased venous
return.
•No change in pulse pressure.
Effect of β activators on Heart rate and
blood pressure
•Systemically, decrease mean BP via vasodilation (β2) and increased HR
(β1)
•Increased Pulse pressure.
Effect of Norepinephrine on Heart rate
and blood pressure
Exercise: Effect of norepinephrine after pre-tretment with
atropine.
Effect of Epinephrine on Heart rate and
blood pressure
 Dose dependent effects
 Low dose: β1 ,β2 stimulation.
 High dose: α1, β1 (β2).
 Β2 specific effects:
 Smooth muscle relaxation.
 Metabolic effects:
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Increased glycogenolysis
Increased gluconeogenesis
Increased mobilization and
use of fat.
 Exercise: Effect of
epinephrine after pretreatment with α1 blocker.
Effect of an unknown drug (R) on Heart rate and blood pressure
NBME
Step1: Go to working section and write Receptor affections
for each of drugs given in the choices ---interpret as the drug R
will essentially work by using any of those receptors

Step2 :What does the drug R do in BP &HR in control tracing?
------Match those effects with the drug from working section in
lite of their receptor affection--------if more than 1 option looks
correct move on to next experiment.
Step3:Visit each experiment (R + Blocker) and ask 2 Qs.
1.Does the blocker changes drug response in anyway?
(compare with control) interpret as if R + Blocker blocks a
response caused by drug R meaning that drug R when given alone
will produce that response (blocker can not produce any response
by its own. It can only block an agonist response.)
2.In +ce of blocker can the drug still do some changes?
(compare baseline/pre t/t vs drug effect in the same tracing)
R is
A. epinephrine
B.norepinephrine
C. phenylephrine
D. isoproterenol
E. terbutaline
Effect of an unknown drug (U) on Heart rate and blood pressure
NBME
Effect of an unknown drug (S) on Heart rate and blood pressure
NBME
Effect of an unknown drug (H) on Heart rate and blood pressure
NBME
Effect of an unknown drug (R) on Heart rate and blood pressure
NBME
Effect of an unknown drug (R) on Heart rate and blood pressure
NBME
 Drug H is
 Isoprotenol
 Epinephrine.
 Norepinephrine
 Phenylephrine
 Tyramine
Effect of an unknown drug (R) on multiple body parameters
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Drug X and Y are, respectively
Isoproterenol and propranolol
Epinephrine and phenoxybenzamine
Norepinephrine and phentolamine
Terbutaline and phenylephrine.
Acetylcholine and hexamethonium
NBME
Effect
Effectofofananunknown
unknowndrug
drug(R)
(R)ononHeart
multiple
rate body
and blood
parameters
pressure
NBME
Effect of unknown drugs on Heart rate and blood pressure in vitro
NBME
NBME
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Horner's syndrome is a clinical syndrome caused
by damage to the sympathetic nervous system.
PAMELa" for Ptosis, Anhidrosis, Miosis,
Enophthalmos and Loss of ciliospinal reflex.
Lesions
First-order neuron disorder: Central lesions that
involve the hypothalamospinal pathway (e.g.
transection of the cervical spinal cord).
Second-order neuron disorder: Preganglionic
lesions (e.g. compression of the sympathetic
chain by a lung tumor).
Third-order neuron disorder: Postganglionic
lesions at the level of the internal carotid artery
(e.g. a tumor in the cavernous sinus).
lesion of the post-ganglionic sympathetic
innervation of the right eye.
1. Alpha 1 agonist
2. Releaser / indirectly acting drug
3. Muscarinic receptor blocker
4. Alpha receptor blocker
Baroreceptor Reflex
 BP = SNS;  PSNS
 BP = SNS;  PSNS
Pretreatment with which drug will amplify the
tachycardia produced by the baroreflex arc
illustrated in the previous slide when an
experimental subject is given an intravenous
injection of histamine?
A. Botulinum toxin
B. Diphenydramine
C. Hexamethonium
D. Metoprolol
E. Physostigmine
Answer: E
Amplifies response
at ganglia
Baroreceptor Reflex
Phenylephrine
Histamine
BP
(mmHg)
SNA
(Units)
PSNA
(Units)
HR
(bpm)
Time (minutes)
NBME
Pretreatment with which of the following will
block the decrease in heart rate shown in the
preceding slide when an intravenous injection
of phenylephrine is given to an experimental
subject?
A. Metoprolol
B. Phenelzine
C. Physostigmine
D. Prazosin
E. Reserpine
Answer: D
Blocks alpha-1 receptors
Predicting Responses
β1 & β2
Epi reversal
β 1, β 2, & α
1
β 1, & α1
NBME
Stimulation of which receptor is responsible for
the slight pressor response seen on the
preceding slide when norepinephrine is injected
intravenously into an experimental subject
pretreated with an alpha blocker?
A. Alpha1
B. Alpha2
C. Beta1
D. Beta2
E. NicotinicN
Answer: C
Increases cardiac output
NBME
Heart Rate
Low dose
Blood Pressure Look
at BP 1st
ACH (2 mg)
ACH (50 mg)
Intermediate dose
(Atropine: Muscarinic Receptor Antagonist)
ACH (50 mg)
ACH (5 mg)
High dose
(Hexamethonium: Neuronal Nicotinic Receptor
Antagonist)
ACH (5 mg)
Which drug will block the pressor response
illustrated on the preceding slide when 5 mg of
ACh was given to an experimental subjects
pretreated with atropine?
A. Butoxamine
B. Cocaine
C. Metoprolol
D. Physostigmine
E. Prazosin
Answer: E
Blocks alpha-1 receptors