Pharm-Part 1

Front 1

nicotinic receptors

Back 1

NICOTINIC TYPE I-R

=autonomic ganglia (SNS & PSNS): in both SNS & PSNS, 1st neuron releases ACh on N1-R
-also, adrenal medulla:
2nd neuron releases Ach on N1 receptor of adrenal medulla. (Then, adrenal medulla secretes Epi (the only thing that releases Epi.))

agonists (enhance Na conductance)
*nicotine
*Ach

antag ("ganglionic blocking drugs"):
*triMETHaphan
*hexaMETHonium
--------------------------

NICOTINIC TYPE II-R

=SkM motor endplate

agonists:
Ach
succinylcholine

antag:
"the --curiums & --roniums":
~d-tubocurarine (d-tc) [non-depol NMB)
~pancuronium

~Mg++

Front 2

sodium channels

Back 2

I. Na+ in cardiac fast fibers (atria, ventricles):

class 1A Rx: proCAINamide, disopyramide, quinidine
*all 3 inhibit repol==>prolong ERP
*only quinidine incr Q-T interval (can lead to Toursaud)

class 1B: lidoCAINe (only affects ventricles)
*accelerates repolarization==>shortens ERP

II. Na+ channels in CNS:
the antiepileptic drugs "PVC" (Phenytoin, Valproate, Carbamazepine; imagine a PVC pipe dripping Na+ out)
inhibit spread of electrical signals by prolonging inactivation state of Na+ channels

III. Na+ channels in sensory nerve fibers
=cationic form of local anesthetic drugs (coCAINE, proCAINE, lidoCAINE) block Na+ conductance by binding site in channel on axoplasmic side (inside cell)

*Na+ channels near CTZ (Chemotactic Trigger Zone) induce vomiting;
-blocked by ondansetron (and other "--setron" drugs)

Front 3

ketamine

Back 3

blocks NMDA receptors (Glutamate's receptor) coupled to Ca++ channels
==>Ca++ channels do not open
==>no depol
==>thus Ketamine's hallucinations (only in adults, not kids; thus, good to use in KIDS=KETamine) & Dissociative Anesthesia (Produces cataleptic trance-like state (pt may appear awake w/ eyes open))

Front 4

phencyclidine

Back 4

"angel dust"
-works the same as Ketamine:
blocks NMDA receptors (Glutamate Receptor) coupled to Ca++ receptors
==>Ca channels do not open
==>no depol
==>thus hallucinations & "dissociative anesthesia"
(=cataleptic trance-like state; pt may appear awake w/ eyes open)

Front 5

felbamate

Back 5

-works the same as Ketamine:
blocks NMDA receptors (Glutamate Receptor) coupled to Ca++ receptors
==>Ca channels do not open
==>no depol

Front 6

Tx neuroleptic malignant syndrome

Back 6

DOC=dantrolene

MOA: blocks internal Ca++ channels of SR
==>prevents release of "trigger" Ca++

Front 7

Tx anesthesia-induced malignant hyperthermia (hyperpyrexia)

Back 7

Tx: dantrolene sodium

MOA: blocks internal Ca++ channels of SR
==>prevents release of "trigger" Ca++

Front 8

sulfonylureas

Back 8

=oral active hypoglycemics

*tolbutAMIDE
*chlorpropAMIDE
*glypizide

MOA: inhibits K+ channels
==>depolarization
==>Ca++ flows in
==>activates PLC
==>incr IP3
==>release more Ca++ from SR
==>secrete insulin

diazoxide opens ATP-regulated K+ channels
==>prevent depolarization and insulin secretion

furosemide and thiazides also inhibit insulin secretion (mechanism unknown)

Front 9

what GABA receptors coupled to?

Back 9

GABA-A reeptors are coupled to Cl- channels (inhibitory: Cl- flows in==>cell less positive and thus hyperpolarized);

GABA-B receptors are coupled to K+ channels (inhibitory: K+ flows out==>cell less positive and thus hyperpolarized)

Front 10

baclofen

Back 10

Tx: spasticity assoc w/cerebral palsy, MS, and stroke

MOA: baclofen is an agonist for GABA-mediated K+ channels in CNS
==>decr release of excitatory glutamate in s.c.

"BACK OFF! Don't be so spastic!" (BACLOFen)

Front 11

drugs that act at GABA-A receptors

Back 11

All the following enhance GABA's effects:

*incr FREQ of opening of GABA channels:
-ethanol
-propanol
-volatile anesthetic agents
-BZ

*incr DURATION of opening of GABA channels:
-Barbiturates ("Barbie is the girl who will never leave the party (incr duration)")

*Valproate incr GABA via
-incr glutamic acid dehydrogenase
-inhibiting GABA transaminase

*GABApentin releases GABA from its neurons

Front 12

glycine receptors

Back 12

*Glycine receptors on Renshaw cells (spinal motorneurons) INHIBT alpha-motor neuron

*strychnine blocks glycine receptors
==>no alpha-motor neuron inhibition
==>convulsions

Front 13

D1-R do what?

Back 13

vd in kidney

*blocked by D1-D2-R blockers like haloperidol

Front 14

H2-R do what?

Back 14

-relax VSM (driect & via NO)==>vd
-incr secretion from oxynitic cells

Front 15

PGI2-R

Back 15

(PGI2=Prostcyclin)

-relax VSM==>vd
==>decr platelet agg (Goljan)

Front 16

PGE-R

Back 16

(PGE=Prostaglandin)

-relax VSM==>vd
==>decr platelet agg (Goljan)

Front 17

V2-AVP-R

Back 17

*in renal CD
*AVP (ADH) absorb water

Inhibited by:
-ANF
-PGE2
-Lithium
-Demeclocycline (Tx SIADH)

Stimulated by:
-chlorpropramide (Tx T2DM)
-carbamazepine

Front 18

5-HT1-R

Back 18

relax VSM==>sustained vd

Front 19

what does Li+ do re Ca++?

Back 19

Li++ inhibits recycling of PIP2
==>interrupts IP3 pathway
==>IP3 does not release Ca++ from SR
==>no SmM contraction

Front 20

digoxin

Back 20

Nl heart functioning:

I. Depolarization allows Ca++ to move into the cell via L-type (voltage-sensitive) Ca++
Channels→Now ↑[Ca++] inside cell

II. After depol is over, now you want to ↓ [Ca++] inside the cell:
1. Some of the Ca++ is pumped into the SR.
2. Additional Ca++ is extruded (sqeezed out, like toothpaste out of a toothpaste tube) by a Na+- Ca++ antiporter (exchanger) which uses the high outside/low inside Na+ gradient to move Ca++ out against its concentration gradient. This outside/inside Na+- gradient is maintained by the membrane Na+- K+ ATPase.

***Digoxin partially blocks the Na+- K+ ATPase
→the outside/inside Na gradient is decreased
→less Ca++ is extruded via Na+- Ca++ exchange
→excess Ca++ inside the cell is stored in the SR
→the next depolariaztion results in a greater release of Ca++ from the SR

Front 21

glucorticoids

Back 21

-incr transcription for lipocortin (inhibits PLA2), the inhibitor of NF-kappa-B (inflammatory cmpd) & enzymes for gluconeogenesis

-decr transcription of:
COX-2
IL-1
IL-6
gene for NF-kapa-B
enzymes for glycogen storage (except glycogen synthetase)

Front 22

cyclosporine

Back 22

immunosuppressant

decr transcription of gene for IL-2 in helper T cells

Front 23

androgens

Back 23

-increase erythropoiesis
-incr hepatic syntehsis of C1-esterase inhibitor of complement

Front 24

estrogen increase the synthesis of what?

Back 24

-TBG (Thyroid Binding Globulin)
-CBG (Cortisol Binding Globulin)
-transferrin (iron-binding protein)
-angiotensinogen (renin substrate)
-fibrinogen
-clotting factors 2,7,9,10

Front 25

malignant hyperthermia

Back 25

AKA hyperpyremia

-genetic defect prevents Ca++ from being sequestered correctly into SR
==>volatile anesthetic agent (i.e. halothane) + succinylcholine causes massive release of Ca++
==>incr BP, HR, cardiac arythmias, lactic acidosis, hyperthermia (the only Sx that's the same in neuroleptic malignant syndrome)

Tx: Dantrolene sodium (prevents release of Ca++ from SR)

Front 26

neuroleptic malignant syndrome

Back 26

NOT related to malignant hyperthermia

-neuroleptics (=antipsychotics=DA antagonists, i.e. haloperidol) block DA receptors==>

Sx ~Park Dz (DA deficiency)w/catatonia:

-EPS
-stupor
-hyperthermia (the only Sx that's the same as in malignant hypthermia)
-incr CPK (indicates damaged SkM)
-myoglobinuria
-ARF

Tx w/dantrolene sodium + bromocriptine (D2-R agonist)