Flashcards in Exam #2 Deck (39):
1
chronotropy
positive chronotropy is increased heart rate (SA node)
2
inotropy
positive inotropy is increased force of contraction (atrial and ventricular cardiac muscle)
3
pharmacologic antagonist
bind to the same receptor as the agonist
competitive reversible:
- curve shifts right
- surmountable
- Emax stays same, EC50 inc., potency dec.
non-competitive (irreversible)"
- curve shifts down
- non-surmountable
- Emax dec, EC50 and potency stay same
4
physiologic antagonist
bind to a different receptor that mediates a physiologic response that is opposite to that of activation of the receptor for the agonist
5
G proteins for specific muscarine receptors
M3 (and M1): Gq = inc. contraction via IP3 and phospholipase C (GI)
M2 (and M2): Gi = dec. contraction via dec. cAMP (Heart)
6
sweat glands - part of ANS, NT released, and receptor type
part of SNS, but Ach is released to muscarinic receptors - exception
- not important in pharmacotherapy
7
G proteins for specific adrenergic receptors
a1: Gq = inc. contraction via IP3 and phospholipase C (vascular SM)
a2: Gi = dec. contraction via dec. cAMP (dec. SNS)
b1 and b2: Gs = inc. contraction via inc. cAMP (inc. HR and bronchodilation)
8
relationship between agonist and antagonist effect and tone
antagonist = effect is proportional to level of tone
- depends on receptor type and quantity
agonist = can overcome tone when use enough
- depends on dose
9
epinephrine reversal
when epi causes hypotension since patient on an a1 blocker (antagonist) --> excess b2 vasodilation
- treat with an a1 agonist (phenylephrine - Sedated PE)
10
sensitization to epi-induced hypertension
see excess inc. in HTN since patient is on a non-selective beta blocker --> unopposed epi a1 vasoconstriction
11
clonidine
activates a2 receptors
- dec. SNS outflow
- dec. release of Ach from cholinergic (muscarinic) neurons innervating the salivary glands
Treatment: HTN and opioid/alcohol withdrawal sxs
SE: dry mouth
- activates a2 receptors on cholinergic neurons in GI tract
- dec. Ach release from cholinergic neurons innervating salivary glands
12
beta-1 antagonists
beta-1 selectivity seen at low doses only - push dose can spill over to beta 2 (bad for asthmatic - bronchospasm)
metoprolol
atenolol
13
if there is no PNS innervation of the vasculature, how does muscarinic activation (Ach) on muscarinic receptors result in vasodilation?
indirect effect mediated via generation of nitric oxide --> cGMP --> dec. BP
14
side effects of muscarinic blocking agent (most sensitive to least sensitive)
Exocrine glands: reduced salivary and bronchial secretions → dry mouth
Sweat glands: impaired sweating and direct vasodilation → increased body temperature (“atropine flush” at high doses); most life-threatening result of overdose
• Children are especially susceptible (OD toxicity)
Heart: block of cholinergic slowing of heart rate → tachycardia
Eye: mydriasis and paralysis of accommodation (cycloplegia) → blurred vision, ↑ IOP (block aqueous humor drainage)
Lungs: relaxation of bronchiolar smooth muscle → bronchodilation
Genitourinary tract: relaxation of ureters and bladder wall muscle (detrusor) → urinary retention
Gastrointestinal tract: reduced gastrointestinal motility → constipation; gastric secretions (HCl, pepsin) blocked less effectively than salivary secretions
CNS effects: restlessness, delirium; sedation with scopolamine
15
lethal injection
Sodium thiopental: IV general anesthetic = unconscious
• Now unavailable in US – benzodiazepines* used
Pancuronium*: neuromuscular blocker = blocks respiration and involuntary muscle movements
Potassium chloride*: Produces complete heart block
• * 2016 – restricted from use in executions by Pfizer
16
baroreceptor reflex
Activation of baroreceptor (increased arterial pressure increases vessels tension and activates)
• Inhibits sympathetic discharge from medulla: vasodilation, dec. HR (reflex bradycardia)
• Vagus nerve activity increases (PNS) → dec. HR
• Overall: decrease blood pressure
Relaxation of baroreceptor (decreased arterial pressure)
• Disinhibits tonic sympathetic discharge, resulting in SNS-mediated release of NE
o Heart: B1 receptors → reflex tachycardia (inc. HR)
o Blood vessels: α1 receptors → vasoconstriction
• Overall: increase in arterial blood pressure
17
indirect acting sympathomimetics (adrenergic agonists) vs. indirect acting parasympathomimetics (cholinergic agonists)
Indirect-acting sympathomimetics (adrenergic agonists) act like NE by being uptaken by NET, transported to storage vesicle (VMAT), and displaces endogenous NE which is released into synapse
Indirect acting parasympathominetics (cholinergic agonists) inhibit the enzyme (AchE) the breaks down Ach; thus, prolonging the time Ach is in synapse
18
substance most associated with the acute bronchospastic response seen in patients with asthma
- target pharmacotherapy
leukotrienes
19
why should NSAIDs be used cautiously in patients with asthma
b/c they inc release of leukotrienes and can cause bronchospastic response
20
effects of endogenous histamines
vasodilation of arterioles via NO (hypotention / reflex tachycardia)
inc. capillary permeability (edema, urticaria, hives)
contraction of GI smooth muscle and inc. secretions
bronchoconstriction
stimulation of nerve endings (pain, itching)
triple response: wheal and flare
anaphylactic reaction
21
most effective physiologic antagonist of histamine in smooth muscle
epinephrine and albuterol
Note: antihistamines are pharmacologic antagonists
22
treatment of acute cough due to the common cold
1st generation antihistamine/decongestant (e.g., diphenhydramine/pseudoephedrine)
Naproxen (tid x 5 days): blocks inflammation that stimulates cough afferents (for pain)
Comments: antitussives mixed results; zinc not recommended; 2nd generation antihistamines ineffective
23
treatment of cough due to upper airway cough syndrome (postnasal drip)
1st generation antihistamine/decongestant (e.g., diphenhydramine/pseudoephedrine
24
treatment of dry, non-productive coughs that keep you up at night
anti-tussives (opioids or opioid agonists work at level of cough center
25
roles of cells in GI tract
parietal cells: pump out H+ via H+/K+ ATPase
epithelial cells: protect GI lining
- prostaglandins dec. H+, inc. HCO3, inc. mucous
26
why do NSAIDS cause ulcers
they wipe out prostaglandins (cytoprotective)
27
why treat h. pylori with ABX
to prevent reoccurrence
28
proton pump inhibitors (PPIs): side effects and DDI
mild: HA, abd pain, nausea, constipation, diarrhea
DDIs: omeprazole may inhibit conversion of anti-platelet drug clipidogreal to active form
Caution: dose reduction in severe hepatic disease
29
H2 antagonists: side effects and DDI
mild: dizziness, HA, constipation, diarrhea
Cimetidine: CNS dysfunction (slurred speech, confusion), endocrine effects (gynecomastia, galactorrhea, dec. sperm count
DDI: Cimetidine inhibits CYP450 oxidative metabolism, inc. toxicity for many drugs
Caution: dose reduction in impaired renal fx
30
how do PPIs protect GI tissues
decrease H+ secretion
31
how to prostaglandins protect GI tissues
dec H+ secretion, inc. HCO3, inc. mucous
32
properties of antacids
rapidly raise pH of stomach content to 4-5 (above ideal oH of pepsin but below gastrin to prevent rebound acid secretion)
use: pain relief due to peptic ulcerations and acute gastritis (doses titrated to sxs relief)
non-absorpable, long-acting, no undesirable side effects (most have constipation or diarrhea)
33
which antacids cause constipation and which cause diarrhea
constipation:
- calcium carbonate
- aluminum hydroxide
diarrhea:
- magnesium oxide (Milk of Magnesia)
34
antacids and DDIs
space drug dosing around antacid dosing to minimize DDIs
35
treatment of simple constipation
proper diet (high fiber: 20-30 g/day)
exercise (esp. abdominal muscles)
adequate fluids (6-8 8oz glasses / day)
36
drugs that cause constipation
o Calcium channel blockers (esp. verapamil)
o Opioid analgesics (cause both pain relief and constipation since interact with opioid (mu) receptors)
o Antimuscarinic agents (antispasmodics, overactive bladder agents)
o Drugs with antimuscarinic side effects (tricyclic antidepressants, antipsychotic agents, 1st generation antihistamines, parkinsonian agents)
o Antacids: aluminum and calcium-containing
o Calcium supplements (esp. carbonate)
o Chemotherapeutic vinca alkaloids
o 5HT3 antagonists - not SSRIs (block serotonin)
37
drugs that cause diarrhea
o Misoprostol: prostaglandin analog stimulates intestinal musculature
o Antibiotics (esp. broad spectrum)
o Muscarinic agonists (SLUDGE)
o Reserpine: sympatholytic agent allows parasympathetic dominance in GI tract
o SSRIs: elevated synaptic 5HT levels stimulates GI motility (inc. serotonin in gut = inc. diarrhea)
o Colchicine (anti-inflammatory for gout)
o NSAIDs
o Digoxin: parasympathomimetic action (similar to muscarinic excess)
o Magnesium antacids: osmotic laxative actions
38
opioid analgesic-injuced constipation
Constipation: managed with stool softeners (docusate), stimulant laxatives (bisacodyl - senna), osmotic laxatives (PEG [Miralax®] - milk of magnesia)
Option for patients taking opioids for non-cancer pain that have failed laxative therapy
- Peripherally acting opioid antagonists
Methylnaltrexone (Relistor®): given SC, doesn’t cross BBB
• Expensive ($700 per day)
Naloxegol (Movantik®): new pegylated derivative of naloxone given orally
• Extensive first-pass metabolism - primarily binds opioid receptors in GI tract only
• $10 per day
39