Pharm T16-21 Flashcards
1
Q
16.1 What is biotransformation in drug metabolism?
A
Biotransformation refers to the chemical modification of drugs in the body, often leading to a loss of biological activity and increased hydrophilicity (water solubility), which promotes drug excretion via the renal route.
2
Q
What are the four potential outcomes of drug biotransformation?
A
Active drug to inactive metabolite
Active drug to active metabolite
Active drug to toxic metabolite
Inactive drug to active metabolite
3
Q
What are Phase I reactions in drug metabolism?
A
Phase I reactions include oxidative, reductive, and hydrolytic reactions.
They may involve cytochrome P450 enzymes (e.g., hydroxylation, dealkylation, oxidation) or be independent of P450 (e.g., amine oxidation, ethanol dehydrogenation).
4
Q
What are examples of cytochrome P450-dependent Phase I oxidative reactions?
A
Hydroxylation: Amphetamines, warfarin, barbiturates
N-dealkylation: Caffeine, morphine
O-dealkylation: Codeine
N-oxidation: Nicotine
S-oxidation: Chlorpromazine, cimetidine
Deamination: Amphetamine, diazepam
5
Q
What are examples of oxidative Phase I reactions independent of cytochrome P450?
A
Amine oxidation: Epinephrine
Dehydrogenation: Ethanol, chloral hydrates
6
Q
What are examples of reductive and hydrolytic Phase I reactions?
A
Reductions: Chloramphenicol, clonazepam, dantrolene
Hydrolyses (esters): Aspirin, procaine, succinylcholine
Hydrolyses (amides): Indomethacin, lidocaine, procainamide
7
Q
What are Phase II reactions in drug metabolism?
A
Phase II reactions involve conjugation (synthetic) reactions, where subgroups like –OH, –NH2, or –SH are added to make drugs more water-soluble and less lipid-soluble, aiding in excretion.
8
Q
What are some examples of Phase II conjugation reactions?
A
Glucuronidation: Acetaminophen, diazepam, digoxin, morphine
Acetylation: Isoniazid, sulfonamides
Glutathione conjugation: Ethacrynic acid
Glycine conjugation: Niacin, salicylic acid
Sulfation: Methyldopa, acetaminophen
Methylation: Dopamine, norepinephrine (NE), epinephrine (E), histamine
9
Q
What is the role of cytochrome P450 in drug metabolism?
A
Cytochrome P450 enzymes are found in the smooth endoplasmic reticulum of the liver and are not highly selective, allowing them to metabolize thousands of different drugs.
10
Q
What are the main cytochrome P450 enzyme subtypes involved in drug metabolism?
A
1A2
2C9
2C19
2E1
3A4
2D6 (3A4 and 2D6 account for approximately 75% of active cytochromes)
11
Q
16.2 What type of neurotransmitter is ATP, and where is it located?
A
ATP is a non-peptide neurotransmitter found in postganglionic sympathetic neurons (e.g., in blood vessels and vas deferens).
12
Q
What is the function of ATP in NANC transmission?
A
ATP causes fast depolarization and contraction, including vasoconstriction.
13
Q
GABA is a non-peptide neurotransmitter. Where is it located, and what is its function?
A
GABA is located in enteric nervous systems (ENS) and its function is peristalsis.
14
Q
Where is serotonin (5-HT) found in the nervous system, and what is its role?
A
Serotonin (5-HT) is found in the ENS and plays a role in peristalsis.
15
Q
What is the role of dopamine in NANC transmission, and where is it located?
A
Dopamine is located in some sympathetic nervous systems (SNS), such as the kidney, and its function is vasodilation.
16
Q
Nitric oxide (NO) is a non-peptide neurotransmitter. What are its locations and functions?
A
NO is found in pelvic nerves and gastric nerves. It functions in erection and gastric emptying.
17
Q
What is the function of neuropeptide Y (NPY), and where is it located?
A
NPY is located in postganglionic sympathetic neurons (e.g., blood vessels) and enhances the vasoconstrictor action of noradrenaline, also acting as a noradrenaline release inhibitor.
18
Q
What is the role of vasoactive intestinal peptide (VIP) in NANC transmission, and where is it found?
A
VIP is found in parasympathetic nerves to salivary glands, NANC innervation to the smooth muscle of airways, and parasympathetic ganglia in sphincters, gallbladder, and small intestine.
Its functions include vasodilation, being an acetylcholine cotransmitter, bronchodilation, and relaxation of intestinal smooth muscle and sphincters.
19
Q
Where is gonadotropin-releasing hormone (GnRH) located, and what is its function?
A
GnRH is located in sympathetic ganglia and functions in slow depolarization and as an acetylcholine cotransmitter.
20
Q
Substance P is a peptide neurotransmitter. Where is it located, and what are its functions?
A
Substance P is located in sympathetic ganglia and ENS, and its function is slow depolarization and acetylcholine cotransmission.
21
Q
What is the function of calcitonin gene-related peptide (CGRP), and where is it found?
A
CGRP is found in non-myelinated sensory neurons, and its functions include vasodilation, increased vascular permeability, and neurogenic inflammation.
22
Q
A
23
Q
16.3 What are the two major groups of drugs used in clotting and bleeding disorders?
A
Anticlotting drugs (to decrease clotting or dissolve clots)
Drugs that facilitate clotting (to increase clotting in patients with clotting deficiencies)
24
Q
What are the types of anticlotting drugs?
A
Anticoagulants
Thrombolytics
Antiplatelet drugs
25
Name examples of anticoagulant drugs.
Heparins
Direct thrombin inhibitors
Indirect thrombin inhibitors
Warfarin
26
What are examples of thrombolytic drugs?
t-PA derivatives
Streptokinase
27
Which drugs are categorized as antiplatelet drugs?
Aspirin
GP IIb/IIIa inhibitors
ADP inhibitors (e.g., Clopidogrel)
PDE/adenosine uptake inhibitors
28
What drugs are used to facilitate clotting in patients with clotting deficiencies?
Replacement factors
Vitamin K
Antiplasmin drugs
29
What is the main function of anticoagulants?
Anticoagulants inhibit the formation of fibrin clots.
30
What are the three major categories of anticoagulants?
Heparin and related products (used parenterally)
2. Direct thrombin and factor X inhibitors (used parenterally or orally)
3. Coumarin derivative (Warfarin, used orally)
31
How is Heparin administered, and what is its source?
Heparin is administered IV or subcutaneously and is a large sulfated polysaccharide polymer obtained from animals.
32
What is LMWH, and how is it different from unfractionated heparin?
LMWH (low molecular weight heparin), such as Enoxaparin, is smaller (2000-6000 Daltons), has better bioavailability, and is longer-lasting.
LMWH is more selective, primarily binding to ATIII.
33
How does unfractionated heparin work, and how is it monitored?
Unfractionated heparin binds to ATIII and thrombin, forming a complex that inactivates thrombin and factor Xa.
Its effects are monitored using activated partial thromboplastin time (aPTT).
34
What are the uses of heparin?
Immediate anticoagulation (e.g., treatment of DVT, pulmonary embolism, AMI)
Combined with thrombolytics for revascularization
Combined with GP IIb/IIIa inhibitors during angioplasty and coronary stent placement
Safe during pregnancy as it does not cross the BPB
35
What are the potential toxicities associated with unfractionated heparin?
Increased bleeding and risk of hemorrhagic stroke
Moderate transient thrombocytopenia
Severe thrombocytopenia and thrombosis in some cases (HIT: Heparin-Induced Thrombocytopenia)
Long-term use can lead to osteoporosis
36
What is Heparin-Induced Thrombocytopenia (HIT)?
HIT occurs when antibodies bind to a complex of heparin and platelet factor 4, causing severe thrombocytopenia and thrombosis.
37
What are the Direct Thrombin Inhibitors based on?
They are based on proteins made by Hirudo medicinalis (medicinal leech).
38
Name some direct thrombin inhibitors and their mode of administration.
Lepirudin, Desirudin, Bivalirudin, Argatroban (all given parenterally)
Dabigatran (orally active)
39
What is a clinical use of Bivalirudin?
Bivalirudin is used in combination with aspirin during percutaneous coronary angioplasty.
40
Name two direct oral Factor Xa inhibitors and their characteristics.
Rivaroxaban and Apixaban
They have a rapid onset of action and shorter half-lives than warfarin.
41
What is the mechanism of action of Warfarin
Warfarin inhibits vitamin K epoxide reductase (VKOR), interfering with the post-translational modification of clotting factors in the liver, which depends on reduced vitamin K.
42
How can Warfarin’s effects be reversed?
Slowly with Vitamin K (requires the synthesis of new clotting factors).
Rapid reversal can be done by injecting fresh or frozen plasma containing normal clotting factors.
43
How is Warfarin monitored?
Warfarin is monitored using the prothrombin test (PT) and INR values.
44
What are the clinical uses of Warfarin?
Chronic anticoagulation in clinical situations like DVT, pulmonary embolism, and atrial fibrillation. Warfarin is never used during pregnancy.
45
What is a major caution with Warfarin use?
It has a narrow therapeutic window and bleeding tendencies are common, so it needs to be tightly monitored.
46
What are Thrombolytic Agents, and how do they work?
Thrombolytic agents include endogenous tissue plasminogen activators (e.g., alteplase, tenecteplase) and streptokinase (synthesized by streptococci).
They work by turning plasminogen into plasmin, which degrades clots.
47
What are the uses of thrombolytic agents in medical emergencies?
Alternative drug for percutaneous coronary angioplasty
Emergency treatment of coronary artery thrombosis
Treatment of acute pulmonary embolism
48
What is the major contraindication for thrombolytic agents?
Thrombolytic agents are contraindicated in patients with cerebral hemorrhage.
49
What is a significant limitation of streptokinase use?
Streptokinase can only be used once during a patient's lifetime because it can evoke the production of antibodies, causing loss of effectiveness or severe allergic reactions.
50
Name some antiplatelet drugs.
Aspirin
NSAIDs
GP IIb/IIIa receptor inhibitors (abciximab, tirofiban, eptifibatide)
ADP receptor antagonists (clopidogrel, ticlopidine)
Phosphodiesterase 3 inhibitors (dipyridamole, cilostazol)
51
17.1 What are the determinants of biotransformation rate?
Biotransformation rates vary due to factors such as genetics, drug-induced differences, smoking, drug compositions, food intake (e.g., grapefruit juice and warfarin), disease, and sometimes gender.
52
How do genetic factors influence drug metabolism?
Polymorphisms in cytochrome enzyme genes affect metabolism.
Abnormal hydrolysis of esters like succinylcholine can lead to prolonged drug effects (paralysis for hours instead of minutes in rare cases).
Differences in acetylation rates can affect responses to drugs like isoniazid and hydralazine, with 50% of White and African American individuals being slow acetylators.
53
Which populations are typically faster acetylators?
Asian and Eskimo populations are usually faster acetylators compared to White and African American individuals.
54
What are enzyme inducers, and which drugs commonly induce them?
Enzyme induction leads to increased synthesis of drug-oxidizing enzymes. Common inducers include carbamazepine, phenobarbital, phenytoin, and rifampin.
55
What is enzyme inhibition, and which drugs are known to inhibit drug metabolism?
Enzyme inhibition slows drug metabolism. Notable inhibitors include amiodarone, cimetidine, grapefruit juice (furanocoumarins), azole antifungals, and the HIV protease inhibitor ritonavir.
56
What are suicide inhibitors?
Suicide inhibitors are drugs metabolized to products that irreversibly inhibit metabolizing enzymes, such as spironolactone, allopurinol, and fluroxene.
57
What is an important modulator of intestinal drug transport?
P-glycoprotein (P-gp) is an important modulator of intestinal drug transport, usually functioning to expel drugs from the intestinal mucosa into the lumen, contributing to presystemic elimination
58
Where else, besides the intestines, is P-glycoprotein found?
P-glycoprotein is also found in the blood-brain barrier (BBB) and in drug-resistant cancer cells.
59
What happens when drugs inhibit P-glycoprotein?
Drugs that inhibit P-glycoprotein mimic drug metabolism inhibitors by increasing drug bioavailability, potentially resulting in toxic plasma concentrations of normally non-toxic dosages.
60
Which drugs inhibit P-glycoprotein?
Verapamil and furanocoumarins (grapefruit juice) inhibit P-glycoprotein.
61
What are examples of drugs expelled by P-glycoprotein?
Important drugs expelled by P-glycoprotein include digoxin, cyclosporine, and saquinavir.
62
17.2 What regulates the activity of ligand-gated ion channels?
The activity of ligand-gated ion channels is regulated by the binding of a ligand to the channel. The response is rapid (a few milliseconds).
63
Give an example of a ligand-gated ion channel and its function.
An example is the nicotinic receptor, which, when stimulated by acetylcholine (ACh), results in sodium influx and generation of an action potential. Another example is the GABA receptor, enhanced by benzodiazepines, resulting in increased chloride influx and hyperpolarization.
64
What are G protein-coupled receptors and how do they work?
G protein-coupled receptors are single peptides with seven membrane-spanning regions, linked to a G protein.
When activated by a ligand, the G protein dissociates, leading to changes in second messenger concentrations. Stimulation lasts from several seconds to minutes
65
What is an enzyme-linked receptor, and what is its function?
An enzyme-linked receptor binds to a ligand on its extracellular domain, activating or inhibiting cytosolic enzyme activity.
The response duration is minutes to hours, commonly seen with receptors like EGF and insulin.
66
What is the role of intracellular receptors?
Intracellular receptors are lipid-soluble ligands that, once activated, migrate to the nucleus and bind to specific DNA sequences, regulating gene expression.
Cellular responses are seen after 30 minutes or more and can last hours to days.
67
Define a substrate in pharmacology.
A substrate is a substance acted upon by an enzyme. In pharmacological terms, it can be understood as an agonist, a drug that activates its receptor upon binding.
68
What is a pharmacologic antagonist?
A pharmacologic antagonist is a drug that binds to a receptor without activating it, preventing the activation of the receptor by an agonist.
69
What is the difference between a reversible and irreversible antagonist?
A reversible antagonist can be overcome by increasing the agonist concentration, while an irreversible antagonist cannot be overcome by increasing agonist concentration.
70
What is a chemical antagonist?
A chemical antagonist is a drug that counters the effects of another by binding to the agonist drug itself, not the receptor.
71
What is a physiologic antagonist?
A physiologic antagonist is a drug that counters the effects of another by binding to a different receptor and causing opposing effects.
72
What is a partial agonist?
A partial agonist is a drug that binds to its receptor but produces a smaller effect at full dosage than a full agonist. Sometimes, it can act as an antagonist.
73
17.3 What are antacids and how do they work?
Antacids are weak bases that neutralize stomach acid by reacting with protons in the gut lumen.
They may also stimulate gastric mucosa functions. Regular high doses reduce the recurrence of peptic ulcers.
74
What are the common antacids used and their effects?
Magnesium hydroxide: Strong laxative action
Aluminum hydroxide: Strong constipation action
Calcium carbonate & sodium bicarbonate: Weak bases that are significantly absorbed from the gut, leading to systemic effects.
75
What are H2 receptor antagonists and what do they treat?
H2 receptor antagonists, like cimetidine, ranitidine, famotidine, and nizatidine, inhibit stomach acid production.
They treat GERD, peptic ulcer disease, non-ulcer dyspepsia, and prevent stress-related gastritis in seriously ill patients.
76
Why are H2 receptor antagonists being replaced?
H2 receptor antagonists are widely used but are being replaced by more effective and equally safe proton pump inhibitors (PPIs).
77
What are proton pump inhibitors (PPIs), and how do they work?
PPIs, such as omeprazole, esomeprazole, lansoprazole, and rabeprazole, are lipophilic weak bases that diffuse into parietal cell canaliculi and become protonated, concentrating more than 1000-fold.
They irreversibly inactivate the parietal cell H+/K+ ATPase, the primary transporter responsible for producing stomach acid.
78
What are the formulations and pharmacokinetics of PPIs?
PPI oral formulations are enteric-coated to prevent acid inactivation in the stomach.
After absorption, they are rapidly metabolized in the liver to become active.
They have a half-life of 1-2 hours, but the duration of action lasts around 24 hours. Full effectiveness takes about 3-4 days.
79
What conditions are treated with proton pump inhibitors?
PPIs are used to treat GERD, peptic ulcer disease, non-ulcer dyspepsia, stress-related gastritis prevention in seriously ill patients, and Zollinger-Ellison syndrome.
80
What are the adverse effects of proton pump inhibitors (PPIs)?
Adverse effects include diarrhea, abdominal pain, headache, hypergastrinemia (with chronic use), decreased bioavailability of vitamin B12 and drugs requiring stomach acidity (e.g., digoxin, ketoconazole), and a slight increase in the risk of respiratory and enteric infections.
81
What is sucralfate, and how does it work?
Sucralfate (aluminum sucrose sulfate) is a poorly soluble molecule that polymerizes in the acidic stomach.
It binds to injured tissue, forming a protective coating over ulcer beds, accelerating healing, and reducing ulcer recurrence. It must be taken 4 times daily and has very low systemic effects.
82
What is misoprostol, and what are its uses?
Misoprostol is a PGE1 analog that increases mucosal protection and inhibits acid secretion.
It is effective in reducing ulcer risk in chronic NSAID users but requires multiple daily doses and can cause diarrhea and GI irritation.
83
What are the actions and effects of colloidal bismuth?
Colloidal bismuth coats ulcers, stimulates mucosal protective mechanisms, has direct antimicrobial effects, sequesters enterotoxins, and reduces stool frequency and liquidity in infectious diarrhea.
Bismuth subsalicylate causes black stools.
84
What antibiotics are used to treat Helicobacter pylori infection?
Antibiotics used to treat Helicobacter pylori infection include clarithromycin, amoxicillin, and sometimes metronidazole.
85
18. What is drug excretion in pharmacology?
Drug excretion (elimination) refers to the process by which a drug is removed from the body, either in its unaltered form (free drugs) or as metabolites (after biotransformation).
The primary organ for excretion is the kidney, although the liver, skin, lungs, glands, and other organs also play a role.
86
What are the common pathways for drug elimination?
Common pathways for drug elimination include:
Urine
Tears
Saliva
Sweat
Respiration
Mother's milk
Feces
Bile
87
How are most drugs eliminated by the kidneys?
Most drugs are eliminated in urine, either in their chemically unaltered form or as metabolites, because the glomeruli filter molecules smaller than 5000 daltons.
Drugs may undergo:
Glomerular filtration
Active secretion in the proximal tubules (energy-consuming, limited capacity)
Passive reabsorption in the distal tubules (dependent on urinary pH)
88
What is ion trapping, and how is it used in poisoning treatment?
Ion trapping refers to a mechanism where weak acids or weak bases are trapped in a form that cannot be easily reabsorbed.
For weak acids, excretion is enhanced when the tubular fluid is alkaline, and for weak bases, excretion is enhanced when the fluid is acidic.
This principle is used in poisoning treatment with forced diuresis to eliminate toxic substances.
89
What role does the enterohepatic circulation play in drug excretion?
Drugs absorbed from the gut enter the portal circulation, are sent to the liver, where they are biotransformed into metabolites.
These metabolites can be conjugated with glucuronic or sulfuric acid and passed into the bile, eventually becoming part of the enterohepatic circulation.
90
How does the conjugation status of drugs affect their excretion?
Drugs can be eliminated through feces or urine based on their conjugation status:
Hydrophilic conjugates are more likely to be excreted via urine.
Lipophilic substances may be excreted via feces.
91
Which drugs are excreted via respiration?
Respiration can excrete certain substances, such as alcohol and anesthetic gases, to a limited extent.
92
Why is drug elimination via mother's milk important?
Drug elimination via mother’s milk is significant because many drugs excreted this way can be harmful to newborns, whose organs (especially liver and kidneys) are not yet fully developed.
93
18.2 What are the effects of α2-selective (Gi-coupled) sympathomimetics like clonidine?
α2-selective sympathomimetics, such as clonidine, cause:
Inhibition of neurotransmitter release at adrenergic and cholinergic nerve terminals.
Platelet aggregation stimulation.
Vascular smooth muscle contraction.
Inhibition of lipolysis in adipocytes.
Inhibition of insulin release from pancreatic β-cells.
94
What is the concept of a false transmitter?
A false transmitter is a substance that is stored in presynaptic vesicles and released into the synaptic cleft but lacks the full biological effect of the true neurotransmitter.
Examples:
- Octopamine – mimics norepinephrine but has weaker effects.
- 5-Methoxytryptamine (5-MeOHT) – mimics serotonin with reduced efficacy.
95
How does octopamine function as a false transmitter?
Octopamine is stored in place of norepinephrine in vesicles and released upon stimulation but does not produce the same strong adrenergic effects as norepinephrine, leading to diminished physiological responses.
96
How does 5-Methoxytryptamine (5-MeOHT) act as a false transmitter?
5-MeOHT mimics serotonin by occupying serotonin receptors, but it lacks the full efficacy of true serotonin, resulting in a reduced or altered effect on synaptic signaling.
97
18.3 What are the mechanisms of action for laxatives?
Laxatives increase the probability of bowel movement by:
Irritant or stimulating action on the bowel wall (e.g., Aloe, Senna, Cascara, Castor oil, Bisacodyl)
Bulk-forming action on stool evoking reflex contractions of the bowels (e.g., Psyllium, Methylcellulose, Polycarbophil)
Softening action on hard/impacted stools (e.g., Docusate, Glycerin, Mineral oil)
Lubricating action easing passage of stool through the rectum.
98
What are examples of osmotic laxatives?
Osmotic laxatives include Magnesium oxide, Sorbitol, Lactulose, Magnesium citrate, Sodium phosphate, and Polyethylene glycol
99
What drug is a chloride channel activator used as a laxative?
Lubiprostone is a chloride channel activator used as a laxative.
100
What drugs are used for pain relief in bowel movements?
Methylnaltrexone and Alvimopan are used for pain relief in bowel movements.
101
What are the most effective types of antidiarrheal agents?
The most effective antidiarrheal agents are opioids and their derivatives, specifically Diphenoxylate and Loperamide.
102
How is Diphenoxylate formulated to reduce the likelihood of abuse?
Diphenoxylate is formulated with anti-muscarinic alkaloids, such as Atropine, to reduce the likelihood of abuse.
103
What is Kaolin, and how is it used as an antidiarrheal?
Kaolin is a naturally occurring hydrated magnesium aluminum silicate combined with pectin (derived from apples) to absorb bacterial toxins and fluid, reducing the liquidity of stools.
104
What are aminosalicylates, and how are they used in IBD treatment?
Aminosalicylates, such as 5-aminosalicylic acid (5-ASA) or Mesalamine, are used as topical therapy for IBD, involving inhibition of prostaglandins, inflammatory leukotrienes, and cytokines.
105
What are the types of drugs used in the treatment of Crohn's disease and ulcerative colitis?
Antibiotics
Glucocorticoids
Immunosuppressive antimetabolites (Azathioprine, 6-Mercaptopurine, Methotrexate)
Anti-Tumor Necrosis Factor (TNF) drugs (e.g., Infliximab)
Humanized monoclonal antibody (e.g., Natalizumab)
106
What is Natalizumab, and what is it used for?
Natalizumab is a humanized monoclonal antibody that blocks integrins on circulating leukocytes.
It is used for severe, refractory Crohn's disease and has a possible association with multifocal leukoencephalopathy
107
What are the mechanisms by which anti-obesity drugs work?
Anti-obesity drugs work by:
Altering appetite
Reducing the absorption of calories
108
What is the main FDA-approved drug for long-term treatment of obesity in the USA, and how does it work?
Orlistat (Xenical) is the main FDA-approved drug for long-term obesity treatment. It reduces intestinal fat absorption by inhibiting pancreatic lipase.
109
What are the side effects of Orlistat (Xenical)?
Side effects of Orlistat include steatorrhea and, in rare cases, severe liver damage.
110
What is Rimonabant, and why is it not widely used?
Rimonabant is a drug used in Europe that blocks the endocannabinoid system to reduce cravings for food ("the munchies").
It is not approved in the USA or Canada and is not widely used due to concerns over side effects.
111
How does Sibutramine work, and why is it not commonly used?
Sibutramine works in the brain to inhibit the deactivation of neurotransmitters, thereby decreasing appetite.
It is not commonly used due to concerns about cardiovascular side effects.
112
Why are anti-obesity drugs typically only used in cases of severe obesity?
Anti-obesity drugs have unfavorable side effects, especially during long-term use.
They are only prescribed when the risk of obesity outweighs the potential risks of the drugs.
113
19. What are the three major interacting factors that determine the effect of a drug on an individual?
1. The drug itself
2. The individual user
3. The environment in which the drug intake occurs
114
What are the primary factors related to the drug itself that influence its effect on an individual?
Type of drug and quantity used
Chemical structure
Active site and receptors
Mode of absorption
Bioavailability
Metabolism mechanisms
115
What individual factors influence the effect of a drug?
Age
State of organs and co-morbid conditions
Health status
Doses and intake
Behavior and attitude (placebo effect)
Alcohol and drug use
Smoking, including cannabis use
116
How does the environment affect the impact of a drug on an individual?
The environment of drug intake can influence the drug's effects through factors like the setting, time, and user's expectations of the drug.
117
What additional factors influence drug effects on an individual?
Time it takes to consume the drug
Tolerance
Gender, weight, muscle mass, pregnancy, lactation
Age, exercise status, stress factors
Other drugs and their interactions
Attitude and expectation of effects
Setting or environment of intake
118
What happens in the preclinical phase of drug development?
Before clinical trials, pharmaceutical companies conduct preclinical studies, which involve in vitro (test-tube, cell culture) and in vivo (animal) experiments to gather preliminary information on efficacy, toxicity, and pharmacokinetics
119
What is the primary goal of the preclinical phase in drug trials?
Testing the drug in non-human subjects to gather efficacy, toxicity, and pharmacokinetic information.
120
What type of researcher monitors the preclinical phase?
A graduate-level researcher (Ph.D.).
121
What type of researcher monitors the preclinical phase?
A graduate-level researcher (Ph.D.).
122
How many participants are involved in the preclinical phase?
None, as this phase involves in vitro and in vivo studies only.
123
What is the dose used in the Phase 0 of clinical trials?
Very small, subtherapeutic doses.
124
What is the primary goal of Phase 0 in clinical trials?
To study pharmacodynamics and pharmacokinetics, particularly oral bioavailability and the half-life of the drug
125
How many participants are typically involved in Phase 0 trials?
10 people
126
What is the primary goal of Phase I in clinical trials?
Testing the drug on healthy volunteers for dose-ranging.
127
How many participants are involved in Phase I clinical trials?
20-100 people.
128
What is the main focus during Phase I clinical trials?
Determining whether the drug is safe to check for efficacy.
129
What is the typical dose used in Phase II clinical trials?
Therapeutic dose.
130
What is the primary goal of Phase II in clinical trials?
Therapeutic dose
131
What is the primary goal of Phase II in clinical trials?
Testing the drug on patients to assess efficacy and safety.
132
How many participants are involved in Phase II clinical trials?
100-300 people.
133
What does Phase II help determine in clinical trials?
Whether the drug can have any therapeutic effect; at this point, the drug is not presumed to have any therapeutic effect whatsoever.
134
What is the primary goal of Phase III in clinical trials?
Testing the drug on patients to assess efficacy and safety.
135
How many participants are involved in Phase III clinical trials?
1000-2000 people.
136
What is the therapeutic focus of Phase III clinical trials?
To determine the drug's therapeutic effect; at this point, the drug is presumed to have some effect.
137
What is the goal of Phase IV in drug development?
Postmarketing surveillance – watching drug use in public.
138
What is the main goal of Phase V in drug trials?
Translational research on the data collected from previous phases.
139
140
19.2 What are cardiac glycosides?
Organic compounds that affect the contractile force of cardiac muscle, found in plants and insects, and are extremely toxic with a narrow therapeutic range.
141
Is Digoxin considered a first-line drug for heart failure?
No, Digoxin is no longer considered a first-line drug for heart failure.
142
How does Digoxin work on a cellular level?
It inhibits Na+/K+ ATPase, leading to an increase in intracellular Na+, which alters Ca2+ transport, increasing intracellular Ca2+ and enhancing contractile force.
143
What is the effect of Digoxin on the autonomic nervous system?
Digoxin modifies autonomic outflow and influences the electrical properties of the heart, increasing parasympathetic effects early on.
144
What are the early effects of Digoxin on heart contractility?
- Increased contractility
Increased cardiac output
Decreased end-systolic and end-diastolic size
Decreased compensatory sympathetic and renal responses
145
How does Digoxin decrease sympathetic tone?
By reducing heart rate, preload, and afterload, allowing the heart to function more efficiently.
146
What are some early parasympathetic effects of Digoxin?
- Increased PR interval
Flattened T-waves
Shortened QT interval
Inverted T-wave and ST depression
147
What toxic responses can occur with Digoxin?
- Increased automaticity due to elevated intracellular Ca2+
Delayed afterdepolarizations leading to extrasystoles, tachycardia, and fibrillation
148
What conditions can amplify the toxicity of Digoxin?
Hypokalemia, hypomagnesemia, and hypercalcemia.
149
What drugs increase the risk of Digoxin toxicity?
Quinidine, amiodarone, and verapamil can raise serum levels of Digoxin, increasing toxicity risk.
150
What is Digoxin primarily used for in heart conditions?
It is used in chronic heart failure and atrial fibrillation, but requires close monitoring due to toxicity risks.
151
Does Digoxin prolong life in heart failure patients?
No, Digoxin reduces symptoms and improves functional status but does not prolong life.
152
Why is dosing important with Digoxin?
Due to its long half-life, Digoxin can accumulate in the body, making proper dosing and monitoring crucial to avoid toxicity.
153
What are the common symptoms of Digoxin toxicity?
Arrhythmias, nausea, vomiting, diarrhea, confusion, hallucinations (rare), and visual or endocrine abnormalities.
154
What can severe or acute Digoxin intoxication result in?
It can result in cardiac arrest, especially in cases of suicide or accidental overdose.
155
What is the first step in treating Digoxin toxicity related to electrolyte imbalance?
Correcting potassium or magnesium levels.
156
What is the first step in treating Digoxin toxicity related to electrolyte imbalance?
Correcting potassium or magnesium levels.
157
How are mild cases of Digoxin toxicity treated?
With antiarrhythmic drugs in less severe cases.
158
What is the most effective treatment for Digoxin toxicity in severe cases?
Digoxin antibodies (Digibind) are extremely effective and should be used if other therapies fail.
159
19.3 What are prokinetic drugs used for in upper GI motility?
Prokinetic drugs stimulate upper GI motility and are helpful for gastroparesis and post-surgical gastric emptying delay.
160
How do prokinetic drugs affect the lower esophageal sphincter?
They increase lower esophageal sphincter pressure, which is beneficial in treating GERD.
161
What are the mechanisms of action for Metoclopramide and Domperidone?
Metoclopramide and Domperidone work on the enteric nervous system and act as D2 dopamine receptor antagonists, promoting GI motility.
162
What additional effect does Metoclopramide have besides promoting GI motility?
Metoclopramide also acts on the area postrema in the brainstem, providing an antiemetic effect, useful after surgical anesthesia and chemotherapy-induced emesis.
163
What are the chronic side effects of Metoclopramide?
Chronic use of Metoclopramide can cause symptoms of Parkinsonism, extrapyramidal effects, and hyperprolactinemia.
164
Why does Domperidone not have CNS toxicity?
Domperidone does not cross the blood-brain barrier (BBB), avoiding CNS toxicity.
165
For what condition is Neostigmine useful?
Neostigmine (an acetylcholinesterase inhibitor) is useful for treating hospitalized patients with acute large bowel distention.
166
How does Erythromycin promote GI motility?
Erythromycin, a macrolide antibiotic, stimulates motilin receptors, promoting motility and benefiting patients with gastroparesis.
167
What type of drugs are used to prevent and treat vomiting, especially chemotherapy-induced vomiting?
A variety of drugs, including H1 histamine blockers, anti-muscarinic drugs, corticosteroids, cannabinoid receptor agonists, 5-HT3 antagonists, and NK1 receptor antagonists, are used.
168
Name an example of H1 histamine-blocking drugs used for antiemetic purposes.
Diphenhydramine and several phenothiazines are examples of H1 histamine-blocking drugs used for antiemetic actions
169
Which anti-muscarinic drug is used as an antiemetic?
Scopolamine is an anti-muscarinic drug used for antiemetic purposes.
170
What corticosteroid is used as an antiemetic?
Dexamethasone is a corticosteroid used for its antiemetic actions.
171
What cannabinoid receptor agonists are used to prevent nausea and vomiting?
Dronabinol and nabilone are cannabinoid receptor agonists used for antiemetic purposes.
172
Which 5-HT3 antagonists are effective in preventing nausea and vomiting, particularly after general anesthesia and chemotherapy?
Ondansetron, granisetron, dolasetron, and palonosetron are 5-HT3 antagonists used for preventing nausea and vomiting.
173
What is the mechanism of action for Neurokinin-1 (NK1) receptor antagonists?
NK1 receptor antagonists, such as Aprepitant, block receptors in the area postrema of the CNS, activated by substance P and other tachykinins, to prevent nausea and vomiting.
174
What are the side effects of Neurokinin-1 (NK1) receptor antagonists?
Side effects of NK1 receptor antagonists include fatigue, dizziness, and diarrhea.
175
What substances are used as emetics to expel toxins before absorption?
Ipecac syrup, saltwater, and mustard water are used as emetics. However, copper sulfate is no longer used due to toxicity.
176
What is the dual action of Ipecac syrup?
Ipecac syrup acts locally by irritating the gastric mucosa and centrally by triggering the area postrema. It is sometimes abused by bulimics.
177
20.1 What is a drug interaction?
A drug interaction occurs when a drug (or substance) affects the activity of another drug when both are administered together, which can result in synergistic (increased effect), antagonistic (decreased effect), or new effects.
178
What are some possible types of drug interactions?
Drug interactions may occur between drugs (drug-drug), food (drug-food), or plants (drug-plant).
179
What are some harmful outcomes of drug interactions?
Harmful outcomes include drug overdosing, dangerous side effects, or reduced therapeutic properties.
180
What processes can cause drug interactions?
Drug interactions can result from alterations in pharmacokinetics (ADME): absorption, distribution, metabolism, and excretion of a drug.
181
How can absorption be affected by drug interactions?
Absorption can be influenced by agents binding drugs (e.g., antacids, calcium-containing foods), changes in pH, and agents altering GI motility or P-glycoprotein activity.
182
How does decreased pH affect drug absorption?
Decreased pH can result in decreased absorption of drugs like digoxin, quinolones, and tetracyclines.
183
What agents can alter GI motility and affect drug absorption?
Agents like metoclopramide (increases motility) or antimuscarinics (decrease motility) can alter GI motility and drug absorption.
184
How does grapefruit juice affect drug absorption?
Grapefruit juice inhibits P-glycoprotein (P-gp), increasing the absorption of drugs that P-gp normally expels from the body.
185
How can absorption from subcutaneous tissue be slowed?
Absorption from subcutaneous tissue can be slowed using vasoconstrictors, such as epinephrine with local anesthetics.
186
How can absorption from subcutaneous tissue be slowed?
Absorption from subcutaneous tissue can be slowed using vasoconstrictors, such as epinephrine with local anesthetics.
187
How can drug distribution be altered?
Drug distribution can be altered by competition for binding sites on proteins, such as antibiotics displacing methotrexate, phenytoin, or warfarin from albumin.
188
How do verapamil and quinidine affect digoxin?
Verapamil and quinidine displace digoxin from its binding sites, potentially increasing its toxicity.
189
What is the role of the liver in drug metabolism interactions?
The liver plays a key role in drug interactions, where substances influence phase I and II drug metabolism processes controlled by cytochrome P450 enzymes.
190
What is a major feature of drug-drug interactions?
A major feature of drug-drug interactions is the involvement of cytochrome P450 enzyme subgroups in the liver.
191
What are the substrates of CYP1A2?
Caffeine, Theophylline, Phenacetin, Clomipramine, Clozapine, Thioridazine.
192
What are the inhibitors of CYP1A2?
Omeprazole, Nicotine, Cimetidine, Ciprofloxacin.
193
What are the inducers of CYP1A2?
Phenobarbital, Fluvoxamine, Venlafaxine, Ticlopidine.
194
195
How does the pH of urine affect the excretion of weak bases?
Weak bases are increasingly excreted as the pH of urine becomes more acidic.
196
How does the pH of urine affect the excretion of weak acids?
Weak acids are excreted more as the pH of urine becomes more alkaline.
197
How can altering urine pH be useful in medical treatment?
Altering urine pH can be used to enhance drug excretion, especially in cases of intoxications.
198
What are some examples of drugs that act as weak acids?
Acetylsalicylic acid
Furosemide
Ibuprofen
Levodopa
Acetazolamide
Sulfadiazine
Ampicillin
Chlorothiazide
Paracetamol
Chlorpropamide
Cromoglicic acid
Ethacrynic acid
Alpha-Methyldopa
Phenobarbital
Warfarin
Theophylline
Phenytoin
199
What are some examples of drugs that act as weak bases?
Reserpine
Amphetamine
Procaine
Ephedrine
Atropine
Diazepam
Hydralazine
Pindolol
Propranolol
Salbutamol
Alprenolol
Terbutaline
Amiloride
Chlorpheniramine
200
201
What happens during additive interactions in pharmacodynamics?
Additive interactions involve the summing of the effects of two drugs, such as combining alcohol with sedatives or antihypertensive drugs.
202
What is an example of a synergistic interaction?
Synergism occurs when two drugs together have a greater combined effect than the sum of their individual effects, e.g., sulfonamide antibiotics and trimethoprim.
203
What is potentiation in drug interactions?
Potentiation occurs when a drug’s effect is increased by another drug that doesn’t have a related effect, e.g., beta-lactamase inhibitors and clavulanic acid.
204
What is potentiation in drug interactions?
Potentiation occurs when a drug’s effect is increased by another drug that doesn’t have a related effect, e.g., beta-lactamase inhibitors and clavulanic acid.
205
How can herbal medications affect anticoagulants?
Herbal products like garlic and ginkgo are suspected to enhance the activity of anticoagulants.
206
How can herbal medications affect antidepressants?
Herbal products like ginseng are suspected to enhance the activity of antidepressants.
207
What is biological therapy?
Biological therapy is treatment that uses the body’s natural immune system to fight infection or disease, or to protect the body from the immune system (immunosuppressants).
208
What are some forms of biological therapy?
Forms include monoclonal antibodies (e.g., rituximab for non-Hodgkin’s lymphoma), interferons, interleukins, and colony-stimulating factors (CSFs).
209
What is an example of a monoclonal antibody used in biological therapy?
Rituximab is an example of a monoclonal antibody used for non-Hodgkin’s lymphoma.
210
What role do colony-stimulating factors (CSFs) play in biological therapy?
Colony-stimulating factors (CSFs) are used in biological therapy to stimulate the production of blood cells.
211
20.2 What is a positive inotropic substance?
A positive inotropic substance increases the strength of cardiac muscular contractions, often used in treating conditions like decompensated congestive heart failure and cardiogenic shock.
212
What is the primary effect of positive inotropic agents on Ca2+ levels?
Positive inotropic agents usually increase the level of Ca2+ in the cytoplasm of cardiac muscle cells.
213
What is Amiodarone and what are its primary effects?
Amiodarone is a Class III antiarrhythmic agent that prolongs phase 3 of the cardiac action potential (repolarization phase) and has antiarrhythmic effects resembling classes Ia, II, and IV.
It also has β-blocker and K+ channel blocker actions and affects intra-cardiac conduction via sodium channels.
214
How does Amiodarone resemble thyroxine?
Amiodarone binds to the nuclear thyroid receptor, which might contribute to some of its pharmacologic and toxic actions, resembling thyroxine.
215
What is Dobutamine and its primary use?
Dobutamine is a positive inotrope and sympathomimetic drug (β-agonist) used to treat acute, reversible heart failure, congestive heart failure, and septic or cardiogenic shock. It directly stimulates β1 receptors.
216
Why is Dobutamine not useful for treating ischemic heart disease?
Dobutamine increases heart rate, which raises oxygen demand of the heart, making it less useful for treating ischemic heart disease.
217
What is the role of phosphodiesterase inhibitors in positive inotropic effects?
Phosphodiesterase inhibitors block the inactivation of intracellular cAMP and cGMP, enhancing positive inotropic effects by increasing calcium-induced calcium release in the heart.
218
What is Inamrione and its effect?
Inamrione is a PDE3 inhibitor that improves prognosis in patients with congestive heart failure by increasing heart contractions through calcium-induced calcium release.
219
What are some other positive inotropes?
Other positive inotropes include epinephrine, norepinephrine, dopamine, angiotensin II, digoxin, and digitalis.
220
20.3 What is a common cause of exocrine pancreatic dysfunction?
Chronic pancreatitis is a common cause of exocrine pancreatic dysfunction, leading to maldigestion, steatorrhea, vitamin malabsorption, and weight loss.
221
How are pancreatic enzyme replacements administered?
Pancreatic enzyme replacements, such as pancreatin or pancrelipase, are taken orally in enteric-coated capsules to avoid inactivation by stomach acid. They are administered with each meal and snack.
222
Why must pancreatic enzyme replacements be enteric-coated?
Pancreatic enzyme replacements must be enteric-coated because they are inactivated at a pH <4.0 in the stomach. The coating helps protect the enzymes until they reach the intestine.
223
What are two drugs that inhibit the formation of cholesterol gallstones?
Chenodiol and ursodiol are bile acid derivatives that inhibit the formation of cholesterol gallstones.
224
How does Chenodiol work in preventing cholesterol gallstones?
Chenodiol works by preventing the production of cholesterol in the liver and helps dissolve cholesterol in the biliary system.
225
For what conditions is Chenodiol used?
Chenodiol is used for the dissolution of small cholesterol gallstones, prevention of gallstones in obese patients undergoing rapid weight loss, and treatment of early-stage primary biliary cirrhosis.
226
21.1 Clinical phase of drug development
227
Summary of clinical trial phase
228
21.2 What is the mechanism of action of Reserpine?
Reserpine is a plant alkaloid that blocks the Mg2+-ATP-dependent transport of biogenic amines (NE, dopamine, and serotonin) from the cytoplasm into storage vesicles in adrenergic nerves, leading to depletion of these amines and impaired sympathetic function.
229
What is the mechanism of action of Reserpine?
Reserpine is a plant alkaloid that blocks the Mg2+-ATP-dependent transport of biogenic amines (NE, dopamine, and serotonin) from the cytoplasm into storage vesicles in adrenergic nerves, leading to depletion of these amines and impaired sympathetic function.
230
How does Reserpine affect the duration and onset of action?
Reserpine has a slow onset, a long duration of action, and its effects persist for many days after discontinuation.
231
Why is Reserpine not used anymore?
Reserpine is not used anymore due to its significant side effects and the development of more effective antihypertensive drugs.
232
What is the mechanism of action of Guanethidine?
Guanethidine blocks the release of stored norepinephrine (NE) and displaces NE from storage vesicles, causing a transient increase in blood pressure followed by a gradual depletion of NE in nerve endings, except in the CNS.
233
What is the mechanism of action of Guanethidine?
Guanethidine blocks the release of stored norepinephrine (NE) and displaces NE from storage vesicles, causing a transient increase in blood pressure followed by a gradual depletion of NE in nerve endings, except in the CNS.
234
What are common side effects of Guanethidine?
Guanethidine commonly causes orthostatic hypotension and interferes with male sexual function.
235
What are common side effects of Guanethidine?
Guanethidine commonly causes orthostatic hypotension and interferes with male sexual function.
236
What is the primary mechanism of action of Cocaine?
Cocaine blocks the reuptake of monoamines (NE, serotonin, and dopamine) into presynaptic terminals by binding to monoaminergic reuptake transporters (uptake 1).
237
What is the primary mechanism of action of Cocaine?
Cocaine blocks the reuptake of monoamines (NE, serotonin, and dopamine) into presynaptic terminals by binding to monoaminergic reuptake transporters (uptake 1).
238
How does Cocaine affect the central nervous system?
Cocaine stimulates the cortex and brainstem, acutely increasing mental awareness and producing euphoria, similar to the effects of amphetamines.
239
What are the effects of Cocaine on the sympathetic nervous system?
Cocaine potentiates the action of NE, producing the "fight or flight" syndrome with tachycardia, hypertension, pupillary dilation, and peripheral vasoconstriction.
240
What unique risk does Cocaine pose among illicit drugs?
Cocaine can cause hyperthermia, which can be fatal not only due to dose but also due to its propensity to cause this condition.
241
What is the therapeutic use of Cocaine?
Cocaine is used as a local anesthetic applied topically during eye, ear, nose, and throat surgeries.
242
What is the therapeutic use of Cocaine?
Cocaine is used as a local anesthetic applied topically during eye, ear, nose, and throat surgeries.
243
How is Cocaine typically administered and what are its pharmacokinetics?
Cocaine is often self-administered by chewing, intranasal snorting, smoking, or IV injection. Peak effects occur 15-20 minutes after intranasal intake, with the "high" lasting 1-1.5 hours. It is rapidly deesterified and demethylated to benzoylecgonine and excreted in urine
244
What are the adverse effects of cocaine?
The adverse effects of cocaine include anxiety and depression.
245
What are the toxic effects of cocaine?
Cocaine's toxic effects include euphoria, tachycardia, increased respiration rate, agitation, hypertension, dyspnea, seizures, arrhythmias, respiratory failure, and death.
246
What are the major members of the amphetamine class?
Dextroamphetamine is the major member of the amphetamine class, while methamphetamine, a derivative of amphetamine, is often smoked and preferred by drug abusers.
247
What is the mechanism of action of amphetamines?
Amphetamines indirectly increase catecholamine neurotransmitter levels in synaptic spaces by releasing intracellular stores of catecholamines and inhibiting monoamine oxidase (MAO).
248
What are the effects of amphetamines on the central nervous system (CNS)?
Amphetamines stimulate the entire cerebrospinal axis, cortex, brainstem, and medulla, increasing alertness, decreasing fatigue, suppressing appetite, and causing insomnia. High doses may lead to psychosis and convulsions.
249
How do amphetamines affect the sympathetic nervous system?
Amphetamines indirectly stimulate the sympathetic nervous system through the release of norepinephrine (NE), leading to effects such as increased heart rate and blood pressure.
250
What are the therapeutic uses of amphetamines?
Amphetamines are used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, a rare sleep disorder characterized by uncontrollable bouts of daytime sleepiness.
251
What newer drug is available for the treatment of narcolepsy?
Modafinil, and its R-enantiomer derivative armodafinil, are newer drugs available to treat narcolepsy and are effective when taken orally.
252
How long do the effects of amphetamines last compared to cocaine?
The euphoria caused by amphetamines lasts 4-6 hours, or 4-8 times longer than the effects of cocaine.
253
What are the central adverse effects of amphetamines?
The central adverse effects of amphetamines include insomnia, irritability, weakness, dizziness, tremor, hyperactive reflexes, confusion, delirium, panic states, suicidal tendencies, and "amphetamine psychosis."
254
What are the cardiovascular adverse effects of amphetamines?
Cardiovascular adverse effects of amphetamines include palpitations, cardiac arrhythmias, hypertension, angina pain, circulatory collapse, headaches, chills, and excessive sweating.
255
What gastrointestinal effects are associated with amphetamines?
Gastrointestinal effects of amphetamines include anorexia, nausea, vomiting, abdominal cramps, and diarrhea.
256
What gastrointestinal effects are associated with amphetamines?
Gastrointestinal effects of amphetamines include anorexia, nausea, vomiting, abdominal cramps, and diarrhea.
257
Who should not be treated with amphetamines?
Patients with hypertension, cardiovascular disease, hyperthyroidism, glaucoma, or a history of drug abuse should not be treated with amphetamines.
258
What is the "cheese effect" related to tyramine?
The "cheese effect" refers to the potential for serious vasopressor episodes caused by tyramine found in fermented foods like ripe cheese and Chianti wine, especially in patients taking MAO inhibitors.
Tyramine can enter nerve terminals, displacing stored norepinephrine (NE), which acts on adrenoreceptors, increasing blood pressure.
259
What is the "cheese effect" related to tyramine?
The "cheese effect" refers to the potential for serious vasopressor episodes caused by tyramine found in fermented foods like ripe cheese and Chianti wine, especially in patients taking MAO inhibitors.
Tyramine can enter nerve terminals, displacing stored norepinephrine (NE), which acts on adrenoreceptors, increasing blood pressure.
260
How does tyramine normally get metabolized in the body?
Tyramine, a normal byproduct of tyrosine metabolism, is usually oxidized by monoamine oxidase (MAO) in the gastrointestinal tract.
261
What happens when a patient on MAO inhibitors consumes tyramine-rich foods?
When a patient on MAO inhibitors consumes tyramine-rich foods, tyramine is not broken down, leading to the release of catecholamines, which can cause dangerous increases in blood pressure.
262
Why are β-blockers effective in treating hypertension?
β-blockers are effective in treating hypertension because they decrease heart rate, cardiac output, and renin release. They also neutralize reflex tachycardia caused by vasodilators.
263
In what conditions are β-blockers especially useful?
β-blockers are especially useful in patients with associated conditions that benefit from the cardioprotective effects of the drugs, such as those with heart disease.
264
What are some side effects of β-blockers?
Side effects of β-blockers include bronchospasm in predisposed patients, sinus node dysfunction, AV conduction depression, nasal congestion, Reynaud phenomenon, and CNS symptoms like nightmares, excitement, depression, and confusion.
265
Are β-blockers recommended for patients with congestive heart failure?
β-blockers have traditionally been considered contraindicated in patients with congestive heart failure, though modern guidelines may allow their cautious use in certain cases.
266
21.3 What are herbal medicines and how are they different from conventional medicines?
Herbal medicines, also known as botanic therapy or phytotherapy, use natural and unprocessed herbs, whereas conventional medicines often use plant-based drugs in a processed form.
Herbal medicines are complex and unregulated, leading to potential contamination and label inaccuracies.
267
21.3 What are herbal medicines and how are they different from conventional medicines?
Herbal medicines, also known as botanic therapy or phytotherapy, use natural and unprocessed herbs, whereas conventional medicines often use plant-based drugs in a processed form.
Herbal medicines are complex and unregulated, leading to potential contamination and label inaccuracies.
268
What is Echinacea used for, and what are its potential side effects?
Echinacea, especially from Echinacea purpurea, is used for its cytokine activation and anti-inflammatory properties, often taken to help treat colds.
Side effects include an unpleasant taste, gastrointestinal issues, dizziness, and headache.
269
What are the uses and risks of Ephedra (Ma Huang)?
Ephedra contains ephedrine and pseudoephedrine, which are used as nasal decongestants and to treat asthma and bronchitis.
However, it can cause dizziness, insomnia, tachycardia, hypertension, and, at high levels, toxic psychosis and arrhythmias.
It's contraindicated in conditions like anxiety, hypertension, heart disease, and pregnancy.
270
What are the medicinal properties of garlic?
Garlic (Allium sativum) contains allicin, which inhibits HMG-CoA reductase and ACE, blocks platelet aggregation, increases nitric oxide, has antibacterial and fibrinolytic properties, and may reduce carcinogen activation. Side effects can include nausea, hypotension, and allergic reactions.
271
What are the potential interactions and contraindications of using garlic medicinally?
Garlic can increase the risk of bleeding, so caution is needed for patients taking anticoagulants or antiplatelet drugs. Other side effects include nausea, hypotension, and allergic reactions.
272
What are the benefits of Ginkgo biloba, and what are its potential side effects?
Ginkgo contains flavone glycosides and terpenoids, which have antioxidant and radical-scavenging effects, increase nitric oxide, and may help improve dementia and cognitive impairment.
Animal studies suggest it also reduces blood viscosity. However, it may interact with anticoagulants and cause bleeding.
273
What are the potential side effects of Ginkgo biloba?
Ginkgo biloba may cause gastrointestinal effects, anxiety, insomnia, and headaches.
It may also have antiplatelet action and is considered potentially epileptogenic, so it should be avoided in patients with seizure disorders.
274
What are the medicinal properties of Ginseng, and what are its risks?
Ginseng (Panax genus) contains triterpenoid saponin glycosides and may improve mental and physical performance, help prevent colds, and lower postprandial glucose levels.
However, it has estrogenic effects (e.g., breast pain, vaginal bleeding) and should be used cautiously with anticoagulant, antihypertensive, hypoglycemic, or psychiatric medications.
275
What are the pharmacological actions of Milk Thistle?
Milk Thistle (Silybum marianum) seeds contain compounds that reduce lipid peroxidation, scavenge free radicals, enhance superoxide dismutase, inhibit leukotriene formation, and increase hepatic RNA polymerase activity. The main side effect is loose stools.
276
What are the uses and risks of St. John's Wort?
St. John's Wort (Hypericum perforatum) contains hypericin and hyperforin, which decrease serotonin reuptake and may have antiviral and anticancer properties when photoactivated. However, it can cause mild GI effects and photosensitivity, and it should be avoided by patients taking SSRIs, MAO inhibitors, or those with bipolar/psychotic disorders.
It can also reduce the effectiveness of birth control, cyclosporin, digoxin, and HIV medications.
277
What are the uses and risks of St. John's Wort?
St. John's Wort (Hypericum perforatum) contains hypericin and hyperforin, which decrease serotonin reuptake and may have antiviral and anticancer properties when photoactivated. However, it can cause mild GI effects and photosensitivity, and it should be avoided by patients taking SSRIs, MAO inhibitors, or those with bipolar/psychotic disorders.
It can also reduce the effectiveness of birth control, cyclosporin, digoxin, and HIV medications.
